TEST BANK for Rodaks Hematology 6th Edition Elaine Catherine Otto, Walenga

TEST BANK Rodak's Hematology Clinical Principles and Applications Elaine M. Keohane, Catherine N. Otto, Jeanine M. Walenga

TABLE OF CONTENTS Part I: Introduction to Hematology 1. An Overview of Clinical Laboratory Hematology 2. Quality Assurance in Hematology and Hemostasis Testing Part II: Blood Cell Production, Structure, and Function 3. Cellular Structure and Function 4. Hematopoiesis 5. Erythrocyte Production and Destruction 6. Erythrocyte Metabolism and Membrane Structure and Function 7. Hemoglobin Metabolism 8. Iron Kinetics and Laboratory Assessment 9. Leukocyte Development, Kinetics, and Functions 10. Platelet Production, Structure, and Function Part III: Laboratory Evaluation of Blood Cells 11. Manual, Semiautomated, and Point-of-Care Testing and Hematology 12. Automated Blood Cell Analysis

13. Examination of the Peripheral Blood Film and Correlation with the Complete Blood Count 14. Bone Marrow Examination 15. Body Fluid Analysis in the Hematology Laboratory Part IV: Erythrocyte Disorders 16. Anemias: Red Blood Cell Morphology and Approach to Diagnosis 17. Disorders of Iron Kinetics and Heme Metabolism 18. Anemias Caused by Defects of DNA Metabolism 19. Bone Marrow Failure 20. Introduction to Increased Destruction of Erythrocytes 21. Intrinsic Defects Leading to Increased Erythrocyte Destruction 22. Extrinsic Defects Leading to Increased Erythrocyte Destruction-- Nonimmune Causes 23. Extrinsic Defects Leading to Increased Erythrocyte Destruction-- Immune Causes 24. Hemoglobinopathies (Structural Defects in Hemoglobin) 25. Thalassemias Part V: Leukocyte Disorders 26. Non-Malignant Leukocyte Disorders 27. Intro to Hematologic Malignancies 28. Flow Cytometric Analysis in Hematologic Disorders 29. Molecular Diagnostics in the Clinical Laboratory

30. Cytogenetics 31. Acute Leukemias 32. Myeloproliferative Neoplasms 33. Myelodysplastic Syndromes 34. Mature Lymphoid Neoplasms Part VI: Hemostasis and Thrombosis 35. Normal Hemostasis and Coagulation 36. Hemorrhagic Disorders and Laboratory Assessment 37. Qualitative Disorders of Platelets and Vasculature 38. Thrombocytopenia and Thrombocytosis 39. Thrombotic Disorders and Laboratory Assessment 40. Antithrombotic Therapies and Their Laboratory Assessment 41. Laboratory Evaluation of Hemostasis 42. Hemostasis and Coagulation Instrumentation Part VII: Hematology and Hemostasis in Selected Populations 43. Hematology and Hemostasis in the Pediatric, Geriatric, and Pregnant Populations

Rodaks Hematology 6th Edition Walenga Test Bank 1. Chapter 01-01 Hematology is the study of: *a. blood cells. b. serum electrolytes. c. plasma hormone levels. d. bacteria in the blood.

General Feedback: Hematology is the study of blood cells—red blood cells, white blood cells, and platelets. Plasma and serum electrolytes and hormone levels are evaluated in various subdivisions of clinical chemistry, and bacteria are evaluated in clinical microbiology.

2. Chapter 01-02 The morphology of blood cells is important to evaluate: a. every time a complete blood count (CBC) is requested on a patient. b. when an instrument-generated flag is obtained. *c. when a profiling instrument result is abnormal. d. when the white count is elevated.

General Feedback: Every laboratory must determine—based on its instrumentation, needs of the clinician and other parameter flags that alert the medical laboratory scientist to the necessity for further evaluation—when it is necessary to evaluate cell morphology. Many instrument-generated flags, although useful, may not require review. If an automated CBC does not suggest the need, no reason exists to evaluate the blood film, even if the white count is elevated.

3. Chapter 01-03 Who is ultimately responsible for determining the specimen integrity before analysis? *a. Medical laboratory professional b. Nursing staff c. Phlebotomist d. Specimen-processing personnel General Feedback: The medical laboratory scientist is responsible for ensuring the integrity of a specimen before analysis. Only he or she can judge whether the specimen is acceptable so that valid results can be obtained. Acceptable criteria include such things as type of specimen for the test ordered (e.g., blood, serum, urine); appropriate additive present (if needed) and amount of specimen relative to the additive; time interval since obtained; and presence or absence of hemolysis, lipemia, and other similar conditions. None of the other personnel named have the education and understanding to fully make that judgment.

4. Chapter 01-04 Hematocrit is also called: a. white cell count. b. bone marrow examination. c. red blood cell (RBC) count. *d. packed red cell volume.

General Feedback: Historically the hematocrit was determined by centrifuging an aliquot of anticoagulated whole blood under specified conditions (e.g., centrifugal force, capillary tube length, and bore diameter) and then determining the ratio of the space occupied by the packed red cells compared with that of the entire blood volume in the capillary tube, often expressed as a percentage. Hence, it is also called the packed red cell volume.

5. Chapter 01-05 The primary function of platelets is to: a. defend the body against bacterial invasion. b. carry oxygen to tissues. *c. facilitate blood clotting. d. regulate acid-base balance.

General Feedback: Whenever disruption occurs to a blood vessel so that bleeding results, platelets respond initially to stop the bleeding in small vessels; they also play an integral role in facilitating the formation of a blood clot. White cells defend against bacterial invasion; red cells (i.e., hemoglobin) carry oxygen to tissues; and a complex interaction of plasma electrolytes, proteins, and carbon dioxide participates in acid-base balance.

6. Chapter 01-06 Which of the following can be evaluated only through the microscopic examination of a stained blood film? a. White blood cell (WBC) count b. Reticulocyte count c. Hemoglobin concentration *d. Presence or absence of cytoplasmic inclusions General Feedback: Making and staining a blood film and then placing it under a microscope allow the medical laboratory scientist to evaluate the morphology of blood cells and examine them for the presence or absence of blood cell inclusions. These inclusions are important for cell identification and, when abnormal inclusions are present, sometimes provide “clues” as to the cause of disease. All the other parameters mentioned are or can be performed using an automated hematology instrument, including reticulocyte counting.

7. Chapter 01-07 Upon centrifugation of a blood specimen, the layer between the red blood cells and plasma is called the: a. hematocrit. *b. buffy coat. c. serum. d. platelet pellet.

General Feedback: When blood is centrifuged, the layer between the red cells and plasma is called the buffy coat. This layer consists of both white blood cells and platelets. The hematocrit is the packed cell volume that reflects the number of red blood cells. The serum is the liquid portion of the blood formed from a clotted blood sample. The platelet pellet is a special layer of platelets that is required for platelet function studies. This layer of platelets is prepared from a whole blood specimen using specific centrifugation time and speed.

8. Chapter 01-08 Select the term that describes a low white blood cell count. *a. Leukopenia b. Leukocytosis c. Neutropenia d. Leukemia General Feedback: The term leukopenia refers to a low total white blood cell count. Leukocytosis is a term that describes an increase in white blood cell count. Neutropenia is a low cell count that is specific to the neutrophils. Leukemia is cancer of the blood cells, most often white blood cells.

2. Chapter 02-02 A patient’s white blood cells (WBCs) are counted on an automated cell counter 10 times. The mean white count is 8000/mL, and the standard deviation (SD) is 300. What is the coefficient of variation (CV)? a. 0.04% b. 2.6% *c. 3.8% d. 26% General Feedback: % CV = (SD/mean) × 100 = (300/8000) × 100 = 3.8%.

3. Chapter 02-03 What does the CV calculated in Question 2 describe about the white cell counts? a. Accuracy b. Reliability c. Proper calibration *d. Precision General Feedback: The CV is a measure of precision, or how well a result can be reproduced. It allows comparisons of assays with different means and is a unitless number, although usually expressed as a percentage. Accuracy is how close a result is to the true value; proper calibration is required to obtain accuracy. Reliability is how well a method holds both accuracy and precision over time.

4. Chapter 02-04 A patient specimen is analyzed on an instrument known to be in control from previous assays performed on a calibrated instrument and gives a hemoglobin result of 13.2 g/dL. Two hours later it is evaluated on another instrument that is being evaluated for purchase by the laboratory. The result is 11.8 g/dL. This result, when compared with the first, is: a. acceptable agreement. b. reportable. c. precise agreement. *d. inaccurate.

General Feedback: This result is inaccurate compared with the first because it is significantly different. Precision is not known, because multiple results are needed to determine precision; in addition, precision must be determined using the same instrument, not between instruments.

Because it is not accurate, it cannot be reported.

5. Chapter 02-05 Which is true regarding reference ranges?

a. Should be derived from reference books b. Need to be determined only for adults c. Can be established by running the test procedure on 10 healthy people *d. Are ranges of values for an analyte in normal healthy people General Feedback: Reference ranges should be determined by evaluating a group of perhaps as many as 120 normal healthy people for the same analyte. If the analyte differs in different groups, based on data such as age and sex, it must be determined for each group if at all possible.

6. Chapter 02-06 A test that is positive in all patients who have the disease but also in some who do not have the disease is: *a. sensitive. b. specific. c. precise. d. reliable.

General Feedback: Sensitivity (diagnostic) is defined by the number of people with the disease who test positive. In this case, all patients with the disease have a positive result, so the test is very sensitive. The test, however, is not specific because it is also positive in some people who do not have the disease. Reliability refers to the performance stability of a test over time. Precision evaluates reproducibility of the result if repeated multiple times on a specimen.

7. Chapter 02-07 The antinuclear antibody (ANA) test is positive in almost all people who have systemic lupus erythematosus (SLE). It is also positive in some patients who do not have SLE. The antideoxyribonucleic acid (antiDNA) test is positive only in people with SLE but not in all who do.

Which of the following is true? *a. The ANA test is a good screening test, and anti-DNA test is a good confirmatory test. b. The anti-DNA test is a good screening test, and the ANA test is a good confirmatory test. c. Both are good screening tests for SLE. d. Neither of these tests is valid.

General Feedback: Because almost all patients with SLE have a positive ANA test, it is a good screening test (if the result is negative, it practically rules out this diagnosis for a patient). However, because the ANA test is also positive in other patients, the anti-DNA test is a good confirmatory test, because only patients with SLE have a positive result. In practice, the ANA test is done first; if it is positive, then the anti-DNA test is done as follow-up. If a patient is positive with both tests, then his or her diagnosis is SLE.

8. Chapter 02-08 A purchased hemoglobin standard is used to adjust a hemoglobinometer.

This standard is being used as a: a. control. b. precision check. c. delta check. *d. calibrator.

General Feedback: Standards are used to calibrate instruments. Controls are used to routinely evaluate the accuracy of a method once it is calibrated.

Precision is a measure of reproducibility, whereas delta checks compare a patient result with a previous result (same test on the same patient). This can only be done for a test result that essentially does not vary significantly from testing time to testing time.

9. Chapter 02-09 The tubing that brings the lyse reagent to the hemoglobin cuvette on an automated cell counter is pinched and not delivering any reagent. All hemoglobin values are greater than 20 g/dL. This represents what type of error? a. Random b. Imprecision *c. Constant systematic d. Proportional systematic General Feedback: A constant systematic error is one in which the magnitude of the error remains the same throughout the range of the test measurement. The error is proportional if the magnitude varies relative to the result. This is not a random error, which happens only infrequently and is not predictable. Precision requires multiple measurements of the same specimen and evaluates the ability to consistently reproduce the result.

10. Chapter 02-10 One of two controls that have been evaluated over the last 28 days gives a result on day 29 between 2 and 3 SDs of the mean; the other control is within 2 SDs of its mean. What is the correct procedure to follow? a. Ignore the result unless it happens again the next day. *b. Rerun the control and, if acceptable, continue with patients. c. Recalibrate the instrument. d. Open new vials of controls and repeat both controls.

General Feedback: One control is acceptable, whereas the other is a warning that the method may be going out of control. The test option in this case is to repeat the analysis of the control, and if it is acceptable, continue with patient analysis, reporting the results. The instrument

does not appear to need recalibration because one control is acceptable and the other is within 3 SDs (1 result of 20 can acceptably be within ±3 SDs). If the repeat on the “out of control” vial is still out between 2 and 3 SDs, then a new vial of that control should be opened and analyzed. The control that was acceptable does need to be repeated.

11. Chapter 02-11 The control values for both controls for the prothrombin test were ranging between the mean and ±1 SD for the first 19 days of use.

Starting on day 20, the values for both were consistently between +1 and +2 SDs. This is an example of a: *a. shift. b. trend. c. random error. d. predictable error.

General Feedback: If all results are consistently different from the previous in the same direction, it indicates a shift in the methodology has occurred. A trend would show a gradual change over time. This is neither a predictable error nor a random error because it is consistent.

12. Chapter 02-12 Which would most likely be associated with the situation described in Question 11? a. Operator error b. Fading light source c. Miscalibrated instrument *d. Starting a new lot number of thromboplastin reagent General Feedback: Shifts can occur when a new reagent is introduced. A fading light source would lead to trend error. If the instrument were calibrated incorrectly, both controls should be out; likewise, operator error would result in both controls being unacceptable.

13. Chapter 02-13 Which group of patients should not be included in establishing moving averages using red cell indices? *a. Chemotherapy patients b. Female patients c. Obstetric patients d. Surgical patients General Feedback: The moving average method works well in institutions that assay specimens from generalized populations that contain minimal numbers of sickle cell or oncology patients. This method is not restricted in female, obstetric, or surgical patients.

14. Chapter 02-14 A laboratory comparing its results to those of other laboratories on the same specimen is an example of: a. precision monitoring. b. internal quality assessment. *c. external quality assessment. d. delta checks.

General Feedback: When results are compared with those of another laboratory, this is part of external quality assessment. Internal quality assessment is done totally within one laboratory. Delta checks compare a patient result with a previous result on the same patient. Precision is determined by multiple analysis of the same specimen.

15. Chapter 02-15 The best way to prevent errors in the laboratory is to: a. purchase high-quality instruments from reputable vendors. *b. hire professionals with integrity. c. have quality management. d. perform external quality control procedures.

General Feedback: Competent professional staff that act with integrity can ensure that the best-quality results are routinely obtained for patients. A high-quality instrument is effective only when it is correctly calibrated and maintained. Management, although ultimately responsible, relies on the laboratory personnel to be aware of potential problems in assays. External quality control programs do not guarantee the daily validity of patient results.

16. Chapter 02-16 A laboratory gets numerous complaints regarding the length of time it takes hematology results to get to the emergency department. What would be an appropriate response? *a. Make this a quality assurance project. b. Ignore the complaints. c. Explain why it takes so long. d. Tell the employees to work faster.

General Feedback: Quality assurance evaluates the process from the time a test is ordered until it is reported to the correct patient chart. One of the responsibilities of a clinical laboratory is to get results to physicians and other caretakers in a timely manner; the acceptable turnaround time for a particular procedure will vary depending on the reason it is ordered. Obviously, an emergency department has a need for rapid turnaround time. Complaints from caregivers should never be ignored; it probably is not reasonable to tell employees to work

faster, and explaining why it takes so long will not help provide good patient care.

17. Chapter 02-17 The precision limits of a method are defined by: a. the mean. *b. the SD. c. sensitivity. d. specificity.

General Feedback: Evaluating the same specimen multiple times and applying statistics to the results determine precision or reproducibility. The SD describes the precision. The mean is the average result (assuming a gaussian distribution). Sensitivity describes how well a test identifies positive patients, whereas specificity is how well it identifies only positive patients.

18. Chapter 02-18 A clinical laboratory scientist performs 30 replicate hemoglobin determinations on a single blood sample. When statistics are used to determine the precision of the method, the mean is 13.8 g/dL and 1 SD is 0.1 g/dL. This means that 95.5% of the results on this specimen lie: a. between 13.4 and 14.2 g/dL. *b. between 13.6 and 14.0 g/dL. c. between 13.5 and 14.1 g/dL. d. between 13.7 and 13.9 g/dL. General Feedback: Because 1 SD is 0.1 g/dL, 2 SD = 0.2 g/dL. Thus 95.5% of the results lie between 13.6 (±2 SDs) and 14.0 (+2 SDs).

19. Chapter 02-19 The following hemoglobin results, reported in g/dL, are obtained on a hospitalized patient on 3 consecutive days: Day 1 Day 2 Day 3 14.3 11.5 14.4 The SD for this hemoglobin method was calculated in Question 18. A delta check was obtained on day 2. Controls were run as appropriate each day and were all within limits for this procedure.

What is the most probable reason for the day 2 result when compared with those for days 1 and 3? a. It is within the 95.5% confidence levels for this test. *b. It may represent an error in patient identification. c. The patient had a major blood loss between days 1 and 2. d. It is within the 99% confidence levels for this test.

General Feedback: The results for days 1 and 3 are statistically the same result (i.e., they are within the 95.5% confidence levels for this procedure and are therefore precise). The result for day 2 is clearly very significantly different, thus giving a delta check (the only possible explanation of those given here is that a patient identification error occurred and the specimen on day 2 is from a different patient). Delta checks are designed to help pick up this kind of critical error. If it had been within the 99% confidence limits, it would have been within 3 SDs, or no less than 14.0 g/dL. Because the results from day 1 and day 3 are the same, blood loss with a drop in hemoglobin cannot explain the day 2 results.

1. Chapter 03-01 What component of the erythrocyte is most responsible for its cytoskeleton and cellular integrity? a. Glycocalyx *b. Cytoskeletal protein c. Nucleus d. Golgi apparatus General Feedback: Cytoskeletal proteins are found on the inner cytoplasmic side of the membrane and form the lattice of the cytoskeleton.

2. Chapter 03-02 What cellular component of the erythrocyte is its control center? a. Heterochromatin b. Golgi apparatus *c. Nucleus d. Cytoplasm General Feedback: The nucleus is the control center of the cell, is responsible for all its chemical reactions, and is the site of deoxyribonucleic acid (DNA) replication and transcription.

3. Chapter 03-03 How does the genetically active portion of the nuclear chromatin look when stained with Wright stain? a. Condensed, darkly stained b. Clumped, dark purple c. Ropelike, pink or red *d. Diffuse, uncondensed and pale blue General Feedback: The genetically active portion of the nuclear chromatin, composed of DNA plus supporting proteins, appears diffuse and uncondensed and stains pale blue with Wright stain. It is also called euchromatin. Chromatin, which is condensed and stains darkly, is also called heterochromatin; it is the genetically inactive portion of the nucleus.

4. Chapter 03-04 What cellular component “directs traffic” for smooth functioning? a. Mitochondria b. Ribosomes *c. Golgi apparatus d. Nucleoli General Feedback:

The Golgi apparatus directs traffic in the cell, where it is responsible for modifying, sorting, and packaging macromolecules for secretion or delivery to other organelles within the cell.

5. Chapter 03-05 If the cytoplasm of a cell is very basophilic or dark blue when stained with Wright stain, it contains: a. low concentration of lysosomes. *b. large number of ribosomes. c. small number of ribosomes. d. high concentration of lysosomes.

General Feedback: Ribosomes, which are made up of ribonucleic acid (RNA), stain dark blue or basophilic with Wright stain. If a cell’s cytoplasm contains many ribosomes, it will stain very blue.

6. Chapter 03-06 Protein synthesis occurs in what part of a cell? *a. Ribosomes b. Nucleus c. Mitochondria d. Lysosomes General Feedback: Protein synthesis occurs on ribosomes, found in rough endoplasmic reticulum.

7. Chapter 03-07 What cellular component is responsible for energy production and metabolic processes? a. Ribosomes b. Nucleus *c. Mitochondria d. Lysosomes General Feedback: Mitochondria are responsible for energy production and metabolic processes of a cell.

8. Chapter 03-08 Lysosomes are found in the cytoplasm of many cells and contain: a. cholesterol. *b. hydrolytic enzymes. c. glycoproteins. d. RNA.

General Feedback: Lysosomes contain hydrolytic enzymes.

9. Chapter 03-09 What cellular structures appear as granules with Wright stain? a. Ribosomes b. Golgi bodies c. Mitochondria *d. Lysosomes General Feedback: With Wright stain, lysosomes are visualized as azurophilic granules.

10. Chapter 03-10 The nucleolus of a cell is composed of: a. hydrolytic enzymes. b. glycoproteins. *c. RNA. d. lipids.

General Feedback: The nucleolus is composed of ribosomal RNA, DNA, and proteins in loose fibrillar form and is found within the nucleus of a cell.

11. Chapter 03-11 Where are surface markers that help in cell identification found? *a. Cell membrane b. Golgi complex c. Rough endoplasmic reticulum d. Nucleus General Feedback: Surface markers are found on the cell membrane and are primarily composed of glycoproteins. Cluster differentiation (CD) numbers are used to identify them.

12. Chapter 03-12 A cell that is actively synthesizing protein has: *a. more nucleoli. b. more heterochromatin. c. fewer ribosomes. d. fewer mitochondria.

General Feedback:

A cell that is active in protein synthesis has more nucleoli, less heterochromatin (and more euchromatin), and more mitochondria and ribosomes.

13. Chapter 03-13 If the lysosomal membrane ruptures, what is the consequence to the cell? a. Activates cell nucleus to replicate DNA. b. Enhances protein synthesis by ribosomes. *c. Damages internal cell structures. d. Facilitates rearrangement of intracellular organelles.

General Feedback: When the lysosomal membrane is ruptured, its contents denature and digest DNA, RNA, and intracellular proteins; and ultimately the cell lyses.

14. Chapter 03-14 After birth, where does hematopoiesis predominantly occur? *a. Bone marrow b. Spleen c. Liver d. Lymph nodes General Feedback: After birth, hematopoiesis predominantly occurs in the bone marrow.

15. Chapter 03-15 Erythropoietin is a growth factor affecting erythroid progenitors and is produced by what organ? a. Bone marrow b. Spleen *c. Kidney d. Liver General Feedback: Erythropoietin is a growth factor affecting erythroid progenitors and is produced by the kidney when it senses hypoxia.

16. Chapter 03-16 In what stage of the cell cycle does DNA replication occur? a. G1 *b. S c. G2 d. M

General Feedback: S is the stage where DNA replication occurs. G1 is a period of cell growth and synthesis of components. M is mitosis. Stage G2 has tetraploid DNA and a large cell volume.

17. Chapter 03-17 Which morphologic characteristic is representative of apoptosis? a. Inflammation b. Cell swelling *c. Cell shrinkage d. Cell lysis General Feedback: Only cell shrinkage is characteristic of apoptosis. The other three are characteristic of cell death by necrosis.

1. Chapter 04-01 What are the major hematopoietic sites in the fetus and in the adult?

Fetus Adult a. Lymph node spleen *b. Liver bone marrow c. Liver spleen d. Bone marrow liver General Feedback: The major site of hematopoiesis in the fetus is in the liver, which retains some minor production until about 2 weeks after birth. In the adult, it is the bone marrow, where production begins in the fifth month of fetal life.

2. Chapter 04-02 How do cells get from the bone marrow into peripheral circulation? a. Stem cells escape the bone marrow and mature in peripheral circulation. b. Mature cells attach to a carrier protein for transport. c. Capillaries flow into the marrow and pluck out precursor cells. *d. Mature cells squeeze through spaces in the vessel endothelial lining.

General Feedback: As mature blood cells come into contact with endothelial cells in the bone marrow, they bind to the surface via a receptor-mediated process. The binding creates a space between the luminal adventitial and endothelial cells. The adventitial cells are capable of contracting, which allows mature blood cells to pass through the basement membrane and interact with the endothelial layer. This allows the bone marrow cells to escape into circulation.

3. Chapter 04-03 When hematopoiesis occurs in the liver in an adult, it is called: a. intramedullary. b. intermedullary. c. normal. *d. extramedullary.

General Feedback: Whenever hematopoiesis occurs outside the bone marrow in an adult, other than lymphopoiesis in lymphatic tissue, it is called extramedullary. This is abnormal.

4. Chapter 04-04 Where are developing red cells located in the bone marrow? *a. Adjacent to the outer surfaces of the vascular sinuses b. Outside the vascular walls of the sinusoids

c. Deep in the cords d. Randomly spaced throughout the cords General Feedback: Maturing red cells are found in two places in the bone marrow: (1) adjacent to the outer surfaces of the vascular sinuses and (2) surrounding iron-laden macrophages.

5. Chapter 04-05 Which splenic process removes inclusions from circulating red blood cells? a. Hemorrhage b. Macrophage c. Culling *d. Pitting General Feedback: Macrophages in the spleen normally remove abnormal inclusions from red cells, which is called pitting. Culling occurs when the cells are phagocytized with subsequent degradation of cell organelles.

6. Chapter 04-06 Where are the venous sinuses of the spleen located? a. White pulp *b. Red pulp c. Gray matter d. White matter General Feedback: The venous sinuses are located in the red pulp of the spleen.

7. Chapter 04-07 What condition is most associated with autosplenectomy? a. Abdominal trauma b. Thrombocytopenia *c. Sickle cell anemia d. Iron deficiency General Feedback: In sickle cell anemia, repeated sickling events in the spleen, where the red cells are stressed, result in multiple splenic infarcts.

Eventually, the spleen is no longer functional. This results in functional loss of the spleen and is called an autosplenectomy.

8. Chapter 04-08 Which is a characteristic of lymph? a. Solid substance

*b. Low protein c. Low red blood cells d. Superficial General Feedback: Lymph is the fluid portion of blood that escapes into the connective tissue and is characterized by a low protein concentration and the absence of RBCs.

9. Chapter 04-09 What bone marrow cells can differentiate into all of the blood cells? a. Burst-forming unit—erythroid (BFU-E) b. Colony-forming unit—granulocyte-monocyte (CFU-GM) c. Colony-forming unit—granulocyte, erythrocyte, monocyte, and megakaryocyte (CFU-GEMM) *d. Hematopoietic stem cells (HSCs) General Feedback: The stem cell from which all blood cells are derived is the HSC. The other stem cells mentioned are all committed to one or more blood cell lineage: BFU-E to erythroid; CFU-GM to granulocytes and monocytes; and CFU-GEMM to granulocytes, erythroid, monocytes, and megakaryocytes (from which platelets are derived).

10. Chapter 04-10 Which condition can nondevelopment of the thymus during gestation cause? *a. Failure to thrive b. Sickle cell disease c. Anemia d. Renal disease General Feedback: Nondevelopment of the thymus during gestation can result in failure to thrive, uncontrollable infections, and death in infancy.

11. Chapter 04-11 Having swollen lymph nodes is called: a. niche. b. porphyrias. *c. adentitis. d. hypersplenism.

General Feedback: Adentitis is infection or inflammation of the lymph node.

12. Chapter 04-12 Blood enters the spleen through:

a. lymph nodes. b. vena cava. c. right renal artery. *d. central splenic artery.

General Feedback: Blood enters the spleen through the central splenic artery located at the hilum and branches outward through the trabeculae.

13. Chapter 04-13 Which function is performed by cytokines except: a. proliferation. *b. regeneration. c. differentiation. d. maturation.

General Feedback: Cytokines are responsible for stimulation or inhibition of production, differentiation, and trafficking of mature blood cells and their precursors.

14. Chapter 04-14 Which is a hematopoietic growth factor? *a. Interleukin b. BFU-E c. Fibroblast d. HSC General Feedback: Only interleukin, of those listed, is a hematopoietic growth factor. The rest are cells found in the bone marrow. Actually several interleukins exist, each of which has a number (IL-1, IL-3, IL-6), that can affect various hematopoietic cells. In addition, other cytokines (e.g., erythropoietin, thrombopoietin) affect blood cell production.

15. Chapter 04-15 What is the primary mechanism for the anemia associated with kidney disease? a. Hemolysis b. Hemorrhage *c. Inadequate synthesis of erythropoietin d. Inadequate synthesis of interleukins General Feedback: Erythropoietin is the cytokine that has its primary effect on red cell production. It is synthesized in the kidney; thus when the kidney is diseased, erythropoietin synthesis is decreased. This decreases red cell production, leading to anemia.

16. Chapter 04-16 Which is not a function of macrophages in the bone marrow? *a. Activating adipose cells b. Secreting cytokines c. Storing iron d. Phagocytizing senescent cells General Feedback: Macrophages do not activate adipose cells. They perform all the other listed functions.

17. Chapter 04-17 Kupffer cells, found in the liver, are: a. adipose cells. *b. macrophages. c. immature red cells. d. immature granulocytes (neutrophils).

General Feedback: Kupffer cells are specialized macrophages found in the liver.

18. Chapter 04-18 Germinal centers in lymph nodes contain primarily: *a. B cells. b. macrophages. c. neutrophils. d. T cells.

General Feedback: Germinal centers contain primarily B cells and their progeny.

19. Chapter 04-19 The thymus is responsible for the initial development of: a. macrophages. *b. T cells. c. B cells. d. neutrophils.

General Feedback: The thymus contains lymphoid cells that undergo conditioning in the thymus and become T cells.

20. Chapter 04-20 Apoptosis is: a. enhanced red cell production.

*b. programmed cell death. c. directed exit of cells from the bone marrow. d. accidental cell death from trauma.

General Feedback: Apoptosis is programmed cell death, which is a normal physiologic process eliminating unwanted, abnormal, or harmful cells.

It is different from accidental death because of trauma—this is called necrosis.

21. Chapter 04-21 Colony-stimulating factors: a. have poor affinity for their target cells. b. require high concentrations to be effective. *c. are produced by many cells. d. are all lineage specific.

General Feedback: Colony-stimulating factors need only be present in a very low concentration to be effective. They have a high affinity for their target cells, binding to specific receptors on the cell surface. Many different cells produce them, and many of them affect several different cell lines.

1. Chapter 05-01 Where is erythropoietin synthesized? a. Bone marrow *b. Kidney c. Lymph nodes d. Spleen General Feedback: Erythropoietin is synthesized primarily in the kidney. A very small amount is produced in the liver.

2. Chapter 05-02 What stimulates production of erythropoietin? a. Decreased red cell number in the bone marrow b. Increased peripheral red cell number c. Decreased iron stores *d. Decreased oxygen level in tissue General Feedback: Peritubular cells in the kidney detect an undersupply of oxygen in tissue (also called hypoxia). They then synthesize erythropoietin. This increases red cell production in the bone marrow, unless the marrow is unable to respond the erythropoietin stimulus.

3. Chapter 05-03 Erythropoietin increases the number of red cells by all of the following mechanisms except: *a. prolonging cell life span. b. shortening cell division times. c. allowing earlier cell egress from the bone marrow. d. increasing the rate of hemoglobin synthesis.

General Feedback: Erythropoietin has no effect on red cell life span. It does perform all the other functions listed.

4. Chapter 05-04 Why do men typically have higher erythrocyte counts than women? a. They weigh more and have more blood vessels. b. They do not lose as much blood each month. *c. Testosterone stimulates erythropoiesis. d. They have more oxygen in their blood.

General Feedback: Testosterone stimulates red cell production.

5. Chapter 05-05 Programmed cell death is called: a. necrosis. *b. apoptosis. c. hemolysis. d. phagocytosis.

General Feedback: Apoptosis is programmed cell death, a normal physiologic process to remove damaged, abnormal, or unneeded cells. Necrosis is abnormal death because of trauma or damage. Hemolysis is cell death by rupture (which is abnormal). Phagocytosis is the primary mechanism for removal of senescent cells, but it also can remove damaged cells.

6. Chapter 05-06 What is the main site for iron storage in the bone marrow? a. Stem cells b. Transferrin molecules c. Endothelial cells *d. Macrophages General Feedback: Macrophages are the primary site for storage of iron in the bone marrow. Stem cells of various kinds are precursors to blood cells.

Transferrin is the protein that binds and transports iron to either storage or developing red blood cells (RBCs). Endothelial cells are the lining cells of the bone marrow and blood vessels.

7. Chapter 05-07 Which is true of red cell precursors as they mature? a. The nuclear-to-cytoplasmic ratio increases. b. The cells become larger. *c. The cytoplasm becomes less basophilic. d. The nucleoli become more prominent.

General Feedback: In general, basophilia decreases as the red cell matures (one exception to this: the basophilic normoblast is characteristically more basophilic than its precursor, the pronormoblast). The nuclear-tocytoplasmic ratio actually decreases, the cells become smaller, and nucleoli become less prominent and eventually disappear.

8. Chapter 05-08 Which has a pyknotic nucleus? a. Pronormoblast b. Basophilic normoblast c. Polychromatophilic normoblast *d. Orthochromic normoblast

General Feedback: The orthochromic normoblast has a pyknotic nucleus, meaning that the chromatin is fully condensed. After this stage, the cell no longer needs the nucleus and it is extruded or expelled. The nucleus of the pronormoblast is diffuse (dispersed), that of the basophilic is beginning to show some condensing, and that of the polychromatophilic is condensing even more.

9. Chapter 05-09 When compared with mature erythrocytes, reticulocytes: *a. are larger and bluer on Wright stain from remnant ribonucleic acid (RNA). b. are larger and have more vacuoles on Wright stain from remnant deoxyribonucleic acid (DNA). c. stain pinker with new methylene blue. d. still have a nucleus.

General Feedback: Reticulocytes still contain some RNA, as well as mitochondria and other organelles; these stain with the basic component of Wright stain and so lend some “blueness” to the cytoplasmic color. They are also slightly larger in both diameter and volume than a mature red cell. New methylene blue is a vital stain used to precipitate residual RNA in these cells so that they can be enumerated. The precipitated material, called reticulum, stains blue with new methylene blue.

Reticulocytes no longer have a nucleus; they are the first stage of development after extrusion of the nucleus.

10. Chapter 05-10 Which correctly describes a normal mature erythrocyte? *a. A 7- to 8-ìm biconcave disc that lives 120 days b. A 7- to 8-ìm spheroid that lives 120 days c. A 12- to 15-ìm spheroid that lives 80 days d. A 12- to 15-ìm biconcave disc that lives 80 days General Feedback: A normal mature red cell has a diameter of 7 to 8 ìm, is biconcave, and lives 120 days in circulation.

11. Chapter 05-11 Abnormal concentrations of cations inside erythrocytes cause: *a. spherocytosis. b. senescence. c. prolongation of survival. d. sickling.

General Feedback: Red cells have a high concentration of potassium and a low concentration of sodium when compared with the plasma environment. To maintain this difference in gradient, adenosine triphosphate (ATP)–

dependent enzymes are needed. When this system fails, sodium increases and potassium falls in the red cells. This results in loss of selective permeability of the red cell membrane, and water enters the cell causing it to sphere. Senescence is a normal aging process that eventually leads to red cell phagocytosis by splenic macrophages.

12. Chapter 05-12 What mechanism is responsible for the destruction of the majority of normal senescent erythrocytes? a. Intravascular hemolysis b. Rupture by complement c. Phagocytosis by peripheral neutrophils *d. Phagocytosis by splenic macrophages General Feedback: As red cells become old (senescent), changes occur in the membrane and intracellularly that lead to their phagocytosis by macrophages in the spleen.

13. Chapter 05-13 The breakdown products of heme go through several biochemical degradations to form: *a. bilirubin. b. protoporphyrin. c. amino acids. d. haptoglobin.

General Feedback: After phagocytosis by the splenic macrophages, hemoglobin is released. It is broken down into its component parts of globin chains and heme. Heme is further degraded in a series of steps eventually forming bilirubin, which is taken to the liver and further processed.

Globin chain amino acids are returned to the amino acid pool for use in protein synthesis.

14. Chapter 05-14 Haptoglobin performs which function when red blood cells are lysed in circulation? a. Prevent hypoxia. b. Cease apoptosis. *c. Salvage hemoglobin. d. Release hematocrit.

General Feedback: When the membrane of a red blood cell has been lysed, the cell contents enter the surrounding blood. The body reacts by activating haptoglobin, a plasma protein, to salvage the released hemoglobin so that its iron is not lost in the urine.

1. Chapter 06-01 Why is the mature erythrocyte unable to synthesize proteins or lipids? *a. It has no nucleus. b. It has no ribonucleic acid (RNA). c. It cannot generate adenosine triphosphate (ATP). d. Carrying oxygen interferes with synthesis.

General Feedback: The mature red cell lacks a nucleus, mitochondria, and other organelles. It is therefore unable to synthesize proteins or lipids. It also cannot perform oxidative phosphorylation.

2. Chapter 06-02 The principle energy source for mature red blood cells (RBCs) is: a. the Krebs cycle. b. the hexose monophosphate pathway. *c. ATP generated from anaerobic glycolysis. d. adenosine diphosphate (ADP) generated from aerobic glycolysis.

General Feedback: Anaerobic glycolysis is the pathway by which glucose is metabolized in the red cell, and ATP is generated through this pathway.

The hexose monophosphate pathway, through which aerobic glycolysis occurs, is the pathway that generates reduced glutathione. Reduced glutathione is essential to prevent oxidant injury to the red cell. The Krebs cycle is no longer operational in the mature RBC.

3. Chapter 06-03 Which erythrocyte activity requires energy? a. Oxygen delivery b. Carbon dioxide exchange c. Glucose transport into the RBC *d. Protecting proteins from oxidative damage General Feedback: Energy is required to protect proteins in the red cell from oxidative damage. This includes hemoglobin and membrane proteins. It is not required for oxygen transport, carbon dioxide exchange, or glucose transport into the cell.

4. Chapter 06-04 What is the fate of erythrocytes when anaerobic metabolic enzymes are reduced in concentration or are absent? a. Destruction by the liver b. Destruction by monocytes in the blood *c. Hemolysis d. Destruction by complement General Feedback:

When metabolic enzymes in the anaerobic pathway of glycolysis are reduced or absent, energy production in the form ATP is diminished.

This ultimately results in hemolysis of the RBC because the functions requiring energy in the form of ATP are not fully operational. This hemolysis occurs primarily in the spleen and so is called extravascular hemolysis (as opposed to occurring in the blood vessels, where it would be considered intravascular hemolysis).

5. Chapter 06-05 What is the normal life span of a red cell in circulation? a. 2 weeks b. 90 days *c. 120 days d. 6 months General Feedback: The normal red cell survives 120 days in circulation after its release from the bone marrow. By that time, changes that have occurred both internally and on the RBC membrane result in its phagocytosis and thus removal by splenic macrophages.

6. Chapter 06-06 Select the metabolic pathway that converts toxic hydrogen peroxide produced by oxidant drugs to water: a. Embden-Meyerhof pathway (EMP). b. 2,3-biphosphoglycerate (2,3-BPG). c. methemoglobin reductase reaction. *d. hexose monophosphate pathway.

General Feedback: Hydrogen peroxide is an oxidant and is detoxified via the hexose monophosphate pathway using reduced glutathione. The EMP generates energy in the form of ATP; the 2,3-BPG pathway is a shunt off of the EMP that is important for the reversible binding of oxygen.

Methemoglobin reductase is an enzyme that reduces the oxidized form of hemoglobin, called methemoglobin, to its reduced functional form.

7. Chapter 06-07 What important function does 2,3-BPG perform? a. Maintains iron in the hemoglobin molecule in the ferrous state. b. Prevents oxidative injury to the red cell. *c. Facilitates the delivery of oxygen to tissue. d. Aids in the exchange of membrane lipids with lipids in plasma.

General Feedback: 2,3-BPG plays a critical role in the effective transport of oxygen to tissue. It is produced via a shunt off the EMP. Elevations in 2,3-BPG are seen in a number of situations such as anemia; they result

in more effective delivery of oxygen to tissue. It has no role in the other functions listed.

8. Chapter 06-08 Which is the metabolic pathway that generates a net gain of two molecules of ATP for erythrocyte energy needs? *a. EMP b. 2,3-BPG c. Methemoglobin reductase reaction d. Hexose monophosphate pathway General Feedback: A net gain of two molecules of ATP occurs for every molecule of glucose metabolized via the EMP. When the 2,3-BPG shunt off of the EMP pathway is taken, no net gain of ATP occurs. No energy is generated via the hexose monophosphate pathway. The methemoglobin reductase reaction reduces methemoglobin, the oxidized form of hemoglobin, to its reduced functional form and does not generate energy.

9. Chapter 06-09 Which is the metabolic pathway that regulates oxygen delivery to tissues? a. EMP *b. 2,3-BPG c. Methemoglobin reductase reaction d. Hexose monophosphate pathway General Feedback: 2,3-BPG plays a critical role in the effective transport of oxygen to tissue. It is produced via a shunt off of the EMP; elevations in 2,3-BPG are seen in a number of situations such as anemia. Elevated levels result in more effective delivery of oxygen to tissue. None of the other pathways or systems listed play a role in the way oxygen is delivered to tissue.

10. Chapter 06-10 What is responsible for erythrocyte deformability and maintaining cell shape? *a. Membrane proteins b. Na+ and K+ pump c. Membrane lipids d. Ca2+ pump General Feedback: Proteins in the membrane are responsible for maintaining the shape and deformability of the red cell. Cation pumps maintain the Na+ and K+ gradient within the red cell. Membrane lipids form the fluid foundation into which the

membrane proteins are inserted. The Ca2+ pump maintains intracellular levels of Ca2+.

11. Chapter 06-11 What components of the erythrocyte membrane are responsible for its negative charge and are also blood group antigens? a. Peripheral proteins b. Cholesterol c. Cation pumps *d. Transmembrane proteins General Feedback: Transmembrane proteins include the glycophorins, which give the red cell its overall negative charge and are also responsible for the blood group antigens including those of the ABO and Rh systems. The peripheral proteins form the skeletal network of the red cell membrane.

12. Chapter 06-12 Which is most responsible for the strength and pliancy of the red cell membrane? a. Glycophorin A *b. Spectrin c. Cholesterol d. Ankyrin General Feedback: Spectrin composes the majority of the membrane’s skeletal mass and is the primary peripheral protein involved in maintaining the skeletal structure of the red cell. By the way it lines up with other spectrin molecules, it also plays an important role in making the red cell membrane deformable (pliant). This flexibility is important for permitting the red cell to “squeeze” through pores that have a diameter smaller than that of the red cell.

13. Chapter 06-13 Glucose-6-phosphate dehydrogenase (G6PD) is: a. an extremely rare enzyme deficiency. *b. necessary to maintain reduced glutathione in the mature red cell. c. important for the production of ATP in the mature red cell. d. important for the transport of carbon dioxide by the mature red cell.

General Feedback: G6PD is an enzyme in the hexose monophosphate pathway and is important for maintaining reduced glutathione in the red cell. This substance (reduced glutathione) is critical for preventing oxidative damage to red cell proteins. This pathway does not produce any energy and has no function in carbon dioxide transport. Its deficiency is very

common worldwide, affecting millions of people; in fact, it is the most common human enzyme deficiency in the world.

2. Chapter 07-02 How many molecules of oxygen can one molecule of hemoglobin carry? a. One b. Two c. Three *d. Four General Feedback: Each heme group is capable of carrying one molecule of oxygen.

Because four heme groups exist in one molecule of hemoglobin, each hemoglobin molecule can carry four molecules of oxygen.

3. Chapter 07-03 Why is heme located inside a globin chain pocket surrounded by hydrophobic amino acids? *a. Protects iron from being oxidized to its ferric form. b. Necessary for oxygen release to tissues. c. Makes hemoglobin insoluble. d. Keeps heme from being dissolved.

General Feedback: This arrangement helps keep iron in the divalent (ferrous) form regardless of whether or not it is carrying oxygen. This is critical for hemoglobin’s ability to reversibly bind oxygen.

4. Chapter 07-04 Where is heme produced? a. Liver b. Macrophages in the bone marrow *c. Red blood cell (RBC) precursors in the bone marrow d. Mature RBCs in peripheral circulation General Feedback: Heme is produced in RBC precursors in the bone marrow.

6. Chapter 07-06 The A1c-modified component of Hb A is increased in what condition? a. Sickle cell anemia b. Thalassemia c. Disorders of heme *d. Uncontrolled diabetes mellitus General Feedback: Hb A1c is a posttranslational modification of hemoglobin in which the hemoglobin molecule is glycated. Its concentration is increased when diabetes is uncontrolled.

7. Chapter 07-07 Which is true of hemoglobin if the oxygen dissociation curve shifts to the left? a. Has a lower affinity for oxygen. b. Picks up less oxygen in the lungs but delivers more to tissues. *c. Picks up more oxygen in the lungs but delivers less to tissues. d. Picks up and delivers more oxygen.

General Feedback: When the oxygen dissociation curve shifts to the left, it will load oxygen more easily in the lungs but also will hold onto it more tightly in tissue, thus delivering less oxygen to tissue. This is an example of high oxygen affinity.

8. Chapter 07-08 Which causes a shift to the right on the oxygen dissociation curve? *a. Severe anemia b. Alkalosis c. High levels of Hb F d. Decreased levels of 2,3-biphosphoglycerate (2,3-BPG) General Feedback: Severe anemia causes a right shift of the oxygen dissociation curve. This means that the affinity of hemoglobin for oxygen is less, so more oxygen will be released to tissue (more effective delivery of oxygen). Alkalosis (increased pH), Hb F, and decreased levels of 2,3BPG all shift the curve to the left.

9. Chapter 07-09 Why does Hb F have a higher oxygen affinity than adult hemoglobin? a. Fetal blood has a higher pH than adult blood. b. Fetal blood has a higher hematocrit than adult blood. c. Body temperature is lower in fetus. *d. It is necessary to extract oxygen from the maternal blood supply.

General Feedback: The fetus has a need for oxygen. In order for the fetus to extract oxygen from the mother’s blood (cord blood), its affinity for hemoglobin must be higher than that of the mother.

10. Chapter 07-10 Select the form of hemoglobin that contains iron in the ferric rather than the ferrous state. a. Myoglobin *b. Methemoglobin c. Deoxyhemoglobin

d. Carboxyhemoglobin General Feedback: Methemoglobin contains iron in the ferric form. This is nonfunctional hemoglobin (i.e., it cannot bind and carry oxygen).

11. Chapter 07-11 In which condition would patients have an increased concentration of methemoglobin? a. Patient receiving drug containing sulfonamide b. Patient exposed to reducing agents c. Patient with hemoglobin S (Hb S) *d. Patient with methemoglobin reductase deficiency General Feedback: A patient with methemoglobin reductase deficiency will have an elevated concentration of methemoglobin. It is normal for some small amount of hemoglobin to be oxidized on a daily basis. However, this does not build up in the RBCs because the iron is constantly being reduced to its functional ferrous state. When this enzyme is deficient, methemoglobin increases in the RBCs. Rare patients taking sulfonamidecontaining drugs may develop sulfhemoglobin. Oxidizing agents can increase hemoglobin M (Hb M), but not reducing agents. Patients with Hb S have normal levels of methemoglobin.

12. Chapter 07-12 Which is true regarding carboxyhemoglobin? *a. Smokers have increased levels. b. It has hydrogen sulfide added to hemoglobin. c. Normal people have none. d. Levels of 15% to 20% cause coma and death.

General Feedback: Smokers, depending on how much and what they smoke (e.g., cigarettes, cigars), may have as much as 15% carboxyhemoglobin in their blood. The concentration of carboxyhemoglobin in normal blood varies depending on the environment in which a person lives (more in an urban environment, for example, than in a rural location), but it is generally less than 1%. Levels greater than 40% cause coma and death.

The addition of hydrogen sulfide to hemoglobin forms sulfhemoglobin.

13. Chapter 07-13 Identify the primary organelle of synthesis site for globin chain and heme in developing RBCs. Globin chains Heme a. Ribosomes ribosomes b. Golgi complex mitochondria *c. Ribosomes mitochondria d. Mitochondria Golgi complex

General Feedback: Globin chains are synthesized on the ribosomes in the cytoplasm of a developing RBC; heme synthesis takes place primarily in the mitochondria.

14. Chapter 07-14 Which statement is true about Hb F? *a. It is the major hemoglobin during fetal life. b. It is increased in concentration in children up to 2 years old. c. It is evenly distributed at low concentration in all RBCs of an adult. d. It has a low oxygen affinity.

General Feedback: Hb F is the major hemoglobin during fetal life and at birth, but its concentration decreases after birth so that by age 6 months it should be less than 1% of the total hemoglobin. It is distributed unevenly in the RBCs of an adult (“F cells”), meaning that it is only found in some RBCs (not in all of them). It has a high oxygen affinity to enable it to extract oxygen from the maternal circulation.

15. Chapter 07-15 The reference range for hemoglobin concentration: a. is lower in a newborn than in a male adult. b. is lower in a newborn than in a female adult. *c. is higher in a newborn than in a male adult. d. is higher in a woman than in a man.

General Feedback: The reference range for hemoglobin concentration is higher in a newborn than in either an adult man or woman. In adults, it is higher in men than in women.

16. Chapter 07-16 Which is true for the relative affinity of hemoglobin for oxygen in the lungs and tissue with the oxygen dissociation curve in its normal position?

Lungs Tissue *a. High low b. Low low c. High high d. Low low General Feedback: The affinity of hemoglobin for oxygen is high in the lungs, so that loading of hemoglobin with oxygen is facilitated. It is lower in tissue to facilitate the delivery of oxygen to tissue.

17. Chapter 07-17 An increase in the concentration of 2,3-BPG: a. puts hemoglobin the relaxed conformation form. b. shifts the oxygen dissociation curve to the left. c. increases the affinity of hemoglobin for oxygen. *d. is present in patients with severe anemia and decreased blood pH (acidosis).

General Feedback: Patients who are severely anemic and those with a decreased blood pH, among others, have increased levels of 2,3-BPG. This shifts the oxygen dissociation curve to the right, thus decreasing the affinity of hemoglobin for oxygen. The result is more effective delivery of oxygen to tissue. An elevated concentration places the hemoglobin molecule in the tense conformational form.

18. Chapter 07-18 Why is it important that synthesis of globin chains and heme be balanced in the RBCs? a. Excess concentration of protoporphyrin increases bilirubin in plasma. *b. An excess of one of the components of hemoglobin decreases RBC survival. c. An excess of one of the components of hemoglobin increases RBC survival leading to an eventual elevated RBC count. d. An excess of globin chains significantly decreases the concentration of globin chain messenger ribonucleic acid (mRNA) in the developing RBCs. General Feedback: An excess of one of the components of hemoglobin can decrease RBC survival in circulation. None of the other listed items are true in the presence of an excess.

19. Chapter 07-19 Which is true of the oxygen dissociation curve? a. The normal partial pressure of oxygen (PO2) at which hemoglobin is 50% saturated is 20 mm Hg. *b. A shift to the right or left in response to blood pH is called the Bohr effect. c. A shift to the left results in lower oxygen affinity. d. A shift to the right results in less effective delivery of oxygen to tissue.

General Feedback: The Bohr effect describes the shift in position of the oxygen dissociation curve in response to blood pH; a decrease in pH (acidosis) shifts the curve to the right and results in a decreased oxygen affinity and more effective oxygen delivery. A decrease in pH (alkalosis) is the reverse—the curve shifts to the left resulting in

increased oxygen affinity and less effective delivery of oxygen to tissue.

20. Chapter 07-20 Which provides a negative feedback for heme synthesis, thus helping to control, by decreasing, its synthesis? *a. Concentration of heme in the developing RBC b. Concentration of hemoglobin in blood c. Concentration of globin chain in the developing RBC d. Number of RBCs in circulation General Feedback: As the concentration of heme increases in the developing RBC; it acts as a negative feedback to decrease further synthesis of heme.

This helps control its rate of production.

21. Chapter 07-21 The globin chains making up Hb A are: a. two epsilon and two gamma chains. b. two sigma and two epsilon chains. c. two alpha and two gamma chains. *d. two alpha and two beta chains.

General Feedback: Hb A is composed of two alpha and two beta chains; sigma and epsilon chains are embryonic chains and are seen only in fetal life. Hb F is composed of two alpha and two gamma chains.

22. Chapter 07-22 What is the effect of an increased concentration of 2,3-BPG in the RBC? a. Puts hemoglobin in the relaxed conformation. *b. Shifts the oxygen dissociation curve to the right. c. Increases the affinity of hemoglobin for oxygen. d. Decreases the synthesis of globin chains.

General Feedback: An increased concentration of 2,3-BPG shifts the oxygen dissociation curve to the right and decreases the affinity of hemoglobin for oxygen. It has no effect on the synthesis of globin chains.

1. Chapter 08-01 Where is the largest percentage of iron in the body located? a. Stored in the bone marrow b. Stored in the liver *c. Attached to hemoglobin in erythrocytes d. In the cytoplasm of macrophages General Feedback: Approximately 70% of total body iron is found in hemoglobin.

Almost 20% of body iron is in storage, mostly within hepatocytes and macrophages in the spleen and bone marrow. The remaining approximately10% is divided among the muscles, the cytochromes, various iron-containing enzymes, and the plasma.

2. Chapter 08-02 What is the mechanism for iron toxicity if iron is present in excess amounts? *a. Acts as a catalyst in forming hydroxyl (free) radicals. b. Impedes hematopoiesis. c. Reduces hemoglobin to methemoglobin. d. Interferes with globin synthesis.

General Feedback: Iron has reduction (redox) potential, and easily cycles between ferrous (reduced) and ferric (oxidized) forms. If it is found in excess, it plays a key role in forming harmful oxygen radicals that can damage cellular structures and harm cells in the process.

3. Chapter 08-03 What is the plasma carrier protein for iron? a. Apoferritin *b. Apotransferrin c. Albumin d. Hemosiderin General Feedback: Apotransferrin is the carrier protein for iron. Apoferritin and hemosiderin are storage forms of iron. Albumin is a carrier protein for many substances but not for iron.

4. Chapter 08-04 Heme is composed of iron and: a. globin chains. b. oxygen. c. methemoglobin. *d. protoporphyrin IX. General Feedback:

Zinc protoporphyrin (ZPP) accumulates in red blood cells when iron is not incorporated into heme and zinc binds instead to protoporphyrin IX.

5. Chapter 08-05 Good dietary sources of iron include all except: a. meat. *b. fruit. c. fortified flour. d. legumes.

General Feedback: Fruit does not contain iron. Meat is a source of heme iron, and legumes and fortified flour are sources of nonheme iron.

6. Chapter 08-06 Which two organs are the major storage sites for iron in a normal individual? a. Lymph nodes and muscle b. Bone marrow and pancreas c. Spleen and heart *d. Liver and spleen General Feedback: The liver and spleen have a large amount of apoferritin, the protein that stores iron; they thus are major storage sites for iron.

7. Chapter 08-07 A patient has a serum iron of 10 g/dL and a total iron-binding capacity (TIBC) of 490 g/dL. What is the percent saturation of transferrin? *a. 2% b. 25% c. 40% d. 60% General Feedback: Percent transferrin saturation is calculated by dividing the serum iron by TIBC and multiplying by 100. Thus in the example here, % saturation = (10/490) × 100 = 2%.

8. Chapter 08-08 The serum iron and TIBC results given in Question 7 are consistent with: a. iron overload. b. iron toxicity. *c. iron deficiency. d. acute infection.

General Feedback: Under normal circumstances, approximately one-third of transferrin is saturated with iron. Iron overload and iron toxicity are situations in which the percent saturation would be high. In an acute infection, the anemia of chronic inflammation (also called anemia of chronic disease) might develop if the infection becomes chronic.

Percent saturation would be decreased below normal, but it would not become this low (and the infection would have to be fairly longstanding and chronic).

9. Chapter 08-09 The serum ferritin is used more often than bone marrow or liver biopsies to assess iron stores because it is: a. a more direct measurement. b. more accurate. c. more precise. *d. less invasive.

General Feedback: The measurement of ferritin is performed on a serum sample; therefore, it requires nothing more than a venipuncture to obtain a blood specimen. It is proportional to the iron in stores, but it is not a more direct measurement. In fact, a bone marrow biopsy followed by staining with Prussian blue to assess iron stores (in the form of hemosiderin) is perhaps the best measurement of iron stores that are readily available for use in hemoglobin synthesis. This is much more invasive.

10. Chapter 08-10 Which is true of apotransferrin? *a. It can bind two molecules of ferric iron. b. It binds to a ferritin receptor found on the cell membrane. c. It is synthesized in the kidney. d. It is normally about 50% saturated with iron.

General Feedback: Transferrin binds two molecules of ferric iron. It binds to receptors on the cell membrane, which are called transferrin receptors.

It is synthesized in the liver and is normally about one-third saturated.

11. Chapter 08-11 Which stains blue with the Prussian blue stain? a. Ferritin *b. Hemosiderin c. Transferrin d. Both Ferritin and Hemosiderin General Feedback:

Only the insoluble form of storage iron, which is hemosiderin, stains with the Prussian blue stain. Ferritin is soluble and is not stained.

12. Chapter 08-12 Soluble transferrin receptor (sTfR) levels increase when intracellular iron levels are: *a. decreased. b. elevated. c. constant. d. both decreased and elevated.

General Feedback: When iron is deficient, the concentration of transferrin receptors (sTfR) increases. sTfR levels are decreased when iron levels are elevated, such as in chronic disease.

13. Chapter 08-13 Select the condition where an acute increase in ferritin levels can be detected without a specific increase in the amount of systemic body iron? a. Myocardial infarction *b. Infection c. Malignancy d. Liver disease General Feedback: Ferritin levels are acutely increased when a patient has an infection. This is a response of the body to sequester the iron away from the bacteria. These increases can be subtle and may or may not be outside the reference interval.

14. Chapter 08-14 Acute (24-hour) assessment of the amount of iron that is available for hemoglobin production is best identified by measuring the: a. sTfR levels on the cell membrane. *b. amount of hemoglobin in reticulocytes. c. amount of hemosiderin with Prussian blue stain. d. zinc protoporphyrin levels in red blood cells.

General Feedback: The amount of hemoglobin in reticulocytes is a real-time assessment of iron available for hemoglobin production. The number of circulating reticulocytes represents the status of erythropoiesis in the prior 24-hour period. The hemoglobin content of reticulocytes will acutely decrease when iron for erythropoiesis is restricted.

2. Chapter 09-02 What pools of neutrophils are included in the marginal neutrophil pool (MNP)? a. All neutrophils inside the blood vessels b. Only freely circulating neutrophils *c. Only cells loosely localized to the vessel walls d. All leukocytes in the body General Feedback: A pool of neutrophils exists that is marginated (clinging to the sides of capillaries). The circulating neutrophils are included in the circulating neutrophil pool (CNP). Cells can move freely between the two pools.

3. Chapter 09-03 What is the last granulocyte in the maturation sequence able to undergo mitosis? a. Myeloblast b. Promyelocyte *c. Myelocyte d. Band General Feedback: The myelocyte is the last granulocyte in the normal maturation sequence that can undergo mitosis. The myeloblast and promyelocyte precede the myelocyte; both can and do undergo mitosis. The band cell is no longer able to replicate its deoxyribonucleic acid (DNA) and so does not undergo mitosis.

4. Chapter 09-04 Mature mast cells are: a. leukocytes. *b. tissue effector cells. c. progenitor cells. d. cytokines.

General Feedback: Mast cells are not considered to be leukocytes. They are tissue effector cells of allergic responses and inflammatory reactions.

They originate from the bone marrow and spleen.

5. Chapter 09-05 What directs the mitosis and maturation action of progenitor neutrophil cells in the bone marrow? a. Erythropoietin b. The number of stem cells c. The number of mature cells in the peripheral circulation *d. Colony-stimulating factor cytokines

General Feedback: Colony-stimulating factor cytokines (G-CSF) bind to receptors on progenitor cells to direct them to undergo mitosis and to mature to identifiable neutrophil precursor cells. Erythropoietin is the primary cytokine for red cell development. Neither the number of stem cells nor the number of mature cells in circulation function in this role.

6. Chapter 09-06 What is the earliest morphologically identifiable cell in the granulocyte maturation sequence? a. Hematopoietic stem cell b. Colony-forming unit–granulocyte, erythrocyte, monocyte, and megakaryocyte (CFU-GEMM) *c. Myeloblast d. Myelocyte General Feedback: The earliest cell that can be identified by morphology, using Wright stain, as belonging to the granulocyte maturation sequence is the myeloblast. The stem cell pool that includes the hematopoietic stem cells (HSC) and the common myeloid progenitor cells (CMPs) is not distinguishable with the light microscope. The myelocyte is a later stage of development than the myeloblast.

7. Chapter 09-07 A cell having a round nucleus with delicate chromatin, two to four prominent nucleoli, and a high N:C ratio of 8:1 with scant basophilic cytoplasm is an accurate description of a: *a. myeloblast. b. myelocyte. c. metamyelocyte. d. band.

General Feedback: The description fits a myeloblast. Often the myeloblast is agranular (without any visible granules). The presence of multiple nucleoli is often noted. A high N:C ratio is observed where the nucleus occupies most of the cell.

8. Chapter 09-08 What is the earliest stage of maturation where a neutrophil can be distinguished from an eosinophil? a. Myeloblast b. CFU-GEMM c. Metamyelocyte *d. Myelocyte General Feedback:

Eosinophil granules differentiate the eosinophils from the neutrophil at the early myelocyte stage. Before this, the myeloblast and promyelocyte stages are indistinguishable by morphology.

9. Chapter 09-09 Select the correct maturation sequence for granulocytes starting with youngest. a. Promyelocyte, myeloblast, metamyelocyte, myelocyte, segmented *b. Myeloblast, promyelocyte, myelocyte, metamyelocyte, band, segmented c. Segmented, band, metamyelocyte, myelocyte, promyelocyte, myeloblast d. CFU-GEMM, promyelocyte, metamyelocyte, myelocyte, segmented General Feedback: The correct maturation sequence is myeloblast, promyelocyte, myelocyte, metamyelocyte, band, segmented.

10. Chapter 09-10 Which neutrophil is capable of chemotaxis? a. Stem cell b. Progenitor cell c. Myelocyte *d. Segmented neutrophil General Feedback: The segmented neutrophil is capable of chemotaxis (i.e., it can move along a chemical gradient). It is a mature polymorphonuclear neutrophil and has full motility, active adhesion properties, and phagocytic ability.

11. Chapter 09-11 Which has the most controversial morphologic identification system? a. Progenitor cells b. Stem cells c. Promyelocytes *d. Bands General Feedback: At least three systems exist for morphologic identification of band neutrophils. They vary with the shape of the nucleus. Hematology analyzers that perform automated differentials classify them (bands) with polymorphonuclear (segmented) neutrophils; therefore, many laboratories now use the same criteria when identifying cells using the microscope.

12. Chapter 09-12 Which is a feature of a normal segmented neutrophil?

a. Basophilic cytoplasm b. Round nucleus with fine chromatin *c. Small lavender-pink granules d. Prominent primary granules General Feedback: Segmented neutrophils contain many lavender-pink granules in their cytoplasm. Secondary neutrophilic granules slowly spread through the cell until its cytoplasm is more lavender-pink than blue. As the cell divides, the number of primary granules per cell is decreased, and their membrane chemistry changes so that they are much less visible.

13. Chapter 09-13 Segmented neutrophils are present in the highest number in: a. central blood of adults. b. central blood of children. *c. peripheral blood of adults. d. peripheral blood of neonates.

General Feedback: Segmented neutrophils are present in the highest numbers in the peripheral blood of adults (50% to 70% of leukocytes in relative numbers and 2.3 to 8.1 × 109/L in absolute terms).

14. Chapter 09-14 Response to parasitic infections is associated with an increase of which type of granulocyte? a. Promyelocytes b. Band neutrophils c. Segmented neutrophils *d. Eosinophils General Feedback: Eosinophil production is increased in infection by parasitic helminthes.

15. Chapter 09-15 Which cell is described as a large cell with abundant blue-grey cytoplasm containing minute granules, lacy or stringy chromatin, and an indented or folded nucleus? *a. Monocyte b. Macrophage c. Lymphocyte d. Basophil General Feedback: The description fits that of a monocyte. This is a transition cell found in blood; it becomes a macrophage once it enters tissue.

16. Chapter 09-16 When monocytes reside in the tissues, they are referred to as: a. mast cells. b. T cells. c. plasma cells. *d. macrophages.

General Feedback: Monocytes migrate to the tissues and differentiate into macrophages. Macrophages reside in the tissues and have a longer life span than tissue neutrophils.

17. Chapter 09-17 Which cells are normally produced in multiple sites including the bone marrow and thymus? a. Monocytes *b. Lymphocytes c. Eosinophils d. Basophils General Feedback: Lymphocytes are produced in the sites mentioned. All the others are produced only in the bone marrow.

18. Chapter 09-18 Which cells are responsible for antibody production? a. Macrophages b. Monocytes c. Neutrophils *d. Plasma cells General Feedback: The terminally differentiated B cell is the plasma cell; its function is to make and secrete specific antibody.

19. Chapter 09-19 B cells and T cells are subgroups of what cell type? a. Monocytes *b. Lymphocytes c. Macrophages d. Plasma cells General Feedback: These are both subgroups of lymphocytes.

20. Chapter 09-20 Why is the bone marrow (storage) pool of granulocytes so large compared with the total number found in peripheral blood? a. They prefer bone marrow to peripheral blood. *b. They can be quickly released when needed to fight bacterial infection. c. It enhances their ability to function. d. It prolongs their life span in circulation.

General Feedback: The storage pool of granulocytes in the bone marrow is composed primarily of mature segmented neutrophils, a smaller number of bands, and metamyelocytes. These cells are fully functional and can be readily released to peripheral blood when needed in response to infection.

1. Chapter 10-01 How many circulating platelets are produced from a single megakaryocyte? a. 200 to 400 *b. 2000 to 4000 c. 6000 to 8000 d. 10,000 to 12,000 General Feedback: A single megakaryocyte sheds approximately 2000 to 4000 platelets with a total turnover in 8 to 9 days.

2. Chapter 10-02 From where are additional platelets first derived when the circulating count decreases? a. Bone marrow b. Stem cells c. Cells marginated on vessel endothelial cells *d. Spleen General Feedback: When the circulating platelet count decreases, platelets are first derived from those sequestered or stored in the spleen (normally one-third of those available).

3. Chapter 10-03 Which is true of megakaryocytes as they mature? *a. Nucleus becomes polyploid. b. Cytoplasmic basophilia becomes more pronounced. c. Size decreases. d. Nucleoli become more prominent.

General Feedback: Platelets arise from unique bone marrow cells called megakaryocytes. Megakaryocytes are the largest cells in the bone marrow and possess multiple chromosome copies (polyploid). On a Wright-stained bone marrow aspirate smear, each megakaryocyte is 30 to 50 ìm in diameter with a multilobulated nucleus and abundant granular cytoplasm.

Megakaryocytes account for less than 0.5% of all bone marrow cells, and on a normal Wright-stained bone marrow aspirate smear two to four megakaryocytes per 10× low-power field may be identified.

4. Chapter 10-04 How are platelets released into peripheral circulation from the bone marrow? a. Mature platelets squeeze between sinusoid endothelial cells. *b. Megakaryocyte cytoplasmic fragments extend through the endothelial cells, lining the sinusoids, into blood and then shed platelets.

c. Platelets adhere to white cells and exit with them. d. Megakaryocytes exit the marrow with white cells, and then platelets fragment off once they reach the blood.

General Feedback: Cytoplasmic extensions elongate and pierce between the endothelial cells that line the marrow sinuses; then they extend into venous blood. These extensions release platelets once they enter blood.

The cytoplasmic extensions are called proplatelet processes.

5. Chapter 10-05 Which accurately describes reticulated (stress) platelets? a. They appear in compensation for thrombocytopenia. b. They are smaller than mature circulating platelets. c. Their diameter exceeds 6 µm. *d. Both a and c are true.

General Feedback: Reticulated platelets, or stress platelets, are released in compensation for a decrease in platelet count. They are larger than normal platelets and appear round in EDTA whole blood.

6. Chapter 10-06 Which is not a function of the platelet surface-connected canalicular system (SCCS)? *a. Produces energy for the cell. b. Delivers granule contents to the surface. c. Connects the internal contents to the surface. d. Stores hemostatic proteins.

General Feedback: Granule contents are delivered to the surface of the platelet and released through the SCCS. It twists throughout the platelet, providing a large system in which additional plasma coagulation proteins are found in the glycocalyx. Because this is part of the platelet membrane, it connects the internal contents to the surface. It does not produce energy.

7. Chapter 10-07 Identify the platelet receptor and plasma protein required for normal platelet adhesion.

Platelet receptor Plasma protein a. Glycoprotein (GP) IV factor VIII b. Platelet factor 4 (PF4) factor V c. Gp IIb/IIIa fibrinogen *d. Gp Ib/IX/V von Willebrand factor (VWF) General Feedback: VWF must bind to its receptor GP Ib/IX/V on the platelet membrane for normal platelet adhesion.

8. Chapter 10-08 Identify the platelet receptor and plasma protein required for normal platelet aggregation.

Platelet receptor Plasma protein *a. GP IIb/IIIa fibrinogen b. GP IV factor VIII c. GP Ib/IX/V VWF d. PF4 factor V General Feedback: Fibrinogen must bind to its receptor GP IIb/IIIa assembled on the platelet membrane after activation for normal platelet aggregation.

9. Chapter 10-09 Which is the liver-secreted plasma enzyme that digests “unused VWF”? a. ADP b. TXA2 *c. ADAMTS-13 d. GPIb General Feedback: ADAMTS-13 is a VWF-cleaving protease. ADP and TXA2 are platelet activators. GPIb is a receptor for adhesion.

10. Chapter 10-10 Which megakaryocyte membrane marker disappears as differentiation proceeds? *a. CD34 b. CD41 c. CD42 d. CD61 General Feedback: CD34 is a stem cell and common myeloid progenitor membrane marker that is not present in mature cells. CD41 and immunologic markers CD42 and CD61 are all present throughout the maturation process.

11. Chapter 10-11 Which glycoprotein platelet membrane receptor increases the avidity of integrins á2â1and áIIbâ3? a. GP Ia/IIa b. GP Ib/IX/V *c. GP VI d. GP IIb/IIIa

General Feedback: GP VI is a key collagen receptor that triggers activation and releases agonists that increase the avidity of integrins á2â1and áIIbâ3.

12. Chapter 10-12 Phospholipids in the platelet membrane are important for all of the following functions except: a. supply of arachidonic acid. *b. receptor for plasma fibrinogen. c. receptor for plasma coagulation enzymes. d. forms part of the platelet glycocalyx.

General Feedback: Fibrinogen binds to the receptor GP IIb/IIIa. Membrane phospholipids supply arachidonic acid, which becomes converted to thromboxane during platelet activation. They form part of the platelet glycocalyx, which is the platelet surface. Many of the coagulation enzymes bind to platelet phospholipids, including factors V, VIII, IX, and X.

13. Chapter 10-13 What system is the “control center” for platelet activation? a. Eicosanoid (prostaglandin) pathway b. Surface connect canalicular system c. Membrane glycoproteins *d. Dense tubular system General Feedback: The dense tubular system is a condensed remnant of the rough endoplasmic reticulum. It sequesters Ca++ and bears a series of enzymes that support platelet activation. It is the control center for platelet activation.

14. Chapter 10-14 Platelet agonists are substances that: a. bind to phospholipid in the platelet membrane. b. promote apoptosis. *c. activate platelets. d. enhance megakaryocyte proliferation.

General Feedback: Platelet agonists include thromboxane A2 (TXA2), ADP, and thrombin. Each of them binds to its transmembrane receptor, and platelet activation is the result.

15. Chapter 10-15 Which substance is stored in dense granules? *a. Serotonin b. Platelet factor 4 c. Fibronectin d. Protein C inhibitor General Feedback: Serotonin is a vasoconstrictor that binds endothelial cells and platelet membranes. It is stored in the dense granules. Platelet factor 4, fibronectin, and protein C inhibitor are not stored in the dense granules.

1. Chapter 11-01 Manual cell counting methods in automated hematology laboratories are used for all of the following except: *a. routine testing. b. very low counts. c. malfunctioning automated instruments. d. field testing in a disaster.

General Feedback: A hematology analyzer does routine testing in an automated hematology laboratory. However, when counts are very low, if the instrument is malfunctioning, or if a disaster occurs that mandates field testing, manual cell counting is usually performed.

2. Chapter 11-02 What is the total volume of one side of a hemocytometer if the ruled area is 3 × 3 mm and the depth is 0.1 mm? a. 0.3 mm3 *b. 0.9 mm3 c. 1.0 mm3 d. 9 mm3 General Feedback: Volume = area × depth = (3 × 3) × 0.1 = 0.9 mm3.

3. Chapter 11-03 Twenty cells are counted in one of the nine large squares of a hemocytometer. The sample is diluted 1:10. How many cells are present per ìL? a. 200 b. 1000 *c. 2000 d. 20,000 General Feedback: Plugging the appropriate numbers into the formula: (20 × 2 10)/(1 mm × 0. 1 mm) = 2000/mm3 = 2000/ìL (= 2.0 × 103/ìL = 2.0 × 109/L).

4. Chapter 11-04 In the four large corner squares of a hemocytometer, 95, 102, 105, and 98 white cells were counted from a 1:20 dilution. Select the correct interpretation for the white blood count calculated from these values. *a. Normal for infant and elevated for an adult b. Normal for any patient c. Elevated for any patient d. Normal for an infant and decreased for an adult

General Feedback: The cell count is (95 + 102 + 105 + 98) × 20)/(4 mm2 × 0.1 mm) = 20.0 × 103/ìL = 20.0 × 109/L. This count is elevated for an adult but normal for a newborn.

5. Chapter 11-05 Ten nucleated red blood cells (NRBCs) are found in a blood film when differentiating 100 white cells. What is the corrected white blood count if the automated cell counter printed a count of 10.0 × 109/L? a. 0.91 × 109/L *b. 9.1 × 109/L c. 91 × 109/L d. Ten NRBCs are not enough to require a correction General Feedback: The corrected white count = (10.0 × 100)/(100 + 10) = 9.1 × 109/L. Corrections for the white count must be made when greater than 5 NRBCs/100 WBCs.

6. Chapter 11-06 Why is it important to have a scrupulously clean hemocytometer when manually counting platelets? a. So few platelets exist that they can be missed if dirt is present. b. They are so refractile they can be confused with dirt. *c. Their small size makes them easily confused with dirt. d. They are easily confused with the red cells that are present.

General Feedback: Platelets are small and can be easily confused with dirt, thus invalidly increasing the platelet count.

7. Chapter 11-07 In the center square on one side of a hemocytometer, 100 platelets were found; 200 were found in the center square on the other side. Select the best course of action. a. Report the count as 150 × 109/L. b. Verify the count by estimating the platelet number on the blood film. c. Recount the hemocytometer on a phase microscope. *d. Repeat the procedure—the two counts are not close enough.

General Feedback: The cell counts on the two opposite sides of the hemocytometers must agree within 10% of each other. Thus if the count is 100 on one side, the other side must be no higher than 100 + (0.1 × 100) = 110. Because 200 exceeds this, the counts do not agree—an error

has been made. The dilutions must be repeated and then the new dilutions counted.

8. Chapter 11-08 The platelet count from the automated cell counter is 80 × 109/L. Platelet satellites around neutrophils are observed on the blood film estimate. A sodium citrate tube is drawn, and the count reads 300 × 109/L from the cell counter. What platelet count × 109/L should be reported? a. 80 b. 300 *c. 330 d. The estimated count from the blood film General Feedback: The platelet count from the automated cell counter cannot be accepted because it is falsely low because of the platelet satellites seen on the blood film. This is an occasional problem in some patients when their blood is drawn in ethylenediaminetetraacetic acid (EDTA).

Drawing the blood into sodium citrate eliminates the satellites.

However, this tube results in a dilution of the blood (nine parts blood plus one part anticoagulant = 9:10 dilution of blood). The platelet count from the instrument must therefore be multiplied by 1.1 (= 10/9) to obtain the valid platelet count. Therefore the platelet count = (300) × (1.1) = 330 (× 109/L).

9. Chapter 11-09 Interpret the following results (all tests performed manually) on an adult female.

RBC: 3.22 × 1012/L Hemoglobin: 16.0 g/dL Hematocrit: 30.0% a. All are normal. b. All are decreased. c. Hemoglobin is elevated and other two are normal. *d. Values do not agree with the “rule of three.”

General Feedback: The rule of three suggests that the hematocrit ?6˜ (3 × hemoglobin). For this example, the hematocrit ?6˜ (3 × 16.0) ?6˜ 48 ?0?

30.0. Therefore one of the values has to be invalid unless the red cell morphology is abnormal. However, in this instance no red cell morphology supports these results (mean cell hemoglobin concentration [MCHC] = 16/30 × 100 = 53 g/dL, which is impossible). Note: An expansion of the rule of three states that the hematocrit ?6˜ 9 × RBC count ?6˜ 9 × 3.22 ?6˜ 27%. In this case, some agreement exists between the two values. Thus just from the information given in this question, it appears that the incorrect value is the hemoglobin.

10. Chapter 11-10 The calculated indices on the patient from Question 9 are: MCV (fL) MCH (pg) MCHC (g/dL) *a. 93 50 53 b. 105 29 37 c. 93 22 28 d. 105 34 35 General Feedback: When the red cell indices are calculated, they are as follows: Mean cell volume (MCV) = (30.0/3.22) × 10 = 93 fL. Mean cell hemoglobin (MCH) = (16.0/3.22) × 10 = 50 pg.

MCHC = (16.0/30.0) × 100 = 53 g/dL.

11. Chapter 11-11 What should the laboratory technician do before working with hemoglobin reagent? *a. Consult the safety data sheet. b. Call the reagent manufacturer. c. Stop working with the reagent. d. Discard the reagent in the sink.

General Feedback: Because the hemoglobin reagent contains cyanide, it is highly toxic and must be used cautiously. Consult the safety data sheet supplied by the manufacturer. Acidification of cyanide in the reagent releases highly toxic hydrogen cyanide gas. A licensed waste disposal service should be contracted to discard the reagent; reagent-specimen solutions should not be discarded into sinks.

12. Chapter 11-12 Which could cause the microhematocrit to be falsely decreased? *a. Introduction of interstitial fluid b. Trapped plasma from abnormally shaped red cells c. Dehydration d. Insufficient centrifugation General Feedback: Proper specimen collection is an important consideration. The introduction of interstitial fluid from a skin puncture or the improper flushing of an intravenous catheter causes decreased hematocrit readings. Trapped plasma from abnormally shaped red cells will elevate the microhematocrit. If a person is dehydrated, he or she has lost plasma volume to extracellular space, and this falsely increases the microhematocrit. Insufficient centrifugation means that the red cells will not be maximally packed, and this too will falsely elevate the microhematocrit.

13. Chapter 11-13 The MCV on a patient is calculated to be 115 fL and the MCHC is 35

g/dL. What, in general terms, must be true of the MCH if it is consistent with the previous two indices? a. It is impossible to know. b. It should be in the reference range. c. It should be below reference range. *d. It should be above reference range.

General Feedback: The MCV is elevated, suggesting that the red cells are macrocytic. The actual weight of hemoglobin/red cell (the MCH) must therefore be elevated (above reference range) for the concentration of hemoglobin/volume (the MCHC) to be reference range.

14. Chapter 11-14 On a standard reticulocyte preparation with new methylene blue, 100 of 1000 total cells that are counted contain blue-stained granulofilamentous material. The red blood count is 3.22 × 1012/L, and the hematocrit is 30%. Calculate the reticulocyte count as a percentage. a. 0.1% b. 1.0% *c. 10.0% d. 100.0% General Feedback: A total of 1000 red cells plus reticulocytes are always counted (and thus 1000 is the denominator when performing a reticulocyte count). The reticulocyte count (%) = (100/1000) × 100 = 10%.

15. Chapter 11-15 Which red cell indices support microcytic hypochromic red cell morphology?

MCV (fL) MCH (pg) MCHC (g/dL) a. 120 36 35 *b. 68 22 28 c. 90 30 34 d. 75 30 34 General Feedback: Because the red cells are microcytic, the MCV must be below reference range. They are also hypochromic, so the MCHC must be below reference range. Both the smaller volume and lower concentration of hemoglobin mean that the MCH has to be significantly below reference range.

16. Chapter 11-16 Which red cell indices support normocytic normochromic red cell

morphology?

MCV (fL) MCH (pg)

MCHC (g/dL)

a. 120 36 35 b. 68 22 28 *c. 90 30 34 d. 75 30 34 General Feedback: Because the red cells are both normal in size and normal in hemoglobin concentration, all the red cell indices must be in the reference range.

17. Chapter 11-17 Which red cell indices support macrocytic normochromic red cell morphology?

MCV (fL) MCH (pg) MCHC (g/dL) *a. 120 36 35 b. 68 22 28 c. 90 30 34 d. 75 30 34 General Feedback: The red cells are large but have a normal concentration of hemoglobin. The MCV and MCH must therefore be above reference range, whereas the MCHC is in the reference range.

18. Chapter 11-18 On a standard reticulocyte preparation with new methylene blue, 100 of 1000 cells that are counted contain blue-stained granulofilamentous material. The red blood count is 3.22 × 1012/L, and the hematocrit is 30%. Calculate the absolute reticulocyte count. *a. 0.32 × 1012/L b. 3.2 × 1012/L c. 32.2 × 1012/L d. 0.99 × 1012/L General Feedback: The absolute reticulocyte count is = relative % reticulocytes × the red count. In this example, the absolute reticulocyte count = (0.10) × 3.22 × 1012/L = 0.32 ×1012/L.

19. Chapter 11-19 On a standard reticulocyte preparation with new methylene blue, 100 of 1000 cells that are counted contain blue-stained granulofilamentous material. The red blood count is 3.22 × 1012/L, and the hematocrit is 30%. Calculate the corrected reticulocyte count. a. 1.5%

b. 3.0% *c. 6.7% d. 15.0% General Feedback: The corrected reticulocyte count “normalizes” the hematocrit to 45%. Thus it is the reticulocyte % × patient’s hematocrit/“normal” hematocrit = 10% × (30/45) = 6.7.

20. Chapter 11-20 On a standard reticulocyte preparation with new methylene blue, 100 of 1000 cells that are counted contain blue-stained granulofilamentous material. The red blood count is 3.22 × 1012/L, and the hematocrit is 30%. Calculate the MCV. a. 80 fL *b. 93 fL c. 98 fL d. 108 fL General Feedback: The MCV = 30/3.22 × 10 = 93 fL.

21. Chapter 11-21 On a standard reticulocyte preparation with new methylene blue, 100 of 1000 cells that are counted contain blue-stained granulofilamentous material. The red blood count is 3.22 × 1012/L, and the hematocrit is 30%. Calculate the reticulocyte production index (RPI). a. 1.5 b. 2.7 *c. 3.4 d. 13.4 General Feedback: The RPI uses the corrected reticulocyte count (calculated in Question 25). It then takes into account, based on the patient’s hematocrit, the early release of RBCs from the marrow so that when the reticulocytes are counted, it is not just those released in the last 24 hours (1 day) but a piling up of those released over a longer period of time. For a hematocrit of 30%, the average length of time a reticulocyte spends in the blood is 2.0 days. Thus the corrected reticulocyte count of 6.7 is divided by 2 = 3.4.

22. Chapter 11-22 Which is a good use of the erythrocyte sedimentation rate (ESR)? *a. Monitor patients with rheumatoid arthritis. b. Diagnose acute appendicitis. c. Diagnose multiple myeloma. d. Monitor patients with osteoarthritis.

General Feedback: The ESR is elevated in patients with rheumatoid arthritis. It decreases when the disease is in remission and increases when it exacerbates; therefore, it is useful for monitoring this disease. It is normal in the first 24 hours of acute appendicitis, so is not useful in diagnosis. It is elevated in multiple myeloma, but also in many other clinical conditions, so it is not diagnostic for it. It is normal in osteoarthritis and thus of no value for monitoring those patients.

23. Chapter 11-23 Why is testing the ESR not recommended when testing for inflammation in asymptomatic individuals? a. It is too complicated and time-consuming. b. It yields too many false-negative results. c. It is not affordable to most people. *d. It is not a reliable predictor of inflammation.

General Feedback: Because of its low specificity and sensitivity, the ESR is not recommended as a screening test to detect inflammatory conditions in asymptomatic individuals. Other tests for inflammation, such as the Creactive protein level, may be a more predictable and reliable alternative to monitor inflammation.

24. Chapter 11-24 Which can cause a falsely increased ESR? a. Concentration of anticoagulant increased *b. Tube not totally vertical c. Tuberculosis d. Increased plasma viscosity General Feedback: The ESR tube must be kept at the absolute perpendicular to obtain a valid ESR result. Even only a slight tilt of the pipette (tube) causes the ESR to increase.

25. Chapter 11-25 How do sickle cells or spherocytes interfere with the ESR? *a. Prevent rouleaux formation, so falsely decrease. b. Encourage rouleaux formation, so falsely increase. c. Agglutinate and increase red cell mass, so falsely increase. d. Decrease plasma viscosity, so falsely decrease.

General Feedback: Abnormally shaped red cells such as sickle cells or spherocytes interfere with rouleaux formation, so they falsely decrease the ESR result.

26. Chapter 11-26 A manual hemoglobin is determined on a patient, and the dilution still appears turbid after letting it sit for 15 minutes. The stained blood film is examined, and sickle cells are observed on the blood film.

Equal volumes of the diluted hemoglobin sample and water are mixed together, and the absorbance of this read on a spectrophotometer. How should the hemoglobin result be determined from the standard calibrated graph? a. Add the results from the turbid and second dilution together and divide by 2. *b. Multiply the result from the standard curve by 2. c. Divide the result obtained from the graph on the diluted specimen by 2. d. There was no reason to perform this second dilution.

General Feedback: Red cells that contain Hb S (sickle hemoglobin) are resistant to lysis in some cyanmethemoglobin reagents. When this occurs, the cyanmethemoglobin dilution should be mixed with an equal part of water, and the optical density (percent transmission) read. Because the diluted specimen was diluted 1:2 by water, this result must be multiplied by 2 to obtain the patient’s result.

27. Chapter 11-27 A manual WBC count is performed using a system that makes a 1:20 dilution of blood. When the cells in the four large corner mm2 of the hemocytometer are counted, the following numbers of cells are obtained: 8, 12, 9, and 11. What would be the next step? *a. Count the cells in all 9 mm2 of the hemocytometer. b. Redo the dilution of blood using a new 1:20 dilution. c. Redo the dilution of blood using a 1:100 dilution. d. Calculate the count using the values from the 4 mm2 and report the result.

General Feedback: This white count appears to be very low, in the neighborhood of 2.0 × 109/L [(8 + 12 + 9 + 11) × 20/0.4]. To make the cell count more accurate, the number of cells counted must be increased. This can be done by counting the cells in all 9 mm2 of the hemocytometer.

28. Chapter 11-28 A 1:20 dilution of blood is made for a white count, and the following number of cells counted in the four large corner mm2 of the hemocytometer: 12, 28, 18, and 15. What should be done next? a. Report the white count as 3.7 × 109/L. *b. Clean the hemocytometer and recharge with a well-mixed dilution. c. Increase the number of mm2 counted. d. Compare this cell count to the one on the other side.

General Feedback: The distribution of cells in these four mm2 is unacceptable (exceeds 10 cells); this is not random distribution. Unacceptable distribution makes the cell count invalid. Ideally, another dilution should be made, and it should be well mixed before charging the chamber. Other possible reasons for poor distribution include uneven flow when charging the chamber, dirt or oil on the surface of the chamber or coverslip, and disturbing the coverslip while counting the cells.

29. Chapter 11-29 Diagnostic testing at or near the site of patient care is known as: a. preanalytic testing. *b. point-of-care testing. c. waived testing. d. Clinical Laboratory Improvement Amendments (CLIA) testing.

General Feedback: Diagnostic testing at or near the site of patient care is known as point-of-care testing.

30. Chapter 11-30 Which regulatory standards mandate the concept of “test site neutrality” for all laboratory procedures? a. OSHA *b. CLIA c. Joint Commissions d. CAP General Feedback: The Clinical Laboratory Improvement Amendments (CLIA) requires test site neutrality, which means that all testing sites must follow the same regulatory requirements based on the complexity of the test method. OSHA sets standards for safety in the workplace. Joint Commissions and CAP are accrediting agencies.

1. Chapter 12-01 Counting the number and size of electrical interferences created by blood cells as they pass through a small aperture is a description of which principle? *a. Electronic impedance b. Optical scatter c. Conductivity d. Laminar flow General Feedback: The electronic impedance principle of cell counting is based on the detection and measurement of changes in electrical resistance produced by cells as they pass through a small aperture.

2. Chapter 12-02 What technology minimizes the problems of a rigid aperture? a. Forward scatter b. Radiofrequency *c. Hydrodynamic focusing d. Fluorescence General Feedback: The use of hydrodynamic focusing avoids pitfalls and potential problems when using a rigid aperture. The outer sheath fluid minimizes protein buildup and plugs, eliminates recirculation of cells, and reduces pulse height irregularity and coincident passage loss.

3. Chapter 12-03 Forward angle light scatter, when used in an instrument using the optical scatter principle, correlates with cell: a. granules. *b. volume. c. nuclear chromatin. d. number.

General Feedback: Forward light scatter correlates with cell volume (size).

4. Chapter 12-04 What does the pneumatic system of cell counters do? *a. Operates the valves and moves the sample. b. Controls computer software. c. Digitizes the pulses generated by cell passage. d. Controls the laser light.

General Feedback: The pneumatic system includes the vacuums and pressures required for operating the valves and moving the sample through the hydraulics system.

5. Chapter 12-05 How do Beckman Coulter and Abbott instruments count red cells and platelets? a. Florescent staining and enumeration b. Survival staining and conductivity c. Optical scatter *d. Electrical impedance General Feedback: Instruments manufactured by these companies both use electrical impedance to count and discriminate red blood cells (RBCs) and platelets.

6. Chapter 12-06 Which is determined by light transmission between 525 and 555 nm on automated counting instrumentation? a. Reticulocytes *b. Hemoglobin c. Mean cell volume (MCV) d. Mean cell hemoglobin (MCH) General Feedback: Hemoglobin is measured by light transmission between 525 and 555 nm.

7. Chapter 12-07 Which is always calculated on cell counters? a. Hematocrit b. MCV *c. Mean cell hemoglobin concentration (MCHC) d. Red blood cell count General Feedback: The MCHC is always a calculated parameter on cell counters.

The clinician determines it by dividing the hemoglobin by the hematocrit (which on some instruments is also calculated from the red count and MCV) and multiplying by 100.

8. Chapter 12-08 What is the mechanism for the three-part differential found in older Coulter machines or those designed for smaller laboratories? a. Volume, conductivity, scatter b. Multiangle polarized scatter separation c. Peroxidase staining and light scatter *d. Impedance after cytoplasm shrinkage

General Feedback: Older Coulter instruments use a special white blood cell (WBC) lysing agent that causes differential shrinkage of white cells, allowing the different white cells to be counted and sized based on their impedance.

9. Chapter 12-09 How do CELL-DYN instruments differentiate red cells and platelets from one another? a. Differences in forward scatter using optical light scatter principle b. Use of a unique reagent that selectively lyses red cells while preserving platelets *c. Differences in volume (fL) using electrical impedance principle d. Use of a unique reagent that selectively lyses platelets while preserving red cells General Feedback: CELL-DYN instruments use electrical impedance for counting and discriminating red cells and platelets. Pulses between 1 and 35 fL are included in the initial platelet data, whereas pulses greater than 35 fL are counted as red cells.

10. Chapter 12-10 What principle does the Sysmex SE-9000/9500 use to analyze and separate white cell populations? a. Electronic impedance b. Optical light scatter c. Volume, conductivity, and scatter *d. Low-frequency direct current and high-frequency current General Feedback: The Sysmex 9000 analyzes WBCs by low-frequency direct current and high-frequency current. A scattergram of radiofrequency detection signals (y-axis) versus direct-current detection signals (x-axis) is plotted and yields separation of the white cells through the application of floating discriminators.

11. Chapter 12-11 Which uses a peroxidase stain channel? *a. Siemens Healthcare Diagnostics ADVIA 2120 b. Coulter LH750 c. Sysmex SE-9000 d. Abbott CELL-DYN 4000 General Feedback: The ADVIA 2120 uses a peroxidase channel to help differentiate white cells based on their peroxidase content.

12. Chapter 12-12 Compared with manual methods, automated reticulocyte counting improved which concept? a. Distribution error b. Statistical sampling error c. Interobserver error *d. All of the options General Feedback: Automated reticulocyte counting improved all of the listed problems encountered in manual reticulocyte counting. This has resulted in an improvement in precision and accuracy.

13. Chapter 12-13 An elevated immature reticulocyte fraction is associated with: a. bone marrow suppression. b. chemotherapy. *c. bone marrow response to anemia. d. renal disease.

General Feedback: An elevated immature reticulocyte fraction is associated with a bone marrow response to anemia. It is a reliable indicator of changes in erythropoietic activity and may prove to be a valuable monitoring tool for patients with anemia, such as those with chronic renal failure who are treated with recombinant erythropoietin.

14. Chapter 12-14 Which is true regarding automated reticulocyte counts? a. This was one of the earlier cell-counting methods to be automated. *b. Ribonucleic acid (RNA) is stained with various dyes that allow for detection of reticulocytes by optical scatter or fluorescence. c. They are more accurate but less precise than the manual method. d. They require significantly more time to count reticulocytes than manual methods.

General Feedback: Automated methods use various dyes that bind to RNA and thus allow for counting of reticulocytes by either optical scatter or fluorescence.

15. Chapter 12-15 What is the greatest limitation of automated cell counters? a. Poor precision b. Speed

c. Unavailability of quality control materials *d. Inherent specimen problems leading to occasional spurious results General Feedback: Limitations and interferences may be related to either the methodology or inherent problems in the blood sample. In its literature, the manufacturer defines instrument limitations. Some of the method limitations are, in fact, the result of inherent specimen problems.

16. Chapter 12-16 Platelet clumps would most likely interfere with which other automated parameter? *a. WBC count b. RBC c. Hemoglobin d. Red cell indices General Feedback: Large platelet clumps may be counted as WBCs. This results in a falsely decreased platelet count and possibly an increased white cell count.

17. Chapter 12-17 An automated hematology analyzer is used to evaluate a blood specimen.

Which, coming off the instrument, would require performance of a manual white cell differential as opposed to blood film review? a. Flagged data *b. Suppression of automated differential data c. Abnormal red cell indices d. A slightly elevated platelet count General Feedback: When internal instrument checks fail or cast doubt on the data, the automated differential data are suppressed. This means that a manual differential should be performed. Flagged data may be released after appropriate blood film review, as dictated by the specific laboratory policy.

18. Chapter 12-18 A patient sample comes off an automated cell counter with a failure of the red cell “rule of three.” The red count is lower than expected given the hemoglobin. The MCV and MCHC are elevated. Which is the most likely reason for this failure? a. Megaloblastic anemia b. Lyse-resistant red cells *c. Cold agglutinin d. Lipemia

General Feedback: The red count is lower than expected for the data; this suggests a cold agglutinin is present. The red cells are thus clumped at room temperature, and the clumps are being counted as one large cell. This lowers the red count and raises the MCV and MCHC. The only red cell parameter that is probably valid is the hemoglobin measurement.

19. Chapter 12-19 Select the most appropriate action for the results in Question 18. a. Report the results. b. Lyse the red cells manually and rerun. *c. Warm sample to 37°C and rerun. d. Replace plasma with saline and rerun.

General Feedback: The blood sample should be warmed to 37°C and rerun when a cold agglutinin is present or suspected of being present. The antibody will disassociate from the red cell membrane at this temperature, and the red cells will “unclump.” This raises the red count and lowers the MCV, MCH, and MCHC.

20. Chapter 12-20 All will be invalid when lipemia is present in a blood sample except: a. MCHC. *b. MCV. c. MCH. d. hemoglobin.

General Feedback: When a blood sample is lipemic, the hemoglobin is falsely elevated. The MCH and MCHC are also falsely elevated because they use the hemoglobin measurement for their calculation. The MCV is valid because it does not depend on the hemoglobin measurement.

21. Chapter 12-21 Which occurs if testing is not performed within 24 hours of specimen collection? a. White blood count rises. *b. WBCs deteriorate and RBCs swell. c. Hemoglobin rises. d. MCV decreases.

General Feedback: Sample age can have a profound effect on blood cell analysis.

Specific problems with older samples include WBC fragility and loss, swelling (which increases the MCV) and possible lysis of RBCs, and the deterioration of platelets.

22. Chapter 12-22 A patient’s white blood count comes off an automated cell counter as 380 × 109/L. Which could be reported without any additional testing? a. Red blood count b. Hemoglobin c. Hematocrit *d. Platelet count General Feedback: The platelet count could be reported, but none of the other results are reportable. White cells are always counted with red cells; however, there normally are so few of them in comparison to the number of red cells that their presence does not significantly affect the red count. When the white count is markedly elevated, it significantly affects the red count and MCV and thus the hematocrit. The hemoglobin is also invalid because the high number of white cells adds turbidity to the hemoglobin measurement, thus falsely increasing the hemoglobin determination (and then also the MCH and MCHC). The markedly elevated white cell count necessitates at least a blood film review, if not a manual white cell differential (varies with the instrument limitations).

23. Chapter 12-23 When the electronic impedance principle is used to count blood cells, what is done to increase platelet-counting sensitivity? *a. Decrease the size of the RBC/platelet aperture. b. Increase the size of the RBC/platelet aperture. c. Use a strong lysing agent to selectively lyse the RBCs. d. Lower the upper threshold for counting platelets so that even microcytic red cells are excluded.

General Feedback: To improve the sensitivity when counting platelets, the size of the RBC/platelet aperture is decreased.

24. Chapter 12-24 Platelet volume normally: a. is 15 to 20 fL. *b. increases as the sample sits in acid. c. is 5 to 18 fL. d. is not reliable on most electronic instruments.

General Feedback: Platelet reference values are approximately 8 to 88 fL, and the MPV increases slightly as the sample sits in the anticoagulant EDTA.

25. Chapter 12-25 What is the recommended method for establishing accuracy of automated hematology analyzers? a. Use at least three levels of controls for calibration. b. Use whole blood calibration methodology. *c. Use commercially prepared whole blood calibrators. d. Perform manual methods for comparison.

General Feedback: Whole blood calibrators are commercially available and are used for calibration of instruments. However, inherent problems exist with their use because these are stabilized and preserved cell suspensions that can deteriorate, and the calibration must be validated before the instrument is used for patient specimen analysis.

1. Chapter 13-01 All can be determined from a blood film except: a. red cell morphology. b. white cell estimate. *c. red cell estimate. d. platelet estimate.

General Feedback: A red cell count estimate cannot be made from a blood film.

White cell and platelet count estimates are routinely made, and red cell morphology is evaluated.

2. Chapter 13-02 A patient’s blood film had marked echinocytes and many broken and vacuolated neutrophils. The same patient’s blood film the day before did not show these features. Select the best course of action. a. Report the results. b. Make a new film. c. Disregard these findings as artifact. *d. Make a new sample film within 5 hours.

General Feedback: Blood films from EDTA tubes that remain at room temperature for more than 5 hours often have unacceptable blood cell artifacts (echinocytic red blood cells [RBCs], spherocytes, necrobiotic leukocytes, and vacuolated neutrophils). Slides should ideally be made within 2 to 3 hours of drawing the specimen if good-quality morphology is desired.

3. Chapter 13-03 Clumped platelets will cause which spurious results when cell counts are performed on an automated hematology analyzer? *a. Platelets low and white count high b. Platelets high and white count low c. Platelets low and white count unaffected d. Platelets low and hemoglobin high General Feedback: The presence of clumped platelets in blood will cause the platelet count to be low and the white count to be high when performed using an automated analyzer. The clumps of platelets may be of a similar size to white blood cells (WBCs) and the instrument cannot distinguish them as nonwhite cells.

4. Chapter 13-04 How can the correct platelet count on a patient be determined when his or her platelets repeatedly clump in an EDTA specimen? a. Recollect in sodium citrate tube (blue top) and multiply by 0.5.

*b. Recollect in sodium citrate tube (blue top) and multiply count by 1.1. c. Report the estimated number from the blood film. d. Recollect in an EDTA tube.

General Feedback: When platelet clumping repeatedly occurs in an EDTA blood, the blood should be drawn in a sodium citrate tube. The dilution of blood by the anticoagulant is 9:10 (9 parts blood to 1 part anticoagulant).

The platelet count obtained on this tube must therefore be multiplied by the reciprocal of the dilution (10/9) = 1.1.

5. Chapter 13-05 Select the best course of action to remedy blood films that typically are too thick from newborns. a. Increase the spreader slide angle. b. Use a larger drop. c. Dilute the blood with saline. *d. Decrease the spreader slide angle.

General Feedback: Decreasing the angle of the spreader slide will make the blood film thinner, as well as longer.

6. Chapter 13-06 Why should bone marrow films be dried quickly? a. To make the cells more visible *b. To avoid drying artifact c. To evaluate morphology d. To decrease evaluation time General Feedback: Regardless of film preparation method, before staining, all blood films and bone marrow smears should be dried as quickly as possible to avoid drying artifact. In some laboratories, a small fan is used to facilitate drying. Blowing breath on a slide is counterproductive because the moisture in breath causes RBCs to become echinocytic (crenated) or to develop water artifact (also called drying artifact).

7. Chapter 13-07 Methods, such as using a fan to dry blood films faster, are especially important when: *a. the patient is very anemic or high humidity exists. b. the patient has polycythemia or high humidity exists. c. the sample is more than 6 hours old. d. no one is available to blow on the blood film.

General Feedback:

When the blood film dries slowly on the slide, red cell and drying artifacts make it extremely difficult to evaluate red blood cell (RBC) morphology. Humidity adds to this problem, as does the high plasma volume found in an anemic patient. Drying the slide with a fan can be beneficial.

8. Chapter 13-08 What is the most common reason for blood films having red cells that are gray and white cells that are too dark? a. Overrinsing b. Buffering for too short a time c. Stain or buffer that is too acidic *d. Stain or buffer that is too alkaline General Feedback: When the stain or buffer is too alkaline, red cells will be gray and white cells will stain too darkly for good morphologic evaluation.

9. Chapter 13-09 Macroscopic holes in a blood film most likely mean the patient has: a. increased blood proteins. b. red cell agglutination. *c. increased lipids. d. increased white blood count.

General Feedback: Increased lipids in the plasma can cause the appearance of holes all over the blood film. Some of the other hematology parameters should be carefully evaluated because they may also be influenced by the presence of these lipids (e.g., hemoglobin).

1. Chapter 14-01 Which site is used for both aspiration and core biopsy of bone marrow? a. Sternum *b. Posterior iliac crest c. Tibia d. Ribs General Feedback: The posterior iliac crest in an adult is used for both bone marrow aspiration and core biopsy. The anterior iliac crest, and occasionally the ribs or vertebrae, can also be used. The sternum is rich in marrow and a good specimen can be obtained from it, but it is not recommended because of the risk of puncture to the underlying heart and great vessels.

2. Chapter 14-02 The best use for bone marrow aspirate smears is: *a. counting the differential. b. determining overall cellularity. c. estimating fat-to-cell ratio. d. evaluating for focal lesions such as lymphoma.

General Feedback: The best use for bone marrow aspirate smear is for counting the differential. The biopsy is better for determining overall cellularity, estimating the fat-to-cell ratio, and evaluating for the possible presence of focal lesions.

3. Chapter 14-03 When is obtaining a bone marrow core biopsy mandatory? a. Anemia is suspected. b. Leukemia is suspected. c. Megakaryocyte disorders are suspected. *d. Aspirate is a dry tap.

General Feedback: When the aspirate is a dry tap, it is imperative that a bone marrow biopsy be obtained. This gives the hematologist and/or pathologist a way of assessing the bone marrow in the absence of an aspirate (dry tap). If the aspirate is a dry tap, then something significant is present in the marrow and the biopsy will help determine the cause.

4. Chapter 14-04 Which would be a valid indication for performing a bone marrow aspiration? a. Iron deficiency b. Folate deficiency *c. Unexpected pancytopenia

d. Leukocytosis from a severe infection General Feedback: An unexpected pancytopenia is a valid reason for performing a bone marrow aspiration so that the cause of the pancytopenia can be determined. Iron deficiency, folate deficiency, and leukocytosis from a severe infection can all be evaluated and diagnosed from tests performed on peripheral blood (and perhaps other tissues and/or fluids such as urine in a urinary tract infection).

5. Chapter 14-05 What type of preparation is preferred for bone marrow aspirates? *a. Coverslip smears from a bone marrow fragment called a spicule. b. Wedge smears made from the blood surrounding marrow fragments. c. Touch preps from rolling the biopsy on a glass slide. d. Smears of the biopsy made with an automated slide maker.

General Feedback: Coverslip smears from a bone marrow spicule are the preferred type of preparation for bone marrow aspirates. The advantage to them over slides is that less trauma occurs to the cells because they weigh so much less (relatively speaking). If done correctly, a good monolayer of cells in the marrow can be stained and then evaluated.

6. Chapter 14-06 Low power (×10) is used to count and evaluate which factor? a. Immature neutrophils *b. Megakaryocytes c. Nucleated red cells d. Plasma cells General Feedback: Megakaryocytes are the largest cell in the bone marrow, and they are easily seen and counted under ×10.

7. Chapter 14-07 Which is excluded in the M:E ratio? a. Reticular cells b. Nucleated erythrocytes c. Phagocytes *d. Lymphocytes General Feedback: Once the differential is completed, the myeloid-to-erythroid (M:E) ratio is computed from the total myeloid to the total nucleated erythroid cell stages. Excluded from the M:E ratio are lymphocytes, plasma cells, monocytes, histiocytes, nonnucleated erythrocytes, and nonhematopoietic stromal cells.

8. Chapter 14-08 Osteoblasts can be easily confused with: a. megakaryocytes. b. osteoclasts. *c. plasma cells. d. macrophages.

General Feedback: Osteoblasts can be easily confused with plasma cells. They have an eccentric nucleus and blue cytoplasm; however, they do not have a well-defined Golgi complex (area of “hof”). Osteoblasts tend to be found in clusters, which is not true of normal plasma cells.

9. Chapter 14-09 A bone marrow aspirate shows copious blue granules with the Prussian blue stain. Select the correct interpretation. *a. Iron overload b. Iron deficiency c. Tumor cells present d. Megakaryocytes increased General Feedback: The Prussian blue stain is an iron-specific stain (nonheme iron). When iron is in the storage form of hemosiderin, it stains blue.

If copious granules are visible, it suggests iron overload. The granules must be found in macrophage cytoplasm to rule out possible contamination of the slide or stain with iron.

10. Chapter 14-10 Which cell type tends to be found in molded clusters in the bone marrow? a. Megakaryocytes *b. Malignant cells c. Immature granulocytes d. Monocytes General Feedback: Malignant cells are often found in clusters or clumps in the bone marrow. Because they are so large, they are most easily searched for under ×10 while scanning, and they are often found at or near the edge of the coverslip (or glass slide).

11. Chapter 14-11 What stain is most commonly used for bone marrow aspirates? a. Prussian blue b. New methylene blue c. Hematoxylin and eosin (H&E) *d. Wright

General Feedback: Wright stain is most commonly used for bone marrow aspirates.

Cells stain in a similar fashion as to what is seen in peripheral blood cells, making it easy to assess their morphology.

12. Chapter 14-12 What bone marrow sample is best to determine fat-to-cell ratio and overall cellularity, as well as for searching for malignant cells? *a. Core biopsy b. Aspirate smears c. Peripheral blood d. Prussian blue stain General Feedback: The core biopsy is the best sample for determining overall cellularity and fat-to-cell ratio and searching for malignant cells. It provides an intact portion of the bone marrow.

13. Chapter 14-13 Which is least helpful in evaluating bone marrow findings? a. Differential performed on the aspirate b. Clinical findings *c. Laboratory data from chemistry, immunology, and microbiology d. Examination of peripheral blood General Feedback: All clinical laboratory findings should be interpreted in light of the clinical findings (physical examination and history). It is also important to compare the bone marrow findings from the differential with what is in peripheral blood, because blood cells are derived from the bone marrow. In general, laboratory data from other sections of the laboratory are not needed; however, this is not the case when working up patients for certain diseases (e.g., protein electrophoresis in a patient suspected to have multiple myeloma).

14. Chapter 14-14 A cell is described as having an eccentric, heavily stained (condensed chromatin) nucleus with blue cytoplasm. A pale perinuclear Golgi complex is noted next to the nucleus. What is this cell? a. Myelocyte *b. Plasma cell c. Lymphocyte d. Myeloblast General Feedback: The description fits that of a plasma cell. These are fully differentiated B cells, whose function is to make and secrete specific immunoglobulin (antibody). Because the cytoplasm is rich in ribonucleic

acid (RNA) needed for this synthesis, the cytoplasm often stains a brilliant blue.

15. Chapter 14-15 The sites of active red marrow differ for adults and young children.

Which site is active in children but not in adults? a. Proximal end of the long bones b. Skull *c. Distal ends of the long bones d. Pelvis General Feedback: Red marrow is found in all the bones in children, including the distal ends of the long bones. It also initially has no fat. As the child grows and the bones lengthen and enlarge, all the available marrow space is no longer needed for blood cell production. The marrow space no longer needed becomes inactive and fatty (“yellow marrow”). It can be converted to active marrow if the demand for blood cells becomes excessive. Red marrow in an adult is composed of both blood-producing cells and fat in a roughly 1:1 ratio.

1. Chapter 15-01 Why should cell counts on body fluids be performed within 30 minutes of collection? a. Erythrocytes begin to deteriorate. b. Plasma cells begin to deteriorate. c. Red blood cells begin to deteriorate. *d. White blood cells begin to deteriorate.

General Feedback: Blood cell counts should be performed and cytocentrifuge slides should be prepared as quickly as possible after collection of the specimen, because WBCs begin to deteriorate within 30 minutes after collection.

2. Chapter 15-02 A hazy spinal fluid has 400 white cells/mm3 that are mostly lymphocytes and reactive lymphocytes. Which condition is most likely? a. Bacterial meningitis *b. Viral meningitis c. Infectious mononucleosis d. Multiple myeloma General Feedback: Meningitis can be either bacterial or viral. In general, WBC counts are much higher (in the thousands) in patients with bacterial meningitis than in patients with viral meningitis (in the hundreds).

3. Chapter 15-03 What determines the amount of fluid used for a cytocentrifuge preparation? a. Type of fluid b. Desired speed of centrifugation *c. Number of cells d. Amount of fluid collected General Feedback: The number of cells, determined when the cell count is done on the body fluid, determines how much fluid should be used in making the cytocentrifuge preparation. This preparation concentrates the cells so that a representative number of them can be morphologically evaluated.

4. Chapter 15-04 What determines whether or not body fluids are diluted before counting? *a. Appearance of the fluid b. Type of fluid c. Patient’s diagnosis d. Whether or not the fluid needs to go to other sections of the laboratory for additional testing

General Feedback: The appearance of the fluid is used to determine whether or not a body fluid is diluted before counting. If the fluid is clear, no dilution is made. If it is hazy or cloudy, an appropriate dilution is made.

5. Chapter 15-05 A cloudy cerebrospinal fluid (CSF) is diluted 1:20. In nine large squares, 99 white cells are counted. What is the total white blood count/mm3 or /ìL? a. 99 b. 1980 *c. 2200 d. 22,000 General Feedback: The same formula used for calculating manual cell counts in blood is used for body fluids. Thus this cell count = (99 × 20)/(9 mm2 × 0.1 mm) = 2200/ìL.

6. Chapter 15-06 If most of the white cells are neutrophils on the previously discussed CSF, what additional test should be performed? a. Cytology b. Flow cytometry c. Lactate dehydrogenase *d. Gram stain and bacterial cultures General Feedback: Neutrophils increase in response to a bacterial infection.

Thus if most of the cells seen in a CSF are neutrophils, a Gram stain and bacterial cultures should be performed on the CSF. It is critical that the specimen be handled in a sterile manner until these tests have been performed; often a separate CSF tube is used for culture than that for cell counts.

7. Chapter 15-07 A CSF is equally bloody in all tubes collected and has a yellowish supernatant. On the differential, macrophages with hemosiderin are noted. Which is most likely? a. Bacterial meningitis b. Viral meningitis *c. Subarachnoid hemorrhage d. Traumatic tap General Feedback: All tubes being equally bloody indicates hemorrhage. If it had been a traumatic tap, there should have been a gradual decrease in the

number of red cells in successive tubes with gradual clearing. The yellow tinge to the supernatant suggests a subarachnoid hemorrhage.

8. Chapter 15-08 Nucleated red blood cells (NRBCs) and immature white cells in a CSF most likely mean: a. bacterial meningitis. b. patient has NRBCs in the peripheral blood. c. subarachnoid hemorrhage. *d. bone marrow contamination.

General Feedback: When immature bone marrow cells are seen in the CSF, it most likely means that bone marrow contamination of the specimen has occurred. If a significant number exist, the CSF differential will be a reflection of what is in the marrow, not the CSF.

9. Chapter 15-09 Which is a feature of malignant cells in fluids? a. Small size *b. Three-dimensional clumps with no “windows” c. Low nuclear-to-cytoplasmic (N:C) ratio d. Uniformity General Feedback: Mesothelial cells are the lining cells of body cavities and are shed into these cavities. They can be confused with malignant cells. However, when mesothelial cells appear in clumps (a frequent occurrence), usually windows are noted between the cells. This is not true of malignant cells that are also commonly found in clumps.

10. Chapter 15-10 Which is normal in a CSF? *a. Ependymal cells b. 100 white cells/mm3 c. Blasts d. Mesothelial cells General Feedback: Ependymal cells, along with choroids plexus cells, are lining cells of the central nervous system and are seen in CSF. None of the other findings would be normal in CSF.

11. Chapter 15-11 A patient has a pleural fluid with 2000 WBCs/mL. Seventy percent of the cells are neutrophils. Which is most likely? a. Normal fluid

b. Transudate on a patient with a pleural bacterial infection *c. Exudate on a patient with a pleural bacterial infection d. Exudate on a patient with heart failure General Feedback: Exudates are formed in response to an infection (viral or bacterial), malignancy, pulmonary embolus, and systemic lupus erythematosus. They generally have a white count greater than 1000/mL. Because the primary cells seen in this fluid are neutrophils, the infection is bacterial.

12. Chapter 15-12 Which is true regarding malignant cells in serous fluids? a. All clumps of large cells should be considered malignant. b. Malignant cells in serous fluids are rarely seen. c. Malignant cells categorize the fluid as a transudate. *d. Care must be taken to distinguish malignant cells from clumps of mesothelial cells.

General Feedback: Both malignant and mesothelial cells can be found in clumps in serous fluids. Mesothelial cells are normal lining cells of body cavities that are shed into these cavities; they are a normal finding in serous fluids. They can be confused with malignant cells. However, when mesothelial cells appear in clumps (a frequent occurrence), usually windows are noted between the cells. This is not true of malignant cells that are also commonly found in clumps.

13. Chapter 15-13 Which is a normal finding in serous fluids? *a. Macrophages b. Bacteria c. Eosinophils (EOs) d. LE cells General Feedback: Of the findings listed, only macrophages are a normal finding in serous fluids. Other normal cells are lymphocytes and mesothelial cells.

14. Chapter 15-14 How must synovial fluids be handled differently than other fluids? a. Perform a Gram stain if bacteria are seen. b. Dilute the fluid if the cell counts are high. *c. Add hyaluronidase to overcome the viscous nature of fluid. d. Carefully search the whole cytospin preparation for malignant cells.

General Feedback:

Synovial fluid contains hyaluronic acid, making it very viscous. Adding a small amount of hyaluronidase powder to the fluid will cause it to liquefy. Cell counts and/or cytocentrifuge slides can then be made.

15. Chapter 15-15 A synovial fluid has a high white cell count and large intracellular needlelike crystals that are yellow when the crystals are parallel to the y-axis of a red compensator. What is the likely diagnosis? a. Pseudo-gout *b. Gout c. Lupus erythematosus d. Bacterial infection General Feedback: These are monosodium urate crystals and are seen in gout.

16. Chapter 15-16 Which is true regarding bronchoalveolar lavage (BAL) fluids? a. The differential is not done on these fluids. b. It is often received from patients suspected of having asthma. c. Moving ciliated cells suggest that the patient has Pneumocystis carinii. *d. A mask should be worn when performing tests.

General Feedback: BAL examination is performed on patients with severe lung dysfunction. They may contain airborne organisms because they are taken from the interior of the lung; they often contain bacteria and/or yeast when cytocentrifuge slides are examined. Aerosol production is a real risk; thus it is critical to wear a mask when working with these specimens.

17. Chapter 15-17 Three CSF tubes are received in the laboratory numbered 1 through 3 based on the order in which they were obtained, with 1 being the first.

The first tube is cloudy pink, but this color diminishes and clearing occurs with each successive tube. What does this suggest? a. Internal bleeding into the CSF has occurred. *b. This is blood contaminating the CSF fluid from a traumatic puncture. c. Bacterial infection is likely present. d. Metastatic tumor is likely present.

General Feedback: The turbid and pink color is due to the presence of red cells in the fluid. Because each succeeding tube becomes clearer and the pink color diminishes, a traumatic tap is most likely the cause. If there had been internal bleeding into the CSF, each tube would appear the

same. The presence of bacterial infection or metastatic tumor cells cannot be determined by simply a gross examination of the fluid.

18. Chapter 15-18 One clinical laboratory scientist is covering the “manual bench” in the hematology laboratory, which is where body fluid examinations are done.

Just as she is preparing to go on break, she simultaneously receives two specimens, one a CSF and one a BAL fluid. Both are marked “stat.”

What should she do first? a. Analyze the BAL. *b. Analyze the CSF. c. Go on break and then return and do the BAL. d. Go on break and then return and do the CSF. General Feedback: A CSF fluid is always “stat,” and evaluation is critical for good patient care. The cells will rapidly disintegrate, just as for all body fluid specimens, and so they must be examined within 30 minutes of draw. Diagnostic information obtained from examination of CSF fluid can be extremely important for timely and appropriate patient care; therefore, in this scenario the CSF must be examined first and immediately. The clinical relevance of information obtained from hematologic examination of BAL fluid is minimal, and some hematology laboratories no longer perform counts and/or cytocentrifuge preparations on these specimens because the biohazard risk outweighs the clinical usefulness.

1. Chapter 16-01 What is the best definition of anemia? a. Red cell count 10% lower than the patient’s baseline *b. Decreased oxygen-carrying capacity of blood c. Hemoglobin below 12 g/dL d. Any clinical condition resulting in shortness of breath General Feedback: The best definition of anemia is a decreased hemoglobin, hematocrit, and red cell count compared with typical results for healthy people in the same demographic group. Ideally it would be a decrease below the patient’s normal baseline, but that is often not known. Reference ages for hemoglobin vary dependent on sex, age, and environmental factors (e.g., altitude); for this reason a single cutoff such as 12 g/dL cannot be used. The symptoms for anemia are nonspecific, although they certainly help support the diagnosis.

2. Chapter 16-02 Two different patients both have hemoglobins in the 5.0 to 6.0 g/dL range. One has pallor, fatigue, and headaches, whereas the other is experiencing life-threatening shock. Which is probably the major difference between the two patients? a. The morphologic classification of the anemia b. Whether other cell lines (platelets or white cells) are also involved c. The patient’s sex *d. How quickly the anemia developed General Feedback: When anemia develops slowly, the body is able to make a number of compensations so that the patient may have few if any symptoms.

Conversely, if it develops rapidly (e.g., massive blood loss), then symptoms will be evident.

3. Chapter 16-03 The red cell histogram is wider than normal. Which is true? a. The red blood cell distribution width (RDW) is decreased. b. Most cells are larger than normal. c. The coefficient of variation was calculated incorrectly. *d. Anisocytosis is present.

General Feedback: The coefficient of variation of the red cell histogram is the RDW. Thus when the histogram is broader than usual, the RDW increases.

4. Chapter 16-04 The reticulocyte response in patients with moderate anemia is often misinterpreted as adequate if: *a. the count is not corrected for anemia.

b. the red cell indices are not considered. c. a bone marrow aspirate is not examined. d. red cell morphology is not considered.

General Feedback: If only the percentage of reticulocytes is considered, a patient may appear to be making an adequate response to anemia.

However, when the red count is considered, and either the absolute reticulocyte count or the reticulocyte production index is calculated, a truer picture can be obtained regarding adequacy of bone marrow response.

5. Chapter 16-05 Which red blood cell (RBC) finding is specific for a certain condition as opposed to being nonspecific and found in many conditions? a. Ovalocytes b. Poikilocytosis *c. Sickle cells d. Burr cells General Feedback: Many different abnormally shaped RBCs are not specific for any one cause for anemia. One exception is the sickle cell, which is almost diagnostic for sickle cell disease.

6. Chapter 16-06 Which condition would warrant a bone marrow aspiration? a. Iron deficiency in a patient with colon cancer b. Severe hereditary spherocytosis c. Disseminated intravascular coagulation (DIC) with very low hemoglobin and marked red cell fragments *d. Not possible to determine obvious reason for anemia General Feedback: When a patient is anemic and testing reveals no obvious reason, a bone marrow aspiration (smear) is warranted. The morphology not only of erythroid but also of all other blood-forming cells in the marrow can be evaluated. This can provide useful information as to the cause of anemia. All the other situations listed can be diagnosed with appropriate testing on blood (may include other tests besides hematologic).

7. Chapter 16-07 What is the approximate average life span of a normal RBC in circulation? a. 10 Days b. 20 Days c. 80 Days *d. 120 Days

General Feedback: The average life span of a normal RBC in circulation is 120 days.

8. Chapter 16-08 What percentage of red cells is destroyed and replaced daily in a normal adult? *a. 1% b. 5% c. 10% d. 20% General Feedback: Because red cells have a normal life span of 120 days, roughly 1% of them die and are replaced daily.

9. Chapter 16-09 Which is an example of a morphologic classification of anemia? *a. Normocytic b. Loss of blood c. Increased destruction d. Impaired production General Feedback: The morphologic classification uses the morphology of red cells to separate anemias into groups that can then be related to potential causes of anemia. The other listed items are possible mechanisms for anemia.

10. Chapter 16-10 Which is typically a macrocytic anemia? a. Thalassemia b. Iron deficiency *c. Folate deficiency d. Aplastic General Feedback: Folate deficiency is a macrocytic anemia. Iron deficiency anemia (stage 3) and thalassemia are microcytic; aplastic anemia is normocytic.

11. Chapter 16-11 What test is used along with the mean cell volume (MCV) to morphologically classify anemias? a. Red blood count b. Hemoglobin c. Hematocrit

*d. RDW General Feedback: By definition, the red count, hemoglobin, and hematocrit are all decreased in anemia, so those cannot be used to separate one cause from another. However, the RDW describes whether the red cell population is homogenous or heterogeneous with respect to size.

Combining it with the MCV can provide very useful information as to possible causes for an anemia.

12. Chapter 16-12 All are physiologic adaptations the body makes when a slow drop in the number of red cells occurs except: a. erythropoietin level increases. *b. oxygen dissociation curve shifts to left. c. cardiac output increases. d. respiratory rate increases.

General Feedback: When anemia develops, the concentration of 2,3biphosphoglycerate (2,3-BPG) increases. This causes a shift to the right in the oxygen dissociation curve, which results in more effective delivery of oxygen to tissue (oxygen affinity of hemoglobin decreases).

13. Chapter 16-13 Describe the morphologic appearance of the red cells given the following results.

RBC: 1.89 × 1012/L Hemoglobin: 7.5 g/dL Hematocrit: 21.0% RDW: 18.5 *a. Macrocytic with anisocytosis b. Normocytic normochromic with anisocytosis c. Microcytic hypochromic with little anisocytosis d. Macrocytic with most cells the same size General Feedback: The red cell indices are calculated as follows: MCV = (7.5/1.89) × 10 = 111 fL; mean cell hemoglobin (MCH) = (7.5/1.89) × 10 = 40 pg; mean cell hemoglobin concentration (MCHC) = (7.5/21) × 100 = 36. The red cells are thus macrocytic (high MCV) and normochromic (normal MCHC). The RDW is elevated at 18.5, so an increased variation in size exists. This then is a macrocytic anemia with anisocytosis.

14. Chapter 16-14 Which disorder would be consistent with the previously mentioned parameters? a. Anemia of chronic disease b. Aplastic anemia

*c. Vitamin B12 deficiency d. Thalassemia General Feedback: Vitamin B12 deficiency leads to a macrocytic anemia with significant variation in size (therefore an increased RDW). Aplastic anemia is normocytic normochromic with a normal RDW; the anemia of chronic inflammation (disease) is either normocytic (MCV low normal) or slightly microcytic but normochromic and a normal or only a mildly elevated RDW. Thalassemia is a microcytic normochromic or hypochromic anemia with a normal RDW.

15. Chapter 16-15 Which is true of ineffective erythropoiesis? a. Lymphopenia and anemia are present. *b. RBC production in bone marrow is increased. c. Release of RBCs to the peripheral blood is normal. d. RBC survival in circulation is less than 40 days.

General Feedback: RBC production in the bone marrow is increased in ineffective erythropoiesis (decreased M:E ratio). However, production is defective, and many of the red cells are destroyed before leaving the marrow. Thus release of RBCs to peripheral blood is decreased. Although survival of these RBCs in circulation may be slightly shortened from the normal of 120 days, it is not significant (the increased rate of production in the marrow could fully compensate for the slight shortening if the red cells were all released to circulation). Lymphopenia is not characteristic of these anemias.

16. Chapter 16-16 Compare results of various tests in effective versus ineffective erythropoiesis. *a. Both have increased rate of erythropoiesis in the bone marrow. b. Both have an elevated reticulocyte production index (RPI) greater than 3. c. Both have normal release of RBCs from the bone marrow. d. Both have significantly shortened red cell survival in circulation.

General Feedback: In both effective and ineffective erythropoiesis, the rate of red cell production in the bone marrow is increased (increased erythropoiesis). However, release to circulation differs in the two: it is successful in effective but not in ineffective, where significant intramedullary loss occurs. Thus the RPI is greater than 3 in effective, but usually less than 2 in ineffective. Red cell survival in circulation is significantly decreased in effective, but essentially normal or insignificantly shortened in ineffective.

17. Chapter 16-17 Which is a microcytic anemia? a. Vitamin B12 deficiency b. Sickle cell anemia *c. Iron deficiency d. Hereditary spherocytosis General Feedback: Iron deficiency anemia is microcytic. Vitamin B12 deficiency is macrocytic; sickle cell anemia and hereditary spherocytosis are both normocytic.

18. Chapter 16-18 The anemia found in liver disease is: *a. macrocytic nonmegaloblastic. b. microcytic hypochromic. c. macrocytic megaloblastic. d. microcytic normochromic.

General Feedback: The anemia found in liver disease is macrocytic, but it is not megaloblastic. The large red cells result because of membrane changes resulting from disruption of the cholesterol-to-phospholipids ratio (in the membrane).

19. Chapter 16-19 Which shape of red cell is described as a round, dense cell with no area of central pallor? a. Sickle cell b. Target cell c. Burr cell *d. Spherocyte General Feedback: This description fits that of a spherocyte. The MCV of a spherocyte is usually normal, although microspherocytes exist that have a low MCV.

20. Chapter 16-20 An appropriately increased RPI greater than 3 is associated with: a. iron deficiency anemia. b. macrocytic megaloblastic anemia. *c. hemolytic anemia. d. sideroblastic anemia.

General Feedback:

Only hemolytic anemias have an appropriately increased RPI. The anemia develops notbecause production is defective but because survival in circulation is significantly shortened. In iron deficiency anemia, insufficient erythropoiesis occurs. In macrocytic megaloblastic and sideroblastic anemias, erythropoiesis is ineffective.

21. Chapter 16-21 Which type of red blood cell has a single pointed extension resembling a pear? *a. Dacryocyte b. Echinocyte c. Acanthocyte d. Keratocyte General Feedback: A dacrocyte is a red blood cell (RBC) with a single pointed extension resembling a pear. A RBC with blunt or pointed, short projections that are usually evenly spaced over the surface of cell is an echinocyte. An acanthocyte is small, dense RBC with few irregularly spaced projections of varying length. A keratocyte is a RBC fragment in shape of a helmet.

1. Chapter 17-01 Lack of accessible iron is the mechanism for iron deficiency in which condition? a. Hemochromatosis b. Hemosiderosis c. Lead poisoning *d. Anemia of chronic inflammation (ACI) General Feedback: Lack of accessible iron results in ACI, as well as iron deficiency. In iron deficiency iron stores are depleted. In ACI iron stores are plentiful, but the iron is cannot be mobilized for use in developing red cells.

2. Chapter 17-02 Which group of patients is most likely to develop iron deficiency from increased need? a. Young men *b. Infants and young children c. Postmenopausal women d. Middle-aged men General Feedback: Infants and young children need more iron to support an expanding erythron.

3. Chapter 17-03 Where is most of the iron in the body found? *a. Attached to hemoglobin in the red blood cells (RBCs) b. Stored in macrophages in the bone marrow c. Attached to transferrin d. Myoglobin General Feedback: Approximately 65% of total body iron is found in hemoglobin.

Another 25% is stored as ferritin or hemosiderin, and about 10% is divided among muscles, plasma, cytochrome of cells, and various ironcontaining enzymes of cells.

4. Chapter 17-04 Which is the best test to distinguish iron deficiency anemia from ACI? a. Serum iron b. Hemoglobin c. Free erythrocyte protoporphyrin (FEP) *d. Ferritin General Feedback: Of the tests listed, only ferritin distinguishes between iron deficiency anemia and ACI; in iron deficiency anemia it is low, whereas

in ACI it is normal to elevated. Serum iron and hemoglobin (if the patient is anemic) are decreased in both; FEP is increased in both.

5. Chapter 17-05 How much iron do adult men need a day? a. 0.5 mg b. 0.75 mg *c. 1.0 mg d. 1.5 mg General Feedback: Adult men need about 1 mg of iron a day to maintain health.

6. Chapter 17-06 What parameter of the routine complete blood count (CBC) is a sensitive indicator of preclinical iron deficiency? *a. Red blood cell distribution width (RDW) b. Hematocrit c. Mean cell hemoglobin (MCH) d. Red blood count General Feedback: As iron deficiency develops, hemoglobin synthesis begins to be impaired leading to the production of microcytic red cells. As these small red cells begin to be released and mix in with the normocytic red cells still circulating, anisocytosis develops. This increases the RDW, which precedes the decrease in hemoglobin. Eventually the red count and hematocrit begin to decrease, and the MCH decreases when enough small cells become present to affect it.

7. Chapter 17-07 Which result is typical in stage 3 iron deficiency anemia? a. Elevated reticulocyte percentage b. Thrombocytopenia c. Macrocytic red cells *d. Low mean cell volume (MCV) General Feedback: In stage 3 iron deficiency, the red cells are microcytic and hypochromic. Therefore the MCV, MCH, and MCHC are all low. (The MCH is actually lower than would be expected for the red cell size if it had been normochromic.) The reticulocyte count (%) is low, sometimes thrombocytosis is seen, and the red cells are not macrocytic.

8. Chapter 17-08 What is most likely if a 10-month-old child who was fed only cow’s milk has the following results? · Serum iron decreased

· Total iron-binding capacity (TIBC) increased · Ferritin decreased a. Lead poisoning b. Chronic disease *c. Iron deficiency from increased need and inadequate diet d. Iron deficiency from chronic blood loss General Feedback: The iron studies all point to iron deficiency: low serum iron and ferritin, with an elevated TIBC. Cow’s milk is a very poor source of iron, so the infant is not getting adequate iron to support an expanding erythron.

9. Chapter 17-09 What would be the likely findings if a bone marrow aspiration were performed in a complicated case of iron deficiency anemia? a. Increased myeloid-to-erythroid (M:E) ratio and increased staining with Prussian blue *b. Shaggy polychromatophilic normoblasts and no staining with Prussian blue c. Polychromatophilic normoblasts with copious pink cytoplasm and no staining with Prussian blue d. Increased M:E ratio and increased ringed sideroblasts General Feedback: Shaggy polychromatophilic normoblasts are seen because of the asynchronous maturation of developing red cells, with the cytoplasm lagging behind that of the nucleus. Prussian blue is an iron-specific stain; in iron deficiency anemia, iron stores are absent, and sideroblasts and siderocytes are markedly decreased to absent. The M:E ratio is increased late in iron deficiency because fewer red cell precursors exist in the marrow, but no staining with Prussian blue occurs.

10. Chapter 17-10 What is the mechanism for ACI? *a. Acute phase reactants impair iron mobilization. b. Inflammation and infections slow heme development. c. Cytokines prevent iron incorporation into protoporphyrin. d. Bone marrow iron stores are depleted by acute phase reactants.

General Feedback: The acute phase reactants hepcidin, lactoferrin, and ferritin all contribute to impairing the mobilization of iron for erythropoiesis. Bone marrow iron stores are actually normal to increased in ACI.

11. Chapter 17-11 Which are typical laboratory results for ACI?

a. Decreased ferritin and decreased bone marrow Prussian blue staining b. Low serum iron and high TIBC *c. Low serum iron and low TIBC d. Increased transferrin saturation and decreased FEP General Feedback: Both serum iron and TIBC are low in ACI. Ferritin is normal to increased, and Prussian blue staining reveals normal to increased storage iron. However, the number of sideroblasts and siderocytes is decreased to absent because iron cannot be moved to developing red cells. FEP is increased, just as it is in iron deficiency anemia.

12. Chapter 17-12 Which red cell inclusion is often found in lead poisoning? a. Howell-Jolly bodies *b. Basophilic stippling c. Heinz bodies d. Cabot rings General Feedback: Basophilic stippling, sometimes quite coarse, is characteristic of lead poisoning. Lead interferes with the breakdown of pyrimidine 5?2'-nucleotides, which in turn are believed to retard the breakdown of ribosomal ribonucleic acid (RNA), thus leading to stippling.

13. Chapter 17-13 How do lead exposure and the porphyrias cause anemia? a. Cause destruction of red cells. b. Chelate iron from the body. c. Impair iron absorption. *d. Interfere with heme production.

General Feedback: Common to lead poisoning and the porphyrias is the impairment of protoporphyrin synthesis, which is required for heme production.

14. Chapter 17-14 Most of the clinical findings in the porphyrias are related to: *a. accumulated porphyrin compounds in tissue. b. anemia. c. reduction in heme production. d. iron being unavailable.

General Feedback: In the porphyrias (generally used to refer to the inherited forms as opposed to acquired), an enzyme is missing in the protoporphyrin IX synthesis pathway. When an enzyme is missing, the products from earlier stages in the pathway accumulate in the blood.

Some of these are excreted, but they also deposit in body tissues, contributing to the clinical picture.

15. Chapter 17-15 Transfusion-related hemochromatosis is seen in patients who: a. had an adverse reaction to a blood transfusion. b. received the wrong type of blood. *c. had repeated red blood cell transfusions. d. received a transfusion from a relative.

General Feedback: When patients with chronic severe anemias are maintained with red cell transfusions, the iron in the transfused red cells adds to any iron that is being absorbed normally. No mechanism exists to rid the body of iron. Over years, this excess iron builds up and acquired hemochromatosis develops. Red cell transfusions are thus a “doubleedged sword” for these patients. On one hand, they improve the quality of life and perhaps even save it for the patient; on the other, the eventual consequence after years of transfusions is acquired hemochromatosis.

16. Chapter 17-16 Why is too much iron dangerous? a. Transferrin, which carries iron, causes cellular swelling and lysis. b. The oxygen carried by excess iron oxidizes neurologic cells. c. Iron’s breakdown products cause excretion of vitamins C and E. *d. Free radicals and superoxide formed from ferrous iron plus oxygen damage cell membranes.

General Feedback: When iron exceeds storage capacity, ferrous iron accumulates in cells. Ferrous iron is easily oxidized and in so doing generates superoxide and other free radicals, which are very damaging to cell membranes, mitochondria, and other cell organelles. Cell death and eventual possible organ failure are consequences.

17. Chapter 17-17 Which promotes increased iron absorption? a. Repeated phlebotomy *b. Diet high in ascorbic acid c. Desferrioxamine d. Vegetarian diet General Feedback: Ascorbic acid enhances iron absorption. Iron in vegetables is nonheme iron, and it is not readily absorbed. Desferrioxamine chelates iron and is used therapeutically for patients with transfusiondependent hemochromatosis. Repeated phlebotomy depletes iron, and it is

the treatment used for patients with the hereditary form of hemochromatosis.

18. Chapter 17-18 Which is decreased in patients with hereditary hemochromatosis? *a. Albumin b. Serum iron c. Transferrin saturation d. Ferritin General Feedback: Liver damage and disease is a consequence of hereditary hemochromatosis; albumin is synthesized in the liver, and with liver damage its concentration decreases. Serum iron, transferrin saturation, and ferritin are all increased.

19. Chapter 17-19 Which test rises first after successful treatment for iron deficiency? *a. Reticulocyte count b. Ferritin c. MCV d. Hemoglobin General Feedback: The reticulocyte count will begin to increase within 5 to 10 days after institution of therapy. Hemoglobin will take roughly 2 months to return to normal, although it will begin to slowly increase within 2 weeks. The MCV will rise more slowly because the microcytic red cells in circulation have to live out their normal life span; they will gradually be replaced with more and more normocytic red cells.

Ferritin will be the last to rise; only after the erythron has been restored to normal will there be any excess iron to go to stores.

20. Chapter 17-20 Which characterizes stage 1 iron deficiency?

Anemia MCV Ferritin a. Present Decreased Decreased b. Present Normal Normal *c. Absent Normal Decreased d. Absent Decreased Normal General Feedback: In early stage 1 iron deficiency, the red cell mass in circulation is unaffected, so anemia is not present and the MCV is normal. However, iron stores are being depleted, so ferritin is decreased.

21. Chapter 17-21 Which is true of stage 3 iron deficiency? a. Serum transferrin receptors are decreased. *b. FEP is increased. c. The number of sideroblasts is normal. d. The red cell count is increased, whereas the hematocrit is decreased.

General Feedback: FEP increases because not enough adequate iron is available to insert into protoporphyrin IX. Transferrin receptors on the membrane of developing cells increase as the cells try to capture as much iron as possible (from what is bound to transferrin); these receptors are shed into plasma so that they increase (actually happens in stage 2).

Sideroblasts will essentially be absent because no excess iron is going to the developing red cells. The red cell count, as well as the hematocrit, is decreased.

22. Chapter 17-22 Chronic blood loss leads to: *a. iron deficiency anemia. b. ACI. c. megaloblastic anemia. d. hemolytic anemia.

General Feedback: Chronic loss of blood leads to loss of red cells and their iron content. Iron is conserved and recycled very tightly in the body.

To maintain normal stores, it requires that only the normal amount be lost on a daily basis. Gradually iron stores will be depleted and iron deficiency will develop.

23. Chapter 17-23 Which would point to iron deficiency anemia as opposed to the ACI? a. Anemia *b. High transferrin c. Low serum iron d. Elevated FEP General Feedback: Transferrin is high in iron deficiency anemia but low in the ACI. All the other test results given are the same for both.

24. Chapter 17-24 Ringed sideroblasts are seen in: *a. inherited sideroblastic anemia. b. acquired hemochromatosis. c. iron deficiency anemia. d. ACI.

General Feedback: Ringed sideroblasts are seen in the inherited forms of sideroblastic anemia but not in any of the other conditions listed.

25. Chapter 17-25 Ringed sideroblasts are a reflection of iron-laden: *a. mitochondria. b. Golgi complex. c. ribosomes. d. rough endoplasmic reticulum.

General Feedback: In the sideroblastic anemias, where ringed sideroblasts are present, plenty of iron is available to developing red cells. However, for one reason or another, the iron cannot be inserted into the protoporphyrin IX ring. Because this is the last step in heme synthesis and it takes place in the mitochondria, the mitochondria become laden with iron. When these cells are stained with Prussian blue, the iron stains; mitochondria encircle the nucleus of the cell, so that what is seen is a “ring” of stained iron granules encircling the nucleus (hence called a ringed sideroblast).

26. Chapter 17-26 Why is lead poisoning of particular concern in children? a. Severe anemia may develop. *b. Impaired mental development may occur. c. Secondary iron deficiency may develop. d. FEP may accumulate.

General Feedback: In children who develop lead poisoning, the biggest concern is the potential for impaired mental development.

27. Chapter 17-27 All are true about hepcidin except that: a. it is an acute phase protein. b. it is a hormone. *c. it decreases in response to increased ferritin. d. it increases in response to increased iron stores.

General Feedback: Hepcidin is a hormone and is also an acute phase protein that increases when iron levels are high. Ferritin is a form of storage iron, so hepcidin increases when ferritin is increased, not decreased.

1. Chapter 18-01 Megaloblastic anemias are caused by a defect in the synthesis of: *a. deoxyribonucleic acid (DNA). b. ribonucleic acid (RNA). c. erythropoietin. d. heme.

General Feedback: Defects in DNA synthesis are the cause of most megaloblastic anemias (an exception would be in the myelodysplastic syndrome).

2. Chapter 18-02 Which vitamins are required for the nuclear development of blood cells? a. Vitamin C and folate b. Vitamin B6 and folate *c. Vitamin B12 and folate d. Vitamin B12 and D General Feedback: Vitamins B12 and folate are required for normal nuclear development (DNA synthesis).

3. Chapter 18-03 Which is not associated with macrocytic red cells? a. Liver disease *b. Iron deficiency anemia c. Megaloblastic anemia d. Myelodysplastic syndrome General Feedback: Iron deficiency is associated with microcytic, not macrocytic, red cells. All the other conditions listed can be associated with macrocytic red cells.

4. Chapter 18-04 Why are the red cells larger than normal in megaloblastic anemia? a. Concentration of erythropoietin is increased. b. Release of reticulocytes is increased. c. Cells are made larger because fewer of them exist. *d. Cell division is impaired.

General Feedback: Red cell production is asynchronous in megaloblastic anemias, with nuclear development lagging behind that of the cytoplasm. Because DNA synthesis is affected, cell division does not occur normally and the cells become larger.

5. Chapter 18-05 Methotrexate and some other chemotherapeutic drugs work by: a. killing cancer cells with immune complexes. *b. competing with folate. c. enhancing folate. d. inhibiting vitamin B12 absorption.

General Feedback: Methotrexate and some other chemotherapeutic drugs work by competing with folate; thus a megaloblastic anemia can develop in these patients.

6. Chapter 18-06 Patients with vitamin B12 or folate deficiency commonly experience symptoms related to: *a. gastrointestinal and neurologic systems. b. liver and lymph node enlargement. c. skeletal and muscle problems. d. kidney and bladder infections.

General Feedback: Any system in the body that depends on replacement of cells with new ones will be affected by a deficiency of vitamin B12 or folate. Symptoms of the deficiency can thus be seen in the gastrointestinal tract, the skin, and the hematopoietic system.

7. Chapter 18-07 Decreased folate is often associated with which condition? *a. Neural tube defects b. Increased potassium c. Microcytic anemia d. Hyperhomocysteinemia General Feedback: Decreased folate in a pregnant woman can lead to neural tube defects in the fetus. Neural tube defects are most commonly associated with folate deficiency.

8. Chapter 18-08 All of the following have increased need for folate except: a. patients on chemotherapy. b. pregnant women. c. infants and children. *d. male adults.

General Feedback:

Men (i.e., male adults) should have a diet adequate to meet their folate requirements. Patients on chemotherapy often are given drugs that interfere with DNA metabolism, and so they require more folate. Pregnant women have an increased need to support the growing fetus, as do infants and children, especially during growth spurts.

9. Chapter 18-09 Which is the best source of dietary vitamin B12? a. Fruit b. Green vegetables *c. Meat d. Legumes General Feedback: Meat provides the best source of vitamin B12; meat by-products such as milk and eggs are sources other than meat. Plants have no need for this vitamin, and so it is not available in green vegetables, legumes, or fruit. Thus it is possible, over time, for a true dietary deficiency to develop for a strict vegetarian (i.e., vegan).

10. Chapter 18-10 Which is normal in patients with pernicious anemia (PA)? *a. Trypsin levels b. Intrinsic factor (IF) c. Stomach acid d. Absorption of vitamin B12 General Feedback: Trypsin is normal in patients with PA. The root cause of PA is a deficiency of IF because of autoimmune attack, either of IF itself or of the parietal cells in which it is synthesized. Atrophic gastritis develops; this affects the secretion of H+, which affects gastric (stomach) acidity, important for normal digestive processes.

11. Chapter 18-11 PA can be distinguished from folate deficiency by the: a. presence of hypersegmented neutrophils. b. mean cell volume (MCV). c. bone marrow findings. *d. presence of autoantibodies to IF. General Feedback: Both PA and folate deficiency have an elevated MCV, the presence of hypersegmented neutrophils, and megaloblastic bone marrow findings. However, only PA has autoantibodies to IF present.

12. Chapter 18-12 Which is decreased in megaloblastic anemia? *a. Reticulocyte count b. MCV c. Lactic dehydrogenase (LD) d. Bilirubin General Feedback: Impaired cell production results in a low absolute reticulocyte count, especially in light of the severity of the anemia.

Intramedullary cell death occurs in ineffective erythropoiesis, and this leads to both an increased LD (released from dying cells) and increased bilirubin (increased breakdown of hemoglobin).

13. Chapter 18-13 Which is elevated in megaloblastic anemia? a. White blood count *b. Mean cell hemoglobin (MCH) c. Red blood count d. Platelet count General Feedback: Pancytopenia is found in the megaloblastic anemias because all the blood-forming cells require DNA synthesis to proliferate and replace those cells that die even under normal circumstances. Thus the white count, red count, and platelet count are all expected to be decreased. However, because the red cells are macrocytic and normochromic, the MCH is elevated (reflection of fully hemoglobinized large red cells).

14. Chapter 18-14 Which would be an unusual finding in megaloblastic anemia? *a. Marked polychromasia on the blood film b. Hypersegmented neutrophils c. Oval macrocytes d. Pancytopenia General Feedback: Ineffective erythropoiesis leads to intracellular death so that many red cells never make it to circulation; thus polychromasia is not typical. However, hypersegmented neutrophils are a hallmark and, in fact, appear before changes in red cells are obvious. This is because of their short T1/2 of 6 to 10 hours in circulation. Oval macrocytes are a characteristic red cell shape in the megaloblastic anemias, and pancytopenia is usually present because all proliferating blood-forming cells in the bone marrow require normal DNA synthesis.

15. Chapter 18-15 Which is true regarding hypersegmented neutrophils?

a. Found in so many conditions that they are not significant b. Reported when neutrophils have four or more nuclear segments *c. Are an early, consistent, and specific finding in megaloblastic anemia d. Usually accompany microcytic red cells General Feedback: Hypersegmented neutrophils are consistently found early in megaloblastic anemia. Because they are not found in any other condition, they are considered specific. Thus they usually accompany macrocytic red cells (including macroovalocytes). Laboratories may use differing criteria for hypersegmentation. However, all would agree that observation of one six-lobed neutrophil is evidence of hypersegmentation. Some will do a neutrophil lobe count, and report hypersegmentation when the average is greater than 3.4.

16. Chapter 18-16 Which bone marrow finding would be unexpected in megaloblastic anemia? a. Nuclear cytoplasmic asynchrony b. Giant bands and metas c. Hypercellularity *d. Myeloid-to-erythroid (M:E) ratio of 10:1 General Feedback: An M:E ratio of 10:1 would imply that 10 times as many myeloid cells exist as do erythroid precursors in the marrow. However, erythroid hyperplasia occurs in the marrow, so the M:E ratio is decreased to about 1:1. The marrow is hypercellular, nuclear cytoplasmic asynchrony occurs in maturation because of the defect in DNA synthesis, and giant bands and metas are characteristic.

17. Chapter 18-17 Which test for PA would be easiest for the patient? *a. Vitamin B12 assay b. Bone marrow c. Gastric analysis d. Schilling test General Feedback: The easiest test for the patient would be a vitamin B12 assay.

All that is required for this test is a venipuncture. The other tests are all much more invasive.

18. Chapter 18-18 What is the most effective treatment for PA? a. Oral folate *b. Injections of vitamin B12 c. Oral vitamin B12

d. Alterations in diet General Feedback: PA is a deficiency of vitamin B12 (not folate) because of a lack of IF, which is required for absorption. The vitamin is usually administered by injection through muscle. Because IF deficiency is the actual defect, taking vitamin B12 orally will be of no benefit because it cannot be absorbed. Administering it by injection bypasses the need for absorption.

19. Chapter 18-19 A patient has a decreased vitamin B12 assay. The Schilling test detects labeled vitamin B12 in the urine when it is given with IF. What is the correct interpretation? a. Vitamin B12 assay probably incorrect *b. Pernicious anemia c. Vitamin B12 deficiency that is not PA d. Gastric analysis should be performed General Feedback: The Schilling test is used to determine if the reason for low vitamin B12 is an inability to absorb because of lack of IF or if the problem in absorption is related to something else. Because IF apparently corrected the problem in absorption, PA is the diagnosis. If some other malabsorption problem existed, the addition of IF would not have corrected the problem and the labeled vitamin B12 would not have appeared in the urine.

20. Chapter 18-20 A patient with moderate anemia has an elevated MCV and hypersegmented neutrophils. Which should be ordered first? a. Schilling test b. Gastric analysis c. Antibodies to IF *d. Vitamin B12 and folate assays General Feedback: The blood picture findings point to a megaloblastic anemia.

The first test to order would be the vitamin B12 and folate assays to determine which of these two vitamins is deficient.

21. Chapter 18-21 What salivary protein is important for the transport of dietary vitamin B12 to the small intestine? a. Trypsin b. IF *c. Haptocorrin

d. Transcobalamin II General Feedback: Haptocorrin is a salivary protein that binds vitamin B12 found in food. In the small intestine, the vitamin is released from haptocorrin by the action of trypsin. IF is then required for its absorption into circulation. Transcobalamin is the most important of the plasma carrier proteins for vitamin B12.

1. Chapter 19-01 Pancytopenia is a term that means: *a. decrease in red cells, white cells, and platelets. b. increase in red and white cells. c. decrease in any two blood cell lines. d. increase in white cells and platelets.

General Feedback: A decrease in all the blood cells (i.e., red cells, white cells, and platelets) is called pancytopenia.

2. Chapter 19-02 Bone marrow failure causes pancytopenia: a. in the peripheral blood only. b. in the bone marrow only. *c. in both the bone marrow and the peripheral blood. d. in the bone marrow, peripheral blood, and spleen.

General Feedback: Bone marrow failure results in a decrease in all the blood cells’ elements in the bone marrow (hence it is called bone marrow failure). Because blood cells are not being produced in adequate numbers in the bone marrow to enter the peripheral blood, pancytopenia is also seen in the blood.

3. Chapter 19-03 Which is most useful for considering the diagnosis of pancytopenia? a. Hemoglobin less than 10g/dL *b. Increased absolute neutrophil count c. Increased absolute lymphocyte count d. Decreased mean cell volume General Feedback: The absolute neutrophil count is decreased, and the absolute lymphocyte count may be normal or decreased. The hemoglobin is usually less than 10 g/dL, the mean cell volume (MCV) is increased or normal, and the percent and absolute reticulocyte counts are decreased.

4. Chapter 19-04 Which patient fits the typical patient demographics for aplastic anemia? a. Infant *b. A 65-year-old adult c. A 45-year-old adult d. A 7-year-old child General Feedback:

Aplastic anemia can be found at any age, but it is most characteristically found in young adults 15 to 25 years old, as well as in those older than 60 years.

5. Chapter 19-05 The red cell morphology associated with aplastic anemia is: *a. normocytic normochromic with no polychromasia. b. normocytic normochromic with marked polychromasia. c. microcytic hypochromic with marked polychromasia. d. microcytic normochromic with no polychromasia.

General Feedback: Red cells are characteristically normocytic normochromic in aplastic anemia, although occasionally some macrocytosis may exist.

Polychromasia is absent.

6. Chapter 19-06 Which would be an unusual bone marrow finding in aplastic anemia? a. Predominance of lymphocytes, plasma cells, and mast cells b. Hypocellular *c. Increased megakaryocytes d. Increased fat General Feedback: In aplastic anemia, the marrow is hypocellular with increased fat. The normal blood-forming cells are greatly diminished, and the cells left in the bone marrow are lymphocytes, plasma cells, and mast cells.

7. Chapter 19-07 What is the treatment of choice for long-term survival for patients younger than 40 years old with aplastic anemia? a. Blood transfusion b. Growth factors c. Antibiotic agents *d. Bone marrow transplant General Feedback: Bone marrow transplant is the treatment of choice for patients with severe aplastic anemia who are younger than 40 years of age and have a human leukocyte antigen (HLA)-identical sibling.

8. Chapter 19-08 What is the treatment of choice for a patient older than 40 years old with aplastic anemia? a. Hematopoietic stem cell transplant b. Antibiotic agents

*c. Antithymocyte globulin (ATG) d. Erythropoietin General Feedback: Immunosuppressive treatment, consisting of antithymocyte globulin and cyclosporine, is used for patients older than 40 years of age and for patients without an HLA-identical sibling.

9. Chapter 19-09 Which is an inherited disorder with pancytopenia, malformed kidneys, and short stature? a. Myelodysplasia *b. Fanconi anemia c. Diamond-Blackfan anemia d. Secondary aplastic anemia General Feedback: Fanconi anemia is an autosomal recessive disorder, which means that the gene must be inherited from both parents to express the phenotype. Myelodysplasia and secondary aplastic anemia are both acquired. Diamond-Blackfan anemia is an inherited form of pure red cell aplasia (PRCA). Neutrophil and platelet precursors are normal.

10. Chapter 19-10 What distinguishes PRCAs such as Diamond-Blackfan syndrome from aplastic anemia? a. Peripheral red blood count b. Number of erythroid stem cells in the bone marrow *c. Normal cellularity of myeloid cells d. Red cell indices General Feedback: Diamond-Blackfan anemia is characterized by an isolated PRCA and normal cellularity of myeloid cells. Red cell indices are not useful.

11. Chapter 19-11 Which is a feature of type II congenital dyserythropoietic anemia (CDA II)? *a. Giant, multinucleated red cell precursors b. Microcytic red cells c. Positive sucrose hemolysis test d. Negative acidified serum test (Ham test) General Feedback: CDA II is also known as hereditary erythroblastic multinuclearity with positive acidified serum (HEMPAS). It is the most common type of CDA, and is, as the alternate name suggests, associated with giant, multinucleated erythroblastic precursors. The acidified

serum test (Ham test) is positive, not the sucrose hemolysis test. Red cells are usually normocytic, although often anisocytosis is noted.

12. Chapter 19-12 Normal bone marrow cells being replaced with malignant cells is called: a. Diamond-Blackfan anemia. b. CDA II. c. PRCA. *d. myelophthisic anemia.

General Feedback: Myelophthisic anemia results when invading or infiltrating cells replace normal bone marrow cells. These invading cells may be malignant.

13. Chapter 19-13 The anemia associated with severe kidney disease is caused primarily by: a. damage to stem cells by urea. b. replacement of bone marrow cells with fat. *c. deficiency of erythropoietin. d. bleeding into the urine.

General Feedback: A deficiency of erythropoietin is the primary cause of the anemia found in chronic renal failure. The kidney is the primary site of synthesis for erythropoietin, which controls red cell production.

14. Chapter 19-14 What surface antigen on cells identifies them as a hematopoietic stem cell? a. CD8+ *b. CD34+ c. CD55+ d. CD59+ General Feedback: Hematopoietic stem cells are identified by the presence of CD34+ on their surface. These are decreased in aplastic anemia.

15. Chapter 19-15 The cause of acquired idiopathic aplastic anemia is: a. Epstein-Barr virus. b. chemicals such as benzene. c. radiation. *d. unknown.

General Feedback: The term idiopathic means unknown; therefore, the cause of idiopathic aplastic anemia is unknown. All the other items listed are possible causes of secondary aplastic anemia.

16. Chapter 19-16 Diepoxybutane causes chromosomal breakage in which disorders? a. Acquired aplastic anemia *b. Fanconi anemia c. Diamond-Blackfan anemia d. CDA General Feedback: Diepoxybutane is a deoxyribonucleic acid (DNA) cross-linking agent. When this is added to Fanconi anemia cells in culture, a characteristic chromosomal breakage occurs. This is the diagnostic test for Fanconi anemia.

17. Chapter 19-17 Paroxysmal nocturnal hemoglobinuria has a high degree of association with which disorders? *a. Aplastic anemia b. Fanconi anemia c. Diamond-Blackfan anemia d. CDA General Feedback: Approximately one-third of aplastic anemia patients develop paroxysmal nocturnal hemoglobinuria.

3. Chapter 20-03 How are normal red cells removed when they lose the ability to deform? *a. Most are phagocytized by splenic macrophages. b. Most are phagocytized by gastrointestinal macrophages. c. Most are destroyed by complement. d. Most are destroyed inside the blood vessels.

General Feedback: At the end of their normal life span, red cells are removed from circulation by splenic macrophages.

4. Chapter 20-04 Which breakdown product of hemoglobin is removed from the body instead of being recycled? a. Globin b. Amino acids *c. Protoporphyrin ring d. Iron General Feedback: The protoporphyrin ring is gradually degraded into bilirubin and eventually excreted from the body. Globin chains are broken down into their component amino acids, which are returned to the amino acid pool for future protein synthesis. Iron is very tightly conserved and recycled.

5. Chapter 20-05 Unconjugated or indirect bilirubin is normally found in: *a. plasma. b. erythrocytes. c. urine. d. intestines.

General Feedback: The bilirubin originally released from macrophages after degradation of the protoporphyrin ring is normally found in plasma before conjugation in the liver.

6. Chapter 20-06 The presence of hemoglobinuria, hemosiderinuria, and hemoglobinemia indicate that hemolysis is: a. severe. b. acquired. c. compensated. *d. intravascular.

General Feedback: When hemolysis is intravascular, red cells are lysed within the circulation releasing hemoglobin; this is called hemoglobinemia. If

the renal threshold is exceeded, some hemoglobin may pass through the kidney and thus be found in urine (i.e., hemoglobinuria). Renal tubular epithelial cells, where the iron is separated from protoporphyrin, take up some hemoglobin passing through the kidney. Some of these renal tubular epithelial cells will gradually be sloughed off into the urine; an iron-specific stain will demonstrate the presence of iron in the form of hemosiderin (as in hemosiderinuria).

7. Chapter 20-07 Which is found normally in urine? a. Conjugated bilirubin *b. Urobilinogen c. Stercobilin d. Unconjugated bilirubin General Feedback: Bacteria in the gut oxidize conjugated bilirubin into various water-soluble compounds that together are called urobilinogen. A small amount of this is normally reabsorbed into the plasma and because of its water solubility will be filtered by the renal glomerulus and excreted into urine.

8. Chapter 20-08 Which are typical findings in extravascular hemolysis? a. Increased serum and urine conjugated bilirubin b. Increased serum and urine unconjugated bilirubin *c. Increased serum, unconjugated bilirubin, and increased urine urobilinogen d. Decreased urine and stool conjugated bilirubin General Feedback: During the process of extravascular hemolysis, macrophages phagocytize and break down hemoglobin into its various component parts.

Unconjugated bilirubin is thus increased. This is taken to the liver, where it is conjugated. Bacteria in the gut oxidize conjugated bilirubin into various water-soluble compounds that together are called urobilinogen. Some of this is reabsorbed into the plasma and because of its water solubility will be filtered by the renal glomerulus and excreted into urine. This results in an increase in urobilinogen in the urine.

9. Chapter 20-09 A urine sediment stains with Prussian blue. The patient probably has: *a. hemoglobinemia. b. a membrane defect. c. compensated hemolysis. d. extravascular hemolysis.

General Feedback:

When the amount of free hemoglobin exceeds the capacity of plasma salvage systems (e.g., haptoglobin, hemopexin), free hemoglobin can be found in plasma. This hemoglobin is filtered through the kidney; some of the iron will be released and taken up by renal tubular cells that are eventually sloughed off into the urine. The iron can be detected in these renal tubular epithelial cells by giving a positive Prussian blue stain.

10. Chapter 20-10 A plasma sample appears hemolyzed or red. Which is true? a. The patient has extravascular hemolysis. b. The patient has increased haptoglobin. c. The patient has increased hemopexin. *d. The plasma hemoglobin is greater than 50 mg/dL. General Feedback: Plasma hemoglobin can be detected when the concentration of hemoglobin is equal to or greater than 50 mg/dL. Free hemoglobin is seen in plasma, giving its red color when excessive intravascular hemolysis exists. Both haptoglobin and hemopexin will be decreased as an attempt to salvage iron occurs.

11. Chapter 20-11 Which is decreased in intravascular hemolysis? *a. Haptoglobin b. Urine hemoglobin c. Serum hemoglobin d. Urine urobilinogen General Feedback: Haptoglobin will be decreased in intravascular hemolysis as the free hemoglobin is bound in an attempt to salvage the iron.

12. Chapter 20-12 Which clinical finding specifically suggests, if it is present, extravascular hemolysis? a. Increased heart rate *b. Splenomegaly c. Pallor d. Fatigue General Feedback: A chronic extravascular hemolytic process can lead to an enlarged spleen (splenomegaly). All of the other clinical findings listed may be found in anemia because of any cause—they are nonspecific findings.

13. Chapter 20-13 Which is the most specific indicator of accelerated intravascular red cell destruction? a. Increased serum bilirubin b. Increased haptoglobin c. Decreased hematocrit *d. Decreased haptoglobin General Feedback: When red cells are destroyed in the circulation, hemoglobin is released into plasma. Haptoglobin binds the free hemoglobin and thus decreases in plasma. This is specific for intravascular hemolysis.

14. Chapter 20-14 An elevated reticulocyte count rules out which condition? a. Acute blood loss *b. Aplastic crisis c. Acute hemolysis d. Successful patient response to iron therapy General Feedback: An elevated reticulocyte count is seen after acute blood loss, acute hemolysis, and after successful patient response to iron therapy.

It is not observed in an aplastic crisis.

15. Chapter 20-15 The reticulocyte count is the most commonly used test to identify: *a. accelerated erythropoiesis. b. erythropoiesis clumping. c. erythrocyte agglutination. d. white blood cell differential.

General Feedback: The reticulocyte count is the most commonly used laboratory test to identify accelerated erythropoiesis, including an elevation of the immature reticulocyte fraction.

16. Chapter 20-16 Which effect does red blood cell fragmentation have on serum? *a. Increases total bilirubin. b. Decreases indirect bilirubin. c. Increases haptoglobin. d. Increases hemopexin.

General Feedback: Blood cell fragmentation in serum increases total bilirubin, increases indirect bilirubin, decreases haptoglobin, and decreases hemopexin.

17. Chapter 20-17 Which is often seen in various types of hemolytic anemia except: a. schistocytes. b. spherocytes. c. polychromasia. *d. hypochromasia.

General Feedback: Hypochromia is present when hemoglobin synthesis is abnormal such as in iron deficiency anemia. It is not observed in hemolytic anemias.

18. Chapter 20-18 Which is related to chronic inherited hemolytic anemia? a. Edema b. Hepatomegaly *c. Cholelithiasis d. Liver disease General Feedback: Major clinical features of chronic inherited hemolytic anemia are varying degrees of anemia, jaundice, splenomegaly, and the development of cholelithiasis.

19. Chapter 20-19 What characteristic red cell shape is associated with extravascular hemolysis? *a. Spherocyte b. Schistocyte c. Target cell d. Burr cell General Feedback: Spherocytes suggest extravascular hemolysis.

20. Chapter 20-20 Which test result suggests red blood cell (RBC) survival is significantly decreased from the normal of 120 days? *a. Decreased glycated hemoglobin b. A T1/2 Cr of 30 days c. Normal haptoglobin d. Decreased lactic dehydrogenase General Feedback: Glycated hemoglobin increases over the life of the red cell as it (the red cell and thus hemoglobin) is continually exposed to glucose in plasma. In hemolytic disease, the red cells have a shortened

survival and thus less exposure to glucose, which results in a lower glycated hemoglobin than normal. Haptoglobin is an acute phase protein and may be normal or even increased even in intravascular hemolysis if the patient has concurrent inflammation; thus a normal haptoglobin does not rule out intravascular hemolysis with a shortened RBC survival.

Lactic dehydrogenase is released from lysed red cells and increases when RBC survival is shortened. A T1/2 Cr of 30 days is normal.

21. Chapter 20-21 The presence of schistocytes in the peripheral blood indicates which of the following processes? a. Iron deficiency anemia *b. Intravascular hemolysis c. Megaloblastic anemia d. Extravascular hemolysis General Feedback: Schistocytes are fragmented red cells that result when the red cell membrane is damaged by trauma as can be seen in some intravascular hemolytic anemias.

1. Chapter 21-01 The most common inherited anemia found in people of northern European ancestry is hereditary: a. elliptocytosis. b. stomatocytosis. *c. spherocytosis. d. pyropoikilocytosis.

General Feedback: The incidence of hereditary spherocytosis is highest in people of northern European ancestry, although it is found worldwide. It is the most commonly inherited hemolytic anemia in this population.

2. Chapter 21-02 Which disorder describes red cells that acquire a reduced surface area from losing unsupported membrane when defective proteins disrupt vertical interactions between transmembrane proteins and the cytoskeleton? *a. Spherocytosis b. Stomatocytosis c. Pyropoikilocytosis d. Acanthocytosis General Feedback: Hereditary spherocytosis has membrane protein deficiencies that result in an unsupported red cell membrane. This leads to a reduced surface area.

3. Chapter 21-03 What causes the destruction of red cells in hereditary spherocytosis? a. Complement activation b. Bound autoantibodies c. Phagocytosis by peripheral monocytes *d. Phagocytosis by splenic macrophages General Feedback: The spherocytes found in hereditary spherocytosis are rigid and not as deformable as the normal biconcave red cell. The spleen selectively sequesters these abnormal red cells as they move through the spleen, where they become further damaged and are selectively removed by macrophages in the red pulp of the spleen.

4. Chapter 21-04 Which is normal in hereditary spherocytosis? a. Red cell morphology *b. Direct antiglobulin test c. Osmotic fragility d. Reticulocyte count

General Feedback: The direct antiglobulin test detects antibodies present on the red blood cell (RBC) membrane. Because they are not present in hereditary spherocytosis, this test will be negative (normal). Red cell morphology ideally shows spherocytes (depending on the number present), the osmotic fragility is increased, and the reticulocyte count is increased.

5. Chapter 21-05 A patient with a previously compensated hereditary spherocytosis has a severe drop in hemoglobin and reticulocyte count after a parvovirus infection. This represents what type of crisis? a. Megaloblastic b. Hemolytic *c. Aplastic d. Anemic General Feedback: After some viral infections, particularly with parvovirus B19 (which invades developing red cells and inhibits their growth), a severe drop in hemoglobin can occur. This is termed an aplastic crisis.

6. Chapter 21-06 Which can distinguish immune hemolytic anemia from hereditary spherocytosis in a patient with spherocytes? a. Osmotic fragility b. Reticulocyte count c. Presence of polychromasia *d. Direct antiglobulin test General Feedback: The immune hemolytic anemias with spherocytes are differentiated from hereditary spherocytosis by the presence of a positive direct antiglobulin test. This test, when positive, demonstrates the presence of antibodies on the red cell membrane.

7. Chapter 21-07 Which is a typical finding in hereditary spherocytosis? *a. Increased mean cell hemoglobin concentration (MCHC) b. Normal reticulocytes c. Reduced fragility of red cells d. Normal spectrin General Feedback: It is common for the MCHC to be abnormally increased greater than 36 g/dL in patients with hereditary spherocytosis. This probably results from cellular dehydration of cells that have gone through the spleen and have low levels of water and potassium. The reticulocyte count is increased, osmotic fragility increased, and spectrin is abnormal.

8. Chapter 21-08 A patient with a small number of spherocytes, increased reticulocytes, and increased MCHC has a normal osmotic fragility. Select the best course of action. a. Dismiss the spherocytes as an artifact. *b. Repeat the osmotic fragility after incubating the blood at 37°C for 24 hours. c. Check the cell counter for errors in the MCHC. d. Collect a new blood sample.

General Feedback: Incubating the blood at 37°C for 24 hours can increase the sensitivity of the osmotic fragility so that a previously normal result becomes abnormal. During this incubation period, red cells become metabolically deprived and tend to lose membrane surface because of their relative membrane instability.

9. Chapter 21-09 All would be expected 1 year after a splenectomy on a patient with severe hereditary spherocytosis except: a. spherocytes on the blood film. b. Howell-Jolly bodies. *c. reticulocyte count of 10%. d. siderocytes.

General Feedback: After splenectomy, the anemia is usually corrected and reticulocyte counts return to high normal. However, the consequences of splenectomy, done for whatever reason, are the appearance of HowellJolly bodies, siderocytes, and target cells in red cells. Spherocytes will still be observable in hereditary spherocytosis.

10. Chapter 21-10 What treatment is most common for hereditary elliptocytosis patients who are anemic and show signs of hemolysis? a. No treatment available b. Drugs to prolong RBC life span *c. Splenectomy d. Transfusions General Feedback: Hereditary elliptocytosis patients who are significantly anemic and show signs of hemolysis respond well to splenectomy.

Transfusions are occasionally needed for life-threatening anemia before splenectomy. No drugs are available to prolong the life of a RBC.

11. Chapter 21-11 Cells with a slit (stomatocytes) instead of a round central pallor can be found in all of the following except: a. liver disease of alcoholism. b. Rh null disease. *c. hereditary elliptocytosis. d. blood films with a drying artifact.

General Feedback: The characteristic red cell morphology in hereditary elliptocytosis is elliptic. All other situations listed can show the presence of stomatocytes.

12. Chapter 21-12 What red cell morphology is often seen in patients with uremia? a. Spherocytes *b. Echinocytes c. Elliptocytes d. Stomatocytes General Feedback: Echinocytes, also called burr cells, are seen in uremic patients and neonates.

13. Chapter 21-13 What red cell morphology is associated with abetalipoproteinemia, liver disease, and McLeod blood group? *a. Acanthocytes b. Stomatocytes c. Spherocytes d. Elliptocytes General Feedback: Acanthocytes are seen in all these situations.

14. Chapter 21-14 What ethnic group most often has glucose-6-phosphate dehydrogenase (G6PD) A?2- in the United States? a. Northern European male subjects b. Asian American female subjects c. African American female subjects *d. African American male subjects General Feedback: In the United States, African American male subjects are the ethnic group that most commonly has G6PD A?2- deficiency. From 10% to 11% of these subjects carry this gene. The gene is X linked, so that

female subjects are carriers and generally do not have clinical problems.

15. Chapter 21-15 What is the typical clinical course for those with G6PD A?2-? a. Severe anemia from infancy onward b. Moderate anemia throughout adulthood *c. No anemia until exposure to an oxidant drug causes acute hemolysis d. Benign because it does not cause anemia General Feedback: Patients with G6PD A?2- are clinically normal unless exposed to an oxidant drug. This can result in acute hemolysis.

16. Chapter 21-16 What red cell morphology, using Wright stain, is seen in patients with G6PD deficiency during a hemolytic episode? *a. Bite cells and polychromasia b. Heinz bodies c. Acanthocytes and crenated cells d. Red cells are normal General Feedback: Bite cells and polychromasia are seen with a Wright stain during a hemolytic episode. Heinz bodies, although present, are not visible with a Wright stain.

17. Chapter 21-17 A patient in the hospital for a hemolytic crisis after an infection has Heinz bodies when his blood is incubated with crystal violet. The fluorescent enzyme-screening test for G6PD is normal. Select the best course of action. a. Repeat the red cell examination with new methylene blue stain. *b. Repeat the enzyme test several weeks after the hemolytic crisis. c. Perform an osmotic fragility test. d. Perform a haptoglobin test.

General Feedback: Reticulocytes have higher levels of G6PD than older red cells.

Because reticulocytes are increased after a hemolytic episode, their presence can give a false-negative (normal) result in the screening test for G6PD. Testing should be repeated when the patient has returned to normal, with a normal cohort of red cells (all ages).

18. Chapter 21-18 What is the most common enzyme deficiency of the glycolytic pathway?

a. Aldolase b. Enolase c. Lactic dehydrogenase (LDH) *d. Pyruvate kinase (PK) General Feedback: PK is the most common enzyme deficiency in the glycolytic pathway.

19. Chapter 21-19 What is the most common red cell morphologic finding in PK deficiency? a. Elliptocytes *b. Polychromasia and echinocytes (crenated) c. Heinz bodies and spherocytes d. Microcytes and hypochromasia General Feedback: Polychromasia and echinocytes are the most common red cell morphologic findings in PK deficiency.

20. Chapter 21-20 What is the best test to confirm the diagnosis of PK? *a. PK enzyme assay b. Reticulocyte count c. Haptoglobin test d. Urine hemosiderin test General Feedback: The clinician makes a diagnosis of PK deficiency by performing an assay for the enzyme.

21. Chapter 21-21 What destroys the red cells in paroxysmal nocturnal hemoglobinuria? a. Macrophages in the bone marrow b. Antibodies against red cell membrane antigens *c. Increased susceptibility to complement d. Macrophages in the spleen General Feedback: Red cells in paroxysmal nocturnal hemoglobinuria are abnormally sensitive to complement, which is activated on their surface and results in premature destruction of the red cells.

22. Chapter 21-22 Which is a typical finding in paroxysmal nocturnal hemoglobinuria? *a. Hemosiderin in urine sediment

b. Normal levels of decay accelerating factor (CD55) c. Hemolysis when blood is alkaline d. Elevated white cells and platelets General Feedback: Hemosiderin is present and a useful diagnostic tool in paroxysmal nocturnal hemoglobinuria. Levels of CD55 are decreased in paroxysmal nocturnal hemoglobinuria. Hemolysis occurs when blood is acidic, and platelets and white cells are usually decreased so that the patient is pancytopenic.

23. Chapter 21-23 Which test can confirm a paroxysmal nocturnal hemoglobinuria diagnosis in a patient? a. Sucrose hemolysis test (sugar water test) b. Reticulocyte count c. Ham test (acidified serum lysis test) *d. Flow cytometry for cell surface markers General Feedback: The reticulocyte count is elevated in all hemolytic anemias at the time of hemolysis (unless an aplastic crisis is present). Of the other procedures listed only flow cytometry is sensitive enough to be useful for the diagnosis of paroxysmal nocturnal hemoglobinuria. The sucrose hemolysis and Ham tests have been replaced by flow cytometry.

24. Chapter 21-24 In most patients with hereditary spherocytosis, the condition is: *a. inherited as an autosomal dominant trait. b. inherited as an autosomal recessive trait. c. inherited as an X-linked recessive trait. d. acquired after viral infection.

General Feedback: Most patients (75% of families) inherit hereditary spherocytosis as an autosomal dominant trait, although autosomal recessive forms exist.

25. Chapter 21-25 Which of the following is a true statement regarding G6PD? a. The gene is located on chromosome 22. *b. The gene has the greatest degree of variability in the human genome. c. The deficiency is primarily expressed as a clinical disease in heterozygous female subjects. d. The normal enzyme is called G6PD A. General Feedback: The G6PD gene has the greatest degree of variability in the human genome; this results in multiple clinical variants. The gene is

found on the X chromosome, so it is only rarely clinically expressed in heterozygous female subjects who have one normal X chromosome. However, they can be shown to have varying numbers of G6PD-deficient red cells.

The normal enzyme is called G6PD B. G6PD A contains one mutation so that its electrophoretic pattern is different, but it is a benign change.

26. Chapter 21-26 Why is G6PD important for normal red cell survival? a. Hemoglobin oxygen affinity is increased in its absence. *b. It is required to regenerate reduced glutathione. c. It is required for insertion of iron into the protoporphyrin ring to form heme. d. Alpha chains are produced in excess in its absence.

General Feedback: G6PD is required to regenerate reduced glutathione in the red cell. Reduced glutathione is essential to generate nicotinamide adenine dinucleotide phosphate, which is necessary to prevent oxidative damage to the red cell.

27. Chapter 21-27 Paroxysmal nocturnal hemoglobinuria is: a. inherited as an X-linked recessive trait. *b. acquired as a clonal disorder. c. inherited as an autosomal dominant disorder. d. acquired after a viral infection.

General Feedback: Paroxysmal nocturnal hemoglobinuria is an acquired disorder that can be shown to be clonal in nature. Some patients have two populations of red cells: (1) normal and (2) defective.

28. Chapter 21-28 The inability to attach proteins requiring a glycosylphosphatidylinositol (GPI) link to the membrane surface is found in: *a. paroxysmal nocturnal hemoglobinuria. b. hereditary spherocytosis. c. paroxysmal cold hemoglobinuria. d. hereditary elliptocytosis.

General Feedback: Proteins missing on the surface of paroxysmal nocturnal hemoglobinuria cells are all linked by GPI to the membrane. This has led to identification of the PIGA (phosphatidylinositol glycan anchor biosynthesis, class A) gene, which is mutated in paroxysmal nocturnal hemoglobinuria; this gene is located on the X chromosome.

1. Chapter 22: Extrinsic Defects Leading to Increased-01 All are examples of microangiopathic hemolytic anemias (MAHAs) except: a. thrombotic thrombocytopenia purpura (TTP). b. hemolytic uremic syndrome (HUS). c. disseminated intravascular coagulation (DIC). *d. immune thrombocytopenia purpura.

General Feedback: Thrombotic thrombocytopenia purpura, hemolytic uremic syndrome, and disseminated intravascular coagulation are all examples of MAHAs. An antibody against platelets causes immune thrombocytopenia purpura, and only the platelet count is affected. No anemia exists unless the patient is bleeding because of the low platelet count; if the bleeding is occult, this eventually could result in iron deficiency anemia but not MAHA.

2. Chapter 22: Extrinsic Defects Leading to Increased-02 Which condition is difficult to differentiate from thrombotic thrombocytopenia purpura (TTP)? a. Disseminated intravascular coagulation (DIC) *b. Hemolytic uremic syndrome (HUS) c. Hemolysis, elevated liver enzymes, low platelet count (HELLP) d. Aplastic anemia General Feedback: TTP and HUS can be difficult to differentiate because they have overlapping clinical and laboratory findings. Definitive diagnosis, however, is critical because they have different etiologies and require different treatments.

3. Chapter 22: Extrinsic Defects Leading to Increased-03 What is the pathogenesis of MAHA? *a. Microthrombi and fibrin formed on damaged endothelial cells trap and break red cells. b. Chemicals or heat destroy red blood cells (RBCs). c. The spleen sequesters red cells in an attempt to remove abnormal inclusions. d. Antibodies that activate complement are formed and destroy the red cell membrane.

General Feedback: As red cells pass through fibrin deposits that have been abnormally formed inside the lumen of blood vessels, they are fragmented as the force of blood flow forces them through the fibrin.

Red cell fragments may also be formed by turbulence of red cells as they pass over damaged endothelial cells that line the blood vessels.

4. Chapter 22: Extrinsic Defects Leading to Increased-04 MAHA is often secondary to all conditions except:

a. infections, especially sepsis. b. obstetric complications. *c. renal disease. d. cancer.

General Feedback: Renal disease does not characteristically result in MAHA. All the other conditions listed can lead to MAHA.

5. Chapter 22: Extrinsic Defects Leading to Increased-05 A mild intravascular hemolytic anemia resulting from forceful repeated effect of the feet on hard surfaces is called: a. traumatic cardiac hemolytic anemia. *b. exercise-induced hemoglobinuria. c. bartonellosis. d. thrombotic thrombocytopenic purpura.

General Feedback: Exercise-induced hemoglobinuria occurs in some individuals after repeated forceful effect of the feet on hard surfaces. This also may be called march hemoglobinuria.

6. Chapter 22: Extrinsic Defects Leading to Increased-06 Which infection is responsible for the most deaths in Africa? *a. Malaria b. Babesia infection c. Bartonella infection d. Clostridial septicemia General Feedback: The majority of deaths are in Africa (91%), followed by Southeast Asia (6%) and the Eastern Mediterranean region (2%). There are more than 216 million people worldwide who have malaria. None of the other agents listed produce such an enormous rate of death.

7. Chapter 22: Extrinsic Defects Leading to Increased-07 Which organism is responsible for the majority of human malaria cases? a. Plasmodium malariae b. Plasmodium ovale *c. Plasmodium falciparum d. Plasmodium knowlesi General Feedback: Plasmodium falciparum is responsible for the majority of human malaria cases.

8. Chapter 22: Extrinsic Defects Leading to Increased-08 Which technique most often diagnoses malaria and Babesia infections?

a. Polymerase chain reaction (PCR) *b. Observing the organisms in blood films c. Serologic tests d. Culture General Feedback: The clinician most often diagnoses malaria and Babesia by observing the organisms in blood films.

9. Chapter 22: Extrinsic Defects Leading to Increased-09 A patient’s red cells show globular fragmentation, budding, and microspherocytes. To what have the red cells probably been exposed? *a. Heat b. Chemicals c. Oxidant drugs d. Bartonellosis General Feedback: Patients with third-degree burns over more than 20% of their bodies may have a severe acute hemolytic anemia. Morphologic red cell changes include globular fragmentation, budding, and microspherocytes.

These cells are present for about 24 hours after the injury before they are removed from circulation.

10. Chapter 22: Extrinsic Defects Leading to Increased-10 Renal failure is a prominent feature of: *a. hemolytic uremic syndrome. b. thrombotic thrombocytopenic purpura. c. Plasmodium malariae infection. d. march hemoglobinuria.

General Feedback: Renal failure is prominent in hemolytic uremic syndrome but not in the other conditions listed.

11. Chapter 22: Extrinsic Defects Leading to Increased-11 Individuals lacking Duffy antigens are resistant to: a. P. knowlesi *b. P. vivax c. P. falciparum d. P. ovale General Feedback: P. vivax requires Duffy antigens on RBCs for invasion, so individuals lacking Duffy antigens are resistant to infection with P. vivax. The expansion of the Duffy-negative population in West Africa seems to be an effective genetic adaptation because P. vivax infection is almost nonexistent in West Africa.

12. Chapter 22: Extrinsic Defects Leading to Increased-12 Why does P. falciparum infection result in the most serious hemolysis of the various forms of malaria? a. Only reticulocytes are invaded. b. Reticulocytes and RBCs less than 10 days old are invaded. c. Only mature RBCs are invaded. *d. RBCs of all ages are invaded.

General Feedback: RBCs in all stages of development are invaded by P. falciparum. This is not true of the other malarial species, which invade only a portion of the circulating RBCs.

13. Chapter 22: Extrinsic Defects Leading to Increased-13 Which describes the appearance of babesia? *a. Rings b. Triads c. Hexagons d. Squares General Feedback: Babesia appears as tiny rings or occasionally as tetrads inside the RBCs. The ring forms may be round, oval, or ameboid; they have a dark purple chromatin dot and a minimal amount of blue cytoplasm surrounding a vacuole.

14. Chapter 22: Extrinsic Defects Leading to Increased-14 Which condition is associated with a deficiency of von Willebrand factor (VWF)–cleaving protease? a. Hemolytic uremic syndrome *b. Thrombotic thrombocytopenic purpura c. March hemoglobinuria d. DIC General Feedback: A severe deficiency of VWF–cleaving protease has been described in patients with thrombotic thrombocytopenic purpura.

1. Chapter 23: Extrinsic Defects Leading to Increased-01 An Rh-negative woman is pregnant with her third child. She received little or no prenatal care during the first two pregnancies. Her anti-D titer is 1:512 at 30 weeks of gestation. What is the likely outcome for the baby? a. ABO hemolytic disease of the newborn *b. Rh hemolytic disease of the newborn c. No or mild hemolysis but spherocytes on the blood film d. Most likely not survive General Feedback: This baby will most likely have Rh hemolytic disease of the newborn. The mother’s antibody titer does not predict the severity of hemolytic disease of the newborn.

2. Chapter 23: Extrinsic Defects Leading to Increased-02 Which is true regarding the mechanism of warm-reactive autoimmune hemolytic anemia? a. Immunoglobulin G (IgG) autoantibodies cause intravascular hemolysis. *b. IgG autoantibodies cause extravascular hemolysis. c. Immunoglobulin M (IgM) alloantibodies cause complement activation. d. IgM autoantibodies cause immune complex formation.

General Feedback: Red cell destruction in warm-reactive autoimmune hemolytic anemia is caused by IgG autoantibodies. IgG-sensitized red blood cells are removed from circulation by macrophages in the spleen.

3. Chapter 23: Extrinsic Defects Leading to Increased-03 A patient’s blood film shows a moderate number of spherocytes and polychromasia. Select the best test to distinguish warm autoimmune hemolytic anemia from hereditary spherocytosis. *a. Direct antiglobulin test b. Bilirubin test c. Haptoglobin test d. Reticulocyte count General Feedback: The only test that distinguishes warm autoimmune hemolytic anemia from hereditary spherocytosis is the direct antiglobulin test, which is positive in warm autoimmune hemolytic anemia and negative in hereditary spherocytosis.

4. Chapter 23: Extrinsic Defects Leading to Increased-04 Secondary cold-reactive autoimmune hemolytic anemia is found most often in patients with: a. hemolytic disease of the newborn caused by anti-A or anti-D.

b. acute myeloid leukemia and chronic myleogenous leukemia. *c. Mycoplasma pneumoniae or infectious mononucleosis. d. hereditary spherocytosis or hereditary elliptocytosis.

General Feedback: Cold-reactive autoimmune hemolytic anemia is sometimes secondary after infections with organisms such as M. pneumoniae and Epstein Barr Virus (infectious mononucleosis).

5. Chapter 23: Extrinsic Defects Leading to Increased-05 Red cell agglutination is found on a blood film. Select the best course of action. a. Report the morphology and all automated results. *b. Warm the blood, and rerun it through the automated cell counter. c. Warm the blood, and make a new blood film. d. Perform a cold agglutinin test.

General Feedback: When red cell agglutination is noted on a blood film, the blood should be warmed to 37°C for 15 minutes and the automated analysis of the specimen repeated while the blood is warm. This patient most likely has a cold agglutinin, and it will disassociate from the red cell membrane and agglutination reverse when the specimen is warmed. Valid results can thus be obtained.

6. Chapter 23: Extrinsic Defects Leading to Increased-06 Monospecific anti-C3b/C3d reveals agglutination with patient’s red cells. Monospecific IgG antisera gives a negative result. Which red cell morphology would most likely be observed? a. Spherocytes b. Schistocytes c. Acanthocytes *d. Agglutination General Feedback: When only complement is present on the membrane, giving a positive direct antiglobulin test using monospecific anti-C3b/C3d, a cold agglutinin is most likely present. Agglutination of red blood cells (RBCs) would be seen on the blood provided it is at room temperature.

7. Chapter 23: Extrinsic Defects Leading to Increased-07 All have been linked to excess erythrocyte destruction except: a. drugs. b. IgM autoimmune antibodies. *c. immunoglobulin E (IgE) alloantibodies. d. IgG alloantibodies.

General Feedback:

Of the items listed, only IgE antibodies have not been associated with excess red cell destruction.

8. Chapter 23: Extrinsic Defects Leading to Increased-08 Which causes of alloimmune hemolytic anemia accounts for the largest number of deaths? *a. ABO blood type errors from patient misidentification b. Drug reactions to antibiotic agents c. ABO hemolytic disease of the newborn d. ABO blood type technical testing errors General Feedback: Of those situations listed, ABO blood type errors from patient misidentification account for the largest number of deaths.

9. Chapter 23: Extrinsic Defects Leading to Increased-09 Which is most often the result of human error? a. Erythroblastosis from anti-D b. ABO erythroblastosis c. Delayed hemolytic transfusion reaction *d. Immediate hemolytic transfusion reaction General Feedback: An immediate hemolytic transfusion reaction, often because of ABO incompatibility, is most often the result of human error.

Erythroblastosis, whether because of ABO or anti-D, occurs as a result of a maternal-fetal incompatibility. A delayed hemolytic transfusion reaction occurs as a result of undetected alloantibodies, where the level of antibody was below the level of sensitivity at the time of transfusion.

10. Chapter 23: Extrinsic Defects Leading to Increased-10 A type-A Rh-negative infant has spherocytes on his blood film and a weakly positive direct antiglobulin test. What antibody will most likely be found on the infant’s red cells? *a. IgG anti-A antibody b. IgM anti-A antibody c. D antibody d. Kell antibody General Feedback: This occurs in infants whose mothers make an IgG anti-A (in this case) or anti-B at a low level. The disease is usually mild because most ABO antibodies are IgM and do not cross the placenta because of their large size.

11. Chapter 23: Extrinsic Defects Leading to Increased-11 A warm-reactive autoimmune hemolytic anemia found in combination with thrombocytopenia in a patient is called: *a. Evans syndrome. b. Wiskott-Aldrich syndrome. c. hereditary spherocytosis with thrombocytopenia. d. paroxysmal cold hemoglobinuria.

General Feedback: When thrombocytopenia and a warm-reactive autoimmune hemolytic anemia are found together, the clinical condition is called Evans syndrome. This syndrome occurs primarily in children.

12. Chapter 23: Extrinsic Defects Leading to Increased-12 The Donath-Landsteiner antibody: a. binds to the red cell membrane at 37°C. *b. is found in serum and causes lysis of donor RBCs. c. has specificity for Ii blood group antigens. d. is associated with lymphoma.

General Feedback: The Donath-Landsteiner antibody is found in paroxysmal cold hemoglobinuria. It is demonstrated by adding patient serum to donor RBCs that have been chilled to 4°C. The antibody binds at this temperature and activates complement. When the cells are warmed to 37°C, the antibody disassociates from the red cell membrane, after which intense hemolysis occurs because complement has been activated.

This antibody is directed against the P blood group antigen. It is not associated with lymphoma but is usually idiopathic. However, it is associated with tertiary or congenital syphilis and is found after some viral infections.

1. Chapter 24-01 The qualitative hemoglobinopathies cause disease by producing hemoglobin chains that are: a. too long. b. produced in inadequate amounts. *c. structurally altered. d. missing.

General Feedback: Structural defects are present in the qualitative hemoglobinopathies.

2. Chapter 24-02 Which hemoglobinopathies is most common? *a. Sickle cell diseases b. Hb E disorders c. Hb C disorders d. Unstable hemoglobins General Feedback: Sickle cell diseases are the most common form of hemoglobinopathies.

3. Chapter 24-03 What clinical feature of sickle cell disease accounts for the highest number of hospital admissions? a. Megaloblastic crisis *b. Vasoocclusion c. Autosplenectomy d. Hand-foot dactylitis General Feedback: Vasoocclusive events are the hallmark features of sickle cell disease, accounting for most hospital and emergency department visits.

4. Chapter 24-04 Sickle cell disease is found in individuals descended from ancestors from all of the following places except: a. Africa. b. Middle East. c. the Mediterranean. *d. Scandinavia.

General Feedback: Individuals having an ethnic origin from Scandinavia do not express sickle cell diseases. This hemoglobin is observed in people originating from all the other areas listed.

5. Chapter 24-05 Sickle cell presence in the blood results in all of the following except: *a. decrease in blood viscosity. b. decrease in oxygen tension. c. decrease in blood pH. d. increase in 2,3-biphosphoglycerate.

General Feedback: Blood becomes more viscous when polymers are formed and sickle cells are created. This transformation results in reduced blood flow, which prolongs exposure of the sickle cells to a hypoxic environment (decreased oxygen tension). A reduction in pH occurs and 2,3biphosphoglycerate levels.

6. Chapter 24-06 Which would be an unusual finding in the blood film of an adult with sickle cell disease crisis? *a. Heinz bodies b. Target cells c. Howell-Holly bodies d. Leukocytosis General Feedback: The blood film of an adult in sickle cell disease crisis exhibits target cells, Howell-Jolly bodies, and an elevated white count (leukocytosis). Heinz bodies are not present.

7. Chapter 24-07 What is the most likely causative association between malaria and sickle cell trait? a. Sickle gene makes people more prone to malaria infection. b. Sickle gene prevents Plasmodium ovale infection. c. They are both found in Asia. *d. Sickle gene offers some protection against malaria.

General Feedback: Sickle cell trait (heterozygosity for hemoglobin S [Hb S]) confers resistance against infection with Plasmodium falciparum. It is believed that this is why the abnormal hemoglobin has such high prevalence in areas where this form of malaria is endemic.

8. Chapter 24-08 Which would be unexpected in homozygous Hb S? a. High reticulocyte count *b. Hemoglobin A (Hb A) c. Elevated hemoglobin F (Hb F) d. Hemoglobin that is less soluble

General Feedback: Both beta-globin genes are abnormal in homozygous Hb S. Therefore Hb A is not present unless the patient has received a red cell transfusion. Hb S is less soluble than normal Hb A, the reticulocyte count is elevated, and patients usually have a high Hb F.

9. Chapter 24-09 A patient has target cells and a positive tube solubility test. This patient probably: a. is normal. b. has sickle cell anemia. c. has sickle trait. *d. has either sickle cell anemia or trait.

General Feedback: The tube solubility test is positive in both sickle cell trait and sickle cell anemia (Hb SS).

10. Chapter 24-10 Select the best test to confirm the diagnosis of the patient in Question 9. a. Mean cell volume (MCV) b. Osmotic fragility *c. Hemoglobin electrophoresis d. Presence of sickle cells General Feedback: The best test to differentiate sickle cell trait from anemia is hemoglobin electrophoresis. Sickle cell trait should have roughly 40% Hb S and 55% Hb A, whereas sickle cell anemia should have predominantly Hb S with a variably increased Hb F and no Hb A.

11. Chapter 24-11 A patient has two bands on alkaline hemoglobin electrophoresis. One lines up with Hb A and the other is in the S position. Select the best course of action. a. Report as normal. b. Report as sickle trait. c. Report as sickle disease. *d. Confirm sickle gene with tube solubility test.

General Feedback: Other abnormal hemoglobins migrate with Hb S on alkaline hemoglobin electrophoresis; Hb D is an example. However, these hemoglobins are not sickling hemoglobins. Therefore, a positive tube solubility test would confirm that the hemoglobin in the S position is Hb S.

12. Chapter 24-12 All improve the clinical outcome of sickle cell anemia (Hb SS) except which of the following? a. Aggressive prevention and treatment of infection b. Presence of Hb F c. Transfusions during crises *d. Keeping the oxygen saturation low General Feedback: Hb S forms insoluble polymers when the oxygen saturation is low. Thus this would precipitate sickling, not improve the outcome of sickle cell anemia. All the other therapies mentioned have been shown to be clinically helpful.

13. Chapter 24-13 A patient has 45% Hb S, 55% Hb A, and a positive tube solubility. Which would likely be found? a. Normal blood film and no disease *b. Target cells on the blood film and no disease c. Normal blood film and severe disease d. Sickle cells on the blood film and severe disease General Feedback: Target cells are present in sickle cell trait (Hb A and Hb S).

This condition is benign.

14. Chapter 24-14 Moderate to marked target cells are found on a blood film. Which can most likely be eliminated? a. Hb C disease *b. Hereditary spherocytosis c. Hb E disease d. Sickle cell disease General Feedback: Target cells are not seen in hereditary spherocytosis. They are present in all the other conditions listed.

15. Chapter 24-15 Which would be an unexpected finding for patients with Hb SC disease or S/beta0- thalassemia? a. Target cells b. Shortened red cell survival *c. Normal tube solubility test d. Mild to moderate clinical features General Feedback:

The presence of Hb S will give a positive tube solubility test. Thus finding a normal result would not be expected.

16. Chapter 24-16 Which is a typical finding in patients with Hb M? a. Severe anemia requiring repeated blood transfusions b. Elevated levels of ferrous iron (Fe2+) in the red cells c. Presence of Heinz bodies on Wright-stained blood film *d. Elevated methemoglobin General Feedback: Methemoglobin is elevated in Hb M. Affected persons may have 30% to 50% methemoglobin (Fe3+). The amino acid substitutions found in the various Hb Ms cause heme iron to autooxidize, forming methemoglobin. Heinz bodies may be present, but they are not visible with a Wright stain.

17. Chapter 24-17 Heinz bodies are found when hemoglobin: *a. precipitates. b. has higher oxygen affinity. c. concentration is decreased. d. forms crystals.

General Feedback: Heinz bodies are found when hemoglobin is unstable and precipitates.

18. Chapter 24-18 What is the correct relationship between red cells’ affinity for oxygen and red cell production? a. When affinity is low, more oxygen is released and the body compensates by making red cells larger. b. When affinity is low, less oxygen is released and the body compensates by increasing erythropoietin and making more red cells. *c. When affinity is high, less oxygen is released and the body compensates by increasing erythropoietin and making more red cells. d. When affinity is high, more oxygen is released and fewer red cells are needed.

General Feedback: When hemoglobin’s oxygen affinity is high, less oxygen is released to tissue. The normal physiologic response to less oxygen delivery is to increase erythropoietin and make more red cells.

19. Chapter 24-19 What is a point mutation? a. Mutation of the stop codon *b. Replacement of one nucleotide in the normal gene with a different nucleotide c. Addition of one nucleotide in the normal gene d. Deletion of one nucleotide in the normal gene General Feedback: Replacement of one nucleotide in the normal gene with a different nucleotide is a point mutation. This results in a different amino acid and can affect the protein’s function.

20. Chapter 24-20 Cellulose acetate is performed on a patient with known homozygous Hb S who has received red cell transfusions in the past week. What hemoglobins would be expected to be found? a. Hb S and Hb F b. Hb A and Hb F c. Hb S, Hb A, and Hb F *d. Hb S, Hb A, Hb F, and Hb A2 General Feedback: Hb S, Hb A, Hb F, and Hb A2 would be seen. Hb A, which is not present in patients with homozygous Hb S, is from the transfused red cells. Hb F and Hb A2 are normal hemoglobins.

21. Chapter 24-21 An adult female patient from Southeast Asia has no anemia, but her complete blood count (CBC) shows an MCV of 68 fL and marked target cells are observed on her blood film. Cellulose acetate alkaline electrophoresis shows two large bands: approximately 55% migrating with Hb A and 40% migrating with Hb C. What is the patient’s most likely genotype? a. Hb A and Hb C *b. Hb A and Hb E c. Hb C and Hb E d. Homozygous Hb E General Feedback: Hb E is a variant found in Southeast Asian populations. It migrates with Hb C on cellulose acetate alkaline electrophoresis.

Because Hb A is also present, this patient probably has Hb E trait (is not homozygous for Hb E). The MCV is low and target cells are present in this trait.

2. Chapter 25-02 Which is the normal approximate percentage of hemoglobins in adults? á2â2 á2ä2 á2 ã2 a. 2% 2% 96% b. 2% 96% 2% *c. 96% 2% 2% d. 40% 20% 40% General Feedback: In adults, the approximate concentration of hemoglobin A (Hb A) (á2â2) is 96%; of Hb A2 (á2ä2), 2%; and of hemoglobin F (Hb F) (á2ã2), 2%.

3. Chapter 25-03 Why are infants with â-thalassemia major not ill until approximately 6 months of age? *a. Infants are protected by their high concentration of Hb F. b. Infants have less need for hemoglobin because of their small body size. c. Infants have less need for hemoglobin because of their smaller lung capacity. d. Infants have a high red count and thus higher hemoglobin from a higher than normal concentration of erythropoietin.

General Feedback: The â globin chain is decreased to absent in â-thalassemia major; however, á globin chain synthesis is normal. Infants up until approximately 6 months of age have an elevated Hb F that does not require â chains. They become symptomatic after the ã-to-â switch.

4. Chapter 25-04 Which is the primary mechanism for anemia in the thalassemias? *a. An imbalance in the rate of globin chain synthesis b. Impaired iron incorporation into the protoporphyrin ring c. Erythroid hypoplasia in the bone marrow d. Abnormal amino acid structure of a globin chain General Feedback: An imbalance exists in the rate of globin chain synthesis in the thalassemias, and this is the primary mechanism leading to anemia.

A buildup of the globin chain is produced in excess, and this causes damage to the red cell. Erythroid hyperplasia is present in the bone marrow (ineffective erythropoiesis).

5. Chapter 25-05 Which is true regarding the clinical features of thalassemias? a. Are mild conditions rarely requiring treatment. b. Are serious conditions requiring frequent blood transfusions.

c. Have abnormal red cells but little clinical implications for patients. *d. Vary from benign forms to those incompatible with life.

General Feedback: The thalassemias are a heterogeneous group of disorders that range from asymptomatic (benign) to death (incompatible with life).

6. Chapter 25-06 Which is an expected finding in â-thalassemia minor? *a. Basophilic stippling b. Normal levels of Hb F and Hb A2 c. Normocytic normochromic red cells d. Hemoglobin levels in the 4- to 6-g/dL range General Feedback: Basophilic stippling is seen in red cells in â-thalassemia minor. Hb F and Hb A2 are both increased. The red cells are microcytic normochromic to microcytic hypochromic, and hemoglobin concentration is generally in the 10- to 13-g/dL range.

7. Chapter 25-07 All can distinguish â-thalassemia minor from major except: a. clinical findings. b. hemoglobin concentration. *c. presence of microcytosis, hypochromasia, and target cells. d. presence of Hb A. General Feedback: Microcytes, hypochromasia, and target cells are found in both â-thalassemia major and minor, so these findings do not distinguish one from the other. All the other findings listed vary significantly between the two types of â-thalassemia.

8. Chapter 25-08 Which would be an unexpected finding in homozygous â0-thalassemia? a. Decreased reticulocyte production index *b. Normal Hb F c. Bone marrow erythroid hyperplasia d. Severe anemia General Feedback: The primary hemoglobin in homozygous â0-thalassemia is Hb F, with the remainder being Hb A2. Because no â globin chains are made, no Hb A exists.

9. Chapter 25-09 A patient has 30% Hb F. Which can be eliminated? *a. Four missing genes for á chain production b. Heterozygous hereditary persistence of Hb F c. Thalassemia intermedia d. The patient is a normal 1-month-old infant.

General Feedback: á Chains are required for Hb F synthesis; therefore, if all four genes for á chain synthesis are missing, no Hb F can be produced.

Thirty percent Hb F can be seen in all the other situations listed.

10. Chapter 25-10 What finding is present in all types of á-thalassemias? a. Hemoglobin H (Hb H) inclusions seen with brilliant cresyl blue b. Anemia c. Microcytic hypochromic red cells *d. Barts hemoglobin present at birth General Feedback: Barts (ã4) hemoglobin is present at birth in all forms of áthalassemia. Hb H inclusions, anemia, and microcytic red cells are not found in all forms.

11. Chapter 25-11 Which is true of patients with Hb H disease? a. Have a severe anemia. *b. Have three missing genes for á chain production. c. Have excess unpaired â chains present. d. Are of Northern European ethnicity.

General Feedback: Hb H disease occurs when three genes are missing for á globin chain synthesis and an excess of â chains (b4), which is named Hb H, is present and easily detectable. A mild to moderate anemia is present.

These individuals are primarily of Asian ethnicity.

12. Chapter 25-12 Which can help distinguish the combination Hemoglobin S (Hb S) â0thalassemia from sickle cell anemia? a. Hematocrit b. Hemoglobin electrophoresis c. Ethnic background *d. Mean cell volume (MCV) General Feedback: Hb S is a structurally abnormal â globin chain; this gene is inherited from one parent. The â0 gene is inherited from the other

parent, which means that no â chain production occurs from that gene.

Thus the patient will not have any normal â chains to combine with á chains and form Hb A. The patient will have primarily Hb S, with an elevated Hb F, which is the same pattern seen in homozygous Hb S (i.e., sickle cell anemia). However, in sickle cell anemia the red cells are normocytic, whereas in Hb S â0-thalassemia the red cells will be microcytic.

13. Chapter 25-13 Which is least useful in diagnosing and differentiating the thalassemias from each other? a. Complete blood count (CBC) results b. Hemoglobin electrophoresis *c. Osmotic fragility d. Clinical findings General Feedback: The osmotic fragility is not useful in differentiating the various forms of thalassemia from one another. Hemoglobin electrophoresis is an important tool for differentiating them, whereas CBC results and clinical findings vary depending on the severity of the thalassemic syndrome present and so can be useful.

14. Chapter 25-14 Which is useful in helping to distinguish mild asymptomatic iron deficiency from thalassemia trait? *a. Low MCV with relatively high red blood count b. Mild anemia c. Increased osmotic fragility d. Increased ferritin General Feedback: The red blood cell (RBC) count is relatively high with a low MCV in thalassemia trait. In iron deficiency the MCV can be low, but the red count is also low. None of the other findings listed distinguish the two from one another.

15. Chapter 25-15 Hb Barts is composed of: a. á4. *b. ã4. c. â4. d. æ4.

General Feedback: Hb Barts is composed of four gamma (ã) chains. It is present at birth in all forms of á-thalassemia, even the silent carrier state (one gene deletion).

16. Chapter 25-16 A patient with â+-thalassemia has, from that gene locus, *a. variable but decreased â globin chain synthesis. b. no â globin chain synthesis. c. variable but decreased ã chain synthesis. d. no ã chain synthesis.

General Feedback: â Globin chain synthesis is decreased from the â+ gene locus.

17. Chapter 25-17 Iron overload in severe â-thalassemia (â-thalassemia major) patients is primarily a consequence of: a. an increased rate of absorption of iron because of the severe anemia. b. a decreased need for iron because fewer RBCs are made. *c. accumulation of iron from massive RBC transfusion therapy. d. decreased rate of use of iron because smaller RBCs are made.

General Feedback: Patients with â-thalassemia major have a severe anemia; many of their clinical problems are related to this anemia. Giving the patient massive red cell transfusion therapy can ameliorate some of these clinical problems. Unfortunately, a serious consequence of this is the buildup of iron in the body from all the transfused RBCs because the body has no mechanism for excreting iron.

18. Chapter 25-18 Patients who are heterozygous for Hb Lepore have a clinical course: a. that is completely benign. *b. similar to that of â-thalassemia minor. c. similar to that of á-thalassemia minor (one gene deletion). d. similar to that of â-thalassemia major.

General Feedback: Hb Lepore is a ä-â fusion globin chain with decreased synthesis of the chain. Heterozygotes have a clinical course similar to that of â-thalassemia minor.

19. Chapter 25-19 Hemoglobin E (Hb E) is primarily found in individuals of which ethnic origin? a. Mediterranean b. African *c. Southeast Asian d. Northern European

General Feedback: Hb E has a high prevalence in Southeast Asia.

20. Chapter 25-20 Hb A2 and Hb F can be quantified by: a. performing a brilliant cresyl blue stain and counting the number of positive cells. *b. performing high-performance liquid chromatography. c. performing cellulose acetate hemoglobin electrophoresis. d. performing citrate agar hemoglobin electrophoresis.

General Feedback: High-performance liquid chromatography can separate and quantify Hb A2 and Hb F, which is important to do when working up patients with possible thalassemic syndromes. None of the other methods quantify them.

1. Chapter 26-01 A chemotherapy patient’s white blood cell (WBC) count is 1.0 × 109 /L. There are 60% segmented neutrophils, 38% lymphocytes, and 2% monocytes.

What is the correct interpretation of the relative differential? *a. Normal b. Neutrophilia c. Neutropenia d. Lymphopenia General Feedback: The relative differential is normal.

2. Chapter 26-02 A chemotherapy patient’s WBC count is 1.0 × 109 /L. There are 60% segmented neutrophils, 38% lymphocytes, and 2% monocytes. What is the absolute neutrophil count? a. 60 × 109/L b. 6 × 109/L *c. 0.6 × 109/L d. 0.16 × 109/L General Feedback: The absolute count is determined by multiplying the total white count by the relative percent of a specific cell type. Thus in this case it is (0.60) × (1.0 × 109 /L) = 0.6 × 109/L.

3. Chapter 26-03 What is the correct interpretation of the absolute neutrophil count in the chemotherapy patient in Question 1? a. Normal b. Neutrophilia *c. Neutropenia d. Qualitative neutrophil disorder General Feedback: An absolute neutrophil count below the reference range is termed neutropenia.

4. Chapter 26-04 A patient has a white count of 15.0 × 109/L. What is the correct interpretation? *a. Normal for an infant b. Abnormal for an infant c. Abnormal for any patient d. Normal for any patient General Feedback:

This is a normal white count for an infant.

5. Chapter 26-05 Necrotic nuclei are rounded fragments of nucleus that lack: *a. filaments. b. light chromatin. c. granulation. d. vacuoles.

General Feedback: Necrotic nuclei are rounded fragments of nucleus with no filaments and no chromatin pattern. Increased numbers of pyknotic or necrotic cells suggest that an extended amount of time has elapsed between blood collection and blood smear preparation.

6. Chapter 26-06 Neutrophilia accompanied by immature neutrophils and nucleated red cells is what kind of reaction? *a. Leukoerythroblastic b. Leukemoid c. Myelophthisic d. Myeloproliferative General Feedback: The presence of both immature neutrophils and nucleated red cells in blood is termed leukoerythroblastic.

7. Chapter 26-07 Döhle bodies are most often found in patients with: a. autoimmune disorder. *b. acute bacterial infection. c. hemolytic anemia. d. acute viral infection.

General Feedback: Patients with a bacterial infection often have Döhle bodies.

8. Chapter 26-08 Which is a prognostic sign for a patient with infectious mononucleosis? a. Decrease in T cells b. Granules fused with liposomes c. Decrease in B cells *d. Natural killer lymphocytes with cytoxic T cells General Feedback: The cellular response in infectious mononucleosis is important in the control of the infection and is characterized by proliferation

and activation of natural killer (NK) lymphocytes, CD4+ T cells, and CD8+ memory cytotoxic T cells (EBV-CTLs) in response to B cell infection. Most of the circulating reactive lymphocytes seen in circulation represent activated T cells.

9. Chapter 26-09 A patient has 20% eosinophils. Which can probably be eliminated? a. Allergy b. Parasitic infection *c. Pertussis d. Chronic myelogenous leukemia General Feedback: Pertussis can be eliminated; a lymphocytosis exists in this condition. All the other listed conditions can show elevated eosinophils.

10. Chapter 26-10 A patient has a white count of 8.3 × 109/L and 65% lymphocytes. What is the correct interpretation? *a. Depends on the patient’s age b. Lymphocytosis c. Lymphopenia d. Patient probably has infectious mononucleosis General Feedback: The absolute number of lymphocytes varies with age. This would be normal for a young child but elevated for an adult.

11. Chapter 26-11 Nonmalignant disorders of leukocytes are: a. inherited and cause no symptoms. b. acquired and cause serious disease. c. acquired and affect the nuclei of cells. *d. acquired or inherited and range from benign to life threatening.

General Feedback: Benign (nonmalignant) disorders of leukocytes are inherited or acquired alterations that do not possess the characteristics of dysplasia or malignancy. Many are asymptomatic, whereas others are life threatening.

12. Chapter 26-12 Nuclear hyposegmentation and denser than normal chromatin clumping are features of: a. Alder-Reilly anomaly.

b. Chédiak-Higashi syndrome. c. May-Hegglin anomaly. *d. Pelger-Huët anomaly.

General Feedback: Nuclear hyposegmentation with denser than normal chromatin clumping is found in Pelger-Huët anomaly.

13. Chapter 26-13 What is the concern if Pelger-Huët anomaly is not recognized? a. Without treatment, the patient will probably die. *b. The cells could be misclassified as immature neutrophils. c. The patient could develop pseudo–Pelger-Huët followed by leukemia. d. The cells could be misclassified as blasts, indicating that the patient has acute leukemia when he or she does not.

General Feedback: Pelger-Huët cells, because they often have bilobed nuclei, may be mistaken for band neutrophils or metamyelocytes. Those with a round nucleus may be mistakenly reported as myelocytes. This left shift is characteristic of a bacterial infection.

14. Chapter 26-14 The abnormal granules seen in Alder-Reilly anomaly could be confused for: *a. toxic granulation. b. intracellular bacteria. c. Döhle bodies. d. intracellular yeasts.

General Feedback: The abnormal granules in Alder-Reilly anomaly are deep-purple to lilac granules that can be mistaken for toxic granulation.

15. Chapter 26-15 What are the abnormal cytoplasmic inclusions in Chédiak-Higashi? a. Nuclear fragments that prevent cell division b. Ribosomal material that looks like Döhle bodies *c. Fused granules that inhibit bactericidal functions d. Mucopolysaccharide lipids that disrupt cell function General Feedback: Abnormally large fused granules that are peroxidase positive are seen in Chédiak-Higashi syndrome. Uncontrolled activity of the granular membrane creates large primary, secondary, and mixed primary/secondary granules. These inhibit the normal bactericidal function of these granules so that patients are susceptible to bacterial infection.

16. Chapter 26-16 What abnormal findings are found in May-Hegglin anomaly? a. Toxic granulation and vacuoles b. Fused primary and secondary granules c. Hypersegmented neutrophils and twinning *d. Döhle body–like cytoplasmic inclusions General Feedback: Döhle body–like cytoplasmic inclusions and thrombocytopenia are characteristic of May-Hegglin anomaly.

17. Chapter 26-17 Toxic granulation, Döhle bodies, and vacuolization in neutrophils are often found together in: a. May-Hegglin anomaly. *b. Bacterial infection. c. Chédiak-Higashi syndrome. d. Alder-Reilly anomaly.

General Feedback: Neutrophils can exhibit toxic granulation, Döhle bodies, and vacuolization in a severe bacterial infection.

18. Chapter 26-18 Partially digested glycoaminoglycans can lead to which condition? *a. Neurologic problems b. Cardiac disorders c. Gastrointestinal disease d. Skin rashes General Feedback: The mucopolysaccharidoses are associated with a specific defect in an enzyme necessary for the degradation of GAG (glycoaminoglycan). Partially digested GAGs buildup and disrupt cellular functions leading to serious physical and neurologic problems.

19. Chapter 26-19 Congenital deficiencies of lysosomal enzymes, impaired digestion of macromolecules which accumulate and impair cellular functions is called: a. chronic granulomatous disease. b. congenital C3 deficiencies. *c. storage cell diseases. d. familial hyperlipidemia disorders.

General Feedback:

Lysosomal storage disorders are congenital deficiencies of lysosomal enzymes, impaired digestion of macromolecules which accumulate and impair cellular functions.

20. Chapter 26-20 Gaucher cells and Niemann-Pick cells are found in: a. peripheral blood. b. bone marrow only. c. spleen only. *d. bone marrow and spleen.

General Feedback: Gaucher cells and Niemann-Pick cells are macrophages with accumulated glucocerebroside or sphingomyelin and are found in both the bone marrow and many other organs but are not seen in the peripheral blood.

21. Chapter 26-21 A college student seeks medical care for extreme fatigue and swollen lymph nodes in the neck. The WBC count is 11.3 × 109/L. The differential shows a relative and absolute lymphocytosis. Many of the lymphocytes are larger than normal, with a basophilic cytoplasm indented by the red blood cells (RBCs). The nuclei are less clumped than normal and some have nucleoli. The rest of the complete blood count (CBC) is normal. What is the most likely diagnosis? a. Infectious lymphocytosis *b. Infectious mononucleosis c. Lymphoma d. Lymphocytic leukemia General Feedback: The description of these cells is that of a reactive lymphocyte. They are a normal response to viral infection. Infectious mononucleosis characteristically shows a lymphocytosis with many reactive T lymphocytes. The age, symptoms, and physical findings also support infectious mononucleosis.

22. Chapter 26-22 The lymphocytes in the student in Question 21 are most likely: *a. differentiated T cells. b. lymphoblasts. c. plasma cells. d. B cells.

General Feedback: The reactive lymphocytes seen in infectious mononucleosis are differentiated T cells.

23. Chapter 26-23 A clinical laboratory scientist sees segmenting nuclei and unusual cytoplasmic borders in monocytes. Which additional finding should the scientist expect? a. Toxic vacuoles b. Increased cytoplasm c. Indented nuclei *d. Changes in granule color General Feedback: Reactive morphology in monocytes includes segmenting nuclei, changes in granule color and size, and irregular cytoplasmic borders.

24. Chapter 26-24 The Epstein-Barr virus is the causative agent for: *a. infectious mononucleosis. b. infectious lymphocytosis. c. lymphocytic leukemia. d. monocytic leukemia.

General Feedback: The Epstein-Barr virus is the causative agent for infectious mononucleosis. It is found in body fluids, especially saliva, in infected individuals.

25. Chapter 26-25 Most often the clinician makes a diagnosis of infectious mononucleosis by which finding? a. Significant lymphocytosis, with reactive lymphocytes predominating b. Presence of mild thrombocytopenia, with a significant lymphocytosis *c. Demonstration of the presence of the heterophil antibody d. Demonstration of the presence of cytomegalovirus antibody General Feedback: A test for the presence of the heterophil antibody is used to diagnose infectious mononucleosis. If this test is negative and the clinician is highly suspicious of the diagnosis, tests for more specific Epstein-Barr virus antibodies may be necessary.

1. Chapter 27-01 Which statement about hematologic malignancies is correct? a. They are localized. b. Treatment is localized. c. Diagnosis includes genetic typing. *d. They include leukemias.

General Feedback: Specific hematologic malignancies include acute leukemias, lymphoblastic and myeloid, myeloproliferative neoplasms, myelodysplastic syndromes, and mature lymphoid neoplasms. Most hematologic malignancies are not localized but rather are systemic at initiation of the malignant process. With rare exceptions, most treatments for hematologic malignancies given with curative intent are not localized, such as radiation or surgery, but must by nature be systemic-type treatments.

2. Chapter 27-02 The type of protooncogenes involved in hematologic malignancies is: a. growth factor receptors. b. signal transducers. c. transcription factors. *d. all of the options.

General Feedback: In hematologic malignancies the type of protooncogenes usually involved are signal transducers (such as tyrosine kinases), growth factor receptors, or transcription factors.

3. Chapter 27-03 Which type of virus has been associated with hematologic malignancies? a. DNA virus *b. Retrovirus c. Cytomegalovirus d. Both DNA virus and Retrovirus General Feedback: Some viruses have been implicated in hematologic malignancies, such as retroviruses and DNA viruses.

4. Chapter 27-04 Which is true of acute leukemia? a. Onset is of slow progression. b. Progression is delayed. c. Onset is insidious. *d. If left untreated, death occurs in weeks.

General Feedback:

Leukemias are divided into lymphoid and myeloid lineages, and further into acute (precursor cell) and chronic (mature cell) categories. In acute leukemias, onset is sudden, progression is rapid, and the outcome is fatal in weeks or months if left untreated.

5. Chapter 27-05 Which is true regarding chronic leukemia? *a. White blood cell count is variable. b. Onset is sudden. c. Progression is fast. d. If left untreated, death occurs in weeks.

General Feedback: In chronic leukemias, onset is insidious, and progression is slower with a longer survival compared to acute leukemia. The WBC count is usually elevated and there is a proliferation and accumulation of mature and maturing cells of a specific lineage.

6. Chapter 27-06 When leukemia is left untreated: *a. bone marrow function is altered. b. the associated fatigue is due to decreased hematocrit. c. symptoms become very specific. d. the bands shift right.

General Feedback: In all untreated leukemias, most normal hematopoietic cells in bone marrow are eventually replaced by leukemia cells thus affecting normal bone marrow function. Due to the rapid expansion of blasts in bone marrow in acute leukemia, bleeding due to thrombocytopenia, fever due to neutropenia-induced infection, and fatigue due to decreased hemoglobin are often found at presentation. Symptoms of chronic leukemias at presentation are generally non-specific and variable; some patients may be asymptomatic and diagnosed after an incidental finding of an elevated white blood cell count or abnormal peripheral blood film. Bands shift left in leukemia.

7. Chapter 27-07 Exposure to which environmental factor can lead to hematopoietic malignancies? a. Chromium *b. Benzene c. Hydrochloric acid d. Ethanol General Feedback: Environmental exposures known to lead to hematopoietic malignancies include radiation exposure, as experienced by survivors of atomic explosions, and exposure to organic solvents, such as benzene.

8. Chapter 27-08 The World Health Organization (WHO), Society for Hematopathology, and the European Association for Haematopathology classifies neoplasms according to: a. clinical features. *b. molecular genetics. c. cytogenetics. d. all of the options.

General Feedback: The World Health Organization in collaboration with the Society for Hematopathology and the European Association for Haematopathology, the classification considers clinical features, morphology, immunophenotyping, cytogenetics, and molecular genetics.

9. Chapter 27-09 Which statement describes the process of leukemogenesis? a. A hematopoietic cell is engulfed by a macrophage and is replaced by a malignant cell. b. Two genetic mutations are required to change healthy hematopoietic cells into malignant cells. *c. A hematopoietic cell accumulates multi-hits that turn healthy cells into malignant clones. d. The membrane of a hematopoietic cell dissolves making it easier for the cytoplasm to attach to a malignant cell.

General Feedback: Leukemogenesis (initiation and maintenance of leukemia) is a stepwise process in which a hematopoietic cell accumulates multiple, independent mutations or “multi-hits” that affect various cellular pathways, which eventually transforms it into a malignant clone. There are exceptions in which only one genetic mutation is required for initiation of the leukemia.

10. Chapter 27-10 Which action causes quantitative mutations in a hematopoietic cell? a. Tumor suppressor gene action on an oncogene b. Gene amplification of an oncogene *c. Overexpression of a normal protooncogene d. DNA repair genes stop protooncogenes General Feedback: In quantitative mutations, there is an overexpression of a normal protooncogene in a hematopoietic cell. An example of this type of mechanism is found in B-lymphoid malignancies in which a protooncogene becomes oncogenic by translocation next to the promoter of the immunoglobulin heavy chain (IGH) locus on chromosome 14.

11. Chapter 27-11 Why are patients diagnosed with hematologic malignancies living longer than in past decades? a. FDA standards for cancer medications have decreased. b. Radiation is used in all cases of cancer. c. Chemotherapy is no longer an accepted treatment. *d. There is an increased availability of less toxic therapies.

General Feedback: In contrast to many solid tumors, numerous hematologic malignancies now have cure rates that are substantially higher than they were two or three decades ago. Many new and exciting therapies that are less toxic are now under development or are already employed in patient settings.

12. Chapter 27-12 How does imatinib mesylate work in treating hematologic malignancies? a. Regulates kinase activity. b. Increases massive cell proliferation. c. Suppresses apoptosis of cancer cells. *d. Blocks tyrosine kinase activity.

General Feedback: In 2001, FDA cleared imatinib mesylate for treatment of chronic phase CML as the first rationally designed molecular targeted therapy for a cancer. The t(9;22) translocation in CML results in production of the BCR-ABL1 fusion protein with constitutive and unregulated tyrosine kinase activity. Imatinib is an orallyadministrated, small, tyrosine kinase inhibitor (TKI) molecule that binds to the ABL1 domain of the BCR-ABL1 fusion protein and selectively blocks its tyrosine kinase activity.

13. Chapter 27-13 In promyelocytic leukemia, which gene is fused with the retinoid acid receptor gene (RARA)? a. ATRA *b. PML c. BCR d. ABL1 General Feedback: In acute promyelocytic leukemia (APL), the t(15;17) translocation results in fusion of the retinoic acid receptor gene, RARA, with the PML gene.

14. Chapter 27-14 What is the function of chimeric antigen receptor T (CAR-T) cells in patients with high-risk hematologic malignancies?

a. Upregulates expression of target genes required for myeloid differentiation. *b. Target leukemia cells for destruction. c. Reverse epigenetic silencing of gene transcription. d. Binds to the CD-20 antigen on B lymphoid cells.

General Feedback: CD19-specific chimeric antigen receptor T (CAR-T) cells work by collecting patient T cells via pheresis that are genetically engineered ex vivo using lentiviral or retroviral vectors to express protein complexes that recognize only the patient’s leukemia cells.

Engineered CAR-T cells then specifically bind to patient’s leukemia cells and target them for destruction.

15. Chapter 27-15 Which are the types of mutations found in hematologic malignancies? a. Chromosomal rearrangement b. Aneuploidy c. Gene deletion *d. All of the options General Feedback: Types of mutations found in hematologic malignancies include chromosomal rearrangement (such as translocation or inversion), gain or loss of chromosomes (aneuploidy), total or partial gene deletion, point mutation, or gene duplication/amplification.

16. Chapter 27-16 Which statement describes how hematopoietic stem cell transplantation (HSCT) is performed? *a. Bone marrow is harvested from the posterior iliac crests using sterile technique under general anesthesia. b. Bone marrow is aspirated from the long bones of the leg using regional anesthesia. c. Embryonic stem cells are harvested from the fetus’s umbilical cord in utero. d. Adult stem cells are aspirated from patients aged 50 and older with no history of chronic disease.

General Feedback: Bone marrow is harvested through multiple needle aspirations typically from the posterior iliac crests, and it is done in a sterile surgical environment usually under general or regional anesthesia.

17. Chapter 27-17 Tumor suppressor genes contribute to the malignant process only if: *a. both alleles have been lost. b. one allele has been lost. c. one allele is inactivated. d. both alleles are active.

General Feedback: In contrast to oncogenes, tumor suppressor genes contribute to the malignant process only if both alleles have been lost or otherwise inactivated.

18. Chapter 27-18 A patient is diagnosed with Epstein-Barr virus. For which condition is the patient at risk? a. Hemophilia A *b. Burkitt lymphoma c. Dietary anemia d. Sickle cell disease General Feedback: Epstein-Barr virus, a DNA virus that invades mainly B lymphocytes and has been implicated as a contributing etiologic factor in Burkitt and other non-Hodgkin lymphomas, and in a subset of classic Hodgkin lymphoma.

19. Chapter 27-19 How do miRNAs inhibit gene expression in hematopoietic malignancies? a. Bind to targeted DNA transcripts. *b. Block mRNA translation to protein. c. Reinforce mRNA in the nucleus. d. Degrade DNA replication.

General Feedback: miRNAs (small 22 nucleotide RNA segments) inhibit gene expression by specifically binding to targeted mRNA transcripts, blocking their translation to protein, and causing their destabilization and degradation.

20. Chapter 27-20 Which condition is a patient diagnosed with acute leukemia likely to experience? a. Neutropenia b. Thrombocytopenia c. Anemia *d. All of the options General Feedback: Patients diagnosed with acute leukemia are likely to experience neutropenia, which causes fever due to infection; thrombocytopenia, which causes bleeding; and anemia, which causes fatigue.

1. Chapter 28-01 Hydrodynamic focusing in flow cytometry is important because it: a. directs the laser light. b. intensifies the laser light with mirrors. c. collects the scattered light. *d. creates a core of individually aligned cells.

General Feedback: Hydrodynamic focusing creates a central stream of individually aligned cells surrounded by sheath fluid. This is essential for consistent illumination of each cell as it passes in front of the gas laser light source.

2. Chapter 28-02 Forward scatter is related to what cellular feature? a. Density *b. Size c. Granularity d. Complexity General Feedback: Information gathered from the detector situated directly in line with the illuminating source is called forward scatter and provides data on particle size.

3. Chapter 28-03 Which is evaluated using fluorochrome dyes that are bound to monoclonal antibodies? *a. Membrane antigens b. Nuclear complexity c. Number of lymphocytes d. Cell size General Feedback: The presence or absence of specific membrane antigens is detected using monoclonal antibodies to which fluorochrome dyes are bound.

5. Chapter 28-05 What cell type expresses CD20 and contains immunoglobulin light chains on the surface but not in the cytoplasm? a. Helper T cells (TH) b. T suppressor cells c. Immature B cells *d. Mature B cells General Feedback:

Mature B cells express CD20 and immunoglobulin light chains, either ê or ë but not both, on their surface.

6. Chapter 28-06 Myeloid stem cells and blasts express which factor on their surface? a. CD4 b. CD8 *c. CD34 d. Terminal deoxynucleotidyl transferase (TdT) General Feedback: CD34 is expressed on the surface of myeloid stem cells and blasts. CD4, CD8, and TdT are all markers of lymphoid lineage. In addition, TdT is not a membrane antigen but rather is found in the nucleus.

7. Chapter 28-07 What marker is most closely related to monocytes leukemia? a. CD3 *b. CD4 c. CD8 d. CD10 General Feedback: Acute monoblastic and monocytic leukemias express myeloid markers and antigens associated with monocytic lineage, such as CD14, CD4, CD11b, and CD64.

9. Chapter 28-09 All are true concerning hematopoietic stem cells except: a. they express both CD34 and CD117 (c-kit). b. they lose some antigens as they mature. *c. they express both CD4 and CD34. d. they gain lineage-specific antigens as they mature.

General Feedback: CD4 is a marker of T cells, not hematopoietic stem cells (HSCs). HSCs express both CD34 and CD117 (c-kit). As they mature, some antigens are lost while lineage-specific antigens are gained.

10. Chapter 28-10 What is an early marker of erythroid precursors? a. CD45 *b. CD71 c. CD34 d. CD8

General Feedback: CD71 identifies the presence of the transferrin receptor and is found on early erythroid precursors.

11. Chapter 28-11 The presence of TdT is characteristic of progenitors of which lineage? a. Megakaryocytes and platelets b. Monocytes c. Erythrocytes *d. Lymphocytes General Feedback: TdT is found in lymphoid precursors and is useful for identifying their presence.

12. Chapter 28-12 A patient has a white cell count of 12.6 × 109/L, hematocrit of 28%, and platelet count of 27 × 109/L. Examination of a Wright-stained blood film reveals that almost all of the white cells in peripheral blood are blasts; the bone marrow is hypercellular with very little fat and is packed with blasts. Flow cytometry is performed on the peripheral blood cells, and a large cluster of cells is present that mark with CD20 and have monoclonal ê light chains present on their surface. This patient has: a. myeloid leukemia. *b. a mature B cell malignancy. c. a reactive B cell hyperplasia. d. a mature T cell malignancy.

General Feedback: Mature B lymphocytes express CD20 and either ê or ë light chains on their surface. In a B cell reactive process, a mixture of ê and ë light chain positivity will be observed. The expression of only one light chain on the surface of a population of B cells is called monoclonality and is indicative of a phenotypically mature B cell malignancy.

1. Chapter 29-01 Molecular testing is useful for all of the following except: *a. evaluating clinical severity of anemia. b. finding chromosomal translocations in malignancies. c. detecting inherited disorders. d. identifying blood pathogens.

General Feedback: Molecular testing is not useful for evaluating the clinical severity of anemia; that is done using the patient’s physical and clinical history, as well as evaluating various red cell parameters (e.g., hematocrit, hemoglobin, red cell morphology). However, it can be useful for the diagnosis of the cause of an inherited anemia (e.g., thalassemia), finding chromosomal translocations in malignancies, detecting inherited disorders, and identifying blood pathogens.

2. Chapter 29-02 How does ribonucleic acid (RNA) differ from deoxyribonucleic acid (DNA)? a. RNA does not contain nucleotides. *b. RNA has uracil-replacing thymine. c. DNA is found primarily in the cytoplasm, and RNA is in the nucleus. d. DNA has a messenger, whereas RNA does not.

General Feedback: RNA differs from DNA in that it has uracil-replacing thymine.

3. Chapter 29-03 What is the preferred specimen for molecular techniques for diagnosis of inherited mutations? a. RNA extracted from peripheral mature red cells. b. RNA extracted from fresh serum. *c. DNA extracted from peripheral blood white cells. d. DNA extracted from peripheral blood mature red cells.

General Feedback: DNA extracted from peripheral blood (or bone marrow) white cells is the preferred specimen for molecular techniques when they are used to diagnose inherited disorders. In inherited disorders, the DNA from any cell could theoretically be used because the DNA at the molecular level will be identical regardless of cell origin. However, DNA from peripheral blood white cells is the easiest tissue to obtain.

Mature red blood cells (RBCs) cannot be used because they do not have a nucleus and therefore do not have any DNA.

4. Chapter 29-04 Before molecular methods are performed, the DNA must be: a. primed.

b. flanked. c. elongated. *d. amplified.

General Feedback: DNA must be amplified before molecular methods are performed on it. This improves the sensitivity and thus the ability to detect the abnormality.

5. Chapter 29-05 Gel electrophoresis, restriction endonucleases, and hybridization techniques are methods to: *a. detect DNA amplification. b. detect DNA extraction. c. measure concentration of DNA. d. identify BCR gene in chronic myelogenous leukemia.

General Feedback: These are all methods used to detect DNA amplification and thus identify the possible presence of a DNA abnormality.

6. Chapter 29-06 Why is the helical configuration of DNA important? a. Permits purines and pyrimidines to bond. b. Permits transcription of DNA by RNA polymerase. *c. Stabilizes the molecular structure. d. Prevents occurrence of protein structural abnormalities (e.g., point mutations, translocations).

General Feedback: The helical configuration of DNA, where the strands twist, stabilizes the DNA molecule and protects the bases from the environmental damage.

7. Chapter 29-07 Where is messenger RNA formed? a. Mitochondria b. Golgi organelle c. Ribosomes *d. Nucleus General Feedback: Messenger RNA is formed in the nucleus and then leaves it to enter the cytoplasm, where it is translated. It is found within the nucleolus of the nucleus.

8. Chapter 29-08 What is the cell type and tissue of choice for molecular techniques used to detect acquired DNA mutations leading to malignancy? a. Peripheral blood mature lymphocytes b. Bone marrow hematopoietic stem cells *c. The malignant tissue d. Peripheral blood mature neutrophils General Feedback: Cells from the malignant tissue should be evaluated for the acquired DNA mutation. Many malignancies, both hematopoietic and solid tumors, have acquired DNA mutations, some of which are characteristic for certain malignancies. Because these are acquired mutations, they will not be found in all cells but only those affected by the mutation or mutations.

9. Chapter 29-09 DNA has been isolated from appropriate cells and placed in an aqueous buffer. If molecular testing cannot be immediately performed, what should be done? a. Reprecipitate the DNA using isopropanol alcohol and then store at 4°C. b. Reprecipitate the DNA using isopropanol alcohol and then store at ?2-80°C. c. Store prepared DNA at 4°C. *d. Store prepared DNA at ?2-80°C. General Feedback: If isolated DNA cannot be immediately evaluated for molecular testing, it should be stored at ?-80° C. The prepared DNA can be stored for an indefinite period of time and still give valid results.

10. Chapter 29-10 Why is a “no-DNA” control used when performing molecular tests using the polymerase chain reaction (PCR)? a. To ensure that the targeted DNA is amplified b. To ensure that nontargeted DNA is negative c. To ensure that the targeted DNA containing the mutation is positive *d. To ensure that no DNA cross-contamination of the samples, controls, or reagents occurs General Feedback: Contamination of reagents, controls, and samples with extraneous DNA from the environment is possible when performing molecular testing. Thus a no DNA control must be run along with the controls and samples to validate the analysis.

11. Chapter 29-11 Which is the gold standard method for the detection of point mutations and single nucleotide polymorphisms? *a. Sanger DNA sequencing b. Next-generation sequencing (NGS) c. Pyrosequencing d. Real-time PCR General Feedback: Sanger DNA sequencing is based on the principle that synthesis of a DNA polymer is terminated upon incorporation of a dideoxynucleotide. DNA fragments are produced and identified through fluorescent labeling. The Sanger method is considered the gold standard for detection of point mutations and single nucleotide polymorphisms.

12. Chapter 29-12 Areas of hematopathologic molecular testing include all except: a. detection of mutation. b. gene rearrangement. c. chromosomal abnormalities. *d. gene splicing.

General Feedback: Detection of mutation, gene rearrangement, and chromosomal abnormalities that result in hematopathologic disorders can all be identified through molecular testing methods. Gene splicing is not a method for molecular identification of hematopathologic disorders.

1. Chapter 30-01 The congenital gain or loss of an entire chromosome in a developing fetus usually results in what type of clinical condition? a. Sexual ambiguity b. Myeloid leukemia c. Mental retardation *d. Usually incompatible with life General Feedback: The congenital gain or loss of an entire chromosome other than sex is usually incompatible with life and ends in a first-trimester spontaneous abortion.

2. Chapter 30-02 What happens to nuclear chromatin at mitosis? a. Opens *b. Condenses c. Disappears d. Develops nucleoli General Feedback: Nuclear chromatin condenses approximately 10,000-fold at mitosis; this results in the formation of chromosomes.

3. Chapter 30-03 What is the best method for detecting chromosomal material that has been structurally altered? *a. Fluorescence in situ hybridization (FISH) b. G banding c. Q banding d. Ag-NOR banding General Feedback: The best method for detecting structurally altered chromosomes is FISH.

4. Chapter 30-04 Which is true regarding the number of chromosomes of different species? a. All mammals have the same number. *b. Numbers vary greatly among mammals unrelated to characteristics. c. Primates have more than lower mammals. d. Primates have fewer than lower mammals.

General Feedback: Different species have different numbers of chromosomes that vary unrelated to characteristics.

5. Chapter 30-05 Where is a gene designated t(9;22)(q34;q11.2 located)? a. Short arm of chromosome 23, region 9 b. Long arm of chromosome 3, region 2, band 9 *c. Between long arms of chromosomes 9 and 22 d. On the translocated part of chromosome 9 on chromosome 23 General Feedback: A gene designated t(9;23) is located between the long arms of chromosomes 9 and 22.

6. Chapter 30-06 All samples are commonly analyzed for chromosomes except: a. bone marrow. b. amniotic fluid. c. peripheral lymphocytes. *d. tissue with a low mitotic rate.

General Feedback: Tissue with a low mitotic rate is not suitable for chromosome analysis. Tissues with a high mitotic rate, or those that can be stimulated to divide in culture, can be used.

7. Chapter 30-07 A chromosome number that is not a multiple of the haploid number is: *a. aneuploidy. b. mosaic. c. polyploidy. d. incompatible with life.

General Feedback: Aneuploidy is the term used to describe a chromosome number that is not a multiple of the haploid number for that species.

8. Chapter 30-08 Cell division to produce daughter cells identical to the parent cell is an example of: a. nondisjunction. b. meiosis. *c. mitosis. d. gamete production.

General Feedback: Mitosis results in the production of daughter cells that are identical to the parent cell.

9. Chapter 30-09 How many chromosomes does a human with triploidy have? a. 3 b. 23 c. 47 *d. 69 General Feedback: The normal haploid number of chromosomes for humans is 23. A patient who has triploidy has three times that number (i.e., tri-), or 69.

10. Chapter 30-10 A break in two chromosomes with each piece uniting with different chromosomes is called: a. deletion. b. duplication. c. insertion. *d. translocation.

General Feedback: Translocation occurs when two chromosomes break and each of the broken pieces reunites with another chromosome. If chromatin is neither lost nor gained in the process, the exchange is called a balanced reciprocal translocation.

11. Chapter 30-11 What tissue is most often studied for hematologic malignancies? a. Peripheral blood *b. Bone marrow c. Spleen d. Lymph node sections General Feedback: Bone marrow is most often studied for hematologic malignancies.

12. Chapter 30-12 What chromosome abnormality was the first to be identified and associated with a specific malignancy? a. Trisomy 8 b. Deletion 7 *c. Philadelphia d. Isocentric chromosome 16 General Feedback: The first chromosome abnormality to be identified and associated with a specific malignancy was the Philadelphia chromosome.

It initially was associated with chronic myelogenous leukemia, although clinicians now know it to be found in other hematologic malignancies.

13. Chapter 30-13 All disorders are associated with acquired chromosome abnormalities except: *a. megaloblastic anemia. b. chronic myelogenous leukemia. c. acute myeloid leukemia. d. acute lymphoblastic leukemia.

General Feedback: Megaloblastic anemia results from a deficiency of either folic acid or vitamin B12. No associated chromosome abnormality exists.

14. Chapter 30-14 Nonrandom chromosomal abnormalities are: a. congenital chromosome abnormalities that are consistently found in all tissues of an affected individual. *b. acquired chromosome abnormalities that are found in the abnormal or malignant tissue of an affected individual. c. acquired chromosome abnormalities that are found in all tissues of an affected individual. d. congenital chromosome abnormalities that are found in only one type of tissue of an affected individual.

General Feedback: Cancer cytogenetics is a field that is built on the finding of nonrandom chromosome abnormalities in many types of cancer. Cytogenetic analysis of malignant cells can help determine the diagnosis and probable prognosis of a hematologic malignancy.

15. Chapter 30-15 The period in the cell cycle when deoxyribonucleic acid (DNA) is synthesized is: a. G1. *b. S. c. G2. d. M. General Feedback: DNA is synthesized during the S phase of the cell cycle.

16. Chapter 30-16 Cytogenetics is performed on the bone marrow of a patient, and 20 cells are examined. The patient’s karyotype is reported as 47, XX, +7(14), indicating that:

*a. this is a female patient with trisomy chromosome 7 found in 14 of the cells examined. b. this is a female patient with monosomy chromosome 7 found in 1 of 4 cells examined. c. this is a male patient with trisomy 7 found in 1 of 4 cells examined. d. this is a male patient with monosomy 7 found in 14 of the cells examined.

General Feedback: This is a female patient (XX). She has an additional chromosome 7 (+7) found in 14 of the 20 cells that were examined.

17. Chapter 30-17 A patient has a hematologic malignancy. Karyotyping is performed for all of the following reasons except: *a. to provide unique cytogenetic profile to confirm the patient’s identification. b. to provide diagnostic information. c. to identify whether the patient will respond to appropriate therapy. d. to provide prognostic information.

General Feedback: Patients with various forms of cancers, including hematologic forms, may exhibit a nonrandom abnormal karyotype. This karyotype can provide useful diagnostic information, identify whether the patient will respond to appropriate therapy, and provide prognostic information for the patient. It does not confirm the patient’s identification.

1. Chapter 31-01 What is the most common leukemia in children between the ages of 2 and 5 years? a. Acute myeloid b. Acute monocytic c. Acute myelomonocytic *d. Acute lymphoblastic General Feedback: The most common leukemia in this age-group is acute lymphoblastic leukemia.

2. Chapter 31-02 A 15-year-old boy is complaining of severe headaches; he has a white count of 76.0 × 109/L, platelet count of 55 × 109/L, and a hematocrit of 33%. When a white cell differential is performed, most of the nucleated cells are blasts. They are CD2, CD4, and CD8 positive. The TdT marker is expressed. What is the most likely diagnosis? a. Immature-B cell acute lymphoblastic leukemia *b. T cell acute lymphoblastic leukemia c. Acute myeloid leukemia without maturation d. Acute myeloid leukemia with maturation General Feedback: T cell acute lymphoblastic leukemia is most often seen in teenage boys with a mediastinal mass, elevated peripheral blast counts, meningeal involvement, and infiltration of extra marrow sites. The blasts commonly mark as CD2, CD4, CD5, and CD8 positive.

3. Chapter 31-03 Which form of acute myeloid leukemia is most often associated with disseminated intravascular coagulation (DIC)? a. Acute myeloid leukemia minimally differentiated b. Acute myeloid leukemia with t(8;21)(q33:q22) *c. Acute myeloid leukemia with t(15;17)(q22:q12) d. Acute myeloid leukemia with maturation General Feedback: Acute myeloid leukemia with t(15;17)(q22:q12), also known as acute promyelocytic leukemia, is associated with DIC. Treatment of this disorder must therefore involve resolution of the DIC.

5. Chapter 31-05 A 27-year-old woman arrives at the emergency department with acute bleeding and is found to have a white count of 25.7 × 109L with pancytopenia: hematocrit 27%, platelet count 35 × 109/L, and absolute neutrophil count 0.8 × 109/L. She has a combination of 97% blasts and abnormal promyelocytes in her peripheral blood; some of these cells contain Auer rods. What form of leukemia does she most likely have?

*a. Acute myeloid leukemia with t(15;17)(q22:q12) b. Chronic myeloid leukemia c. Acute monoblastic leukemia d. Acute myeloid leukemia with t(8;21)(q33:q22) General Feedback: Acute myeloid leukemia with t(15;17)(q22:q12) is characterized by abnormal promyelocytes, which may have Auer rods. Patients are most often young adults.

6. Chapter 31-06 Acute myelomonocytic leukemia is positive for which factor? a. CD10 b. periodic acid–Schiff (PAS) c. HLA-DR1a *d. CD13 and CD14 General Feedback: The cells in acute myelomonocytic leukemia are positive for CD13 (a myeloid antigen) and CD14 (a monocytic antigen).

7. Chapter 31-07 What leukemia is most likely in a patient whose bone marrow is composed of predominantly large, multinucleated, vacuolated, dysplastic erythroid precursors? a. Acute myelomonocytic leukemia b. Acute megakaryocytic leukemia *c. Acute erythroleukemia d. Acute myeloid leukemia with minimal maturation General Feedback: The bone marrow erythroid precursors display significant dysplastic features, including multinucleation, megaloblastoid asynchrony, and vacuolization, in acute erythroleukemia. Abnormal megakaryocytes may also be present.

9. Chapter 31-09 Which form of acute leukemia has megakaryoblasts and antibodies to platelet glycoprotein IIb/IIIa? a. Acute myeloid leukemia with minimal differentiation b. Acute monoblastic leukemia c. Acute erythroleukemia *d. Acute megakaryoblastic leukemia General Feedback: Acute megakaryoblastic leukemia has blasts that are positive for the platelet antigens glycoprotein IIb/IIIa. They may also be positive for glycoprotein Ib or factor VIII–related antigen.

10. Chapter 31-10 Which would stain most strongly for myeloperoxidase? a. Lymphoblasts *b. Auer rods c. Monocytes d. Normal myeloblasts General Feedback: Auer rods are strongly positive for myeloperoxidase. Sometimes Auer rods that cannot be seen with Wright stain are visible after staining for myeloperoxidase. Monocytes are only very weakly positive for this enzyme, whereas normal myeloblasts and lymphoblasts (both normal and malignant) are negative.

11. Chapter 31-11 Sudan black is used to distinguish which types of leukemia? *a. Acute myeloid leukemia from acute lymphoblastic leukemia b. Acute myeloid leukemia from chronic myelogenous leukemia c. Acute myeloid leukemia from acute promyelocytic leukemia d. Acute promyelocytic leukemia from acute monocytic leukemia General Feedback: Lymphoid cells are generally negative, whereas myeloblasts are positive. Thus a positive result with this stain can be used to differentiate acute myeloid leukemia from acute lymphoblastic leukemia.

The entire myeloid series through neutrophils is positive, so it is not useful in differentiating different types of myeloid leukemia.

Monocytes are negative to weakly positive.

1. Chapter 32-01 All are included in the chronic myeloproliferative disorders except: *a. acute myeloid leukemia. b. chronic myelogenous leukemia. c. polycythemia vera. d. essential thrombocythemia.

General Feedback: Acute myeloid leukemia is not included in the chronic myeloproliferative disorders. All the other conditions listed are part of this classification.

2. Chapter 32-02 What do all chronic myeloproliferative disorders share? a. Philadelphia chromosome b. Increased red cell mass *c. Increased blood cells; overlapping clinical and laboratory features d. Serious thromboembolic complications General Feedback: The chronic myeloproliferative disorders all have increased blood cells, although which one (or ones) varies depending on the condition. They also all have overlapping clinical features. The Philadelphia chromosome is found only in chronic myelogenous leukemia within this classification. Polycythemia vera uniquely has an increased red cell mass, and serious thromboembolic complications are primarily seen in essential thrombocythemia, although they also can be a complication of polycythemia vera when the patient is treated with phlebotomy only.

3. Chapter 32-03 Which is an unexpected finding in chronic myelogenous leukemia? a. Increased eosinophils (EOs) and basophils in the peripheral blood *b. 20% blasts in the peripheral blood c. Hypercellular bone marrow with granulopoiesis d. White blood count of 100 × 109/L General Feedback: Myeloblasts plus promyelocytes are usually present between 1% and 5% in chronic myelogenous leukemia. A total of 20% blasts plus promyelocytes is proposed for the classification of chronic myelogenous leukemia accelerated phase. All the other findings listed are characteristic of chronic myelogenous leukemia.

4. Chapter 32-04 Which is the most specific laboratory test to diagnose chronic myelogenous leukemia?

a. Increased bone marrow fibrosis and reticulin fibers b. Increased EOs and basophils in peripheral blood c. 5% blasts in the bone marrow *d. Leukocyte alkaline phosphatase General Feedback: Of the laboratory tests listed, the leukocyte alkaline phosphatase score is most specific for the diagnosis of chronic myelogenous leukemia (where it is below normal in most cases). None of the other findings are specific for chronic myelogenous leukemia.

5. Chapter 32-05 Chronic myelogenous leukemia often progresses to: a. chronic neutrophilic leukemia. b. chronic lymphocytic leukemia. *c. acute leukemia, either myeloid or lymphoblastic. d. chronic idiopathic myelofibrosis.

General Feedback: Chronic myelogenous leukemia often progresses to acute leukemia, which may be either myeloid or lymphoblastic.

6. Chapter 32-06 Which chronic myeloproliferative disorder is treated with imatinib mesylate, a drug that inhibits tyrosine kinase? a. Polycythemia vera *b. Chronic myelogenous leukemia c. Essential thrombocythemia d. Primary myelofibrosis General Feedback: Chronic myelogenous leukemia is effectively treated with imatinib mesylate. This drug inhibits most of the transforming capability stemming from the tyrosine kinase (P210) activity of the bcr/abl fusion gene. This P210 fusion protein is not found in the other myeloproliferative disorders, so the drug is ineffective in these disorders.

7. Chapter 32-07 Which is an expected finding in polycythemia vera? *a. Thrombocytosis b. Anemia c. Low leukocyte alkaline phosphatase d. Normal white count General Feedback: Thrombocytosis, or an elevated platelet count, is characteristically present in polycythemia vera. Polycythemia vera has

an elevated red cell mass, so anemia is not present. The leukocyte alkaline phosphatase score and the white count are both elevated.

8. Chapter 32-08 A high red count, hemoglobin, and hematocrit are found in all except: a. polycythemia vera. *b. bone marrow aplasia. c. blood hyperviscosity. d. erythrocytosis secondary to hypoxia.

General Feedback: A high red count is not found in bone marrow aplasia. It is characteristic of all the other disorders listed.

9. Chapter 32-09 A patient has an increased red count, hemoglobin, and hematocrit. Which feature points to secondary polycythemia over polycythemia vera? a. Increased white count b. Increased red cell mass c. Bone marrow erythroid hyperplasia *d. Decreased arterial oxygen saturation General Feedback: Decreased arterial oxygen saturation is characteristic of secondary polycythemia. Arterial oxygen saturation is normal in polycythemia vera. Decreased arterial oxygen saturation leads to hypoxia, resulting in increased production of erythropoietin. This stimulates the bone marrow to increase red cell production (erythroid hyperplasia), also found in polycythemia vera. This results in an increase in red cell mass, again also found in polycythemia vera, as is an increased white count.

10. Chapter 32-10 A patient has a platelet count of 1200 × 109/L. Many platelets are giant and have abnormal shapes. A mild anemia is present. The bone marrow has increased megakaryocytes in clusters; iron stores are present. Which is most likely? *a. Essential thrombocythemia b. Chronic myelogenous leukemia c. Thrombocytosis secondary to blood loss d. Polycythemia vera General Feedback: Platelet counts are often over 1000 × 109/L in essential thrombocythemia. Polycythemia vera also has an elevated platelet count but usually not in this range. In addition, a mild anemia is present in the presence of iron stores; this rules out polycythemia vera. Although the platelet count is usually elevated in the chronic phase of chronic

myelogenous leukemia, it is not this high, nor would it be this elevated in thrombocytosis secondary to blood loss.

11. Chapter 32-11 What clinical feature is more often associated with essential thrombocytosis than with the other chronic myeloproliferative disorders? a. Splenomegaly *b. Bleeding and thrombosis c. Fatigue d. Infections General Feedback: Bleeding and thromboembolic complications are characteristic of essential thrombocytosis. Patients with polycythemia vera who are treated only with phlebotomy are at increased risk for bleeding and thrombosis, but it is otherwise not characteristic of polycythemia vera. Splenomegaly is seen in all the myeloproliferative disorders, as are fatigue and infections.

12. Chapter 32-12 Although found in most chronic myeloproliferative disorders, increased fibrosis detected by the silver techniques and trichrome stain is the key feature of: a. secondary polycythemia. b. chronic myelogenous leukemia. c. essential thrombocythemia. *d. primary myelofibrosis.

General Feedback: This is a key feature of primary myelofibrosis.

13. Chapter 32-13 A patient has a normal white blood count, a moderately high platelet count, and mild anemia. The differential shows immature granulocytes, nucleated red cells, and teardrop-shaped red cells. Which is most likely? a. Polycythemia vera b. Chronic myelogenous leukemia *c. Primary myelofibrosis d. Essential thrombocythemia General Feedback: These findings would all be characteristic of primary myelofibrosis. Polycythemia vera and chronic myelogenous leukemia would both be expected to have an elevated white count. The platelet count is markedly increased in essential thrombocythemia.

15. Chapter 32-15 The Philadelphia chromosome: a. is a balanced reciprocal translocation between chromosomes 7 and 19. *b. results in a chimeric gene (bcr/abl). c. is diagnostic for polycythemia vera. d. manifests as a tyrosine kinase that blocks cell maturation.

General Feedback: The Philadelphia chromosome results in the chimeric gene bcr/abl. It is a balanced reciprocal translocation between chromosomes 22 and 9. This chimeric gene manifests as a tyrosine kinase (P210), which appears to induce clonal cell proliferation. Although it affects maturation, as well as proliferation, it results in increased numbers of mature granulocytes in peripheral blood, so it does not block cell maturation.

16. Chapter 32-16 Which is true for chronic myelogenous leukemia? *a. It is a clonal process arising from the pluripotent stem cell. b. It is most commonly found in children 5 to 10 years old. c. Common symptoms include an elevated red cell mass. d. Lymphadenopathy is common.

General Feedback: Chronic myelogenous leukemia is a clonal process arising from the pluripotent stem cell. It is most commonly found in middle-aged adults. A mild anemia that progresses is common, not an elevated red cell mass; enlarged lymph nodes are not characteristic.

17. Chapter 32-17 Bone marrow or stem cell transplantation is the therapy of choice for patients younger than 55 years old with: a. essential thrombocytosis. b. polycythemia vera. *c. chronic myelogenous leukemia. d. all of the options.

General Feedback: Bone marrow or stem cell transplantation is the therapy of choice for patients younger than 55 years old with chronic myelogenous leukemia if an HLA-matched donor can be found. It is not a therapeutic choice for either essential thrombocytosis or polycythemia vera.

18. Chapter 32-18 Which is true for the mutated erythroid progenitors in polycythemia vera?

a. They require extremely high levels of erythropoietin for growth in vitro. *b. They are more resistant to apoptosis than normal erythroid progenitors. c. They mature abnormally, giving rise to a marked increase in poikilocytosis in peripheral blood. d. They are Philadelphia chromosome positive.

General Feedback: The mutated erythroid progenitors in polycythemia vera are more resistant to apoptosis than normal erythroid progenitors. Thus they do not divide more rapidly (as once believed) but accumulate abnormally because they do not die normally. This results in an increased red cell mass in peripheral blood. Maturation is normal, giving rise to essentially morphologically normal red cells. They grow in vitro with trace concentrations of erythropoietin and are Philadelphia chromosome negative.

19. Chapter 32-19 The bone marrow fibrosis observed in primary myelofibrosis is due to: a. malignant proliferation of fibroblasts. b. increased erythropoietin, which stimulates fibroblast proliferation. *c. increased release of fibroblastic growth factors such as platelet-derived growth factor. d. decreased apoptosis of normal fibroblasts.

General Feedback: An increased release of fibroblastic growth factors occurs, including platelet-derived growth factor, in primary myelofibrosis; this results in fibrosis. The fibroblasts in primary myelofibrosis are normal, not malignant.

20. Chapter 32-20 The Janus kinase (JAK) mutation is seen in more than 90% of cases of what disease? a. Chronic myelogenous leukemia b. Primary myelofibrosis c. Plasma cell myeloma *d. Polycythemia vera General Feedback: The diagnosis of polycythemia vera requires the presence of two major criteria and one minor criteria, or it requires the first major criteria and two minor criteria. The JAK mutation is the second of the major criteria.

1. Chapter 32-01 All are included in the chronic myeloproliferative disorders except: *a. acute myeloid leukemia. b. chronic myelogenous leukemia. c. polycythemia vera. d. essential thrombocythemia.

General Feedback: Acute myeloid leukemia is not included in the chronic myeloproliferative disorders. All the other conditions listed are part of this classification.

2. Chapter 32-02 What do all chronic myeloproliferative disorders share? a. Philadelphia chromosome b. Increased red cell mass *c. Increased blood cells; overlapping clinical and laboratory features d. Serious thromboembolic complications General Feedback: The chronic myeloproliferative disorders all have increased blood cells, although which one (or ones) varies depending on the condition. They also all have overlapping clinical features. The Philadelphia chromosome is found only in chronic myelogenous leukemia within this classification. Polycythemia vera uniquely has an increased red cell mass, and serious thromboembolic complications are primarily seen in essential thrombocythemia, although they also can be a complication of polycythemia vera when the patient is treated with phlebotomy only.

3. Chapter 32-03 Which is an unexpected finding in chronic myelogenous leukemia? a. Increased eosinophils (EOs) and basophils in the peripheral blood *b. 20% blasts in the peripheral blood c. Hypercellular bone marrow with granulopoiesis d. White blood count of 100 × 109/L General Feedback: Myeloblasts plus promyelocytes are usually present between 1% and 5% in chronic myelogenous leukemia. A total of 20% blasts plus promyelocytes is proposed for the classification of chronic myelogenous leukemia accelerated phase. All the other findings listed are characteristic of chronic myelogenous leukemia.

4. Chapter 32-04 Which is the most specific laboratory test to diagnose chronic myelogenous leukemia?

a. Increased bone marrow fibrosis and reticulin fibers b. Increased EOs and basophils in peripheral blood c. 5% blasts in the bone marrow *d. Leukocyte alkaline phosphatase General Feedback: Of the laboratory tests listed, the leukocyte alkaline phosphatase score is most specific for the diagnosis of chronic myelogenous leukemia (where it is below normal in most cases). None of the other findings are specific for chronic myelogenous leukemia.

5. Chapter 32-05 Chronic myelogenous leukemia often progresses to: a. chronic neutrophilic leukemia. b. chronic lymphocytic leukemia. *c. acute leukemia, either myeloid or lymphoblastic. d. chronic idiopathic myelofibrosis.

General Feedback: Chronic myelogenous leukemia often progresses to acute leukemia, which may be either myeloid or lymphoblastic.

6. Chapter 32-06 Which chronic myeloproliferative disorder is treated with imatinib mesylate, a drug that inhibits tyrosine kinase? a. Polycythemia vera *b. Chronic myelogenous leukemia c. Essential thrombocythemia d. Primary myelofibrosis General Feedback: Chronic myelogenous leukemia is effectively treated with imatinib mesylate. This drug inhibits most of the transforming capability stemming from the tyrosine kinase (P210) activity of the bcr/abl fusion gene. This P210 fusion protein is not found in the other myeloproliferative disorders, so the drug is ineffective in these disorders.

7. Chapter 32-07 Which is an expected finding in polycythemia vera? *a. Thrombocytosis b. Anemia c. Low leukocyte alkaline phosphatase d. Normal white count General Feedback: Thrombocytosis, or an elevated platelet count, is characteristically present in polycythemia vera. Polycythemia vera has

an elevated red cell mass, so anemia is not present. The leukocyte alkaline phosphatase score and the white count are both elevated.

8. Chapter 32-08 A high red count, hemoglobin, and hematocrit are found in all except: a. polycythemia vera. *b. bone marrow aplasia. c. blood hyperviscosity. d. erythrocytosis secondary to hypoxia.

General Feedback: A high red count is not found in bone marrow aplasia. It is characteristic of all the other disorders listed.

9. Chapter 32-09 A patient has an increased red count, hemoglobin, and hematocrit. Which feature points to secondary polycythemia over polycythemia vera? a. Increased white count b. Increased red cell mass c. Bone marrow erythroid hyperplasia *d. Decreased arterial oxygen saturation General Feedback: Decreased arterial oxygen saturation is characteristic of secondary polycythemia. Arterial oxygen saturation is normal in polycythemia vera. Decreased arterial oxygen saturation leads to hypoxia, resulting in increased production of erythropoietin. This stimulates the bone marrow to increase red cell production (erythroid hyperplasia), also found in polycythemia vera. This results in an increase in red cell mass, again also found in polycythemia vera, as is an increased white count.

10. Chapter 32-10 A patient has a platelet count of 1200 × 109/L. Many platelets are giant and have abnormal shapes. A mild anemia is present. The bone marrow has increased megakaryocytes in clusters; iron stores are present. Which is most likely? *a. Essential thrombocythemia b. Chronic myelogenous leukemia c. Thrombocytosis secondary to blood loss d. Polycythemia vera General Feedback: Platelet counts are often over 1000 × 109/L in essential thrombocythemia. Polycythemia vera also has an elevated platelet count but usually not in this range. In addition, a mild anemia is present in the presence of iron stores; this rules out polycythemia vera. Although the platelet count is usually elevated in the chronic phase of chronic

myelogenous leukemia, it is not this high, nor would it be this elevated in thrombocytosis secondary to blood loss.

11. Chapter 32-11 What clinical feature is more often associated with essential thrombocytosis than with the other chronic myeloproliferative disorders? a. Splenomegaly *b. Bleeding and thrombosis c. Fatigue d. Infections General Feedback: Bleeding and thromboembolic complications are characteristic of essential thrombocytosis. Patients with polycythemia vera who are treated only with phlebotomy are at increased risk for bleeding and thrombosis, but it is otherwise not characteristic of polycythemia vera. Splenomegaly is seen in all the myeloproliferative disorders, as are fatigue and infections.

12. Chapter 32-12 Although found in most chronic myeloproliferative disorders, increased fibrosis detected by the silver techniques and trichrome stain is the key feature of: a. secondary polycythemia. b. chronic myelogenous leukemia. c. essential thrombocythemia. *d. primary myelofibrosis.

General Feedback: This is a key feature of primary myelofibrosis.

13. Chapter 32-13 A patient has a normal white blood count, a moderately high platelet count, and mild anemia. The differential shows immature granulocytes, nucleated red cells, and teardrop-shaped red cells. Which is most likely? a. Polycythemia vera b. Chronic myelogenous leukemia *c. Primary myelofibrosis d. Essential thrombocythemia General Feedback: These findings would all be characteristic of primary myelofibrosis. Polycythemia vera and chronic myelogenous leukemia would both be expected to have an elevated white count. The platelet count is markedly increased in essential thrombocythemia.

14. Chapter 32-14 Which is an unexpected finding in primary myelofibrosis? *a. 80% blasts in the peripheral blood b. Micromegakaryocytes in the peripheral blood c. Autoantibodies d. Extramedullary hematopoiesis General Feedback: Eighty percent blasts in the peripheral blood is acute leukemia, not primary myelofibrosis. All the other findings can be present in primary myelofibrosis.

15. Chapter 32-15 The Philadelphia chromosome: a. is a balanced reciprocal translocation between chromosomes 7 and 19. *b. results in a chimeric gene (bcr/abl). c. is diagnostic for polycythemia vera. d. manifests as a tyrosine kinase that blocks cell maturation.

General Feedback: The Philadelphia chromosome results in the chimeric gene bcr/abl. It is a balanced reciprocal translocation between chromosomes 22 and 9. This chimeric gene manifests as a tyrosine kinase (P210), which appears to induce clonal cell proliferation. Although it affects maturation, as well as proliferation, it results in increased numbers of mature granulocytes in peripheral blood, so it does not block cell maturation.

16. Chapter 32-16 Which is true for chronic myelogenous leukemia? *a. It is a clonal process arising from the pluripotent stem cell. b. It is most commonly found in children 5 to 10 years old. c. Common symptoms include an elevated red cell mass. d. Lymphadenopathy is common.

General Feedback: Chronic myelogenous leukemia is a clonal process arising from the pluripotent stem cell. It is most commonly found in middle-aged adults. A mild anemia that progresses is common, not an elevated red cell mass; enlarged lymph nodes are not characteristic.

17. Chapter 32-17 Bone marrow or stem cell transplantation is the therapy of choice for patients younger than 55 years old with: a. essential thrombocytosis. b. polycythemia vera. *c. chronic myelogenous leukemia.

d. all of the options.

General Feedback: Bone marrow or stem cell transplantation is the therapy of choice for patients younger than 55 years old with chronic myelogenous leukemia if an HLA-matched donor can be found. It is not a therapeutic choice for either essential thrombocytosis or polycythemia vera.

19. Chapter 32-19 The bone marrow fibrosis observed in primary myelofibrosis is due to: a. malignant proliferation of fibroblasts. b. increased erythropoietin, which stimulates fibroblast proliferation. *c. increased release of fibroblastic growth factors such as platelet-derived growth factor. d. decreased apoptosis of normal fibroblasts.

General Feedback: An increased release of fibroblastic growth factors occurs, including platelet-derived growth factor, in primary myelofibrosis; this results in fibrosis. The fibroblasts in primary myelofibrosis are normal, not malignant.

20. Chapter 32-20 The Janus kinase (JAK) mutation is seen in more than 90% of cases of what disease? a. Chronic myelogenous leukemia b. Primary myelofibrosis c. Plasma cell myeloma *d. Polycythemia vera General Feedback: The diagnosis of polycythemia vera requires the presence of two major criteria and one minor criteria, or it requires the first major criteria and two minor criteria. The JAK mutation is the second of the major criteria.

21. Chapter 33-01 Which is a common feature of the myelodysplastic syndromes? a. Peripheral blasts between 5% and 20% *b. Progressive cytopenias c. Macrocytic red cells and leukocytosis d. Low mean cell volume (MCV) and thrombocytopenia General Feedback: Progressive cytopenias is characteristic of myelodysplastic syndromes. Although blasts may be increased in the peripheral blood, they are generally less than 5%. Macrocytic red cells may be present, so the MCV may be elevated; however, the white count is usually normal or decreased (depends on type), and platelets are normal to decreased.

23. Chapter 33-03 What is the cause of myelodysplastic syndromes? a. Decreased apoptosis b. Are inherited disorders *c. Proliferation of mutated myeloid cells d. Epstein-Barr virus General Feedback: Proliferation of mutated myeloid stem cells is the cause for myelodysplastic syndromes. Apoptosis is increased in early myelodysplastic syndrome, giving rise to the cytopenia (or cytopenias); however, later, if the disease progresses and acute leukemia appears, apoptosis decreases. They are not inherited, and no association exists with the Epstein-Barr virus.

24. Chapter 33-04 What red cell morphology is expected in the myelodysplastic syndromes? a. Oval macrocytes b. Dimorphic c. Hypochromic, microcytic *d. Any of the above General Feedback: Red cell morphology is usually abnormal, and all of the findings listed can be found.

25. Chapter 33-05 Myelodysplastic syndromes sometimes share similar peripheral and bone marrow cellularity with all except: a. vitamin B12 deficiency. *b. aplastic anemia. c. acute leukemia. d. folate deficiency.

General Feedback: The bone marrow in aplastic anemia is hypocellular, containing primarily fat cells, lymphocytes, and plasma cells. Cytopenias exist in the peripheral blood, but cell morphology is normal and no immature cells are present. The myelodysplastic syndromes in general have a hyperplastic bone marrow but cytopenia (or cytopenias) in peripheral blood. These two findings can also be seen in acute leukemia and both vitamin B12 and folate deficiencies.

27. Chapter 33-07 Which is typical in the peripheral blood in patients with myelodysplastic syndrome?

a. Lymphocytosis b. Plasma cells *c. Hypogranular or agranular neutrophils d. Low levels of vitamin B12 or folate General Feedback: Maturation of granulocytes is abnormal in several of myelodysplastic syndromes, and as a result hypogranular or agranular neutrophils may be seen.

28. Chapter 33-08 What test is most important in distinguishing one myelodysplastic syndrome from another? a. White blood count *b. Percentage of blasts in the bone marrow c. Red cell morphology and MCV d. Presence of ringed sideroblasts in the peripheral blood General Feedback: The primary distinguishing feature of the various myelodysplastic syndromes is the percentage of blasts in the bone marrow.

29. Chapter 33-09 Which is a typical finding in chronic myelomonocytic leukemia? a. Thrombocytosis b. Leukopenia c. 10% to 15% blasts in the peripheral blood *d. Persistent monocytosis General Feedback: Chronic myelomonocytic leukemia is characterized by persistent monocytosis greater than 1.0 × 109/L in peripheral blood.

30. Chapter 33-10 On what does the World Health Organization (WHO) base its classification for the myelodysplastic syndromes? a. Cell morphology b. Molecular analysis c. Immunologic similarities *d. All of the options General Feedback: The 2016 WHO classification system described in this chapter identifies types of MDS based on similarities in morphology, molecular, genetic, immunologic, and clinical characteristics, but it has limited ability to provide a prognosis.

31. Chapter 33-11 The observed heterogeneity in MDS is driven by: a. allele burden. *b. cytokine concentrations. c. karyotype abnormalities. d. all of the options.

General Feedback: The observed heterogeneity in MDS is driven by allele burden, karyotype abnormalities, cytokine concentrations, bone marrow microenvironment, clinical context, and numerous other factors.

32. Chapter 33-12 Which type of mutation are scientists trying to integrate into models to enhance the accuracy of prognoses for patients? *a. Somatic b. Advanced c. Long-term d. Stem General Feedback: Researchers are trying to integrate somatic mutations into existing or novel prognostic models to enhance the accuracy of prognoses for patients.

33. Chapter 33-13 What treatment for the myelodysplastic syndromes has the best chance for cure in these patients? a. Corticosteroid agents b. Chemotherapy *c. Bone marrow transplant d. Vitamins and hormones General Feedback: Bone marrow transplantation with an HLA-matched donor has the greatest chance for cure in patients with myelodysplastic syndrome.

34. Chapter 33-14 Which is an unexpected finding in myelodysplastic syndrome with a deletion of 5q? a. Refractory anemia b. Thrombocytosis c. Less than 1% blasts in peripheral blood *d. Auer rods General Feedback: 5q syndrome predominantly affects older women. Typical findings are anemia, thrombocytosis, and hypolobulated megakaryocytes.

Less than 1% blasts are seen on peripheral blood. Auer rods are not seen.

35. Chapter 33-15 Cell dysfunction in the myelodysplastic syndromes may be present in: a. red cells. b. granulocytes. c. platelets. *d. all of the options.

General Feedback: All blood cells produced in the bone marrow (i.e., red cells, granulocytes, platelets) may exhibit abnormal cell function.

36. Chapter 33-16 Which are useful for determining prognosis for patients with the myelodysplastic syndromes? *a. Bone marrow blasts b. Karyotypic abnormalities c. Depth of cytopenias d. All of the options.

General Feedback: Prognosis in MDS depends on several factors, including percentage of bone marrow blasts, depth of cytopenias, and karyotypic abnormalities.

1. Chapter 34-01 Which are common examples of chromosomal translocated genes associated with lymphomas? a. MYC b. BCL2 c. BCL6 *d. All of the options General Feedback: Common examples of translocated genes are MYC which stimulates entry into the cell cycle, BCL2 which suppresses apoptosis, and BCL6 which can suppress the transcription of other genes necessary for cell growth. These mutations are found in a number of lymphomas.

2. Chapter 34-02 In which population is acute lymphoid leukemia (ALL) with a stem cell phenotype most common? *a. Children b. Adults c. Older adults d. Pregnant women General Feedback: Acute lymphoid leukemia (ALL), with a stem cell or precursor phenotype, is more commonly found in the pediatric population.

3. Chapter 34-03 Which primary laboratory test is ordered for a patient with lymphadenopathy? a. Biochemical analysis b. Immunophenotyping c. Flow cytometry *d. Complete blood cell count General Feedback: The CBC is one of the first laboratory tests ordered to investigate patient symptoms in which a quantitative abnormality may be the first indication of underlying pathology. Biochemical analysis may be useful for three purposes: (1) evaluating organ systems for compromise due to tumor involvement, (2) as an indirect measure of tumor burden and (3) assessing prognosis. Immunophenotyping is undertaken with standard consensus panels and the pattern of staining with a series of monoclonal antibodies (MoAbs) associated with lineages and degree of maturation establishes an immunologic (CD) profile. Flow cytometry is often used to document clonality associated with lymphoid malignancies.

4. Chapter 34-04 What is the clinical significance of an enlarged lymph node?

a. Usually benign related to an infection b. Usually indicates lymphoma *c. Can be benign or malignant depending on the microscopic evaluation d. Diagnostic for an autoimmune disorder General Feedback: Lymphadenopathy can occur in either benign or malignant conditions.

5. Chapter 34-05 Which is true regarding the staging process of chronic lymphocytic leukemia? a. It pinpoints genetic mutations. b. It divides patient into healthy and unhealthy groups. c. It offers a solid prognosis. *d. It guides clinical management.

General Feedback: Staging systems are important prognostic determinants for CLL and are used to guide clinical management.

6. Chapter 34-06 A middle-aged man has a white blood cell (WBC) count of 80 × 109/L with 90% lymphocytes and many smudge cells. Which is most likely? *a. Chronic lymphocytic leukemia b. Hairy cell leukemia c. T cell lymphoma d. Sézary syndrome General Feedback: Chronic lymphocytic leukemia is characterized by the accumulation of small lymphoid cells in the peripheral blood with condensed chromatin pattern without a defined nucleolus. Smudge cells, representing disintegrated lymphoid cells, are also present. They are of diagnostic significance.

7. Chapter 34-07 Which are characteristics of monoclonal B cell lymphocytosis? a. Less than 5x109/L circulating B lymphocytes b. Absence of cytopenia c. No organomegaly *d. All of the options General Feedback: Patients who are asymptomatic, without any lymphadenopathy, organomegaly, cytopenias or systemic symptoms with less than 5x109/L circulating B lymphocytes are referred to as having monoclonal B cell lymphocytosis (MBL)(19).

8. Chapter 34-08 Where are malignant plasma cells found in multiple myeloma? *a. Bone marrow b. Lymph nodes c. Liver d. Spleen General Feedback: The malignant plasma cells in multiple myeloma are found in the bone marrow.

9. Chapter 34-09 Cells that are medium to large in size and have accentuated, convoluted nuclei, coarsely clumped chromatin and deeply basophilic cytoplasm are associated with: a. Reed-Sternberg lymphoma. b. mantle cell lymphoma. c. small-cell lymphoma. *d. adult cell leukemia lymphoma.

General Feedback: The prototypical ATLL cells are medium to large in size and have accentuated, convoluted nuclei, coarsely clumped chromatin and deeply basophilic cytoplasm. The term “flower cell” has been coined for this morphology.

10. Chapter 34-10 Which is true regarding classic Hodgkin lymphoma? *a. It is seen in young adults. b. It is seen in young children. c. It is seen in middle-aged adults. d. It is seen in older adults.

General Feedback: Hodgkin lymphoma occurs preferentially in young adults. It is one of the first tumor types cured with combination chemotherapy and therefore serves as a model for the evolution of therapeutics in modern oncology.

11. Chapter 34-11 What is the diagnostic cell, found in involved lymph nodes, for Hodgkin lymphoma? a. Small B lymphocyte b. Plasma cell c. Small T lymphocyte *d. Reed-Sternberg cell

General Feedback: Presence of the Reed-Sternberg cell is highly diagnostic of Hodgkin lymphoma when it is encountered in the appropriate background.

12. Chapter 34-12 Malignant proliferation of plasma cells in the bone marrow with osteolytic lesions describes: a. Waldenström macroglobulinemia. b. marginal zone B cell lymphoma. c. follicle center lymphoma. *d. multiple myeloma.

General Feedback: MM is a bone marrow-based disease with extramedullary extension to bone or soft tissue. Strict criteria are followed to establish the diagnosis of MM based on the overall tumor burden as reflected by percent of plasma cells in the bone marrow as well as the extent of systemic manifestations of disease such as such as hypercalcemia, renal failure, anemia and osteolytic lesions.

13. Chapter 34-13 Which are some of the B cell markers in chronic lymphocytic leukemia? a. CD4 and CD8 b. CD33 and CD45 *c. CD19 and CD20 d. CD33 and CD59 General Feedback: On immunophenotyping, CLL lymphocytes exhibit B cell markers CD19, CD20. and CD23 but also aberrantly co-express the T cell antigen CD5.

14. Chapter 34-14 Which is true of chronic lymphocytic leukemia cells? a. They are post-thymic T cells. b. They are large and pleomorphic. *c. They demonstrate surface immunoglobulin. d. They are CD4+ T cells General Feedback: Although CLL cells demonstrate surface immunoglobulin, the level of expression may be dim and the ability to discern light chain restriction indicating B cell clonality may be difficult. Antigen expression may be variable, not all cases fit into a classical CLL immunophenotypic profile.

15. Chapter 34-15 Mycosis fungoides is a disorder of which kind of cell? *a. T cell b. B cell c. Hairy cell d. Small cell General Feedback: Mycosis fungicides is a disorder of CD4+ T cells.

16. Chapter 34-16 The strongest risk factor for development of a lymphoproliferative disorder is: a. age 15 to 34 years. *b. altered immune function. c. female sex. d. cytomegalovirus infection in childhood.

General Feedback: Patients with altered immune function have the strongest risk factor for development of a lymphoproliferative disorder. This includes patients who are immunocompromised and those with autoimmune disease.

17. Chapter 34-17 Serum protein electrophoresis on an elderly patient reveals a monoclonal protein spike. Increased plasma cells are present in the bone marrow. They are CD19 and CD20 negative but demonstrate highdensity CD38 and monoclonal cytoplasmic immunoglobulin. What is the most likely diagnosis? *a. Multiple myeloma b. Hodgkin lymphoma c. Burkitt lymphoma d. Chronic lymphocytic leukemia General Feedback: Increased bone marrow plasma cells that are CD19 and CD20 negative but have high-density CD38 and monoclonal cytoplasmic immunoglobulin are characteristic of multiple myeloma. A monoclonal protein spike is present when serum electrophoresis is performed.

18. Chapter 34-18 Why are patients with multiple myeloma susceptible to infection? a. Decreased lymphocytes b. Neutropenia c. Suppressed normal immunoglobulin levels *d. Both Neutropenia and Suppressed normal immunoglobulin levels General Feedback:

As plasma cells multiply in the bone marrow, normal hematopoiesis, including granulopoiesis, is suppressed. This leads to neutropenia. In addition, normal immunoglobulin (antibodies) is suppressed. Together these contribute to the increased susceptibility to infection seen in these patients.

19. Chapter 34-19 What are the subtypes of Burkitt lymphoma? a. Endemic b. Sporadic c. HIV associated *d. All of the options General Feedback: Burkitt lymphoma has three subtypes—endemic, sporadic, and HIV associated. The endemic form is found primarily in childhood in equatorial Africa along a geographic distribution similar to malaria.

20. Chapter 34-20 What lymphoproliferative disorder has a very favorable response to highly aggressive chemotherapy with no radiotherapy? a. Chronic lymphocytic leukemia b. Mycosis fungoides c. Hodgkin lymphoma *d. Burkitt lymphoma General Feedback: Burkitt lymphoma has a very favorable response rate to aggressive chemotherapy, primarily because most of the cells are in an active phase of the cell cycle at any one time. Cure rates are 60% to 90%, depending on the stage of the disease.

1. Chapter 35-01 Which is part of primary hemostasis? a. Fibrinolysis *b. Blood vessels c. Intrinsic system d. Inhibitors General Feedback: Blood vessels and platelets are important in primary hemostasis, where they play roles in forming the primary hemostatic plug.

2. Chapter 35-02 What are the primary procoagulant roles of the blood vessel? *a. Constrict and provide collagen and other compounds to activate clotting. b. Prevent the blood from escaping and promote fibrinolysis. c. Secrete platelet growth factors and manufacture calcium. d. Constrict and synthesize most plasma coagulation factors.

General Feedback: Blood vessels play a role in constriction of the vessel once it has been damaged. Collagen is located in the subendothelial tissue and is exposed once a vessel is damaged. They also provide other compounds, such as von Willebrand factor (VWF), which is necessary for platelet adhesion.

3. Chapter 35-03 Which aids in preventing excess clotting? a. Thrombin b. Factor VII c. Nitric oxide *d. Protein C General Feedback: The protein C pathway helps regulate the coagulation mechanism by digesting activated coagulation factors V and VIII. Thrombin is the activated form of prothrombin; it plays a number of roles in promoting coagulation, including the splitting of fibrinogen to form fibrin.

Nitric oxide counteracts vasoconstriction.

4. Chapter 35-04 Which is necessary for platelet aggregation? a. Protein S b. Kallikrein c. Vitamin K *d. Fibrinogen General Feedback:

Platelet aggregation, the binding of platelets to one another, requires fibrinogen.

5. Chapter 35-05 Where are most of the plasma procoagulant proteins produced? *a. Liver b. Megakaryocytes c. Endothelial cells d. Spleen General Feedback: Most of the procoagulant proteins found in plasma are synthesized in the liver.

6. Chapter 35-06 Which is true regarding the plasma coagulation zymogens? a. Circulate normally in their active form. *b. Are serine proteases that form complexes to activate other zymogens to ultimately generate thrombin. c. Activation normally occurs throughout the body when vascular injury occurs. d. Are cofactors that induce peptide bonding to make larger active molecules.

General Feedback: Zymogens are the inactive forms of the procoagulant enzymes.

They are serine proteases that form complexes to activate other zymogens. The end result of this process is to generate thrombin.

7. Chapter 35-07 What happens to the fibrin monomers created when thrombin cleaves fibrinopeptides A and B from fibrinogen? a. Immediately inactivated to prevent excess clotting b. Converted to plasminogen c. Digested quickly by tissue plasminogen activator (TPA) *d. Polymerized and are stabilized by factor XIIIa General Feedback: Once thrombin splits fibrinopeptides A and B from fibrinogen, the fibrin monomers are formed. These spontaneously polymerize to form the initial soluble fibrin polymer, which is cross-linked by XIIIa and then becomes insoluble. Fibrin monomers spontaneously polymerize to form the fibrin clot, which is then stabilized by factor XIIIa. TPA activates plasminogen to plasmin, which lyses the clot.

8. Chapter 35-08 On what does factor VIII depend for stability?

*a. VWF b. Platelets c. Thrombin d. Protein S General Feedback: Factor VIII circulates bound to VWF. Free factor VIII is unstable in plasma, so much so that it cannot even be detected.

9. Chapter 35-09 Patients who have a deficiency of protein C or protein S have which type of disorder? a. Bleeding disorder *b. Thrombotic disorder c. Bruising disorder d. Hypercalcemia General Feedback: Patients with a deficiency of either protein C or protein S have a thrombotic disorder. These two proteins are important in regulating, by downgrading, thrombin generation and thus clotting.

Activated protein C binds free protein S to form a complex that inactivates factors Va and VIIIa.

10. Chapter 35-10 Oral anticoagulation is based on: a. increasing plasminogen. b. activating plasmin. c. combining with antithrombin. *d. vitamin K antagonism.

General Feedback: Vitamin K antagonism is the basis for oral anticoagulation.

11. Chapter 35-11 Which are components of the contact group of factors? a. Fibrinogen and thrombin b. VIII and VWF *c. XII and prekallikrein d. Calcium and IX General Feedback: The contact factors include factor XII, prekallikrein (Fletcher factor), and high-molecular-weight kininogen (Fitzgerald factor).

12. Chapter 35-12 Which is the most important protease of the coagulation pathway because of its role in so many different catalytic functions? *a. Thrombin b. Factor XIa c. Plasmin d. Factor VIIa General Feedback: Thrombin is considered the most important protease of the coagulation pathway because of its multiple functions. These include splitting fibrinogen to form fibrin monomers; activating the cofactors V and VIII; activating factor XIII; binding to thrombomodulin to activate protein C; and aggregating platelets, to name just a few.

13. Chapter 35-13 What is the role of the thrombin-thrombomodulin complex? a. Initiates vasoconstriction. b. Activates thrombin. c. Inhibits factor Xa. *d. Activates protein C. General Feedback: Thrombin binds the endothelial cell membrane protein thrombomodulin, and the complex then activates protein C. Activated protein C complexes with protein S, and the complex degrades factors Va and VIIIa, which downregulates thrombin generation.

14. Chapter 35-14 What protein does heparin work with to inhibit coagulation? a. Protein S *b. Antithrombin c. Vitamin K d. Factor VII General Feedback: Heparin binds to antithrombin, thus bringing thrombin in close proximity to antithrombin. It also changes the configuration of antithrombin so that it can effectively bind thrombin. The thrombinantithrombin complex renders thrombin inactive; the complex is taken to the liver and cleared.

15. Chapter 35-15 What substance digests the fibrin clot after healing? *a. Plasmin b. Activated protein C c. TPA d. alpha2-antiplasmin

General Feedback: Plasmin is the active form of the zymogen plasminogen. Plasmin systematically digests (i.e., degrades, lyses) the fibrin clot after healing.

16. Chapter 35-16 Which therapy actually lyses the clot rather than prevents future clots? a. Aspirin b. Heparin *c. TPA d. Coumadin General Feedback: TPA is normally released from endothelial cells and activates plasminogen, which then gradually lyses the fibrin clot. TPA is used therapeutically to lyse pathologic clots in thrombotic disease. Aspirin inhibits platelet function, heparin binds to antithrombin to inhibit thrombin, and Coumadin interferes with normal synthesis of the vitamin K–dependent proteins.

17. Chapter 35-17 Absence of D dimers is useful for ruling out: *a. thromboembolism. b. von Willebrand disease (vWD). c. protein C deficiency. d. factor VII deficiency.

General Feedback: The D dimer is a specific marker for thrombosis; when the assay is negative, it is useful for ruling out thromboembolism.

18. Chapter 35-18 All are functions of thrombin except: a. activates factors V and VIII. *b. activates plasminogen. c. activates factor XIII. d. initiates platelet aggregation.

General Feedback: Thrombin does not activate plasminogen. It does perform all of the other functions listed.

19. Chapter 35-19 What role do cofactors play in the procoagulant process? a. Bind fibrinolytic factors to slow down lysis of the clot.

b. Bind Ca2+ to form a bridge with platelet phospholipids. *c. Bind to their specific activated serine protease to stabilize the protease and increase its activity. d. Bind to collagen to aid in platelet adhesion.

General Feedback: Cofactors bind to their specific activated serine protease to stabilize the protease and increase its activity. One example is the binding of the cofactor Va to factor Xa, which then magnifies the activity of factor Xa to activate prothrombin.

20. Chapter 35-20 What plasma protein is important for normal wound healing and stabilization of the fibrin clot? a. Tissue factor b. Prothrombin c. Factor Xa *d. Factor XIIIa General Feedback: Factor XIIIa stabilizes the fibrin polymer and is essential for normal wound healing, as well as tissue integrity.

21. Chapter 35-21 What vitamin is essential for normal synthesis of prothrombin group proteins, thus enabling them to bind Ca2+? *a. Vitamin K b. Vitamin B12 c. Vitamin C d. Vitamin D General Feedback: Vitamin K is necessary for carboxylation of glutamic acid residues on the precursor prothrombin group proteins. This carboxylation enables these proteins to bind Ca2+.

22. Chapter 35-22 What substance is known to inactivate arachidonic acid, causing impairment of platelet function? *a. Aspirin b. Calcium c. Tylenol d. Vitamin K General Feedback: Aspirin inactivates the enzyme cyclooxygenase, blocking thromboxane A2 production and causing impairment of platelet function

(called aspirin effect). Thromboxane A2 causes Ca+2 to be released and promotes platelet aggregation and vasoconstriction.

1. Chapter 36-01 Two children in the same family have recurrent, chronic bruising in multiple sites, repeated long-lasting epistaxis, and minor bleeding after dental work. Which type of disorder is most likely? a. Localized, acquired, anatomic b. Localized, congenital, anatomic *c. Generalized, congenital, systemic d. Generalized, acquired, systemic General Feedback: Because the two affected children are in the same family, this is most likely congenital. Recurrent, chronic bruising in multiple sites, along with long-lasting epistaxis and minor bleeding after dental work, make this generalized and systemic rather than localized and anatomic.

2. Chapter 36-02 Which is appropriate initial testing for the siblings in Question 1? a. Fibrinogen, D-dimer, and platelet aggregation studies b. Factor VIII assay, liver function tests, and vitamin K level c. von Willebrand factor (VWF) antigen, Bethesda titer, and reptilase time *d. Prothrombin time (PT), partial thromboplastin time (PTT), and platelet count General Feedback: The initial hemostasis profile should consist of the PT, PTT, and platelet count.

3. Chapter 36-03 What is the possible mechanism for bleeding in patients with severe liver disease? a. Thrombocytopenia b. Inadequate production of procoagulants c. Disseminated intravascular coagulation (DIC) *d. All of the options General Feedback: All of the findings listed are possible causes for bleeding in patients with severe liver disease.

4. Chapter 36-04 Which is decreased in DIC? *a. Fibrinogen b. PT c. PTT d. Fibrin degradation products General Feedback:

Fibrinogen is decreased in DIC. The PT and PTT are both increased (prolonged), whereas fibrin degradation products are increased.

5. Chapter 36-05 The bleeding associated with renal disease is related most to defective: a. blood vessels. b. plasma procoagulants. *c. platelets. d. inhibitors.

General Feedback: Platelet dysfunction is the primary cause for prolonged bleeding in patients with renal failure.

6. Chapter 36-06 Which patient group is most susceptible to bleeding because of a deficiency of vitamin K–dependent proteins? a. Those with poor diets b. Those on antibiotic agents c. Pregnant women *d. Newborns General Feedback: Newborns are the most susceptible to vitamin K protein deficiency because the levels of the vitamin K–dependent proteins at birth are significantly lower than those for adults, and they drop even further the first few days of life. Breastfeeding prolongs the deficiency because passively acquired maternal antibodies delay establishment of the gut flora.

7. Chapter 36-07 Clot-based mixing studies and Bethesda titers are used to test for: a. vitamin K deficiency. *b. inhibitors (antibodies) against coagulation factors. c. DIC. d. hemophilia.

General Feedback: An inhibitor against a coagulation protein is confirmed using clot-based mixing studies. The Bethesda titer is then performed to determine the concentration of the inhibitor.

8. Chapter 36-08 What are the primary roles of VWF?

*a. Mediates platelet adhesion and carrier molecule for factor VIII. b. Mediates platelet aggregation and carrier molecule for factor IX. c. Inhibits excess coagulation and activates protein C. d. Activates plasmin and enhances vitamin K factors.

General Feedback: VWF is required for normal platelet adhesion; it is also the carrier protein for factor VIII, protecting it from proteolysis and thus prolonging the in vivo half-life from just a few minutes (in the absence of VWF) to 8 to 12 hours.

9. Chapter 36-09 Which is the most common form of von Willebrand disease (VWD)? *a. Type 1 b. Type 2A c. Type 3 d. Acquired General Feedback: Type 1 VWD is seen in more than 70% of patients with VWD.

10. Chapter 36-10 A 21-year-old woman has a primary complaint of menorrhagia. Her coagulation screen gives the following results.

Test Test Result Reference range Prothrombin time 12.0 seconds 11–15 seconds (PT) Partial 40 seconds 25–37 seconds thromboplastin time (PTT) Factor VIII 35% 50%–150% activity Platelet count 225 × 109/L 150–400 × 109/L

What disorder is most likely? a. Hemophilia A b. Hemophilia B *c. VWD, type 1 d. Factor X deficiency General Feedback: VWD is the most prevalent of the congenital bleeding disorders, affecting both female and male subjects; hemophilia A and B both affect primarily male subjects. Female patients with VWD often complain of menorrhagia. Most patients with VWD have factor VIII levels in the range of 35% to 50%.

11. Chapter 36-11 Desmopressin acetate (DDAVP) is used to treat: a. dysfibrinogenemia. b. warfarin overdose. c. vitamin K deficiency. *d. VWD, type 1.

General Feedback: DDAVP, which triggers the release of VWF from storage organelles, is used to treat type 1 VWD. It is also useful in type 2A, but it is contraindicated in type 2B.

12. Chapter 36-12 Which single-factor inherited deficiencies are most common as the cause for hemophilia? a. Factor V *b. Factor VIII c. Factor IX d. Factor XI General Feedback: Eighty-five percent of congenital single-factor deficiencies are of factor VIII. This results in hemophilia A.

13. Chapter 36-13 What is common in patients with severe hemophilia A? a. Generalized bleeding after trauma or dental work b. Generalized hemorrhage c. Major bruising on extremities and chronic nosebleeds *d. Serious anatomic bleeds into joints General Feedback: Hemophilia A causes anatomic bleeds, including deep muscle and joint bleeds. Major bruising is associated with platelet abnormalities.

14. Chapter 36-14 Which test is increased in a patient with severe hemophilia A? *a. PTT b. Thrombin time (TT) c. PT d. Factor VIII assay General Feedback: The PTT is increased (prolonged) in patients with severe hemophilia A because of a significant decrease in factor VIII. The PT and TT are both normal.

15. Chapter 36-15 What test is useful for detection of a female carrier of hemophilia A? a. PTT b. PT *c. Factor VIII to VWF ratio d. VWF antigen test General Feedback: Approximately 90% of female carriers of hemophilia A are detected using the ratio of factor VIII activity to VWF antigen. This is because VWF production is unaffected by factor VIII deficiency, so it should be normal in a female hemophilia A carrier, whereas the factor VIII activity will be less than that of VWF. Thus a discrepancy exists in the concentration of these two proteins.

16. Chapter 36-16 What is the purest form of factor VIII that is available for treating a bleeding patient with hemophilia A? a. Cryoprecipitate *b. Recombinant factor VIII concentrate c. Fresh frozen plasma d. Factor VIII concentrate prepared by chemical concentration General Feedback: Recombinant deoxyribonucleic acid (DNA) technology provides a high-purity factor VIII concentrate.

17. Chapter 36-17 What is the best test to distinguish hemophilia A from B or C? *a. Specific factor assays b. PTT c. TT d. Bleeding time General Feedback: Hemophilia A (factor VIII deficiency), hemophilia B (factor IX deficiency), and hemophilia C (factor XI deficiency) are differentiated from one another using specific factor assays.

18. Chapter 36-18 In which substance is a patient with the following coagulation test results most likely deficient?

Test Test Result Reference Range Prothrombin time 17 seconds 11–15 seconds (PT) Partial 31 seconds 25–37 seconds thromboplastin time (PTT)

Thrombin time (TT) 16 seconds

15–21 seconds

a. Fibrinogen *b. Factor VII c. Factor VIII d. Factor X General Feedback: Factor VII deficiency shows a prolonged PT with a normal PTT result. A deficiency of fibrinogen ideally should prolong the PT, PTT, and TT. Factor VIII deficiency prolongs the PTT but not the PT and TT, whereas a factor X deficiency should prolong both the PT and PTT but not the TT.

19. Chapter 36-19 The urea solubility test is used to detect deficiencies in which factor? a. Fibrinogen b. Factor V c. Factor XII *d. Factor XIII General Feedback: The plasma from patients with a factor XIII deficiency forms weak clots that dissolve within 2 hours when suspended in a 5M urea solution because the clot has not been cross-linked by XIIIa.

20. Chapter 36-20 What coagulation screening test is the most sensitive for detecting mild liver disease? a. Fibrinogen b. PTT *c. PT d. TT General Feedback: Liver disease particularly affects production of the vitamin K–dependent proteins. Because the PT is sensitive to factor VII activity and it (factor VII) has a short half-life of 3 to 5 hours, the PT is the most sensitive for detecting mild liver disease.

21. Chapter 36-21 Which protein is the best test to distinguish moderate to severe liver disease from vitamin K deficiency? *a. Factor V concentration b. Factor VII concentration c. Factor VIII concentration d. Factor IX concentration

General Feedback: Factor V is not vitamin K dependent, but it is produced in the liver, so it is decreased in moderate to severe liver disease. Factors VII and IX are both vitamin K dependent, so they are decreased in both liver disease and vitamin K deficiency. Factor VIII is not decreased in either liver disease or vitamin K deficiency; in fact, because it is an acute phase reactant, it may actually be elevated in mild to moderate liver disease.

22. Chapter 36-22 A 67-year-old woman arrives at the emergency department with acute bleeding into the back of the throat. A coagulation screen is ordered with the following results: 1:1 Mix With Reference Test Result Normal Range Plasma Prothrombin 12 11–15 time (PT) seconds seconds Partial 36 seconds 57 25–37 thromboplastin seconds seconds (immediate) time (PTT) Fibrinogen 450 mg/dL 150–400 mg/dL What would be a reasonable next step to perform? a. Perform factor IX assay. b. Perform factor VII assay. *c. Incubate the 1:1 mix at 37°C for 1 hour. d. Perform TT. General Feedback: Factor VIII autoantibodies are usually time and temperature dependent. Thus the 1:1 mix must be incubated at 37°C for 1 to 2 hours to give the antibody time to react with the factor VIII added by the normal plasma. Prolongation of the PTT on this incubated 1:1 mix indicates that an antibody to VIII is present. A factor VIII assay, when performed, will show a low factor VIII (less than 30%).

23. Chapter 36-23 What procedure is used to quantitate a factor VIII inhibitor? *a. Bethesda assay b. Reptilase time c. Factor VIII concentration d. VWF assay General Feedback: The Bethesda assay is used to quantitate a factor VIII inhibitor.

24. Chapter 36-24 All can mask a deficiency of VWF and thus of type 1 VWD except: *a. fibrinogen levels. b. pregnancy. c. acute stress. d. type ABO blood group.

General Feedback: The concentration of VWF is low in VWD, type 1. VWF is an acute-phase reactant and is thus elevated in acute stress. Higher estrogen levels during pregnancy also elevate VWF. Individuals with type ABO blood type have higher levels of VWF. All these can thus mask VWD.

25. Chapter 36-25 Which type of VWD gives a positive response to low-dose ristocetininduced platelet aggregation? a. 1 b. 2A *c. 2B d. 2N General Feedback: The low-dose ristocetin-induced platelet aggregometry identifies VWD, subtype 2B.

26. Chapter 36-26 A 39-year-old male patient shows evidence of poor wound healing and a history of joint bleeding. What protein deficiency is most likely present? a. Factor VIII b. Factor IX c. Factor V *d. Factor XIII General Feedback: Patients with a deficiency of factor XIII have evidence of poor wound healing and anatomic bleeds.

27. Chapter 36-27 Which screening test would be normal when the plasma for the patient in Question 26 is analyzed? a. PT b. PTT c. TT *d. All of the options General Feedback:

The PT, PTT, and TT are all normal in a patient with factor XIII deficiency. Factor XIII deficiency is evaluated by placing the clot in 5M urea; the uncross-linked clot is weak and dissolves within 2 hours in this solution.

1. Chapter 37-01 The qualitative platelet disorders and vascular disorders typically exhibit what type of symptoms? *a. Superficial bleeding b. Deep tissue bleeding c. Hemarthrosis d. Thrombosis General Feedback: Superficial bleeding, including petechiae, epistaxis (nose bleeds), and gingival (gum) bleeding, is characteristic of qualitative bleeding disorders.

2. Chapter 37-02 Which is an autosomal recessive disorder in which the GP Ib/IXI/V complex is missing from the platelet surface? a. von Willebrand disorder (VWD) *b. Bernard-Soulier syndrome c. Glanzmann thrombasthenia d. Dense granule deficiency General Feedback: Bernard-Soulier syndrome is inherited as an autosomal recessive disorder in which the GP Ib/IX/V complex is missing from the platelet surface or exhibits abnormal function. Inability to bind to VWF accounts for the inability of platelets to adhere to exposed subendothelium and the resultant bleeding characteristic of this disorder.

3. Chapter 37-03 Which is the most likely diagnosis for an infant who experiences bleeding after circumcision with epistaxis and gingival bleeding? a. Aspirin ingestion b. Gray platelet syndrome c. Vitamin C deficiency *d. Glanzmann thrombasthenia General Feedback: Glad Glanzman thombobasthenia is a rare disorder which manifests itself clinically in the neonatal period or infancy, occasionally with bleeding after circumcision and frequently with epistaxis and gingival bleeding. Hemorrhagic manifestations include petechiae, purpura, menorrhagia, gastrointestinal bleeding, and hematuria.

4. Chapter 37-04 Which is the most common cause of acquired platelet dysfunction? a. Myeloproliferative disorders b. Wiskott-Aldrich syndrome

*c. Drugs, especially aspirin d. Afibrinogenemia General Feedback: Aspirin and other drugs are the most common causes of acquired platelet dysfunction.

5. Chapter 37-05 Which is normal in a patient regularly taking aspirin? a. Platelet aggregation b. Platelet cyclooxygenase function c. Synthesis of thromboxane A2 *d. Platelet count General Feedback: Only the platelet count, of those evaluations listed, is normal in a patient who regularly takes aspirin. Aspirin acetylates cyclooxygenase, which is necessary for the synthesis of thromboxane A2.

6. Chapter 37-06 What types of hemostatic complications are found in patients with myeloproliferative disorders? a. Hemorrhagic b. Thrombotic c. Abnormal platelet function *d. All of the options General Feedback: Patients with one of the chronic myeloproliferative disorders, such as polycythemia vera and essential thrombocythemia, may have abnormal platelet function; clinically, they may result in either abnormal bleeding or abnormal thrombosis. Some patients develop both, although this is rare.

7. Chapter 37-07 What is the mechanism for the platelet dysfunction in multiple myeloma and Waldenström macroglobulinemia? a. Granules become deficient. *b. Platelets are coated with paraprotein. c. Nitric oxide is not produced. d. Cyclooxygenase is acetylated.

General Feedback: Platelet dysfunction results from coating of the platelet membranes by paraprotein and does not depend on the type of paraprotein present. In addition to interacting with platelets, the paraprotein likely interferes with fibrin polymerization and the function of other coagulation proteins.

8. Chapter 37-08 All are common conditions or situations that interfere with platelet function except: a. liver disease. b. uremia. *c. allergic purpura. d. cardiopulmonary bypass surgery.

General Feedback: Allergic purpura does not interfere with platelet function.

All of the other listed conditions or situations can affect platelet function.

9. Chapter 37-09 Which is true regarding testing for the diagnosis of vascular disorders? *a. Most do not have abnormal clinical laboratory tests. b. The platelet count and aggregometry are useful. c. The prothrombin time (PT) and partial thromboplastin time (PTT) are most useful. d. Evaluation of von Willebrand factor (VWF) is useful.

General Feedback: Clinical laboratory tests are not available for evaluation and diagnosis of vascular disorders. Ruling out other sources of bleeding disorders often makes the diagnosis. The usual clinical signs are easy bruising and spontaneous bleeding, especially from mucosal surfaces. In that respect they are similar to platelet dysfunction disorders.

10. Chapter 37-10 A 78-year-old patient recently noticed dark blotches on his forearms and on the backs of his hands. He seems to bruise even when a phlebotomy is performed using excellent technique with no problems encountered. No other symptoms exist, and all laboratory tests are normal. Which is the most likely diagnosis? a. Hereditary hemorrhagic telangiectasia b. Ehlers-Danlos syndrome c. Paraproteinemia and amyloidosis *d. Senile purpura General Feedback: Senile purpura is the most likely diagnosis for this 78-yearold man who only recently began to notice abnormal bruising and/or bleeding. The hereditary abnormalities would have presented earlier in life. Paraproteinemia and amyloidosis would demonstrate other abnormal clinical laboratory testing.

11. Chapter 37-11 Platelet count and function studies are performed on a patient with a history of easy bruising, and the following results are obtained: Test Result Platelet count 295 × 109/L Platelet function assay Prolonged Platelet aggregation Primary but no with epinephrine secondary wave Platelet aggregation Primary but no with low-dose adenosine secondary wave diphosphate (ADP) Platelet aggregation Normal with ristocetin What is the most likely diagnosis for this patient? a. Bernard-Soulier disease *b. Dense granule deficiency c. Glanzmann thrombasthenia d. Gray platelet syndrome General Feedback: The platelet count on this patient is normal; however, the platelet function assay is abnormal, which suggests platelet dysfunction. Of the disorders listed, only dense granule deficiency has the platelet aggregation results that are listed. Patients with Bernard-Soulier disease have normal aggregation studies with every agonist except ristocetin, which is abnormal. The reverse is true for Glanzmann thrombasthenia—they have normal aggregation with ristocetin but have no primary wave, as well as no secondary wave with other agonists. Patients with gray platelet syndrome have a moderate thrombocytopenia, prolonged bleeding time, and large platelets that appear gray on a Wright-stained blood film because of the absence of alpha-granules. Platelet aggregation studies are unremarkable.

12. Chapter 37-12 Clopidogrel (Plavix) is a drug used therapeutically for patients with a risk of arterial thrombi because it: a. inhibits thrombin. b. activates the protein C pathway. *c. inhibits platelet function. d. activates plasminogen.

General Feedback: Clopidogrel is an antiplatelet function drug used for three reasons: (1) to treat patients with arterial occlusive disease; (2) for prevention of myocardial infarction; and (3) to decrease the risk of thrombotic stroke in patients with cerebrovascular disease and in patients who are intolerant of aspirin.

1. Chapter 38-01 What is the correct term to describe a platelet count of 550 × 109/L when all other complete blood count (CBC) results are basically normal? a. Normal *b. Thrombocytosis c. Thrombocytopenia d. Essential thrombocythemia General Feedback: This platelet count is elevated, so the correct terminology to describe it is thrombocytosis; this is most probably a reactive thrombocytosis. Platelets are also elevated in essential thrombocythemia, but they usually exceed 1 million/mL (1000 × 109/L), and other abnormalities would also be seen in the CBC.

2. Chapter 38-02 Chemotherapy results in which condition? *a. Acquired thrombocytopenia b. Inherited thrombocytopenia c. Acquired splenic sequestration d. Inherited thrombocythemia General Feedback: Wide arrays of chemotherapeutic agents used for the treatment of hematologic and nonhematologic malignancies suppress bone marrow megakaryocyte production and the production of other hematopoietic cells. Drug-induced thrombocytopenia is often the dose-limiting factor for many chemotherapeutic agents.

3. Chapter 38-03 What is the single most common cause of clinically important bleeding? a. Hemophilia b. Fibrinogen deficiency *c. Thrombocytopenia d. Qualitative platelet disorders General Feedback: The single most common cause of clinically important bleeding is thrombocytopenia with a platelet count less than 100 × 109/L.

4. Chapter 38-04 Which results in ineffective thrombopoiesis? a. Immune thrombocytopenic purpura b. Thrombotic thrombocytopenic purpura c. Disseminated intravascular coagulation (DIC) *d. Megaloblastic anemia General Feedback:

Thrombocytopenia because of ineffective thrombopoiesis is one of the usual features of megaloblastic anemias. Vitamin B12 and folic acid are both required for normal maturation of megakaryocytes in the bone marrow.

5. Chapter 38-05 A 28-year-old woman sees her family physician complaining of easy bruising and menorrhagia. She has a platelet count of 60 × 109/L. All other hematology and routine coagulation tests are normal. She has a platelet-associated immunoglobulin G (IgG) autoantibody in her serum.

Which is most likely? *a. Chronic immune thrombocytopenic purpura b. Thrombotic thrombocytopenic purpura c. Acute immune thrombocytopenic purpura d. Hemolytic uremic syndrome General Feedback: Chronic immune thrombocytopenic purpura is most often seen in women between the ages of 20 and 50 years of age. Patients most often complain of easy bruising, recurrent epistaxis, and menorrhagia.

Platelet destruction in chronic immune thrombocytopenic purpura is the result of an IgG autoantibody, with various membrane glycoproteins being the most frequent targets.

6. Chapter 38-06 Which patient group is most commonly diagnosed with acute immune thrombocytopenic purpura? a. Older men after an infection b. Infants born to women who had eclampsia *c. Children after having an infection d. Adult patients with enlarged spleens General Feedback: Acute immune thrombocytopenic purpura is primarily a disorder of children. It frequently occurs 1 to 3 weeks after an infection.

7. Chapter 38-07 Which is a commonly used drug that can cause thrombocytopenia? a. Warfarin b. Aspirin c. Ibuprofen *d. Heparin General Feedback: Heparin is associated with drug-induced thrombocytopenia; this is called heparin-induced thrombocytopenia, and it can have serious thrombotic complications. Warfarin does not affect the platelet count.

Aspirin and ibuprofen both affect platelet function.

8. Chapter 38-08 What kind of antibody causes neonatal alloimmune thrombocytopenia? *a. Maternal antibody against a fetal platelet antigen inherited from the father b. Fetal antibody directed against maternal platelet antigen c. Fetal antibody against a fetal platelet antigen inherited from the father d. Maternal autoantibody against a mother’s platelet antigen General Feedback: Neonatal alloimmune thrombocytopenia develops when a mother develops an alloantibody against a platelet antigen inherited by the fetus from the father. These antibodies cross the placenta, bind to the antigen-bearing fetal platelets, and cause their premature destruction.

9. Chapter 38-09 A 35-year-old woman with neurologic symptoms presents with a markedly decreased platelet count. She has moderate anemia with many red cell fragments on the blood film, as well as polychromasia and nucleated red blood cells (RBCs). The prothrombin time (PT) and partial thromboplastin time (PTT) are both normal. Which is the most likely diagnosis? a. Immune thrombocytopenic purpura *b. Thrombotic thrombocytopenic purpura c. Hemolytic uremic syndrome d. DIC General Feedback: Thrombotic thrombocytopenic purpura is characterized by thrombocytopenia, a microangiopathic hemolytic anemia with schistocytes (red cell fragments), and neurologic abnormalities. It is most common in women 30 to 40 years of age.

10. Chapter 38-10 A 4-year-old child becomes very sick after drinking contaminated water.

Kidney function tests are markedly elevated. Thrombocytopenia is mild, and a few schistocytes are noted on the blood film. Which is most likely the diagnosis? a. Immune thrombocytopenic purpura b. Thrombotic thrombocytopenic purpura *c. Hemolytic uremic syndrome d. DIC General Feedback: Hemolytic uremic syndrome is found primarily in children between the ages of 6 months to 4 years. In outbreaks of HUS associated with consumption of E. coli–contaminated water, both children and adults have developed HUS.

11. Chapter 38-11 Which is successfully treated with therapeutic plasma exchange? a. Immune thrombocytopenic purpura b. Chronic DIC c. Acute DIC *d. Thrombotic thrombocytopenic purpura General Feedback: The most effective treatment for thrombotic thrombocytopenic purpura is therapeutic plasma exchange using fresh frozen plasma.

Dramatic effects may be seen within just a few hours.

12. Chapter 38-12 A patient in the intensive care unit has anemia, schistocytes, and thrombocytopenia. The PT and PTT are elevated, and the fibrinogen is low. What diagnostic test should be used? *a. D dimer to confirm acute DIC b. Bone marrow to confirm immune thrombocytopenic purpura c. Platelet antibody against P1A1 to confirm heparin-induced thrombocytopenia d. Platelet aggregometry to confirm posttransfusion purpura General Feedback: In acute DIC, the D dimer is elevated, along with the other laboratory findings listed. None of the other conditions listed have the prolonged PT and PTT, low fibrinogen, and elevated D dimers.

13. Chapter 38-13 Which is an example of a quantitative platelet disorder related to distribution? a. Thrombotic cytopenic purpura b. Essential thrombocythemia *c. Splenomegaly d. Hemolytic uremic syndrome General Feedback: An abnormal distribution of platelets may cause thrombocytopenia. The spleen sequesters approximately one-third of the total platelet mass. When the spleen is enlarged (splenomegaly), most platelets are sequestered in the enlarged spleen, resulting in a lower venous blood count.

14. Chapter 38-14 Which factor does the Coppo score consider in thrombotic thrombocytopenic purpura? a. Creatinine levels b. Platelets counts c. Antinuclear antibodies

*d. All of the options General Feedback: The score described by Coppo, which considers creatinine levels, platelet counts, and the presence of antinuclear antibodies, offers high positive predictive values and specificity, but low sensitivity in TTP.

15. Chapter 38-15 A patient has a platelet count of 650 × 109/L. The other hematology tests are normal. No evidence of hemostasis failure exists. Which is most likely? *a. Reactive thrombocytosis b. Essential thrombocythemia c. DIC d. Polycythemia vera General Feedback: The term reactive thrombocytosis refers to an abnormally high platelet count, typically more than 450 × 109/L, secondary to inflammation, trauma, or some other underlying and seemingly unrelated conditions. The platelet count does not usually exceed 800 × 109/L, and the elevation is transient.

16. Chapter 38-16 All are often associated with thrombocytosis except: a. hemorrhage. *b. alcoholic liver disease. c. iron deficiency. d. inflammation.

General Feedback: The only condition listed that is not associated with reactive thrombocytosis is alcoholic liver disease.

17. Chapter 38-17 A 23-year-old man is brought by helicopter to a major trauma center after a severe motorcycle accident. He has major abdominal trauma, including a ruptured spleen, and is taken to surgery, where his spleen is removed. Two weeks after surgery, his platelet count peaks at 950 × 109/L. What is the most likely cause for this high platelet count? a. Reactive thrombocytosis secondary to trauma b. Essential thrombocythemia *c. Postsplenectomy thrombocytosis d. Reactive thrombocytosis secondary to acute blood loss General Feedback:

Removal of the spleen characteristically results in a thrombocytosis that can reach or even exceed 1000 × 109/L (1 million/mL). The platelet count usually peaks 1 to 3 weeks after surgery and generally remains elevated for 1 to 3 months. Platelet counts generally are not this elevated in reactive thrombocytosis, and they do not peak 2 to 3 weeks after surgery.

18. Chapter 38-18 The terms petechiae, purpura, and ecchymoses all describe: a. varying degrees of thrombocytopenia. b. varying degrees of thrombocythemia. c. varying qualitative platelet disorders. *d. varying size hemorrhages into the skin because of smallvessel bleeding.

General Feedback: These terms all refer to small-vessel bleeding into the skin that is caused by thrombocytopenia or many of the qualitative platelet disorders. Petechiae are small pinpoint hemorrhages, purpura are about 1 cm in diameter, whereas ecchymoses are 3 cm or larger.

19. Chapter 38-19 What is the most common infectious cause of congenital neonatal megakaryocytic hypoplasia? a. Epstein-Barr virus b. Human immunodeficiency virus (HIV) *c. Cytomegalovirus d. Rubella General Feedback: Cytomegalovirus is the most common infectious agent causing congenital neonatal megakaryocytic hypoplasia. Cytomegalovirus appears to inhibit megakaryocytes and their precursors, resulting in impaired platelet production.

20. Chapter 38-20 What is believed to be the cause for acute immune thrombocytopenia purpura in children? a. Development of a platelet-specific autoantibody b. Development of a white cell autoantibody that cross-reacts with platelet membrane antigens c. Development of an allogeneic antibody after transfusion of random allogeneic platelets *d. Nonspecific binding of immune complexes to the platelet membrane after a viral illness General Feedback: Acute immune thrombocytopenia purpura in children often follows a viral illness. This suggests that some children produce

antibodies and immune complexes against viral antigens and that platelet destruction may result from their binding to the platelet membrane.

21. Chapter 38-21 What is the most serious clinical consequence of heparin-induced thrombocytopenia? a. Hemorrhage *b. Thrombosis c. Factor XII activation d. Resistance to aspirin therapy General Feedback: Patients with heparin-induced thrombocytopenia develop thrombotic problems. Patients who develop heparin-induced thrombocytopenia should be removed from heparin therapy as soon as the diagnosis is made, because continued heparin therapy can lead to significant morbidity and mortality. After discontinuation of heparin, the platelet count begins to rise and should return to normal within a few days.

22. Chapter 38-22 Binding of therapeutic heparin to platelet factor 4 is used in testing to confirm: *a. heparin-induced thrombocytopenia. b. acute immune thrombocytopenic purpura. c. chronic immune thrombocytopenic purpura. d. aspirin resistance.

General Feedback: Heparin-induced thrombocytopenia (HIT) is a good example of immune complex-induced thrombocytopenia, the fourth mechanism of druginduced thrombocytopenia. Binding of therapeutic heparin to platelet factor 4 (PF4), a protein released by activated platelets, or binding of PF4 to the platelet membrane causes a conformational change in PF4, resulting in the exposure of neoepitopes.

23. Chapter 38-23 What is the probable cause for thrombotic thrombocytopenic purpura? *a. Deficiency of a metalloprotease needed to enzymatically degrade unusually large von Willebrand factor (VWF) multimers b. Abnormal synthesis of unusually large VWF multimers by endothelial cells c. Abnormal synthesis of unusually large VWF multimers by megakaryocytes d. Abnormal complexing of normal VWF multimers to create unusually large VWF multimers General Feedback:

Patients with the more common form of thrombotic thrombocytopenic purpura are deficient in a metalloprotease (ADAMTS 13) needed to cleave unusually large VWF into the smaller VWF multimers normally found in plasma. Both endothelial cells and megakaryocytes normally make these unusually large VWF multimers.

24. Chapter 38-24 What are the primary clinical manifestations of essential thrombocythemia? a. Platelet dysfunction b. Hemorrhage c. Thrombosis *d. All of the options General Feedback: Patients with essential thrombocythemia have platelet dysfunction and may either bleed or experience thrombosis.

1. Chapter 39-01 Inappropriate formation of platelets or fibrin clots that obstructs blood vessels is called: a. thrombophilia. *b. thrombosis. c. embolus. d. factor V Leiden.

General Feedback: Thrombosis is the inappropriate formation of platelets or fibrin clots that obstruct blood vessels. Thrombophilia refers to congenital abnormalities that increase the risk of thrombosis; factor V Leiden is one such risk factor. An embolus forms when a piece of a thrombus breaks off and travels to another location via the circulatory system.

2. Chapter 39-02 Which is the cause for most strokes and heart attacks in the United States? a. Hemorrhage b. Thrombocytopenia c. Cancer *d. Consequences of thrombotic events General Feedback: About 80% of heart attacks and 85% of strokes in the United States are caused by thrombi that block coronary or carotid arteries.

3. Chapter 39-03 All are associated with an increased risk of thrombosis except: *a. high high density lipoprotein (HDL) cholesterol. b. increased homocysteine. c. immobilization of extremities. d. increased high-sensitivity C-reactive protein.

General Feedback: High HDL cholesterol is actually believed to be protective (the so-called good cholesterol). All the other listed findings are risk factors for thrombosis.

5. Chapter 39-05 A thrombosis risk testing profile is ordered on a patient being treated with warfarin for a blood clot in the leg. Select the best course of action. a. Run the tests immediately. b. Reject the order. c. Perform only the tests for protein C and protein S. *d. Recommend the testing be postponed until the warfarin is discontinued.

General Feedback: Testing should be postponed until the warfarin has been discontinued for 10 to 14 days. Warfarin blocks the normal synthesis of vitamin K–dependent proteins, which include protein C and protein S.

6. Chapter 39-06 A patient who is not on heparin and has no history of a factor deficiency has a prolonged partial thromboplastin time (PTT). Select the test that should be performed next. a. High-sensitivity C-reactive protein *b. Mixing studies for lupus anticoagulant c. Thrombin time (TT) d. Lipid panel General Feedback: The lupus anticoagulant results in a prolonged PTT. It is characterized by lack of correction when the patient plasma is mixed 1:1 with normal platelet-poor plasma and the PTT repeated. None of the other listed findings prolong the PTT.

7. Chapter 39-07 Which result puts the patient at an increased risk for thrombosis? a. Total cholesterol of 180 mg/dL b. PTT of 25 seconds c. Deficiency of factor V *d. Chronically elevated fibrinogen General Feedback: High fibrinogen levels have a positive correlation to relative risk of myocardial cardiovascular risk, especially in patients with angina pectoris. Care must be taken in evaluating patients because fibrinogen is an acute phase reactant and increases under stress.

8. Chapter 39-08 Select the next best test to run given the following PTT results on a patient’s plasma: Initial PTT: 75 seconds Immediate 1:1 mix with normal plasma: 38 seconds Incubated 1:1 mix with normal plasma: 36 seconds a. Dilute Russell’s viper venom time *b. Factor assays c. Factor V Leiden d. Bethesda titer General Feedback: Factor assays should be performed on this plasma to determine the factor deficiency (or deficiencies) present. The PTT corrects on a 1:1 mix. If this were the lupus anticoagulant, the prolonged PTT should remain prolonged on the 1:1 mix; thus no reason exists to perform the

dilute Russell’s viper venom time to confirm the presence of the lupus anticoagulant. If it were a factor VIII inhibitor, which can fully correct on the immediate 1:1 mix, it would prolong after incubation of the 1:1 mix. Then it would be appropriate to perform a Bethesda titer.

Factor V Leiden does not result in a prolonged PTT.

9. Chapter 39-09 What is the best test to perform if a patient’s PTT does not rise after the typical heparin dose? a. Immunoassay for anticardiolipin antibody b. Lipoprotein(a) assay *c. Chromogenic antithrombin d. Mixing studies General Feedback: When a patient has a deficiency of antithrombin, heparin may be administered in therapeutic or even higher dosages, but it will not exert an anticoagulant effect in vivo, nor will it be detected by the PTT. This is called heparin resistance.

10. Chapter 39-10 What is the best method to prevent warfarin-induced skin necrosis during treatment for thrombosis? a. Use higher dose of warfarin early in treatment. b. Give the patient injections of protein C. c. Stop warfarin at the first sign of necrosis. *d. Use heparin for first 5 days in conjunction with warfarin.

General Feedback: To prevent warfarin-induced skin necrosis, heparin is given along with the warfarin until a therapeutic and stable international normalized ratio (INR) is obtained.

12. Chapter 39-12 Which unusual laboratory finding may be present in sepsis-induced DIC? *a. Fibrinogen may be high because it is an acute phase reactant. b. Schistocytes are absent because the fever destroys them. c. D dimer is low because the toxins prevent fibrin lysis. d. The PT and PTT are low because bacteria interfere with these tests.

General Feedback: Fibrinogen levels may drop in DIC, but because fibrinogen is an acute phase reactant it may actually be increased in the presence of an inflammatory process such as sepsis.

13. Chapter 39-13 A patient has a quantitative D dimer of 800 ng/mL. Which can be ruled out from the following list? a. DIC b. Deep vein thrombosis c. Pulmonary embolus *d. Patient is normal General Feedback: A D dimer of 800 ng/mL is significantly elevated, so that the patient is not normal. D dimers are elevated in DIC, pulmonary embolus, and deep vein thrombosis.

14. Chapter 39-14 Which is an expected finding in DIC? a. Thrombocytosis *b. Schistocytes on the blood film c. Normal hemoglobin and hematocrit d. Macrocytic red cells General Feedback: Schistocytes are seen in about 50% of DIC cases.

Thrombocytopenia is expected, along with anemia, because red cells are being destroyed in circulation. Red cells are not macrocytic.

15. Chapter 39-15 Which is used to treat DIC? a. Prothrombin complex b. Platelet transfusions c. Fibrinogen concentrates *d. All of the options General Feedback: All the products listed, in the appropriate clinical setting, may be used for therapy of DIC.

16. Chapter 39-16 What tests should be performed on a regular basis on patients receiving therapeutic heparin? a. PT and hematocrit b. PTT and white count *c. PTT and platelet count d. Factor assays and platelet count General Feedback: Patients on heparin must have platelet counts performed daily.

A significant drop in the platelet count is a signal for heparininduced thrombocytopenia. The PTT is also regularly performed to monitor the heparin dosage.

17. Chapter 39-17 A 37-year-old female patient has a PTT of 76 seconds (reference range, 25 to 37 seconds). Her plasma is mixed 1:1 with normal plasma. An immediate PTT performed on the mix is 74 seconds. Which is the most likely diagnosis? a. Hemophilia A b. Factor VIII inhibitor c. Intrinsic factor deficiency *d. Lupus anticoagulant General Feedback: A prolonged PTT that remains prolonged after an immediate repeat of the PTT on the 1:1 mix is seen in patients (either male or female subject) with the lupus anticoagulant. A patient with hemophilia A would most likely be a male subject (female hemophilia A is rare). In addition, the immediate 1:1 mix should correct, as it also would with an intrinsic factor deficiency. The PTT on an immediate 1:1 mix in the presence of a factor VIII inhibitor would also essentially correct.

18. Chapter 39-18 What is important about the test systems used for detection of the lupus anticoagulant? a. The phospholipid concentration should be high. b. Ellagic acid should be the PTT activator substance. *c. The patient plasma and normal plasma used for mixing studies should be platelet poor. d. A 1:1 mix should be performed when the initial test is normal to improve the sensitivity.

General Feedback: Platelets contain phospholipid in their membrane, and this can overcome and thus mask the lupus anticoagulant when it is present. Thus both the patient and the normal plasma used for mixing studies must be platelet poor. The phospholipid concentration in the reagent used for detection must also have a low concentration of phospholipid to be sensitive. The initial test before the 1:1 mix must be prolonged to even suggest the possible presence of the lupus anticoagulant, providing a lupus anticoagulant–sensitive reagent is used.

19. Chapter 39-19 Why does the factor V Leiden mutation increase thrombotic risk? *a. Makes factor Va resistant to degradation by activated protein C. b. Makes blood more viscous. c. Makes factor V more susceptible to activation by thrombin. d. Decreases the binding of factor Va to the inhibitor antithrombin.

General Feedback:

Activated factor V Leiden is resistant to degradation by activated protein C, which is critical for slowing down thrombin generation. This results in an increased thrombotic risk for the patient.

20. Chapter 39-20 Why does prothrombin G20210A increase the risk of thrombosis? a. Makes prothrombin activation easier. *b. Elevates prothrombin levels. c. Decreases binding of thrombin by antithrombin. d. Decreases binding of plasminogen to prothrombin.

General Feedback: The prothrombin G20210A mutation results in elevated levels of prothrombin; this increases the risk of thrombosis, although the reason why is not clear.

21. Chapter 39-21 When the chromogenic assay for antithrombin is performed, which is true? *a. The colored end-product intensity is inversely proportional to the antithrombin concentration. b. The chromogenic substrate is bound by antithrombin. c. Warfarin is added to the patient sample before testing to improve sensitivity. d. Activated protein C competes for the chromogenic substrate, so it must first be selectively removed.

General Feedback: Antithrombin concentration is inversely proportional to the intensity of end-product color. Heparin is added to the patient plasma before testing to improve sensitivity to antithrombin. A protease, often Xa, is added in excess to an aliquot of the patient sample. Some of this Xa will be bound by the heparin-antithrombin complex and thus inhibited. After this, a chromogenic substrate is added that is specific for Xa. When the residual Xa hydrolyzes this substrate, color will be released. The more antithrombin present in the patient sample, the more Xa will be bound and the less chromogen will be released.

22. Chapter 39-22 What substance is used to activate protein C in the chromogenic assay to determine its concentration? a. Partial thromboplastin *b. A specific snake venom c. Kaolin d. Heparin General Feedback: A specific snake venom is used to activate protein C in its chromogenic assay.

23. Chapter 39-23 A patient arrives at the emergency department complaining of pain in the calf of his left leg and shortness of breath. A “stat” D dimer is ordered. Why is this useful information for this patient’s care? *a. An elevated D dimer supports the possibility of deep vein thrombosis. b. An elevated D dimer is diagnostic for deep vein thrombosis. c. A normal D dimer is diagnostic for deep vein thrombosis. d. This was not an appropriate test to order on this patient.

General Feedback: An elevated D dimer supports the possibility of a deep vein thrombosis, but it is not diagnostic. Many other clinical situations can lead to elevation of this test. A normal D dimer has negative predictive value (i.e., a normal D dimer result is useful for ruling out deep vein thrombosis). With the patient’s presenting symptoms, pulmonary embolism may also be present, which can be a consequence of deep vein thrombosis. Thus this was an appropriate requisition for this patient.

1. Chapter 40-01 Why is it important to monitor patients who are receiving anticoagulant therapy? a. Drugs are expensive. b. Prophylactic and therapeutic dosage ranges are unknown. c. Patients commonly abuse these drugs. *d. Clinical consequences for overdosing are significant.

General Feedback: The clinical consequences for incorrect dosage of anticoagulant drugs are significant. Overanticoagulation can lead to serious bleeding that may even require a visit to the emergency department.

2. Chapter 40-02 Warfarin skin necrosis occurs within the first 2 to 3 days after starting warfarin therapy because: a. the platelet count decreases to fewer than 100 × 109/L, and significant bleeding occurs. *b. protein C decreases significantly before full anticoagulation, and skin thrombosis results. c. prothrombin decreases rapidly generating less thrombin, and significant bleeding occurs. d. plasminogen increases, and rapid clot lysis occurs.

General Feedback: Protein C has a 6-hour half-life, and so it rapidly decreases when warfarin therapy is begun, along with factor VII (both are vitamin K–dependent proteins). Full anticoagulation with warfarin is not obtained until factors X and prothrombin are decreased to less than 50%, requiring 4 to 7 days based on their half-lives. Because protein C is important in controlling clot formation, its decrease actually puts the patient in a prethrombotic state until full anticoagulation is obtained.

3. Chapter 40-03 Once a patient is stabilized on warfarin therapy, how often should he or she be monitored? a. Once every 6 months b. Once every week c. Once a year *d. Once a month General Feedback: Once a patient is stabilized on warfarin therapy, monitoring should continue every 4 to 6 weeks until therapy is complete. Changes in diet, metabolism, renal function, other drugs being taken, as well as additional factors all change the response to warfarin and may require making dosage adjustments.

4. Chapter 40-04 A patient is stabilized on warfarin therapy and being monitored using the prothrombin time (PT) followed by calculation of the international normalized ratio (INR). The formula for calculating the INR is: INR = (PTpatient/PTnormal)ISI (where ISI = international sensitivity index) What is used for the PTnormal? a. arithmetic mean PT for the control. *b. geometric mean PT for the reference population. c. arithmetic mean PT as found in a standard reference textbook. d. geometric mean PT reported by the manufacturer of the PT reagent being used.

General Feedback: The PTnormal is the geometric mean for the PT reference interval determined by the clinical laboratory scientists in the laboratory where the testing is being performed. Using the wrong value in this calculation has led to major reporting errors that have resulted in bad patient outcomes.

5. Chapter 40-05 An INR of 6.5 is obtained on a patient taking warfarin. All quality control is acceptable. What should be done? a. Report the result. b. Report only the PT in seconds and ignore the INR. c. Send an e-mail to the health care provider. *d. Call the clinician immediately.

General Feedback: INRs greater than 5 are associated with increased risk of hemorrhage, and require immediate communication with the clinician who is managing the patient’s case.

6. Chapter 40-06 Unfractionated heparin is commonly monitored by the: a. PT. *b. partial thromboplastin time (PTT). c. thrombin time (TT). d. kinetic fibrinogen.

General Feedback: The PTT is the most commonly used test for monitoring heparin therapy because it responds in a linear fashion over the therapeutic range. The PT is relatively insensitive to heparin, whereas the TT is too sensitive. The kinetic fibrinogen is the least sensitive of these tests to therapeutic heparin.

7. Chapter 40-07 A patient is admitted through the hospital emergency department with thrombosis, and heparin is initially begun. Her baseline PTT, before heparin therapy, is prolonged at 68 seconds. Further laboratory studies determine that she has the lupus anticoagulant. What test should be used to monitor her heparin therapy? a. PTT b. PTT after first adding antithrombin to her plasma *c. Chromogenic anti-Xa assay d. TT after first making a 1:10 dilution of the patient plasma General Feedback: The PTT is already prolonged by the lupus anticoagulant, so the heparin therapeutic range for the PTT reagent becomes meaningless.

In this case a chromogenic anti-Xa assay should be used.

8. Chapter 40-08 A clinical laboratory receives a new lot of PTT reagent, so clinical laboratory scientists in the laboratory need to establish the heparin therapeutic range for this new reagent lot. How should this be done? a. Compare PTT results for patient heparinized samples to those for the lot of PTT reagent that is presently being used. *b. Perform chromogenic Xa and PTT assays on patient heparinized samples, and do a statistical analysis of result comparisons. c. Add heparin at various therapeutic concentrations to normal plasma, and perform PTT on each concentration using the new lot of reagent. d. Add heparin at high concentration to one normal plasma, make dilutions of this plasma, and then perform PTT on each diluted sample using the new lot of reagent.

General Feedback: Accrediting agencies for clinical laboratories require that the PTT heparin therapeutic range be determined using samples from patients who are receiving heparin therapeutically; they cannot be receiving simultaneous warfarin therapy (thus their PT must be normal).

Both a chromogenic anti-Xa assay and PTT are performed on each patient sample, and the paired results are plotted in a linear graph. The range that corresponds to 0.3 to 0.7 chromogenic anti-Xa is the therapeutic range.

9. Chapter 40-09 Why is the platelet count monitored daily for a patient receiving heparin therapeutically? a. Platelets increase when a patient is overheparinized. b. Platelets decrease when a patient is overheparinized. *c. A significant decrease in the platelet count is evidence for heparin-induced thrombocytopenia. d. A significant increase in the platelet count is early evidence for heparin-induced thrombocytosis.

General Feedback: A decrease of 40% or greater in the platelet count, even if the platelet count remains in the reference range, is evidence for heparin-induced thrombocytopenia. This is a serious consequence, and unfractionated heparin therapy must be immediately stopped and replaced with a direct thrombin inhibitor.

10. Chapter 40-10 All of the following serine proteases are bound and inhibited by antithrombin except: a. Xa. b. IXa. *c. VIIa. d. XIa. General Feedback: Antithrombin covalently binds and inhibits XIIa, XIa, Xa, IXa, and thrombin. It does not bind VIIa.

11. Chapter 40-11 Which is true related to the use of aspirin to prevent cardiovascular disease? *a. It is used to prevent arterial thrombosis. b. New studies show it is not effective. c. It works well but must be carefully monitored with monthly bleeding times. d. Aspirin monitoring tests such as thromboxane B2 are now easy to perform and widely available.

General Feedback: Aspirin, as well as other antiplatelet drugs, have been shown to be effective for prevention of arterial thrombosis, especially myocardial infarction, stroke, and peripheral artery occlusion. This therapy is not monitored. However, some individuals are resistant to aspirin therapy, and thromboxane B2 tests are available, although they are not easily performed or widely available.

12. Chapter 40-12 After confirmation of a deep vein thrombosis (DVT) and pulmonary embolus in a patient, a baseline coagulation screen and platelet count are obtained. His fibrinogen is 620 mg/dL. When the PTT is performed at 6 hours after initiation of therapy, it is 45 seconds (reference range, 25 to 37 seconds). What should be done? a. Report the PTT as not responding. *b. Monitor the patient with the chromogenic anti-Xa assay. c. Add an additional standard amount of heparin to the patient plasma to improve the sensitivity. d. Add a standard amount of antithrombin to the patient plasma to improve the sensitivity.

General Feedback: An elevated fibrinogen tends to shorten the PTT and makes it less sensitive to the effect of heparin; this is called heparin resistance. The chromogenic anti-Xa assay should then be used to monitor this patient.

13. Chapter 40-13 All are true about the activated clotting time (ACT) except: *a. it is useful for monitoring warfarin therapy. b. is a popular point-of-care test. c. blood for the test is collected with negative tube pressure. d. the median reference interval is 98 seconds.

General Feedback: The ACT can be used to monitor heparin therapy, not warfarin.

ACT is a popular point-of-care test that has a median reference interval of 98 seconds. The ACT evacuated blood specimen collection tubes have no anticoagulant but have a particulate clot activator and a small magnet. The negative tube pressure collects 2 mL of blood.

14. Chapter 40-14 Low-molecular-weight heparin (LMWH): *a. is essentially as effective therapeutically as unfractionated heparin (UFH). b. has the same antithrombin effect as UFH. c. can be monitored using the PTT. d. has a shorter in vivo half-life than UFH. General Feedback: LMWH has essentially the same therapeutic efficacy as UFH. Because of its lower molecular weight, it does not have the same bridging effect as UFH, and so the antithrombin effect is reduced (not the same). For this reason, the PTT cannot be used to monitor LMWH; it is not responsive. The chromogenic anti-Xa must be used. LMWH has a longer in vivo half-life than UFH; this is one of the advantages.

16. Chapter 40-16 What anticoagulant therapy is monitored using the ecarin clotting time (ECT)? a. Unfractionated heparin b. Warfarin c. LMWH *d. Direct thrombin inhibitors General Feedback: The ECT uses an enzyme extracted from Echis carinatus venom.

Direct thrombin inhibitors yield a linear, dose-dependent response to the ECT. The test is useful for monitoring direct thrombin inhibitors when the patient has lupus anticoagulant or factor deficiencies.

17. Chapter 40-17 Elevated urinary levels of 11-dehydrothromboxane B2 identify patients who are: a. at risk for heparin-induced thrombocytopenia. b. overanticoagulated with warfarin. *c. resistant to aspirin antiplatelet therapy. d. resistant to direct thrombin inhibitors.

General Feedback: 11-Dehydrothromboxane B2 is a metabolite derived from thromboxane A2, synthesized by the platelet in the eicosanoid pathway.

This pathway is blocked by aspirin’s effect on cyclooxygenase. When it is not blocked, and platelet activation occurs, 11-dehydrothromboxane B2 is secreted and found in urine at an elevated level. Thus its elevation indicates that platelet activation is occurring and has not been blocked by aspirin. This is called aspirin resistance.

1. Chapter 41-01 Which is good practice in regard to phlebotomy on patients with hemostasis testing ordered? a. Make sure the patient is fasting. b. Always draw the sodium citrate tube last. c. Collect the blood in a glass syringe. *d. Use a 20- or 21-gauge needle.

General Feedback: For routine coagulation draws, a 20- or 21-gauge needle is used. The patient does not need to be fasting, the sodium citrate tube should be drawn first, and glass (syringe) should never be used for coagulation specimens because glass activates the contact phase.

2. Chapter 41-02 Which will cause spuriously prolonged clot-based coagulation tests? *a. An evacuated 3.2% sodium citrate tube filled to 50% capacity b. An evacuated 3.2% sodium citrate tube filled to 90% capacity c. Prolonged tourniquet application d. Plasma collected from a traumatic tap General Feedback: Filling an evacuated 3.2% sodium citrate only halfway (50%) will lead to falsely prolonged clot-based coagulation test results. The relative excess anticoagulant will bind (some) of the calcium added in the test system. A 90% fill gives valid results and can be used.

Prolonged tourniquet application and plasma collected from a traumatic tap both have the potential of activating coagulation, thus leading to shortened, not prolonged, results.

3. Chapter 41-03 Which is an acceptable sample for testing on a photo-optical clotdetecting instrument? a. Lipemic plasma b. Hemolyzed plasma c. Serum *d. Plasma collected using a 9:1 ratio of whole blood to 3.2% sodium citrate General Feedback: Plasma should be collected at a 9:1 ratio of blood to anticoagulant (3.2% sodium citrate). Lipemia and hemolysis are possible interfering substances when using an instrument that uses the photooptical principle for end-point detection. Serum cannot be used for coagulation testing because the sample has already clotted, with resultant loss of several coagulation proteins.

4. Chapter 41-04 Which practice is necessary when collecting blood specimen from a heparin or saline lock?

*a. Flush the IV line with 5-mL saline before collecting the specimen. b. The first 5 mL of blood that is collected must be immediately inserted into the blood tube for testing. c. Flush the IV line with heparin before collecting the specimen. d. Collect the blood directly into an evacuated tube.

General Feedback: Collection of blood from a heparin or saline lock is usually performed by physicians or nursing staff. The IV line must be flushed with 5-mL saline before the blood draw to avoid specimen contamination.

The first 5 mL of blood that is collected should be discarded. IV lines should never be flushed with heparin before collecting blood for coagulation testing. Blood should be collected into a syringe, and a transfer device is used to transfer the blood to an evacuated tube.

5. Chapter 41-05 A patient has a hematocrit of 65%. Which is true related to coagulation testing? a. Hematocrit does not affect coagulation testing. b. Tube must be recollected with heparin as the anticoagulant. *c. Tube must be recollected using 0.34 mL of sodium citrate to 4.5 mL of blood. d. Tube must be recollected using 0.62 mL of sodium citrate to 4.5 mL of blood.

General Feedback: The plasma volume is relatively low in a patient who has a high hematocrit. This unacceptably raises the anticoagulant-to-plasma ratio, invalidating test results that become falsely prolonged. When the hematocrit is greater than 55%, the volume of citrate must be decreased to optimize the anticoagulant-to-plasma ratio. Blood is not collected in heparin for coagulation tests.

6. Chapter 41-06 Which is an acceptable sample for a prothrombin time (PT) test? *a. One that was collected 24 hours before testing. b. One with a very small clot that was easily removed. c. 3.2% sodium citrate blood sample immediately collected following a serum separator tube. d. Blood anticoagulated with heparin and brought to the laboratory within 1 hour.

General Feedback: Specimens collected for PTs may be held uncentrifuged or centrifuged at 15° to 25°C and tested within 24 hours of the time of collection. Any clot in a specimen makes the sample useless for coagulation testing. Serum separator tubes contain a clot activator; this can contaminate the next tube drawn, and, for coagulation, is the same as having a clot. Heparinized samples are not used for coagulation testing.

7. Chapter 41-07 The platelet function test will be normal and is no value to perform in patients who have: a. a qualitative platelet disorder. b. von Willebrand disease (VWD). c. Glanzmann thrombasthenia. *d. factor VIII deficiency.

General Feedback: The platelet function test will be normal in patients with a factor VIII deficiency. It ideally will be prolonged in all the other listed settings. The bleeding time test is being used less often because it has poor predictive value and leaves scarring.

8. Chapter 41-08 Which is necessary for normal platelet aggregation? a. Ristocetin b. von Willebrand factor (VWF) c. Epinephrine *d. Fibrinogen General Feedback: Normal platelet aggregation requires fibrinogen. Ristocetin is a substance added in vitro that causes platelet to clump. VWF is needed for normal platelet adhesion. Epinephrine is a platelet agonist stimulating platelet aggregation, but it is not necessary.

9. Chapter 41-09 Which is the purpose ristocetin? *a. Checks for plasma abnormalities in VWD. b. Provides info about platelet secretion conditions. c. Cleaves two protease-activatable receptors. d. Binds P2Y1 and P2Y12.

General Feedback: Ristocetin is used to check for abnormalities of plasma VWF in VWD. Lumiaggregometry provides more definitive information for conditions where recording platelet secretion, in addition to platelet aggregation, is an important diagnostic factor. Thrombin (or TRAP) cleaves two platelet membrane protease-activatable receptors (PARs), PAR-1 and PAR-2, both members of the seven-transmembrane repeat receptor family. ADP binds platelet membrane receptors P2Y1 and P2Y12, also members of the seven-transmembrane repeat receptor family.

10. Chapter 41-10 A prolonged bleed time could signal:

a. Glanzmann thrombasthenia. b. von Willebrand disease. c. scurvy. *d. all of the options.

General Feedback: A prolonged bleeding time could theoretically signal von Willebrand disease (VWD), a functional platelet disorder such as Glanzmann thrombasthenia, or a vascular disorder such as scurvy or vasculitis, and was thought to have a predictable result in therapy using aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs).

11. Chapter 41-11 A patient’s platelet count drops 4 days after being placed on heparin.

Select the correct interpretation. a. The patient has heparin-induced thrombocytopenia. b. The patient has benign, limited thrombocytopenia related to heparin. c. A bleeding time should be performed to evaluate qualitative platelet disorders. *d. An immunoassay for heparin-dependent anti–platelet factor 4 (PF4) should be performed to distinguish heparin-induced thrombocytopenia from benign, limited thrombocytopenia related to heparin.

General Feedback: This pattern, a drop in the platelet count 4 days after being placed on heparin, suggests heparin-induced thrombocytopenia. It could also be a benign, limited thrombocytopenia related to heparin. Assays such as the immunoassay for heparin-dependent anti-PF4 can distinguish the two.

12. Chapter 41-12 How often must the partial thromboplastin time (PTT) reference interval be determined? a. Only when both the normal and abnormal controls are outside their acceptable limits b. At least every 6 months *c. With each new lot of reagent d. Only when the normal control is outside its acceptable limits General Feedback: The PTT reference interval must be determined with each new lot of reagent and at least once per year.

13. Chapter 41-13 What is the test commonly used to monitor the high heparin doses used in cardiac bypass surgery? *a. PTT b. Prothrombin time

c. Thrombin clotting time d. Fibrinogen General Feedback: The high heparin doses used in cardiac bypass surgery can be monitored using the PTT.

14. Chapter 41-14 Patients with which condition would have a normal PT? a. Liver disease b. Disseminated intravascular coagulation (DIC) c. Factor VII deficiency *d. Factor IX deficiency General Feedback: Patients with a deficiency of factor IX will have a normal PT. The PT does not require this protein.

16. Chapter 41-16 A patient is stabilized on warfarin with an international normalized ratio (INR) of 2.7. He develops pneumonia and is admitted to the hospital. His appetite is depressed and he is placed on broad-spectrum antibiotic agents. At 1 week after the admission, his INR is 5.0. What is the most likely interpretation? a. The patient should be given more warfarin. b. A PTT should be performed to rule out heparin administration. c. A new sample should be collected to rule out a clotted specimen. *d. Vitamin K is reduced, increasing the effects of warfarin.

General Feedback: This elevated INR is probably the result of a deficiency of vitamin K, which increases the effects of warfarin. Vitamin K deficiency is seen during use of broad-spectrum antibiotic agents that destroy gut flora and in people with a poor diet, both of which are present in this patient.

17. Chapter 41-17 Which patient would likely have a normal PT? a. Patient with a factor VII deficiency *b. Patient with a factor VIII deficiency c. Patient on warfarin d. Clotted blood General Feedback: A patient with a factor VIII deficiency would have a normal PT. All the others listed would have a prolonged PT.

18. Chapter 41-18 Which condition would have a normal PTT? a. Lupus anticoagulant b. Fibrinogen of 50 mg/dL *c. Factor VII deficiency d. Heparin therapy General Feedback: Factor VII deficiency would have a normal PTT. All the other listed conditions would have a prolonged PTT.

19. Chapter 41-19 A patient admitted to the hospital with thrombosis is given the standard heparin dosage. Twenty-four hours after the heparin is started, the PTT is 38 seconds (reference range, 25 to 37 seconds).

Both normal and abnormal controls are within their limits. Which is most likely? a. Laboratory error *b. Patient has low antithrombin c. Heparin-induced thrombocytopenia d. Patient should be switched to low-molecular-weight heparin (LMWH) General Feedback: When a patient has a deficiency of antithrombin, heparin may be administered in therapeutic or even higher dosages, but it will not exert an anticoagulant effect in vivo or be detected by the PTT. This is called heparin resistance.

20. Chapter 41-20 A prolonged PTT is corrected when mixed with normal plasma and tested immediately and after a 2-hour incubation. Which test (or tests) should be performed next? a. Bethesda titer b. High-phospholipid PTT c. Anti-Xa assay *d. Factor VIII assays General Feedback: This pattern suggests a factor deficiency, and factor VIII assay should be performed. The Bethesda titer is performed when a specific factor inhibitor is present; no evidence exists for this because the PTT on the incubated 1:1 mix did not prolong. Highphospholipid PTT testing is done to confirm the lupus anticoagulant; this is not present because the immediate 1:1 mix on this sample corrected. No reason exists to perform an anti-Xa assay, often used to monitor LMWH.

21. Chapter 41-21 A patient has an elevated thrombin time and normal reptilase time.

Which situation is most likely? *a. Heparin therapy b. Low fibrinogen c. Elevated fibrin split products d. Dysfibrinogenemia General Feedback: Heparin prolongs the thrombin time but does not prolong the reptilase time. A low fibrinogen, elevated fibrin split products, and dysfibrinogenemia prolong both, although differences exist in sensitivity to some of these between the two tests.

22. Chapter 41-22 Which condition is associated with an elevated fibrinogen? a. Acute DIC *b. Chronic inflammation c. Severe liver disease d. Increased plasmin levels General Feedback: An elevated fibrinogen is present in chronic inflammation because fibrinogen is an acute phase protein. It is decreased in all the other situations listed.

23. Chapter 41-23 A patient has a factor VIII level of 50% activity. Which is most likely true regarding what can be expected for this patient’s clinical situation? a. Severe bleeding b. Moderate bleeding c. Mild bleeding *d. Normal with respect to factor VIII General Feedback: The reference range for factor VIII activity is 50% to 150%.

Thus this patient is normal.

24. Chapter 41-24 A patient undergoing thrombolytic therapy has a plasminogen level of 3.5 mg/dL. Which condition does this patient most likely have? a. Pregnancy b. Hemorrhage c. Acute inflammation *d. Hepatitis General Feedback:

A typical plasminogen reference interval is 5 to 13.5 mg/dL. Plasminogen levels are decreased in thrombolytic therapy, DIC, hepatitis, and cancer, or may be hereditary. Decreased plasminogen is associated with thrombosis. Plasminogen rises in systemic fibrinolysis, acute inflammation, and during pregnancy, and high levels may be associated with hemorrhage.

25. Chapter 41-25 Which laboratory test identifies genetic variants in platelet-related bleeding disorders? *a. HTS b. Sanger c. TEG d. ROTEM General Feedback: High-throughput genetic sequencing (HTS) has become the reference approach to identifying the genetic variants that underlie platelet-related and coagulopathy-related bleeding disorders, having replaced the pioneering but less precise Sanger sequencing.

Thromboelastography (TEG) and modification rotational thromboelastometry (ROTEM) measure clotting time and the dynamics of clot formation and dissolution as effected by the kinetics of thrombin generation, platelet activation, fibrin generation, clot strength, clot stability, and inhibitory effects on any aspect.

26. Chapter 41-26 A patient is positive for fibrin degradation products and negative for D dimers. Which condition is most likely? *a. Systemic fibrinolysis b. DIC c. Hypofibrinogenemia d. Deep vein thrombosis (DVT) General Feedback: Fibrin degradation products are positive and D dimers are negative in systemic (also called primary) fibrinolysis. Plasmin is present, which degrades fibrinogen so that it is decreased. However, thrombin is not present, so no D dimers are formed. They are both elevated in DIC and DVT. Neither is useful for hypofibrinogenemia, which is diagnosed using a fibrinogen assay.

27. Chapter 41-27 An elevated tissue plasminogen activator (TPA) is associated with: *a. abnormal bleeding. b. aspirin use. c. DIC. d. decreased fibrinolysis.

General Feedback:

An elevated TPA is associated with abnormal bleeding. TPA activates plasminogen to plasmin, which lyses a clot; when TPA is elevated, this occurs prematurely and bleeding ensues.

28. Chapter 41-28 Which specimen would be acceptable for platelet aggregation studies? a. Blood drawn in ethylenediaminetetraacetic acid (EDTA) and kept at room temperature for 6 hours. b. Blood drawn in 3.2% sodium citrate and transported to the laboratory on ice (2° to 4°C). c. Blood drawn in a serum separator tube. *d. Blood drawn in 3.2% sodium citrate and kept at room temperature for 2 hours after drawing.

General Feedback: Platelet function studies must be performed within 3 hours of drawing, and the specimen must be kept at room temperature because chilling damages platelets. The blood sample must be drawn in 3.2% sodium citrate.

29. Chapter 41-29 A 53-year-old woman arrives at the hospital with bleeding into the back of the throat and has a coagulation screen performed. She has no history of abnormal bleeding before this despite major stress to hemostasis in the past—she was in a major automobile accident at age 37 and has had impacted wisdom teeth extracted. Her coagulation results follow: 1:1 Mix Patient’s Reference Range With Results Normal Plasma Prothrombin 13.1 11–15 time (PT) seconds seconds Partial 87 seconds 25–37 35 thromboplastin seconds time (PTT) Fibrinogen 380 mg/dL 200–400 mg/dL Which is the most likely cause for her bleeding? a. Factor XII deficiency b. Factor IX deficiency c. Factor VIII deficiency *d. Factor VIII inhibitor General Feedback: This patient is bleeding abnormally. However, she has had major trauma in the past with no abnormal bleeding; this suggests the problem is acquired, not congenital. The PTT is prolonged, so the common pathway appears to be intact. The prolonged PTT fully corrects on a 1:1 mix, although at the upper end of the reference range. Putting

all of this together, the most likely problem is an acquired factor VIII inhibitor.

30. Chapter 41-30 Which deficiency prolongs the PTT but does not lead to abnormal bleeding? a. Factor V b. Factor VIII c. Factor XI *d. Factor XII General Feedback: A deficiency of factor XII prolongs the PTT. However, patients with this deficiency do not have abnormal bleeding.

1. Chapter 42-01 All are considered routine coagulation tests that are available in most large and small clinical laboratories except: a. prothrombin time (PT). b. fibrinogen assay. c. partial thromboplastin time (PTT). *d. antithrombin assay.

General Feedback: The antithrombin assay traditionally has not been available in most clinical laboratories, and that is still true today in small laboratories.

2. Chapter 42-02 Diagnostica Stago coagulation instruments are based on what clot detection principle? a. Photo-optical *b. Mechanical c. Chromogenic d. Nephelometric General Feedback: Diagnostica Stago coagulation instruments use a mechanical end-point clot detection principle. These instruments magnetically monitor the movement of a steel ball within plasma. As the clot forms, the sensor detects the slowing of the ball.

3. Chapter 42-03 Which is the most common clot detection principle used for coagulation testing? *a. Photo-optical b. Mechanical c. Chromogenic d. Immunologic General Feedback: The most common clot detection principle used by automated coagulation instruments is photo-optical.

4. Chapter 42-04 Using which principle does plasma become more opaque as a clot forms and the amount of light being detected decreases? *a. Photo-optical b. Mechanical c. Chromogenic d. Immunologic General Feedback:

A light source of specified wavelength is made to pass through plasma; some light normally gets through to the detector. As a fibrin clot forms, the amount of light detected decreases. When light decreases to a predetermined deflection from the baseline, the timer stops, indicating clot formation.

5. Chapter 42-05 Which assay uses indirect measurement using a chromogenic substrate to quantitate heparin? a. Protein C b. Thrombin time (TT) *c. Anti-Xa assay d. Fibrinogen assay General Feedback: The heparin anti-Xa assay is used to indirectly measure the concentration of heparin. In this system, heparin has an inhibitory effect on the enzyme Xa. Xa normally proteolytically cleaves the chromogenic substrate, releasing the chromogen with a color intensity that is then measured. Because heparin has inhibited some of the Xa, less free Xa will be available to cleave the substrate and less color will be released. Thus the concentration of heparin is inversely proportional to the activity of Xa. This is classified as an indirect measurement.

6. Chapter 42-06 Which principle measures the actual coagulation protein rather than fibrin formation? a. Photo-optical b. Mechanical c. Chromogenic *d. Immunologic General Feedback: Immunologic methods measure the actual coagulation protein rather than fibrin formation. These assays are based on antigenantibody reactions.

7. Chapter 42-07 Which is true regarding advances in automated coagulation instrumentation? a. Less staff training is required to operate and maintain the equipment than was necessary for earlier semiautomatic instruments. *b. Single-sample testing is possible because of increased precision. c. Newer instruments are less expensive. d. Accuracy is so improved that controls do not need to be run.

General Feedback:

Increased precision on the new automated coagulation instruments means that single-sample testing is possible. Before this, every sample had to be tested in duplicate and the duplicates had to agree within certain preset limits before they could be averaged and the result reported.

8. Chapter 42-08 Which single instrument development has been the most important improvement in coagulation instrumentation? a. Multiple-sample dilutions b. Improved flagging *c. Random access testing d. Graphing of clot formation General Feedback: The most significant improvement in automated coagulation analyzers is the ability to provide random access testing. This means that a variety of tests can be run in any order on the same plasma specimen or many specimens within the same testing batch. This vastly improves the efficiency of the clinical laboratory.

9. Chapter 42-09 Which is most improved safety for laboratory scientists? *a. Closed tube sampling b. Random access c. Expanded computer capabilities d. Improved flagging capabilities General Feedback: Closed tube sampling has improved the safety and efficiency of coagulation testing. This reduces the chances of the clinical laboratory scientist being exposed to the patient specimen through spillage or aerosol formation.

10. Chapter 42-10 Automatic performance of certain tests based on the results of other tests is called: *a. reflex testing. b. interpretive liberty. c. programming flexibility. d. random access.

General Feedback: Reflex testing is the automatic ordering of tests based on preset parameters or the results of other tests. These reflex tests must be clearly indicated to the ordering health care provider at the time the initial screening test (or tests) is ordered.

11. Chapter 42-11 What is the greatest disadvantage to photo-optical coagulation instruments? a. High cost b. Complexity of operation c. Availability is limited *d. Interference from lipemia, hemolysis, and hyperbilirubinemia General Feedback: Possible interference from the presence of lipemia, hemolysis, or hyperbilirubinemia is the greatest disadvantage for photo-optical end-point detection methods.

12. Chapter 42-12 Aspirin-induced bleeding and von Willebrand disease (VWD), type 1, are detected reliably by: a. platelet count. b. point-of-care testing (POCT). *c. PFA 100 Platelet Function Analyzer. d. nephelometry.

General Feedback: The PFA 100 Platelet Function Analyzer assesses platelet dysfunction. Aspirin and VWD both negatively affect platelet function, although by entirely different mechanisms. Aspirin acetylates cyclooxygenase, thus preventing the eventual production of thromboxane A2, an important platelet agonist. In type 1 VWD, von Willebrand factor (VWF) is decreased and therefore platelet adhesion is abnormal. The platelet count is not a reliable test for platelet function.

13. Chapter 42-13 Who should select the coagulation instruments for a given laboratory? *a. Medical staff b. Patients c. Vendors d. Billing department General Feedback: The decisions regarding which tests are the most appropriate for the clinical situations encountered by each laboratory should be made in conjunction with the medical staff. When that input has been obtained, the laboratory can determine the availability and cost of instruments that would meet those requirements.

14. Chapter 42-14 Examples of instrument malfunction flags include all except: a. temperature error. b. probe not aspirating.

c. mechanical movement. *d. hemolysis.

General Feedback: The presence of hemolysis is not flagged by the instrument but must be noted by the clinical laboratory scientist. All the other flags are instrument generated.

1. Chapter 43-01 At what age is it normal for bone marrow cellularity to be 80% to 90% (i.e., has very little fat)? *a. At birth b. In an 8-year-old c. In a 20 to 40-year-old d. In those older than 70 years General Feedback: At the time of birth, the bone marrow is fully active and extremely cellular with very little fat. It contains all hematopoietic cell lineages.

2. Chapter 43-02 Which age-group normally has the lowest mean cell volume? *a. Newborn b. Young child c. Adult d. Older adult General Feedback: The erythrocytes of newborn infants are markedly macrocytic at birth. The average MCV for full-term infants is 119 ± 9.4 fL; however, a sharp decrease occurs during the first 24 hours of life.1,2 The MCV continues to decrease to 90 ± 12 fL in 3 to 4 months.2,9,17 The more premature the infant, the higher the MCV.

3. Chapter 43-03 What is the most likely reason that the red blood cell (RBC) count remains elevated in a newborn for the first 2 weeks of life? a. Loss of plasma during the birth process b. Longer RBC life span *c. Hypoxia in utero d. Switch from fetal to adult hemoglobin General Feedback: Partial hypoxia occurs in utero, which causes the normal physiologic response to increase erythropoietin, which stimulates erythropoiesis. About 2 weeks after birth, as the infant makes the transition from its placenta-dependent oxygenation to the increased tissue oxygenation of the lungs, erythropoietin decreases, and the red cell count begins to decrease.

4. Chapter 43-04 All are normal peripheral blood RBC findings at birth in a full-term infant except: a. nucleated RBCs. *b. mean cell volume (MCV) less than 90 fL.

c. reticulocytosis of 5%. d. hemoglobin of 20.2 g/dL. General Feedback: An MCV of 90 fL in a newborn is abnormal and cause for a thalassemia/iron deficiency work-up. The mean MCV in a full-term newborn is 109 fL; an MCV less than 94 fL is cause for evaluation for alpha-thalassemia or iron deficiency. All the other results given are normal for a full-term newborn.

5. Chapter 43-05 A complete blood count (CBC) is requested on a full-term newborn girl, and the following results are obtained: RBCs 5.07 × 1012/L Hemoglobin 14.4 Hematocrit 44.5% MCV 88 fL White blood cells 26.8 × 109/L (WBCs) Platelets 295 × 109/L What conclusion can be made regarding these data for this infant? a. All results are normal. b. The white count is elevated. *c. Hemoglobin, hematocrit, and MCV are all decreased. d. Red cell count, hemoglobin, and hematocrit are all normal, but MCV is decreased.

General Feedback: The hemoglobin, hematocrit, and MCV are all low for a fullterm newborn (the red count is actually in the reference range).

Because the red count is relatively high for the hematocrit and hemoglobin, with the low MCV, thalassemia should be suspected.

6. Chapter 43-06 Why is the white count in a normal full-term newborn elevated shortly after birth? a. A relative loss of plasma occurs. *b. An absolute increase in neutrophils occurs. c. An absolute increase in lymphocytes occurs. d. An absolute increase in both neutrophils and lymphocytes occurs.

General Feedback: An absolute increase in neutrophils occurs within hours of birth; this elevates the white count. Bands and occasionally myelocytes may also be present. At day 2, the count begins to drop progressively, primarily because of an absolute decrease in neutrophils.

7. Chapter 43-07 A normal 3-month-old boy has a hemoglobin of 11.2 g/dL. Which is true about his hemoglobin? It is: a. higher than that of a normal full-term newborn. *b. lower than that of an adult of the same age. c. higher than that of a 14 year old of the same sex. d. the same as that of an adult of the same sex.

General Feedback: Hemoglobin is lower in a 3 month old than in an adult of the same sex. It is normally higher at birth but quickly begins to decrease so that by 3 months old this would be a normal hemoglobin (abnormal at birth). It is lower than that of both a 14 year old and an adult of the same sex.

8. Chapter 43-08 Why is there a relative lymphocytosis in a 2 year old? a. An absolute neutropenia occurs. *b. The absolute number of lymphocytes is increased as the immune system develops. c. A greater proportion of neutrophils are marginated. d. Fewer lymphocytes are marginated.

General Feedback: An absolute increase in lymphocytes occurs, presumably because the immune system is developing as more antigens are encountered; this increases the absolute number of lymphocytes, as well as the relative percent. The number of marginated neutrophils is not increased; lymphocytes do not marginate.

9. Chapter 43-09 What is the normal bone marrow cellularity in the population older than 65 years? a. 90% b. 70% c. 50% *d. 30% General Feedback: Bone marrow cellularity decreases in the older population and is approximately 30%. That of a young adult is 50%. This change may be caused by an increase in the volume of spongy tissue in the bone, as well as an increase in fat, rather than an actual decrease in hematopoietic tissue.

10. Chapter 43-10 An 85-year-old woman has a hemoglobin of 10.5 g/dL. This is: a. high for a woman of this age.

b. normal for this age regardless of sex (i.e., for both male and female patients). *c. a sign of an underlying disease that requires further evaluation. d. most likely a myelophthisic anemia.

General Feedback: The majority of geriatric individuals maintain a normal hemoglobin for their sex so that this hemoglobin of 10.5 g/dL in an 85year-old woman is low and a sign of an underlying disease. This requires further work-up. Most anemias in older adults are iron deficiency or the anemia of chronic inflammation (disease).

Myelophthisic anemia, in which the bone marrow is invaded by something foreign, such as metastatic malignant cells, certainly occurs but is not the most common cause of anemia in older adults.

11. Chapter 43-11 Iron deficiency anemia in older adults is most often a result of: a. poor nutritional intake of iron. b. malabsorption of iron. c. decreased ability to transport iron because of a decrease in transferrin. *d. bleeding in the gastrointestinal tract.

General Feedback: Bleeding from the gastrointestinal tract is the most common cause of iron deficiency anemia in older adults.

12. Chapter 43-12 Which is more likely to result from poor absorption than from inadequate nutritional intake in older adults? a. Folic acid deficiency b. Iron deficiency *c. Vitamin B12 deficiency d. Lead deficiency General Feedback: Vitamin B12 deficiency is most likely to develop from inadequate intestinal absorption, rather than an inadequate vitamin intake. This can progressively lead to the development of pernicious anemia.

13. Chapter 43-13 Which is true concerning age-related changes of hemostasis in older adults? a. Decreased factor VIII b. Decreased platelet activity *c. Increased fibrinogen d. Increased fibrinolysis

General Feedback: Fibrinogen levels, factor VIII, and platelet activity all increase during aging. Plasminogen activator inhibitor, the major inhibitor of fibrinolysis, increases with aging, so fibrinolysis of clots decreases.

14. Chapter 43-14 Which is most commonly seen in the population older than70 years? *a. Chronic lymphocytic leukemia b. Chronic myelogenous leukemia c. Essential thrombocytosis d. Acute lymphocytic leukemia General Feedback: Chronic lymphocytic leukemia is the most common leukemia in the population older than 70 years of age, although acute myeloid leukemia and chronic myelogenous leukemia do show increased age-related incidence. Essential thrombocytosis is rare. Chronic myelogenous leukemia is seen more often in the middle aged, and acute lymphocytic leukemia most commonly occurs in children.

This Page is Intentionally Left Blank

This Page is Intentionally Left Blank