Clinical Diagnosis AND Management BY Laboratory Methods
RICHARD A. MCPHERSON
MATTHEW R. PINCUS
ASSOCIATE EDITORS
Katalin Banki, MD
Associate Professor Department of Pathology
SUNY Upstate Medical University Syracuse, New York
Martin H. Bluth, MD, PhD
Chief, Blood Bank/Transfusion Services
Assistant Director, Clinical Laboratories
Director of Translational Research Department of Pathology
Maimonides Medical Center Brooklyn, New York; Professor of Pathology
Wayne State University School of Medicine Detroit, Michigan;
Adjunct Professor of Pathology
SUNY Downstate Medical Center Brooklyn, New York; Global Medical Director Kids Kicking Cancer Founder, Bluth Bio Industries Southfield, Michigan
Jay L. Bock, MD, PhD
Professor Emeritus Department of Pathology
Stony Brook Medicine Stony Brook, New York
Wilbur B. Bowne, MD
Professor of Surgery and Chief of Oncological Surgery Jefferson Medical Center Philadelphia, Pennsylvania
Robert E. Hutchison, MD Professor Department of Pathology
SUNY Upstate Medical University
Syracuse, New York State University of New York Upstate Medical University Syracuse, New York
Donald S. Karcher, MD
Professor and Immediate Past Chair Department of Pathology
George Washington University Medical Center Washington, DC
Mark S. Lifshitz, MD Clinical Professor
Department of Pathology, Molecular, and Cell-Based Medicine
Icahn School of Medicine at Mount Sinai New York, New York
H. Davis Massey, DDS, MD, PhD Chief, Department of Pathology and Laboratory Medicine
McGuire VA Medical Center
Associate Professor Department of Pathology Virginia Commonwealth University Richmond, Virginia
A. Koneti Rao, MBBS, FACP, FAHA Sol Sherry Professor of Medicine Professor of Clinical Pathology and Laboratory Medicine Co-Director, Sol Sherry Thrombosis Research Center Director, Benign Hematology, Hemostasis and Thrombosis Lewis Katz School of Medicine at Temple University Philadelphia, Pennsylvania
Gail L. Woods, MD Former Professor University of Arkansas for Medical Sciences Chief of Pediatric Pathology Department of Pathology
Arkansas Children’s Hospital Little Rock, Arkansas
HENRY’S Clinical Diagnosis AND Management BY Laboratory Methods
Richard A. McPherson, MD, MSc
Professor Emeritus
Department of Pathology
Virginia Commonwealth University School of Medicine
Richmond, Virginia
Matthew R. Pincus, MD, PhD
Professor
Department of Pathology
SUNY Downstate Medical Center
Brooklyn, New York
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HENRY’S CLINICAL DIAGNOSIS AND MANAGEMENT BY LABORATORY
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CONTRIBUTORS
Naif Z. Abraham Jr, MD, PhD
Director, Division of Clinical Pathology
Assistant Professor of Pathology State University of New York Upstate Medical University Syracuse, New York
Katsumi Aoyagi, PhD
Head, Research and Development Division Fujirebio, Inc.
President and CEO
Advanced Life Science Institute, Inc. Hachioji-shi, Tokyo, Japan
Yoshihiro Ashihara, PhD President and CEO
Fujirebio Holdings, Inc. Tokyo, Japan
Jaya Ruth Asirvatham, MBBS
Assistant Professor Department of Pathology, Immunology, and Laboratory Medicine University of Florida College of Medicine Gainesville, Florida
Constantine A. Axiotis, MD
Professor Department of Pathology
SUNY Downstate Health Sciences University Brooklyn, New York
Yu Bai, MD, PhD Professor of Pathology
The University of Texas Health Science Center at Houston McGovern Medical School Director, Molecular Pathology at UT Outreach Pathology Houston, Texas
Ulysses G.J. Balis, MD Professor Department of Pathology University of Michigan Ann Arbor, Michigan
Katalin Banki, MD
Associate Professor Department of Pathology SUNY Upstate Medical University Syracuse, New York
Katie V. Bean, MD
Nephrology Fellow Department of Internal Medicine Virginia Commonwealth University Richmond, Virginia
Kathleen G. Beavis, MD
Medical Director of Microbiology, Immunology, and Laboratories’ Quality Professor of Pathology University of Chicago Chicago, Illinois
Sylva Bem, MD
Assistant Professor Department of Pathology
SUNY Upstate Medical University Syracuse, New York
Jonathan Ben-Ezra, MD
Department of Pathology
Tel Aviv Sourasky Medical Center
Tel Aviv, Israel
Tim B. Bigdeli, PhD
Assistant Professor
Department of Psychiatry SUNY Downstate Medical Center Brooklyn, New York
Martin H. Bluth, MD, PhD
Chief, Blood Bank/Transfusion Services
Assistant Director, Clinical Laboratories Director of Translational Research Department of Pathology Maimonides Medical Center Brooklyn, New York; Professor of Pathology
Wayne State University School of Medicine Detroit, Michigan; Adjunct Professor of Pathology SUNY Downstate Medical Center Brooklyn, New York; Global Medical Director Kids Kicking Cancer Founder, Bluth Bio Industries Southfield, Michigan
Aleh Bobr, MD
Medical Director, Blood Bank and Tissue Services
Associate Medical Director, Apheresis Service Assistant Professor Department of Pathology and Microbiology University of Nebraska Medical Center Omaha, Nebraska
Jay L. Bock, MD, PhD Professor Emeritus Department of Pathology Stony Brook Medicine Stony Brook, New York
Michael J. Borowitz, MD, PhD Professor
Department of Pathology and Oncology
Johns Hopkins Medical Institutions Baltimore, Maryland
Wilbur B. Bowne, MD Professor
Director, Division of Oncological Surgery Department of Surgery
Sidney Kimmel Medical College
Thomas Jefferson University Philadelphia, Pennsylvania
Paul Brandt-Rauf, MD, PhD, DScD, DrPH
Dean, School of Biomedical Engineering
Drexel University
Philadelphia, Pennsylvania
Robert Bray, PhD Professor
Department of Pathology
Emory University School of Medicine Atlanta, Georgia
Cindy L. Bredefeld, DO, FACE
Attending Physician
Division of Endocrinology, Diabetes, and Metabolism
Assistant Professor of Clinical Medicine Department of Medicine
NYU Long Island School of Medicine Mineola, New York
Gary Briefel, MD
Clinical Associate Professor Department of Medicine
SUNY Downstate Medical Center Brooklyn, New York
M. Jana Broadhurst, MD, PhD, DTM&H Director, Nebraska Biocontainment Unit Clinical Laboratory Director, Emerging Pathogens Laboratory Assistant Professor, Pathology & Microbiology University of Nebraska Medical Center Omaha, Nebraska
Robert P. Carty, PhD
Associate Professor Department of Biochemistry
SUNY Downstate Medical Center Brooklyn, New York
Angela Ceribelli, MD, PhD Unit of Rheumatology
Department of Internal Medicine
Humanitas Clinical and Research Center – IRCCS Rozzano, Milan, Italy
Edward K.L. Chan, PhD
Professor Department of Oral Biology University of Florida Gainesville, Florida
Angella Charnot-Katsikas, MD Medical Director, MolDx Chief Medical Officer, Palmetto GBA Columbia, South Carolina
Sindhu Cherian, MD
Associate Professor
Department of Laboratory Medicine University of Washington Seattle, Washington
Spencer Chiang, PhD
Graduate Research Assistant
Weldon School of Biomedical Engineering Purdue University West Lafayette, Indiana
William L. Clapp, MD
Professor of Pathology
Director of Renal Pathology
Department of Pathology, Immunology, and Laboratory Medicine University of Florida College of Medicine Gainesville, Florida
Laura Lee Cooling, MD, MS
Professor
Department of Pathology University of Michigan Ann Arbor, Michigan
Lynsey Daniels, MD
General Surgery Fellow Department of Surgery
Drexel University College of Medicine Philadelphia, Pennsylvania
Robertson D. Davenport, MD Professor
Department of Pathology University of Michigan Ann Arbor, Michigan
Robert P. DeCresce, MD, MBA, MPH Director of Clinical Laboratories Department of Pathology
Rush University Medical Center Chicago, Illinois
Julio C. Delgado, MD, MS
Professor
Department of Pathology University of Utah Salt Lake City, Utah
Robert A. DeSimone, MD
Assistant Professor
Department of Pathology and Laboratory Medicine
Weill Medical College of Cornell University New York-Presbyterian Hospital New York, New York
Margaret A. DiGuardo, MD
Medical Director
Immunohematology Laboratory Division of Transfusion Medicine Mayo Clinic Rochester, Minnesota
Jorge A. Di Paola, MD
Professor of Pediatrics and Molecular Genetics and Genomics
Elizabeth Finney McDonnell Endowed Chair in Pediatric Hematology Oncology
Division Chief, Pediatric Hematology and Oncology
Washington University School of Medicine in St. Louis St. Louis, Missouri
Theresa Downs, BS Laboratory Supervisor Pathology Blood Bank University of Michigan Ann Arbor, Michigan
M. Tarek Elghetany, MD
Professor of Pathology and Immunology and Pediatrics Department of Pathology
Baylor College of Medicine
Texas Children’s Hospital Houston, Texas
Matthew B. Elkins, MD, PhD
Associate Professor
Department of Pathology
SUNY Upstate Medical University Syracuse, New York
Ayman Fanous, MD
Professor and Chairman Department of Psychiatry
SUNY Downstate Medical Center Brooklyn, New York
Marvin J. Fritzler, PhD, MD
Professor
Department of Medicine
Cumming School of Medicine
University of Calgary Calgary, Alberta, Canada
Howard M. Gebel, PhD
Professor Department of Pathology
Emory University Hospital Atlanta, Georgia
Eve Goldstein, MD
General Surgery Fellow
Department of Surgery
Drexel University College of Medicine Philadelphia, Pennsylvania
Susan S. Graham, MS
Associate Professor and Chair
Department of Clinical Laboratory Science
SUNY Upstate Medical University Syracuse, New York
Wayne W. Grody, MD, PhD
Professor
Department of Pathology & Laboratory Medicine, Pediatrics, and Human Genetics
UCLA School of Medicine
Los Angeles, California
Helena A. Guber, MD
Chief, Department of Endocrinology, Metabolism and Diabetes
NY Harbor Healthcare System
Assistant Professor of Medicine
Department of Endocrinology
SUNY Downstate Health Sciences University Brooklyn, New York
Gaurav Gupta, MD
Associate Professor Department of Internal Medicine
Virginia Commonwealth University Richmond, Virginia
Robert G. Hamilton, PhD, D(ABMLI)
Professor
Department of Medicine and Pathology
Johns Hopkins University School of Medicine Baltimore, Maryland
Amanda Harrington, PhD, D(ABMM)
Associate Professor
Department of Pathology and Laboratory Medicine
Loyola University Chicago Maywood, Illinois
Neil Selwyn Harris, MBChB, MD
Clinical Professor
Department of Pathology, Immunology, and Laboratory Medicine
University of Florida College of Medicine Gainesville, Florida
Rong He, MD
Consultant, Department of Laboratory Medicine and Pathology (Hematopathology)
Co-Director, Molecular Hematopathology Laboratory
Mayo Clinic Rochester, Minnesota
Tim Hilbert, MD, PhD, JD
Medical Director
Blood Bank
NYU Langone Medical Center
New York, New York
Julie Woolworth Hirschhorn, PhD, HCLD
Assistant Professor
Department of Pathology and Laboratory Medicine
Medical University of South Carolina Charleston, South Carolina
Catherine A. Hogan, MDCM, MSc
Instructor
Department of Pathology
Stanford University Stanford, California
Joseph Holup, PhD, (D)ABMLI
Assistant Clinical Professor
Department of Pathology
NYU Grossman School of Medicine
New York, New York
Henry A. Homburger, MD
Professor Emeritus
Mayo College of Medicine
Department of Laboratory Medicine and Pathology
Mayo Clinic Rochester, Minnesota
Yen-Michael S. Hsu, MD, PhD
Director of Immunologic Monitoring and Cellular Products Laboratory
Associate Professor of Medicine
Division of Hematology and Oncology
University of Pittsburgh School of Medicine
UPMC Hillman Cancer Center Pittsburgh, Pennsylvania
M. Mahmood Hussain, PhD Director
Diabetes and Obesity Research Center
NYU Langone Hospital–Long Island Endowed Chair
Department of Foundations of Medicine
NYU Long Island School of Medicine Mineola, New York; Distinguished Professor Emeritus Department of Cell Biology
SUNY Downstate Medical Center Brooklyn, New York
Robert E. Hutchison, MD Professor
Department of Pathology
SUNY Upstate Medical University Syracuse, New York
Peter C. Iwen, PhD, D(ABMM), F(AAM) Professor
Department of Pathology and Microbiology
University of Nebraska Medical Center Omaha, Nebraska
Shilpa Jain, MD
Associate Professor
Department of Pathology and Immunology
Director of Gastrointestinal Pathology
Baylor College of Medicine Houston, Texas
Roohi Jeelani, MD
Director of Research and Education
Reproductive Endocrinology and Infertility Vios Fertility Institute Chicago, Illinois
J. Charles Jennette, MD Professor
Department of Pathology and Laboratory Medicine
University of North Carolina at Chapel Hill Chapel Hill, North Carolina
Jeffrey S. Jhang, MD, MBA
Professor and Vice Chair
Department of Pathology, Molecular and Cell-Based Medicine
Icahn School of Medicine at Mount Sinai Medical Director, Center for Clinical Laboratories Mount Sinai Health System New York, New York
Donald S. Karcher, MD
Professor and Immediate Past Chair Department of Pathology
George Washington University Medical Center Washington, DC
Yasushi Kasahara, PhD, DMSc
Visiting Professor Department of Clinical Pathology Showa University School of Medicine Tokyo, Japan
Samuel W. Kaskovich
MD/MSc Candidate Medicine & Biomedical Informatics University of Chicago Chicago, Illinois
Craig M. Kessler, MD, MACP
Professor of Medicine and Pathology Director, Division of Coagulation Georgetown University Medical Center Washington, DC
Marian Khalili, MD
General Surgery Fellow Department of Surgery Drexel University College of Medicine Philadelphia, Pennsylvania
Jason Kidd, MD
Associate Professor
Department of Internal Medicine, Division of Nephrology
Virginia Commonwealth University Medical Center Richmond, Virginia
Michael J. Klein, MD
Pathologist-in-Chief and Director Emeritus
Department of Pathology and Laboratory Medicine Hospital for Special Surgery
Professor of Pathology and Laboratory Medicine Department of Pathology and Laboratory Medicine
Weill Cornell School of Medicine New York, New York
Katrin M. Klemm, MD
Medical Director
Aperian Laboratory Solutions Medical Director
EAMC Hospital Laboratory Department of Pathology East Alabama Medical Center Opelika, Alabama
Stefanie Krick, MD, PhD
Assistant Professor Department of Medicine
The University of Alabama at Birmingham Birmingham, Alabama
Scott Krummey, MD, PhD
Assistant Professor Johns Hopkins School of Medicine Baltimore, Maryland
Attila Kumánovics, MD
Senior Associate Consultant
Department of Laboratory Medicine and Pathology
Mayo Clinic Rochester, Minnesota
Anthony Kurec, MS, MASCP, MLT(ASCP)H, DLM
Clinical Associate Professor, Emeritus
Clin Lab Science
SUNY Upstate Medical University Syracuse, New York
Charles LaDoulis, MD
Chairman Emeritus Department of Pathology
Maimonides Medical Center Brooklyn, New York
Raymond G. Lau, MD
Clinical Assistant Professor Director of Medical Weight Management Division of Endocrinology, Diabetes, and Metabolism Division of Bariatric Surgery Department of Medicine
NYU Long Island School of Medicine Mineola, New York
Eszter Lázár-Molnár, PhD Assistant Professor Department of Pathology University of Utah Salt Lake City, Utah
Grace Ming Lee, MD Assistant Professor Division of Hematology Department of Medicine
Duke University Durham, North Carolina
Peng Lee, MD, PhD
Professor of Pathology and Urology
New York University Langone Medical Center and School of Medicine
Chief, Pathology and Laboratory Medicine Service VA NY Harbor Healthcare System New York, New York
Jing Li, PhD Professor Department of Oncology Karmanos Cancer Institute
Wayne State University School of Medicine Detroit, Michigan
Mark S. Lifshitz, MD Clinical Professor
Department of Pathology, Molecular, and Cell-Based Medicine
Icahn School of Medicine at Mount Sinai New York, New York
Bo Lin, MD, PhD Resident Physician Department of Pathology
SUNY Downstate Medical Center Brooklyn, New York
Ronald P. Mageau, MD KWB Pathology Associates Tallahassee, Florida
Mariana Markell, MD Professor Department of Medicine
SUNY Downstate Health Sciences University Brooklyn, New York
H. Davis Massey, DDS, MD, PhD
Chief Department of Pathology and Laboratory Medicine
McGuire VA Medical Center
Associate Professor Department of Pathology
Virginia Commonwealth University Richmond, Virginia
Blaine A. Mathison, BS, M(ASCP)
Scientist Institute for Clinical and Experimental Pathology ARUP Laboratories Salt Lake City, Utah
Sharad C. Mathur, MD
Associate Chief of Staff for Education VA Medical Center
Kansas City, Missouri; Professor Department of Pathology and Laboratory Medicine University of Kansas Medical Center Kansas City, Kansas
Richard A. McPherson, MD, MSc
Professor Emeritus Department of Pathology
Virginia Commonwealth University School of Medicine Richmond, Virginia
Lauren A. McVoy, MD, PhD
Vice Chair of Clinical Integration Department of Laboratory Medicine
Memorial Sloan Kettering Cancer Center New York, New York
Kimberly Merkel, MD
Adjunct Assistant Professor Department of Dermatology University of Florida College of Medicine Gainesville, Florida
Jacquelyn L. Meyers, PhD
Assistant Professor Department of Psychiatry
SUNY Downstate Medical Center Brooklyn, New York
W. Greg Miller, PhD Professor Department of Pathology
Virginia Commonwealth University Richmond, Virginia
Paul D. Mintz, MD
Chief Medical Officer
Senior Vice President
Verax Biomedical Inc. Marlborough, Massachusetts
Golam Mohi, PhD
Professor
Department of Biochemistry and Molecular Genetics
University of Virginia School of Medicine Charlottesville, Virginia
Angela Mojica, MD
Assistant Professor Department of Pediatrics
SUNY Upstate Medical University Syracuse, New York
Michel R. Nasr, MD
Interim Chair of Pathology and Laboratory Medicine Director of Clinical Pathology and Genomics
SUNY Upstate Medical University Syracuse, New York
Dejan Nikolic, MD, PhD
Director of Microbiology and Immunology
Site Pathology Residency Program Director Department of Pathology and Laboratory Services
Cooper University Health Care Assistant Professor of Pathology
Cooper Medical School of Rowan University Camden, New Jersey
Frederick S. Nolte, PhD Professor and Vice-Chair for Laboratory Medicine Department of Pathology and Laboratory Medicine Medical University of South Carolina Charleston, South Carolina
Man S. Oh, MD Professor Department of Medicine
SUNY Downstate Medical Center Brooklyn, New York
Juan P. Olano, MD Professor
Department of Pathology University of Texas Medical Branch Galveston, Texas
Mihaela Oprea, MD Attending Physician Department of Endocrinology NY Harbor Healthcare System Brooklyn, New York
Thomas L. Ortel, MD, PhD Professor Departments of Medicine and Pathology Duke University Medical Center Durham, North Carolina
Zheng Ouyang, PhD Professor Department of Precision Instrument Tsinghua University Beijing, China
Mary Ann Perle, PhD Director of Cytogenetics Department of Pathology
NYU School of Medicine, Bellevue Hospital Center New York, New York
Roseann E. Peterson, PhD Assistant Professor Virginia Commonwealth University Virginia Institute for Psychiatric and Behavioral Genetics Richmond, Virginia
Matthew R. Pincus, MD, PhD Professor Department of Pathology
SUNY Downstate Medical Center Brooklyn, New York
Benjamin A. Pinsky, MD, PhD Associate Professor
Departments of Pathology and Medicine (Infectious Diseases) Stanford University School of Medicine Director, Clinical Virology Laboratory Stanford Health Care and Stanford Children’s Health Stanford, California
Anna R. Plourde, MD, MPH Director, Clinical Microbiology Laboratory Clinical Assistant Professor Department of Pathology
SUNY Downstate Health Sciences University Brooklyn, New York
Bobbi S. Pritt, MD, MSc, (D)TMH
Professor
Department of Laboratory Medicine and Pathology
Mayo Clinic Rochester, Minnesota
Simon Rabinowitz, PhD, MD
Vice Chairman
Department of Pediatrics
SUNY Downstate Children’s Hospital Brooklyn, New York
Nikita Raje, MD, MSc
Section of Allergy/Asthma/Immunology
Department of Pediatrics
Children’s Mercy
University of Missouri Kansas City Kansas City, Missouri
Jacob H. Rand, MD
Professor
Department of Pathology and Laboratory Medicine
Weill Medical College of Cornell University New York-Presbyterian Hospital New York, New York
A. Koneti Rao, MBBS, FACP, FAHA
Sol Sherry Professor of Medicine
Professor of Clinical Pathology and Laboratory Medicine
Co-Director, Sol Sherry Thrombosis Research Center Director, Benign Hematology, Hemostasis and Thrombosis
Lewis Katz School of Medicine at Temple University Philadelphia, Pennsylvania
Virginia Commonwealth University School of Medicine Richmond, Virginia
Rhonda K. Roby, PhD, MPH
Technical Leader/Supervising DNA Criminalist
Crime Laboratory Forensic Biology Unit Alameda County Sheriff’s Office Oakland, California
Kyle G. Rodino, PhD
Assistant Professor
Department of Pathology and Laboratory Medicine University of Pennsylvania Perelman School of Medicine Philadelphia, Pennsylvania
Yan Xue Russell, MD
Fellow
Department of Endocrinology
NY Harbor Healthcare System Brooklyn, New York
Ravi Sarode, MD
Director, Division of Transfusion and Hemostasis Professor of Pathology and Internal Medicine (Hematology/Oncology) UT Southwestern Medical Center Dallas, Texas
Cynthia A. Schandl, MD, PhD
Professor
Department of Pathology and Laboratory Medicine
Medical University of South Carolina Charleston, South Carolina
Shabnam Seydhafkan, MD
Resident Physician
Department of Pathology
SUNY Downstate Medical Center Brooklyn, New York
Haseeb A. Siddiqi, PhD Professor
Departments of Cell Biology, Pathology, and Medicine
SUNY Downstate Health Sciences University Brooklyn, New York
Natthapol Songdej, MD, MPH
Assistant Professor of Medicine and Pediatrics Department of Medicine
Penn State Health Milton S Hershey Medical Center Hershey, Pennsylvania
Constance H. Stein, PhD Professor Emeritus Department of Pathology
SUNY Upstate Medical University Department of Clinical Pathology University Hospital Syracuse, New York
Lisa M. Stempak, MD
System Director of Clinical Pathology Department of Pathology
University Hospitals Cleveland Medical Center
Clinical Assistant Professor Case Western Reserve University Cleveland, Ohio
H. Clifford Sullivan, MD, D(ABHI)
Assistant Professor Department of Pathology and Laboratory Medicine Emory University School of Medicine Atlanta, Georgia
George R. Thompson III, MD, FIDSA Associate Professor of Medicine Division of Infectious Diseases Department of Internal Medicine University of California–Davis Medical Center Sacramento, California
Neerja Vajpayee, MD Laboratory Director Oneida Health Oneida, New York
David S. Viswanatha, MD
Consultant, Department of Laboratory Medicine and Pathology (Hematopathology)
Co-Director, Molecular Hematopathology and Clinical Genome Sequencing Laboratories Mayo Clinic Rochester, Minnesota
Carlos Alberto von Mühlen, MD, PhD Chairman of the Board Department of Immunology
Brazilian Society of Autoimmunity Porto Alegre, Rio Grande do Sul, Brazil; Consultant
Immunology and Rheumatology San Diego, California
David H. Walker, MD Professor
Department of Pathology
Executive Director Center for Biodefense and Emerging Infectious Diseases
University of Texas Medical Branch Galveston, Texas
Hannah Wang, MD
Resident Department of Pathology
Stanford University Stanford, California
Victor W. Weedn, MD, JD
Chief Medical Examiner
Office of the Chief Medical Examiner
Maryland Department of Health Baltimore, Maryland
Eric T. Weimer, PhD, D(ABHI, ABMLI)
Assistant Professor
Department of Pathology and Laboratory Medicine University of North Carolina Chapel Hill, North Carolina
Ruth S. Weinstock, MD, PhD
SUNY Distinguished Service Professor Department of Medicine
SUNY Upstate Medical University Syracuse, New York
Nancy L. Wengenack, PhD
Professor Department of Laboratory Medicine and Pathology Mayo Clinic Rochester, Minnesota
Nathan P. Wiederhold, PharmD, FCCP, FIDSA, FECMM Professor
Department of Pathology and Laboratory Medicine
University of Texas Health Science Center San Antonio, Texas
William E. Winter, MD
Professor
Departments of Pathology, Immunology, and Laboratory Medicine, Pediatrics, and Molecular Genetics and Microbiology University of Florida College of Medicine Gainesville, Florida
Jeffrey L. Winters, MD
Medical Director
Therapeutic Apheresis Treatment Unit Division of Transfusion Medicine Mayo Clinic Rochester, Minnesota
Christina M. Wojewoda, MD
Director, Clinical Microbiology Laboratory
Department of Pathology and Laboratory Medicine
University of Vermont Medical Center
Associate Professor
Department of Pathology and Laboratory Medicine
University of Vermont Burlington, Vermont
Brent L. Wood, MD, PhD Professor
Department of Pathology and Laboratory Medicine
Childrens Hospital Los Angeles University of Southern California Los Angeles, California
Gail L. Woods, MD Former Professor
University of Arkansas for Medical Sciences Chief of Pediatric Pathology Department of Pathology
Arkansas Children’s Hospital Little Rock, Arkansas
Wenpeng Zhang, PhD Postdoctoral Research Associate Department of Chemistry
Purdue University West Lafayette, Indiana
Yaxia Zhang, MD, PhD
Chief of Clinical Pathology Head of Pathology Research Associate Director of Fellowship Program Department of Pathology and Laboratory Medicine Hospital for Special Surgery Associate Professor of Pathology and Laboratory Medicine Department of Pathology and Laboratory Medicine
Weill-Cornell School of Medicine
New York, New York
PREFACE
Clinical laboratory measurements form the scientific basis upon which medical diagnosis and management of patients is established. These results constitute the largest section of the medical record of patients, and laboratory examinations will only continue to grow in number as new procedures are offered and well-established ones are ordered more frequently in the future. The modern concept of an electronic health record encompasses information from a patient’s birth through that individual’s entire life, and laboratory testing is a significant component of that record from prenatal and newborn screening through childhood, adulthood, and geriatric years. Traditional areas of testing are well established in clinical chemistry, hematology, coagulation, microbiology, immunology, and transfusion medicine. Genetic testing for disease detection, hereditary disease risk assessment and definitive diagnosis and prognosis is becoming a reality, beginning with individual disease testing that is expected to be followed by whole genome screening for a multitude of conditions. The rapid pace in the introduction of new testing procedures demands that laboratory practitioners be experts in several divergent aspects of this profession. The environment of clinical laboratories is extremely well-suited for translation of research procedures into diagnostic assays because of their traditional involvement in basic analysis, quality control, professional competencies, and cost-effective strategies of operation. All of these applications are made stronger for occurring under regulations of federal and state governments, as well as the standards of accreditation of professional pathology organizations. Clinical laboratories excel in these tasks, and they are now responding to pressures for even greater accomplishments in areas of informatics, advanced analytic methods, interpretation of complex data, and communication of medical information in a meaningful way to physician colleagues and even directly to patients in some health care models. The most successful practitioners of laboratory medicine will incorporate all of these approaches into their daily lives and will be leaders in their institutions for developing initiatives to promote outstanding health care in a fiscally responsible endeavor. This textbook strives to provide the background knowledge by which trainees can be introduced to these practices and to serve as a resource for pathologists and other laboratory personnel to update their knowledge to solve problems that they encounter daily.
This twenty-fourth edition marks more than 100 years since A Manual of Clinical Diagnosis, authored by James Campbell Todd, was introduced in 1908. In its current format as Henry’s Clinical Diagnosis and Management by Laboratory Methods, this textbook remains the authoritative source of information for residents, students, and other trainees in the disciplines of clinical pathology and laboratory medicine, and for physicians and laboratory practitioners. The current edition continues the tradition of partnership between laboratory examinations and the formulation and confirmation of clinical diagnoses followed by monitoring of body functions, therapeutic drug levels, other results of medical treatments, and risk assessment for disease. Beginning with the twenty-first edition, color illustrations have been used throughout the book to accurately and realistically depict clinical laboratory test findings and their analysis. The overriding mission of this book is to incorporate new discoveries and their clinical diagnostic applications alongside the wealth of information that forms the core knowledge base of clinical pathology and laboratory medicine. It is also our objective to call the reader’s attention to important unsolved problems in diagnostic medicine and to stimulate the reader to formulate ways to solve these problems. Our contributing authors, who are experts in their specialties, present to the reader the essential basic and new information that is central to clinical laboratory practice.
Part 1, The Clinical Laboratory, covers the organization, purposes, and practices of analysis, interpretation of results, and management of the clinical laboratory from quality control through informatics and finances. The general structure of this section includes general management principles, with emphasis on preanalytic, analytic, and postanalytic components of laboratory analysis as well as oversight functions. Administrative concepts for the laboratory are considered in Chapter 1, with optimization of workflow presented in Chapter 2. Preanalytic factors such as variations arising
from specimen collection, transport, and handling and other variables are discussed in Chapter 3. The principles of analysis and instrumentation are presented in Chapter 4. Since the field of mass spectroscopy has begun to play an important role in a wide variety of areas of laboratory medicine, including clinical chemistry and microbiology, we have now introduced a new chapter, Chapter 5, in this new edition that is devoted to the principles and practice of mass spectrometry. Chapter 6 covers laboratory automation. The growing arena of near-patient laboratory services beyond central hospital laboratories in the format of point-of-care testing is presented in Chapter 7 along with presentation on this application in the military. Postanalysis processes of result reporting and medical decision making, are presented in Chapter 8 while a systematic approach that allows the clinician and laboratorian to interpret and assess laboratory results is presented in Chapter 9. This chapter provides the basis for formulation of differential diagnosis from laboratory values, choice of possible reflex testing and the ordering of further testing to confirm diagnoses. A key component to all phases of laboratory processes, interpretation of results, and decision making is statistical analysis, which is presented in Chapter 10. Explicit applications of statistics are in quality control and proficiency testing for oversight of the entire analytic process (Chapter 11). Maintaining order for the complexities of laboratory test result ordering and reporting and the management of clinical information are possible only through sophisticated information systems that are essential to all clinical laboratories (Chapter 12). Management decisions in the clinical laboratory involve the choice of analytic instrumentation, automation to process and deliver specimens to analytic stations, and computer systems to coordinate all of the preanalytic, analytic, and postanalytic processes to meet the mission of the institution. These choices determine the productivity that a laboratory can achieve (especially its ability to respond to increased volumes of testing and complexity of measurements and examinations as the standards of practice advance). Paramount is the manner in which the laboratory can muster its resources in equipment, personnel, reagent supplies, and ingenuity of its leadership to respond to the needs of health care providers and patients in terms of access, timeliness, cost, and quality of test results. New challenges continue to emerge for the laboratory to provide excellent quality services at a fiscally responsible expense; the changing models of reimbursement for medical and laboratory services demand that pathologists and laboratory leaders develop and maintain a strong understanding of the principles of financial management and be well aware of mechanisms that laboratories can utilize for responding to these new approaches to reimbursement (Chapter 13). Chapter 14 on ethics in laboratory medicine provides a framework for appropriate delivery of clinical laboratory testing and human subjects research in accordance with accepted principles of behavior.
Part 2, Clinical Chemistry, is organized to present laboratory examinations according to organ systems and their disorders. Some of the most commonly ordered laboratory tests are directed at the evaluation of renal function, water, electrolytes, metabolic intermediates and nitrogenous wastes, and acid-base balance, all of which are critically important for monitoring acutely ill patients and in the management of patients with kidney and pulmonary disorders (Chapter 15). The important field of bone metabolism and bone diseases, stemming from the enormous public interest in osteoporosis of our aging population, is covered in Chapter 16. The significance of carbohydrate measurements, with particular emphasis on diabetes mellitus, the overall hormonal regulation of glucose metabolism, and disorders of other sugars, is reviewed in Chapter 17. Chapter 18 covers the extremely important topic of lipids and disorders in their metabolism and highlights the critical patterns in lipoprotein profiles that indicate disposition to atherosclerosis and cardiac malfunction, especially myocardial infarction. In Chapter 19, the serodiagnostic markers for cardiac injury evaluation and the related disorders of stroke are elaborated. The clinical significance of specific proteins and their analysis, with emphasis on electrophoresis of blood and body fluids, is covered in Chapter 20. The field of clinical enzymology, with applications to assessment of organ injury,
is covered in Chapter 21. The principles of enzymology (e.g., transition state theory) have been used directly in the design of new effective drugs against specific diseases such as hypertension and AIDS. A new section has been introduced into this chapter concerning the mechanism of infection of cells by the Coronavirus-19, (Covid-19), the cause of the current world pandemic, because, incredibly, this virus binds uniquely to the angiotensin converting enzyme, ACE2, which acts as its receptor on cell surfaces. Laboratory assessment of liver function is presented in Chapter 22 (which includes new treatments for hepatitis C) and that of gastrointestinal and pancreatic disorders in Chapter 23. Toxicological analysis and therapeutic drug monitoring are covered in Chapter 24, with applications of both immunoassays and mass spectroscopy emerging in endocrinology (Chapter 25) and pregnancy and perinatal testing as well (Chapter 26). Nutritional analysis, with examination of vitamins and trace metals, is presented in Chapter 27 Chapter 28 elaborates the chemical principles of analysis, which is crucial to the understanding of virtually all laboratory measurements and the common interferences encountered with blood and biological fluids.
Part 3, Urine and Other Body Fluids, reviews the utility and methods for examining fluids other than blood. Chapter 29 presents the basic examination of urine, with extensive discussions of both chemical testing and microscopic examination of urine sediment. A special area for consideration is body fluid analysis, which has received national attention recently in terms of standardizing the approach to testing of typical fluids and other alternative specimens (Chapter 30). A large range of specimen types is considered in this discussion, with extensive coverage of both microscopic and chemical examinations.
Part 4, Hematology and Transfusion Medicine, introduces techniques for the basic examination of blood and bone marrow (Chapter 31) and provides a wealth of background on the physiological processes involved in hematopoiesis (Chapter 32). Erythrocytic disorders and leukocytic disorders and their diagnosis are covered in Chapters 33 and 34, respectively. Modern techniques for use of flow cytometry for diagnosis of hematopoietic neoplasias are presented in Chapter 35 to round out the approaches to diagnosis in this rapidly changing field. Immunohematology, which is so important for the understanding of erythrocyte, leukocyte, and platelet antibodies and their impact on transfusion, is covered in Chapter 36 Blood component manufacture and utilization are covered in Chapter 37 along with transfusion reactions. Chapters 38 and 39 deal with the rapidly expanding areas of apheresis, with its applications to therapy of multiple blood disorders as well as the collection, processing, and dispensing of hematopoietic progenitor cells (adult stem cells) from bone marrow, peripheral blood, and cord blood for treatment of both malignant and nonmalignant diseases.
Part 5, Hemostasis and Thrombosis, covers the vast increase in our knowledge of the pathways involved in clotting and in fibrinolysis and the panoply of new testing and therapeutic modalities that have evolved as a result. This section continues to reflect the impact of our growing knowledge of coagulation and fibrinolysis (Chapter 40) plus that of platelet function disorders, with emphasis on von Willebrand disease (Chapter 41). Advances in the diagnosis and monitoring of thrombotic disorders are covered extensively in Chapter 42, with particular interest in the prediction of thromboembolic risk. Along with our better understanding of thrombosis have come new drugs for treatment of patients with vascular occlusive disorders, particularly ischemic events in the heart or brain. Principles of antithrombotic therapy and the laboratory’s role in its monitoring are covered in Chapter 43. Also discussed in this section is the major advance in pharmacogenomics (fully discussed later in Chapter 75) as it impacts anticoagulant therapies for individual patients.
Part 6, Immunology and Immunopathology, presents a framework both for classifying disorders of the immune system and for the role of laboratory testing in diagnosing those diseases (Chapter 44). Measurements based on immunoassays have long been the essential components of understanding a multitude of disorders; an excellent and comprehensive account of the principles of immunoassay and immunochemistry is included in Chapter 45. Evaluation of the cellular immune system for diagnosing and monitoring immune defects is described in Chapter 46, which is newly updated. Humoral immunity and the examination of immunoglobulins in disease are covered in Chapter 47, with particular emphasis on the evaluation of monoclonal disorders in the blood. Material on complement and its role in inflammation is presented in Chapter 48 Chapter 49 presents cytokines and adhesion molecules that are vital to inflammation and have become targets for therapeutic interventions. Also brought up to date are Chapter 50 on the major histocompatibility complex (MHC), with its significant applications to organ transplantation, and Chapter 51, which looks at MHC and disease associations. The evaluation of immunodeficiency
disorders includes many standard examinations for protein and cellular functions plus new genetic tests for specific abnormalities (Chapter 52). The assessment of autoimmune diseases is presented for the systemic rheumatic diseases (Chapter 53), with new chapters covering the vasculitides (Chapter 54) and organ-specific autoimmune diseases (Chapter 55). Allergic diseases, with their ever-increasing laboratory evaluations, are presented in Chapter 56
Part 7, Medical Microbiology, covers an enormous spectrum of infectious diseases and related topics that include medical bacteriology (Chapter 57); susceptibility testing of antimicrobial agents (Chapter 58); mycobacteria with immense concern for the emergence of resistant strains (Chapter 59); mycotic diseases with a wide array of photographs of cultures and photomicrographs (Chapter 60); spirochete infections (Chapter 61); chlamydial and mycoplasmal infections (Chapter 62); rickettsiae (Chapter 63); viral infections with new material on human coronavirus-19 (Chapter 64); and medical parasitology which has a worldwide significance that is growing as large numbers of people move between countries and continents(Chapter 65). In line with the importance of achieving maximum diagnostic benefit from the laboratory, specimen collection and handling for diagnosis of infectious disease are detailed in Chapter 66. Although classic techniques have consisted of culturing microbiological organisms with identification and antimicrobial susceptibility testing through functional bioassays, modern methods of nucleic acid amplification and detection are now becoming widespread for each type of microbiological organism; these applications are described in each chapter about the various organisms. In addition, the use of mass spectroscopy, that has revolutionized the microbiology laboratory in the identification of pathogens, is likewise discussed in each appropriate chapter.
Part 8, Molecular Pathology, covers some of the most rapidly changing and exciting areas of clinical laboratory testing. Chapter 67 provides an introduction to the role of molecular diagnostics, with an updated discussion of the principles and techniques of the field in Chapter 68. Similar updates are provided for the vital molecular diagnostic techniques of polymerase chain reaction and other amplification methods (Chapter 69) and newer approaches to nucleic acid hybridization (Chapter 70). The application of cytogenetics, with modern methods of karyotyping, including fluorescent in situ hybridization and examination for chromosomal abnormalities, is covered in Chapter 71. Chapter 72 comprehensively presents the application of molecular diagnostics to genetic diseases, for which screening is becoming more widely practiced. In view of the revolutionary development of genome-wide association studies (GWAS), major discoveries of genomic alterations in neuropsychiatric diseases such as Alzheimer’s disease, schizophrenia, and post-traumatic stress disorder (PTSD) have been found. Therefore, a new presentation (Chapter 73) on the molecular biology of neuropsychiatric diseases provides understanding for diagnosis and therapy of these disorders. Identity testing as used in modern parentage testing and forensic analysis is presented in Chapter 74. Chapter 75 on pharmacogenomics provides an understanding of how molecular analysis of selected genes crucial for response to therapeutic drugs or for the metabolism of drugs can be used to optimize individualized treatment plans, also known as personalized or precision medicine.
Part 9, Clinical Pathology of Cancer, is a further outgrowth of this section that was introduced in the twenty-first edition. Because of the explosion of new diagnostic information as a result of the successful sequencing of the human genome, genetic profiles of different forms of cancers are now available. Specific forms of cancer are beginning to be diagnosed using microchips containing gene arrays in which patterns of gene expression and mutation are evaluated. In addition, new methods of proteomics (i.e., determination of the patterns of expression of multiple proteins in patients’ body fluids and tissues) allow for cancer detection, monitoring, and treatment. Thus there has been a vast increase in information about the principles and applications of laboratory methods for diagnosis and monitoring of malignancies in just the past few years. Chapter 76 deals with the important protein markers for cancer in blood and tissues that are commonly used for the diagnosis and management of malignant diseases. Chapter 77 extends this discussion through exciting new applications of oncoproteins and growth factors and their receptors in the assessment of malignancies and modification of therapies. A broad spectrum of molecular and cytogenetic markers is now commonly used for the initial evaluation of hematopoietic neoplasms (Chapter 78) that could well become a model for assessment of most, if not all, malignancies. Because the methods in molecular pathology used in diagnosing cancer in body fluids are the same as in solid-tissue diagnosis, breaking down the barriers between anatomic and clinical pathology, we include Chapter 79 on the evaluation of solid tumors by these methods.
The prospects for early detection, prognosis, and implementation of treatment regimens for cancer based on specific alterations in the genome have never been more apparent. These chapters on cancer diagnostics emphasize genome-based approaches and other new methods such as proteomics, which has the potential to identify patterns of protein alterations that can be used both for discovery of new targets for examination and for direct detection of clinical abnormalities. Many of these technologies have been developed in the past few years, and many more versions of them are sure to appear as the competitive advantage of rapid and inexpensive genomic analysis emerges. We think it is vital for pathologists to understand the bases of molecular diagnostics, the power of this type of analysis for clinical decision making, and the paths such testing is likely to take in the future. To this end, the final chapter (Chapter 80) presents the diagnostic and prognostic impact of high-throughput genomic and proteomic technologies and the role they can play in the present and future practice of pathology.
The fundamental task for trainees in laboratory medicine is to achieve a sound understanding of analytic principles and the power and limitations of laboratory examinations so that they can interpret whether abnormal results are due to a patient’s physical condition or to other potential interferences such as altered physiological state, drug interactions, or abnormalities introduced by specimen mishandling. Based on mastery of these technical aspects of test performance and interpretation, pathologists should be able to recommend strategies to provide the appropriate level of care for multiple purposes: to screen for disease, to confirm a diagnosis, to establish a prognosis, to monitor the effects of treatment, and (more recently) to assess the future risk of disease. National practice recommendations from the American Medical Association and the U.S. Department of Health and Human Services have led to the formulation of standardized panels of multiple individual tests that are targeted to several organ systems, such as the basic metabolic panel and comprehensive metabolic panel (Appendix 7, available online with the other appendices). These panels consist of individual tests that are highly automated and can be conveniently and inexpensively delivered through most hospital laboratories. Such convenience was not always the case when the assays for basic constituents such as potassium, sodium, chloride, bicarbonate, calcium, bilirubin, and all the various metabolites, proteins, and enzyme activities were performed manually, as documented in previous editions of this textbook. Beyond those relatively simple tests, immunoassays have also undergone a similar transformation. A few decades ago, the rapid assay for thyroid-stimulating hormone (TSH) required 2 days, whereas today a third-generation TSH measurement can be completed in 20 minutes or less. Conversion from highly complex and operator-interactive testing to immediately available and inexpensive assays will almost certainly occur with procedures that are now at the cutting edge of technology and require elaborate instrumentation and special expertise to perform. These include tandem mass spectrometry for small molecules such as hormones, vitamins, and drugs; whole genome sequencing for assessing the risk of developing hereditary disorders and diagnosing malignancies; and proteomics
for screening a wide array of proteins in blood, body fluids, and tissues for disease detection and evidence of progression. The configuration of these assays will consolidate multiple analyses onto miniature platforms such as chip technologies.
We also note that new methods of microanalysis have now been implemented so as to enable rapid point-of-care testing on critically ill patients on small volumes of whole blood. These include the “stat” analytes (sodium, potassium, chloride, bicarbonate, calcium, BUN, creatinine and glucose and, now, several critical enzymes) in addition to blood gas determinations, all performed on hand-held analyzers and also on blood gas analyzers. In a recent breakthrough in testing, a new mass spectrometer has been devised that is the size of a brief case allowing for point-of-care testing by mass spectroscopy.
Although these new technologies will likely be expensive to implement initially, the hope is that they will reduce costs in other parts of the health care system through initiating prevention or treatment earlier than would be possible without such complex and intimate information about a patient’s disease state or propensity to develop a disease.
Within this context, it is clear that the role of the clinical laboratory in the future will involve more than simply providing numeric results for physicians to glance at during rounds or after clinic duty. The complexity and enormity of the test results that will be routinely available will require entirely new approaches to data presentation and interpretation to provide useful information for clinical diagnosis and management. The challenge to laboratories and clinicians alike is to develop “meaningful uses” in which electronic health records can store and present all of this information about a patient—from cradle through an entire life—into which several segments are integrated: genetic background, environmental factors, previous diagnostic and monitoring tests, and contemporaneous monitoring tests. All of these aspects of a patient’s history have the potential to be meaningful in the most rigorous sense to provide personalized medical treatments.
This textbook provides grounding in the practice of modern laboratory medicine, and it points the way to new disciplines that will contribute to the evolution of strategies for creating, analyzing, and presenting medical information in the future. We hope that the discussions in this textbook will stimulate our colleagues at all levels to conceive of and/or embrace new diagnostic laboratory technologies (in addition to those that are now standard) and to retain the most valuable from each of these into practices of the future. The legacy of this book over the past century has been to provide a clear and useful account of laboratory tests that generate the solid scientific information upon which medical decisions are based. Building on that foundation, we enthusiastically anticipate new diagnostic capabilities, and we hope that this textbook will be a stimulus to their development.
It is a privilege and an honor to serve as editors for this twenty-fourth edition.
Richard A. McPherson, MD, MSc
Matthew R. Pincus, MD, PhD April 2021
ACKNOWLEDGMENTS
We gratefully acknowledge the outstanding contributions made by our expert colleagues and collaborators who served as associate editors: Katalin Banki, MD; Martin H. Bluth, MD, PhD; Jay L. Bock, MD, PhD; Wilbur B. Bowne, MD; Robert E. Hutchison, MD; Donald S. Karcher, MD; Mark S. Lifshitz, MD; H. Davis Massey, DDS, MD, PhD; A. Koneti Rao, MBBS; and Gail L. Woods, MD. They all have made extensive contributions to the quality of this book, both through development of textual matter and through the exercise of practiced review of the chapters under their guidance. We deeply appreciate their efforts in this edition. We gratefully acknowledge the participation in previous editions of Elizabeth R. Unger, MD, PhD.
It is with sadness that we note the passing of four authors who made significant contributions to the previous edition of this text. We wish to honor their memories and recognize their professional achievements.
Martin J. Salwen, MD. Dr. Salwen was a Distinguished Service Professor at the State University of New York (SUNY) Downstate Medical Center and former Director of Pathology at both SUNY Downstate University Hospital and the Kings County Hospital. After graduating from SUNY Downstate, he performed his residency in Pathology and Laboratory Medicine at Yale University Medical Center after which he served with distinction in East Asia as a Captain in the medical corps in the United States Air Force. After his military service, he became the Director of Laboratories at Monmouth Medical Center, New Jersey. He then became Director of Pathology at both the Downstate University Hospital and the Kings County Hospital, and Professor of Pathology at SUNY Downstate Medical Center, where he revolutionized the practice of laboratory medicine and trained several generations of pathology residents. Under his leadership the laboratories were equipped with advanced instrumentation using state-of-the art technology, and embarked on the use of efficient laboratory information systems. He revolutionized the clinical pathology services at both medical centers whereby attending physicians and house officers made joint rounds on patients with unusual laboratory findings, greatly increasing the efficacy of both the clinical and anatomic pathology services. His elective course in the interpretation of laboratory data for senior medical students was immensely popular and benefitted them in understanding clinical medicine. In collaboration with Drs. William Sunderman Sr. and Jr., Dr. Salwen helped found and promote the clinical pathology journal, Annals of Clinical and Laboratory Science and served on its editorial board for many years. Dr. Salwen made enormous contributions to the clinical pathology literature in many areas including documentation of multisystem failure in gram-negative sepsis, and the graphic presentation of laboratory data that facilitated clinical interpretation and understanding. He received many awards during his tenure at SUNY Downstate Medical Center, including the prestigious Ailanthus Award, the Jean Redmond Oliver Teaching Award, and the Dr. Frank L. Babbott Memorial Award for distinguished service to the medical profession and community. Dr. Salwen’s passing is a tremendous loss to SUNY Downstate Medical Center, to the field of clinical pathology, and especially to this book to which he contributed over its many editions.
Geraldine S. Hall, PhD. Dr. Hall was a Clinical Microbiologist at the Cleveland Clinic and served as the Section Head of Microbiology. She was dedicated to education and excelled in the practice of microbiology which she conveyed to numerous trainees. She served in many leadership
positions for the American Society of Microbiology both nationally and regionally.
Omar Fagoaga, PhD. Dr. Fagoaga was director of the Histocompatibility Laboratory of the Detroit Medical Center and Wayne State University having immigrated to the United States from El Salvador where he had been the target of terrorists as a youth. Despite that experience, he was known for his warm personality and for being a fast learner of laboratory methodologies. He was at the forefront of DNA typing in histocompatibility testing. Among his greatest accomplishments was the mapping of HLA alleles and antibodies in African American populations.
Nancy S. Jenny, PhD. Dr. Jenny was Associate Professor in the Department of Pathology and Laboratory Medicine at the University of Vermont. Her research in the biochemical mechanisms of diseases of aging including atherosclerosis, dementia, and general frailty led to numerous prestigious publications.
All of our students, residents, and colleagues have for decades contributed enormously to the development of our knowledge of human disease and the use of laboratories for diagnosis and patient management. We are grateful for all of their questions and the stimulus they have provided to our professional growth. We are especially grateful for the mentorship and encouragement provided in our careers by Alfred Zettner, MD; Cecil Hougie, MD; Abraham Braude, MD; Charles Davis, MD; James A. Rose, MD; Robert P. Carty, PhD; Donald West King, MD; George Teebor, MD; Phillip Prose, MD; Fred Davey, MD; and Gerald Gordon, MD. We will always remember them and the standards for excellence they set.
The development of this edition, with its myriad details, would not have been possible without the outstanding professional efforts of our editors at Elsevier: Kathryn DeFrancesco, Michael Houston, and John Casey, each of whom added tremendously to this enterprise. We are sincerely grateful to them and to all the staff of Elsevier. They have made this endeavor a happy one. We also send very special thanks to Anne Erickson, a supreme medical illustrator, who has drawn many of the illustrations in the most recent four editions with a fine eye to beauty in presentation and ease of comprehension.
We are grateful to all of the authors for accepting the challenge to participate in the education of future and present laboratorians and physicians in all fields of medicine by distilling the essential information from each of their fields of expertise and creating a readable and authoritative text for our audience. Special thanks to the authors who have created wholly new chapters on mass spectroscopy, ethics in laboratory medicine, and molecular biology of psycho-neurologic disease for this edition.
We also remember with perpetual gratitude the inspiration provided to us by John Bernard Henry, MD. He provided leadership for seven editions of this book. Moreover, he encouraged us, guided us, and demanded excellence from us in our profession.
Upon the completion of this twenty-fourth edition, we humbly thank all the individuals who have played roles in making it possible. It is not possible to name all of the individuals who have contributed to this textbook. To those mentioned here and to those not explicitly named, we thank you for your prodigious efforts and support. We also gratefully acknowledge the loving support of our wives, Stephanie Sammartino McPherson and Naomi Pincus, in developing this edition and in all our endeavors.
Richard A. McPherson, MD, MSc
Matthew R. Pincus, MD, PhD
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