REPRINT ENCLOSED
Solvent/Detergent-Treated Plasma in the Management of Pediatric Patients Who Require Replacement of Multiple Coagulation Factors: An Open-Label, Multicenter, Post-marketing Study
PC, Borasino S and Alten J
Introduction:
• Clinical practice guidelines recommend plasma transfusion in children and newborns with abnormal coagulation profiles and clinically significant bleeding or prior to invasive procedures that have a high risk of significant bleeding
• Several types of plasma products are available: fresh frozen plasma (FFP), plasma frozen within 24 h (FP24) and solvent/detergent (S/D) treated plasma
Pooled Plasma (Human), Solvent/Detergent Treated Solution for Intravenous Infusion
OctaplasTM is a solvent/detergent-treated, pooled human plasma approved for multiple indications. The safety of Octaplas was evaluated in a post-marketing study in order to provide real-world data supporting its use in critically ill pediatric patients who require replacement of multiple coagulation factors.
Patients and Methodology:
• Open-label, multicenter, phase 4 (post-marketing) study conducted in patients <16 years old who required replacement of multiple coagulation factors due to liver dysfunction associated with coagulopathy and/or required cardiac surgery or liver surgery
• 50 patients enrolled (≤2 years old, n = 37; >2 years old, n = 13; female, n = 24); 49 patients completed the study
• Indications for the use of Octaplas include:
– Planned cardiac surgery (n = 40, 80%)
– Liver transplant surgery (n = 5, 10%)
– Liver dysfunction ( n = 5, 10%)
• All 50 patients had ≥1 infusion episode, ten had 2 infusion episodes, five had 3 infusion episodes and one had 6 infusion episodes
• Octaplas was administered intravenously based on ABO-group compatibility.
• Primary endpoints: incidence of serious adverse events (SAEs), adverse drug reactions (ADRs), thrombotic events (TEs), thromboembolic events (TEEs) and hyperfibrinolytic events (HFEs)
Indications and Usage
Octaplas™ is a S/D treated, pooled human plasma indicated for replacement of multiple coagulation factors in patients with acquired deficiencies due to liver disease or who are undergoing cardiac surgery or liver transplantation; and plasma exchange in patients with thrombotic thrombocytopenic purpura (TTP).
Important Safety Information
Octaplas is contraindicated in patients with immunoglobulin A (IgA) deficiency; severe deficiency of protein S; history of hypersensitivity to fresh frozen plasma or to plasma-derived products including any plasma protein; or a history of hypersensitivity reaction to Octaplas.
Please see accompanying full Prescribing Information.
OctaplasTM Was Well Tolerated in This Multicenter
Phase 4 Study of Critically Ill Pediatric Patients
“EXCELLENT” SAFETY
For all 50 patients, investigator assessment of safety was “excellent”
No ADRs, HFEs, or treatment-related TEs and TEEs were reported. No SAEs were considered to be related to Octaplas.
ZERO
ADRs, HFEs,TEs, & TEEs
9 SAEs Were Reported in 5 of the 50 (10%) Total Patient Population
Total Population (n = 50) Infants ≤2 years (n = 37) Children >2 years (n = 13)
Occurrence of any SAE
• Among infants ≤2 years (n = 37): 3 SAEs were reported in 3 patients (hemorrhage, hemorrhagic shock, portal vein thrombosis)
• Among children >2 years (n = 13): 6 SAEs were reported in 2 patients (hypotension, coronary artery hemorrhage, intracardiac thrombus, supraventricular tachycardia, fatal iatrogenic injury, respiratory failure)
• There were no clinically significant changes in vital signs between pre- and postinfusion
Treatment Response Appeared Favorable in the Majority of Patients
• TEG (thromboelastographic) values were either stable preinfusion vs postinfusion or changed from abnormal (non clinically significant) to normal pre- vs postinfusion for most TEG parameters
• Only three clinically significant abnormal hemostatic parameters were observed pre- or posttransfusion during the first infusion episode. One patient each showed a clinically significant elevated INR pre- and postinfusion, and one patient showed a clinically significant elevated aPTT value postinfusion
Discussion & Conclusions
There are notable differences between S/D-treated plasma (such as Octaplas) and FFP and FP24:
• FFP and FP24 are collected from a single donor, resulting in a significant variability in coagulation factor levels between individual units
• S/D-treated plasma is pooled from multiple units collected from different donors, resulting in significantly less variability in coagulation factor levels and less variability in thrombin generation vs FFP and FP24
• Additionally, S/D treatment inactivates any lipid-enveloped viruses (eg, HIV, HBV, HCV, Zika virus) that may be present in the donated plasma
• Also, S/D-treated plasma is practically cell free compared with FFP, containing significantly lower residual platelet concentrations and negligible amounts of microparticles due to its manufacturing process
Results of this open-label, multicenter, phase 4 study provide real-world clinical evidence supporting the use of Octaplas in critically ill pediatric patients who require replacement of multiple coagulation factors due to major surgery or acquired deficiencies associated with liver dysfunction.
• No ADRs, hyperfibrinolytic events or treatment-related thrombotic events and TEEs occurred during the study
• No SAEs that occurred were considered to be related to Octaplas
• Treatment response appeared favorable in the majority of patients
RESULTS OF THE PRESENT STUDY SUPPORT THE USE OF OCTAPLAS in the management of preoperative or bleeding pediatric patients who require replacement of multiple plasma coagulation factors.
Important Safety Information
Warnings and Precautions
Transfusion reactions can occur with ABO blood group mismatches. Administration of Octaplas must be based on ABO-blood group compatibility. High infusion rates can induce hypervolemia with consequent pulmonary edema or cardiac failure. Excessive bleeding due to hyperfibrinolysis can occur due to low levels of alpha2antiplasmin (also named plasmin inhibitor). Thrombosis can occur due to low levels of Protein S. Citrate toxicity can occur with volumes exceeding one milliliter of Octaplas per kg per minute. Octaplas is made from human plasma and may carry a risk of transmitting infectious agents, e.g. viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent.
Please see accompanying full Prescribing Information.
IN CONCLUSION, this post-marketing study provides data on the safety of Octaplas in critically ill pediatric patients who require replacement of multiple coagulation factors. The results of the present study, and those of previous studies of Octaplas, support its use in this patient population.
Important Safety Information
Adverse Reactions
The most common adverse reactions observed in ≥ 1% of patients included pruritus, urticaria, nausea, headache, paresthesia. Serious adverse reactions seen in clinical trials were anaphylactic shock, citrate toxicity and severe hypotension.
Please see accompanying full Prescribing Information.
Plasma (Human), Solvent/Detergent Treated Solution for Intravenous Infusion
Octaplas Is a Solvent/Detergent-Treated, Pooled Human Plasma Indicated for:
• Replacement of multiple coagulation factors in patients with acquired deficiencies due to liver disease or who are undergoing cardiac surgery or liver transplantation
• Plasma exchange in patients with thrombotic thrombocytopenic purpura (TTP)
Contraindications
Since 1992, more than 13.5 million bags of Octaplas have been transfused to more than 4.5 million patients worldwide*1
Octaplas is contraindicated in patients with immunoglobulin A (IgA) deficiency; severe deficiency of Protein S; history of hypersensitivity to fresh frozen plasma or to plasma-derived products including any plasma protein; or a history of hypersensitivity reaction to Octaplas.
Important Safety Information
Warnings and Precautions
Transfusion reactions can occur with ABO blood group mismatches. Administration of Octaplas must be based on ABO-blood group compatibility. High infusion rates can induce hypervolemia with consequent pulmonary edema or cardiac failure. Excessive bleeding due to hyperfibrinolysis can occur due to low levels of alpha2-antiplasmin (also named plasmin inhibitor). Thrombosis can occur due to low levels of Protein S. Citrate toxicity can occur with volumes exceeding one milliliter of Octaplas per kg per minute. Octaplas is made from human plasma and may carry a risk of transmitting infectious agents, e.g. viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent.
Adverse Reactions
The most common adverse reactions observed in ≥ 1% of patients included pruritus, urticaria, nausea, headache, paresthesia. Serious adverse reactions seen in clinical trials were anaphylactic shock, citrate toxicity and severe hypotension.