Use of pharmacokinetic modelling to individualize FFP dosing in factor V deficiency

Abstract

Therapy with fresh frozen plasma (FFP) confers serious risks, such as contraction of blood-borne viruses, allergic reaction, volume overload and development of alloantibodies. The aim of this study was to apply principles of pharmacokinetic (PK) modelling to individual factor content of FFP to optimize individualized dosing, while minimizing potential risks of therapy. We used PK modelling to successfully target individual factor replacement in an 8-month-old patient receiving FFP for treatment of a severe congenital factor V (FV) deficiency. The model fit for the FV activity vs. time data was excellent (r = 0.98) and the model accurately predicted FV activity during the intraoperative and postoperative period. Accurate PK modelling of individual factor activity in FFP has the potential to provide better targeted therapy, enabling clinicians to more precisely dose patients requiring coagulation products, while avoiding wasteful and expensive product overtreatment, minimizing potentially life-threatening complications due to undertreatment and limiting harmful product-associated risks.

Management of intracranial hemorrhage in severe factor V deficiency and definitive treatment with liver transplantation

“…An individual pharmacokinetic study was performed in an attempt to optimize SDP management. 1 After a single infusion of 24.7 mL/kg given over 4 hours, FV levels at 0.5, 2, 4, 6, and 8 hours after the conclusion of the infusion equaled 40%, 33%, 29%, 23%, and 19%, respectively…”

“…Underscoring the tenuous condition of the patient under optimal medical management, FV activity levels intermittently continued to decrease below 5%, leading to a second acute intracranial bleed at age 4 months in the same distribution as the first bleed (Figure ). An individual pharmacokinetic study was performed in an attempt to optimize SDP management . After a single infusion of 24.7 mL/kg given over 4 hours, FV levels at 0.5, 2, 4, 6, and 8 hours after the conclusion of the infusion equaled 40%, 33%, 29%, 23%, and 19%, respectively (Figure ).…”

Design and Usability of an Electronic Health Record—Integrated, Point-of-Care, Clinical Decision Support Tool for Modeling and Simulation of Antihemophilic Factors

“…1 In fact, PK strategies have been used to guide the replacement of various clotting factors for more than two decades. [2][3][4][5] Successful application of PK-guided dose individualization to routine patient care requires (1) comprehensive knowledge of the patient, (2) a thorough understanding of the pharmacologic principles that drive the relationship between doseexposure, and (3) expertise in mathematical and PK modeling and simulation. 6 Providers with expert knowledge of the latter often have limited involvement with the patient or their primary medical team and engaging them outside the normal flow of care can introduce delays in arriving at the best dosing solution for the patient.…”

“In vitro” correction of the severe factor V deficiency‐related coagulopathy by a novel plasma‐derived factor V concentrate

“…However, repeated FFP infusions may lead to serious side effects, such as transfusion‐related acute lung injury (TRALI), fluid overload, transmission of infections, development of alloantibodies and allergic reactions . Although these risks can be reduced using pharmacokinetic modelling and virus inactivation by solvent/detergent treatment of plasma, FV activity levels can be elevated to only ~20 IU/dL in severely affected patients (FV activity levels <1 IU/dL). Platelet transfusions have also been used to treat severe bleeding because FV stored in platelets in a preactivated form has a greater procoagulant activity than plasma FV and is released locally at the site of vascular injury .…”