Therapeutic Monitoring-Guided Dosing of Factor Viii in Hemophilia A: From Pharmacodynamics and Pharmacokinetics toward Precision Therapy

Abstract

Hemophilia is a rare hypocoagulation disorder that, depending on the lacking coagulation cascade factor, has different denominations. This review focuses on Hemophilia A (HA), particularly on the FVIII concentrates that are available in clinical practice to replace the scarce levels of FVIII observed in these patients. In fact, pharmacological responses are strongly heterogenic namely due to disease evolution and FVIII concentrates pharmacokinetic profiles. Therefore, therapeutic drug monitoring (TDM) is essential to maximize FVIII effectiveness and decrease adverse event rates. We provide a critical overview of current FVIII concentrates their mechanistic and pharmacokinetic differences as well as the factors that determine those profiles. Precision dosing through therapeutic drug monitoring is expanding and is essential in populations with altered pharmacokinetics and/or pharmacodynamics. However, there is still a need for studies correlating pharmacokinetics and patient outcomes. Herein, a pharmacokinetic-based optimization of FVIII therapy was revised and in deeply explained hot it can be successfully applied in clinical practice.