Prophylaxis in hemophilia A: beyond PK – the potential role of procoagulant platelet in the hemostatic activity of rFVIII a

Hemophilia A (HA), a hereditary bleeding disorder arising from mutations in the clotting factor VIII (FVIII) gene, disrupts the intrinsic blood coagulation pathway. Treatment primarily aims to prevent bleeding episodes by replenishing deficient clotting factor levels through intravenous clotting factor concentrate infusion. The advent of replacement therapy using FVIII concentrates has significantly advanced treatment, enhancing protection against bleeds and reducing arthropathy. This narrative review seeks to provide an overview of the importance of eradicating bleeds and the therapeutic potential of recombinant FVIII (rFVIII)-based replacement therapy. We explored the available evidence on the hemostatic mechanisms triggered by rFVIII in prophylaxis and the role of phospholipid membranes of activated platelets in FVIII-mediated FX-activation and thrombin burst. Key insights from the congresses of the International Society on Thrombosis and Hemostasis (2022) and the European Association for Hemophilia and Allied Disorders (2023) are also discussed. This review discusses the importance of optimizing prophylactic FVIII regimens through personalized approaches considering each patient’s bleeding profile clinical conditions, and lifestyle preferences for achieving joint health and quality of life. We also explored the potential role of rFVIII affinity for procoagulant platelets in hemostasis among HA patients.