Exploring nonreplacement therapies' impact on hemophilia and other rare bleeding disorders

Abstract

The management of hemophilia, von Willebrand disease (VWD), and rare coagulation disorders traditionally relied on replacement therapies, such as factor concentrates, to address clotting factor deficiencies. However, in recent years, the emergence of nonreplacement therapies has shown promise as an adjunctive approach, especially in hemophilia, and also for patients with VWD and rare bleeding disorders. This review article offers an overview of nonreplacement therapies, such as FVIII-mimicking agents and drugs aimed at rebalancing hemostasis by inhibiting natural anticoagulants, particularly in the management of hemophilia. The utilization of nonreplacement therapies in VWD and rare bleeding disorders has recently attracted attention, as evidenced by presentations at the International Society on Thrombosis and Haemostasis 2023 Congress. Nonreplacement therapies provide alternative methods for preventing bleeding episodes and enhancing patients' quality of life, as many of them are administered subcutaneously and allow longer infusion intervals, resulting in improved quality of life and comfort for patients.

Keywords: hemophilia; mimic factor; nonreplacement therapy; rare bleeding disorders; rebalancing therapy; von Willebrand disease.

Figure

Schematic representation of the coagulation cascade with the sites of action of natural anticoagulants and the novel nonreplacement drugs. APC, activated protein C; F, factor; Pro S, protein S; TF, tissue factor, TFPI, tissue factor pathway inhibitor.