Extending half-life in coagulation factors: where do we stand?

The human coagulation factor VIII (FVIII) and von Willebrand factor (VWF) are two distinct glycoproteins that circulate in the plasma as a non-covalently bound complex (VWF/FVIII complex). Deficiencies or structural defects in FVIII and VWF are responsible for the most common inherited plasma bleeding disorders haemophilia A and von Willebrand disease (VWD), respectively. Current therapies for the treatment of haemophilia have favourable efficacy, tolerability and safety profiles. However, multiple, frequent infusions are usually required to manage a bleeding episode, owing to the short half-life of FVIII. This makes treatment inconvenient and impacts patient quality of life. Several strategies are currently being pursued in an attempt to reduce the number of infusions required per bleeding episode. One of the more promising approaches involves prolonging the half-life of FVIII. This article summarizes the methods that are being used to extend FVIII half-life.