Vwf Modulates The In Vivo Fviii Recovery Of Different Fviii Concentrates In A Mice Model Of Severe Hemophilia With Inhibitors

About 25% of severe hemophilia A patients undergoing factor VIII (FVIII) replacement therapy develop antibodies against FVIII (FVIII inhibitors). The formation of inhibitor is generally accepted as the most common and challenging complication of hemophilia treatment. In the circulation, FVIII is tightly bound to von Willebrand factor (VWF), forming a complex that plays a significant role in FVIII protection from premature degradation (Delignat S et al, Haemophilia 2012;18:248-54). Several laboratory and clinical studies suggest that the presence of VWF in FVIII concentrates might have some benefits due to the protective effect against antibodies (Shi Q et al, J Thromb Haemost 2012;10:2328-37; Mannucci PM, Haemophilia 2012;18 Suppl 2:2-7). Plasma-derived (pd) FVIII/VWF concentrates show higher residual FVIII activity and more thrombin generation after incubation with inhibitors compared to isolated FVIII concentrates (pdFVIII or recombinant, rFVIII). The protective effect of VWF observed in native pdFVIII/VWF complex is not completely restored for isolated FVIII even after mixing with VWF before analyzing the reaction with inhibitors (Bravo MI et al, Haemophilia 2014; in press).