Improved prevention of bleeding episodes with emicizumab in 3 patients with concomitant hemophilia A and von Willebrand disease.

Abstract

The typical phenotype of hemophilia A (HA) is that of frequent bleeding episodes, up to several per month, unless prophylactic factor VIII (FVIII) replacement or alternatives are given. Related bleeding may be heightened in severity or frequency by co-morbid bleeding disorders. Based on the reported prevalence of von Willebrand disease (VWD) of up to 1% of the general population, the co-existence of HA and VWD occurs, but is likely less recognized. Prophylactic FVIII replacement may or may not adequately prevent bleeding in persons with HA and mild VWD, and plasma-derived concentrates containing FVIII and von Willebrand factor (VWF) may be used for more successful bleeding prophylaxis. However, therapy adherence remains problematic for many reasons, one being treatment via intravenous access. Emicizumab is a nonfactor subcutaneous prophylactic therapy for HA that may overcome this concern. We describe three patients, with severe HA and VWD, for whom regular FVIII/VWF prophylaxis was deemed inadequate. FVIII/VWF prophylaxis was replaced with weekly prophylactic injections of the bispecific monoclonal antibody, emicizumab. When the patients were transitioned to emicizumab, all experienced a significant reduction in their annualized bleed rate (ABR). Although the mechanism of action does not directly affect or replace VWF function, emicizumab may be an effective prophylaxis alternative to FVIII/VWF concentrate in patients with concomitant severe HA and VWD.