von Willebrand Factor (VWF) Inhibitors in Two Brothers with von Willebrand Disease: A Case Report.

The development of inhibitors to von Willebrand factor (VWF) is a rare but potentially serious complication of VWF replacement therapy in patients with von Willebrand disease (VWD). Patients who develop VWF inhibitors may become unresponsive and/or may develop severe anaphylactic reactions to VWF concentrates. Data on inhibitor development and management in VWD remain limited, and better understanding of inhibitor development is an important goal in VWD management. The WIL-31 study demonstrated the efficacy and safety of prophylaxis with wilate, a plasma-derived VWF/factor VIII (pdVWF/FVIII) concentrate, in children and adults with VWD of all types. The annualized bleeding rate (ABR) was reduced by 84% with wilate prophylaxis compared with on-demand treatment, and prophylaxis was well tolerated. No inhibitors developed during the WIL-31 study. Here, we report two brothers with type 3 VWD who at the 6-month visit were found to have VWF inhibitors, which on further investigation were found to have already been present before the study. Despite the presence of inhibitors, neither patient showed any clinical symptoms, and prophylaxis with wilate led to a ≥85% reduction in ABR in both boys compared with on-demand treatment.