Factor VIII-von Willebrand factor binding defects in autosomal recessive von Willebrand disease type Normandy and in mild hemophilia A. New insights into factor VIII-von Willebrand factor interactions

Abstract

This concise review is focused on genetic, molecular and clinical aspects of von Willebrand disease (VWD) type 2N and of mild hemophilia A due to mutations impairing FVIII-von Willebrand factor (VWF) interactions. Missense mutations in the VWF gene impairing the binding to FVIII do not impair the structure of VWF multimers nor the ability of VWF to aggregate platelets but causes an accelerated clearance of FVIII. Missense mutations in the FVIII gene impairing the binding to VWF are a common cause of mild/moderate hemophilia A. The implications of these observations for the treatment of patients with coagulation factor concentrates and desmopressin are discussed.