Clinical, Laboratory, and Molecular Markers of Type 3 von Willebrand Disease

Type 3 von Willebrand disease (VWD) is the most severe form of this bleeding disorder owing to a virtually complete deficiency of von Willebrand factor (VWF). Type 3 VWD is inherited as a recessive trait-heterozygous relatives have mild or no bleeding symptoms, while most patients with type 3 VWD show severe bleeding because they are characterized by undetectable levels of VWF antigen and reduced concentrations (<0.10 IU/dL) of factor VIII. Although rare, type 3 VWD is of major interest because of its severe clinical presentation, the need for replacement therapy, and the risk of occurrence of alloantibodies after the infusion of plasma-derived VWF concentrates. The molecular basis of type 3 VWD has been studied in detail and numerous molecular defects have been identified. This chapter will focus on the clinical, laboratory, and molecular aspects of type 3 VWD that can be useful for a correct therapeutic approach in these patients.