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

Abstract

Type 3 von Willebrand disease (VWD3) is due to a virtually complete deficiency of von Willebrand factor (VWF), and it is inherited as an autosomal recessive trait: heterozygous relatives have mild or no bleeding symptoms. The prevalence of VWD3 is very low, ranging from 0.1 to 5.3 per million population. VWD3 patients are characterized by undetectable levels of VWF antigen and reduced concentrations of factor VIII (FVIII). Clinical manifestations are excessive mucosal bleeding and prolonged oozing after surgical procedures. In women, menorrhagia might be very severe. In contrast with other VWD types, soft tissue and joint bleeding can occur in VWD3 because FVIII is always reduced. VWF large and small gene deletions have been identified in the most severe forms of VWD3 and have been associated with the development of anti-VWF inhibitors. These inhibitors not only make therapy with VWF/FVIII concentrates ineffective but also might trigger life-threatening anaphylactic reactions.