New development in von Willebrand disease

Von Willebrand disease (VWD) is an autosomally inherited bleeding disorder caused by a deficiency or abnormality of von Willebrand factor (VWF). VWF is a multimeric adhesive protein produced mainly by the endothelial cells. VWF is crucial in primary hemostasis because it promotes platelet adhesion to the subendothelium at the sites of vascular injury and in coagulation because VWF is the carrier of factor VIII. VWD is highly heterogeneous because the molecular mechanisms underlying the different clinical and laboratory phenotypes may be complex. VWD is classified into quantitative deficiencies of VWF (type 1 and type 3 VWD) and qualitative variants (type 2 VWD), because of a dysfunctional VWF. Whereas inheritance is autosomal dominant and bleeding tendency is heterogeneous in type 1 and 2, type 3 patients present moderate-to-severe bleeding diathesis and display a recessive pattern of inheritance.

Although the responsible genetic background has been extensively clarified over the recent years, providing insights on the structure-function relationship of the protein, the cellular basis of the disorder is being investigated for a few mutations only recently. In several cases, increased clearance of the mutant VWF may be responsible for the disease. Standardized criteria for the definition of bleeding history and appropriate history collection are now available, but estimates of bleeding risk are largely lacking.

VWD, the most frequent inherited bleeding disorder, has been the subject of extensive pathophysiological and clinical studies. The novel evidences provide accurate insights on the mechanisms of the disease and the bleeding risk associated with VWF deficiency or abnormality.