Recent progress in von Willebrand disease type 2B

von Willebrand disease type 2B (VWD-type 2B) is characterized by gain-of-function mutations in von Willebrand factor (VWF) that enhance its binding to the platelet GPIb alpha receptor, causing increased platelet clearance and loss of high molecular weight VWF multimers. In VWD-type 2B, the clinical outcome is strongly dependent on the mutation. The bleeding phenotype in VWD-type 2B is often explained by i) the absence of high-molecular-weight VWF multimers, ii) the unavailability of GPIb alpha, due to constitutively bound VWF mutants and iii) the moderate to severe thrombocytopenia observed in these patients. Thrombocytopenia may originate from impaired platelet production and/or from the incorporation of platelets into circulating VWF/platelets aggregates. Recent investigations have revealed that mutated VWF in VWD-type 2B is able to induce a thrombocytopathy explaining in part the bleeding tendency. The diversity of phenotypes and genotypes associated to the VWD-type 2B, as well as the variability inter-and intra-individual of the clinico-biological signs according to the physiopathological situations (pregnancy, surgery, inflammation etc.) are reflected by the multiplicity of the therapeutic attitudes, which vary of a simple administration of DDAVP, to VWF concentrates and platelet transfusion. A better knowledge of mechanisms responsible for the hemorrhagic tendency observed in this pathology will allow to optimize its care.