Diagnosis and classification of von Willebrand disease

von Willebrand disease (VWD) is the most frequent inherited disorder of hemostasis and is due to quantitative (VWD type 1 and 3) or qualitative (VWD type 2) defects of von Willebrand factor (VWF). Due to the large heterogeneity of VWF defects and to the external variables (blood groups and other physiologic modifiers) influencing VWF levels in the circulation, VWD diagnosis can be difficult especially in relatively mild forms. Three criteria should be always satisfied for a correct VWD diagnosis: 1) a positive bleeding history in the patients; 2) reduced levels of VWF activity in plasma; 3) a positive family history suggestive of VWD. According to the most recent clinical prospective studies, bleeding history in the patients and in their family members should be now derived from a detailed questionnaire on 11 bleeding symptoms and a bleeding severity score (BSS) can be calculated. The ristocetin cofactor activity of VWF (VWF:RCo) is the most useful test for VWD screening in the general population because it reproduces in vitro the first VWF interactions with its platelet receptor: however other assays are required to identify and classify the different VWD types The current classification in different VWD types (1, 2A, 2B, 2M, 2N, 3) is important to understand the basic mechanisms of VWF defects, to determine the risk of bleeding and to select the best therapeutic approach. Molecular screening can be important to confirm phenotypic diagnosis. Compared to hemophilia, most VWD patients show relatively mild bleeding symptoms. Therefore, prenatal diagnosis is required mainly in case of parents already known to be carrier of VWD type 3, with gene defects identified in their first affected child. No major bleeding problems usually occur at birth also in severe type 3 VWD. Neonatal diagnosis can be performed in case of children born from parents with VWF defects already characterized, but phenotypic diagnosis of VWD should be always confirmed and compared with the other affected members within the same family. Since young children with VWD type 3 might carr y deletions of VWF gene that predispose to the allo-antibodies to VWF, every new child with VWD type 3 should be intensively investigated by searching deletions, before starting extensive therapy with exogenous VWF concentrates.