von Willebrand factor: from cell biology to the clinical management of von Willebrand's disease

Remarkable progress has been made in the pathogenesis, classification and treatment of von Willebrand disease. The structure and function of vWf have been delineated, and correlated to the phenotype of the various forms of vWd. Efficient and reasonably safe therapies such as DDAVP and FVIII/vWf concentrates are now available. However, many challenges remain. Several forms of clinical vWd, in particular type 1 and some forms of type 2, remain to be explained at the molecular level. It is striking that type 1, although the most frequent form of the disease, is also the least understood. Future research into the determination of plasma vWf levels, in particular the transcriptional regulation of the pro-vWf gene could provide a better understanding of the variable penetrance of vWf mutations. More standardized confirmatory diagnostic tests and treatment protocols would also be welcome for clinicians. The cellular mechanism of action of DDAVP and its coordinate effect on vWf, FVIII and tissue plasminogen activator still need to be firmly established. Future research into the biology of vWf can be expected to provide novel insights not only into the pathogenesis of vWd, but also into a variety of disorders such as thrombotic thrombocytopenic purpura and atherosclerosis, where vWf-dependent platelet adhesion is likely to play a key role.