von Willebrand factor and its disorders: an overview of recent molecular studies.

von Willebrand factor (vWF) is a plasma protein with multiple functions in haemostasis. The vWF gene, located on chromosome 12p2.1, encodes a primary gene product of 2813 amino acids. Post-translational modification, assembly and secretion of vWF are highly complex. The pro vWF promoter is covalently linked by intermolecular disulphide bonds to form a dimer of MW approximately 440 kDa. This then polymerises to form multimers ranging in MW from 1-20 x 10(6). Simultaneously the pro piece of vWF is cleaved, releasing a 741 amino acid peptide known as vW Ag II from the polymerised protomers. Two distinct secretion pathways are found in the endothelial cell, a regulated pathway with storage in Weibl-Palade bodies and a constitutive pathway. Platelets store vWF in their alpha-granules. Mature vWF participates in platelet adhesion, spreading and aggregation and is a carrier of factor VIII, protecting the latter from degradation. Disorders of vWF are highly diverse. At least 20 subtypes of von Willebrand's disease have been described to date, based on features of the vWF present in or absent from patients plasma and platelets. Some patients have reduced amounts of apparently normal vWF whilst others have clearly abnormal vWF with aberrant structure and function. Rare patients virtually or completely lack vWF. The genetic and structural basis of some of these abnormalities is just beginning to emerge. This article outlines the molecular biology and physiology of vWF, and reviews some recent progress on the molecular pathology and genetics of von Willebrand's disease.