von Willebrand factor and platelet function.

vWF is an adhesive protein that binds to two distinct platelet glycoproteins, GP Ib and GP IIb-IIa complex. Its interaction with GP Ib is primarily responsible for platelet adhesion to the subendothelium. The current model is that vWF binds to collagen and/or another component of the subendothelium, after which a conformational change in the vWF molecule exposes the GP Ib binding site. This interaction may not only promote the initial attachment of platelets to the subendothelium but also play a role in thrombus formation through exposure of GP IIb-IIIa to which vWF and fibrinogen can bind. The second important function of vWF is to be a carrier for F. VIII, protecting it from degradation and playing a role in its activation by thrombin. Circulating vWF has a complex multimeric structure that ranges in Mrs from 0.5 to 20 x 10(6) Daltons. The basic subunit has a Mr of 270 kDa. Amino acid sequencing of vWF demonstrated that the basic subunit or mature vWF is made up of 2050 amino acids. Molecular cloning of the vWF cDNA revealed that the primary transcript consists of 8900 base pairs that encode for 2813 amino acids, including a 22 amino acid signal peptide and a propolypeptide of 741 amino acids, called vWF antigen II. Recent studies on the expression of recombinant vWF molecules indicate that the propolypeptide is involved in the multimerization of vWF. The domains on the vWF molecule involved in the interactions of vWF with GP Ib, GP IIb-IIIa, collagen, F. VIII and heparin have been localized to varying extents. It is anticipated that peptide analysis and recombinant DNA techniques, such as in vitro mutagenesis, will further define the structural requirements of these binding domains. vWF is synthesized in a cell-specific manner by endothelial cells and megakaryocytes. It undergoes a complex intracellular biosynthesis involving transcription of a 200 kb gene, splicing out more than 42 introns, translation of a 8900 bp mRNA, glycosylation, disulphide bond formation, sulphatation, multimerization and proteolytic cleavage. The molecule can be secreted in a constitutive or regulated manner upon perturbation of the endothelial cells with physiological and non-physiological secretagogues. The mechanisms that control the synthesis of vWF should be an exciting area of further research. vWD is probably the most common of all congenital disorders of haemostasis. It is an extremely heterogeneous syndrome involving quantitative or qualitative disorders of vWF.(ABSTRACT TRUNCATED AT 400 WORDS)