von Willebrand disease (VWD) is a family of bleeding disorders caused by an abnormality of the von Willebrand factor (VWF) molecule. von Willebrand disease is the most common hereditary bleeding disorder.
Described by Erik Adolf von Willebrand in 1926, von Willebrand disease is a congenital bleeding disorder characterized by a lifelong tendency toward bruising, nosebleeds, and menorrhagia.
von Willebrand disease is due to an abnormality, either quantitative or qualitative, of the von Willebrand factor molecule. This protein molecules which is a large multimeric glycoprotein that functions as a carrier protein for factor VIII (FVIII). von Willebrand factor is also required for normal platelet adhesion. von Willebrand factor functions in both primary (involving platelet s) and secondary (involving FVIII) hemostasis.
In primary hemostasis, von Willebrand factor attaches to platelets by its specific receptor to glycoprotein Ib on the platelet surface and acts as an bridge between the platelets and damaged subendothelium at the site of vascular injury. In secondary hemostasis, von Willebrand factor protects FVIII from degradation and delivers it to the site of injury.
von Willebrand factor is composed of dimeric subunits that are linked by disulfide bonds to form complex multimers of low, intermediate, and high molecular weights. The small multimers function mainly as carriers for FVIII.
High–molecular weight multimers have higher numbers of platelet-binding sites and greater adhesive properties. Each multimeric subunit has binding sites for the receptor glycoprotein Ib on nonactivated platelets and the receptor glycoprotein IIb/IIIa on activated platelets. This facilitates both platelet adhesion and platelet aggregation, making high molecular weight multimers most important for normal platelet function.
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