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Von Willebrand Disease (VWD)
Part 1: NHLBI Diagnosis Guidelines

Introduction & Clinical Assessment Recommendations



VWF Biology

Slide 3

May 2011

I will review key points about the biology of von Willebrand factor (VWF), because this information is important for understanding von Willebrand disease (VWD). Von Willebrand factor is mainly synthesized in vascular endothelium, but also in bone marrow megakaryocytes (which produce blood platelets). During its synthesis, VWF is multimerized into an extremely large polymeric glycoprotein with molecular weight up to 20 million Daltons. Endothelial cells secrete VWF multimers into the blood, and they also package it into storage organelles called Weibel-Palade bodies — from which VWF can be secreted by endothelial stimulation such as by desmopressin (DDAVP), vasopressin, or epinephrine. Platelet VWF is stored in alpha (a) granules from which it is secreted with platelet activation, and by which platelet adhesion and aggregation are enhanced. VWF has important hemostatic functions including:

  • (1) VWF is the principal protein mediating platelet adhesion to injured blood vessels, and it thereby initiates and localizes platelet accumulation at vascular injury sites, resulting in primary hemostasis, which is the process for initial cessation of blood loss.
  • (2) VWF binds and stabilizes coagulation factor VIII, abbreviated FVIII, the anti-hemophilic procoagulant cofactor that is synthesized from its X-chromosome gene (rather than from the VWF gene on chromosome 12). Factor VIII bound to VWF is protected from proteolytic inactivation that shortens its survival. Also, the factor VIII bound to VWF accelerates thrombin generation within primary hemostatic plugs; this process is called secondary hemostasis.
  • (3) Lastly, recent research identifies that VWF plays a role in down-regulating angiogenesis — the process of generating new blood vessels in tissues. This evolving information may help us better understand why some VWD patients develop microvascular arterio-venous malformations or AVMs,that can cause gastrointestinal mucosal bleeding.
VWF Biology

 


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