von Willebrand Disease

• Von Willebrand factor (VWF) plays an important role in primary hemostasis by binding to both platelets and endothelial structures, forming an adhesive bridge between them and between adjacent platelets at sites of endothelial injury
• VWF also contributes to fibrin clot formation by acting as a carrier protein for factor VIII, which has a greatly shortened half-life and abnormally low concentration unless it is bound to VWF
• Von Willebrand disease (VWD) is an inherited or acquired deficiency in VWF.  VWD is the most common inherited bleeding disorder, affecting up to 1% of the population, although less than 5 % of affected individuals are symptomatic
• Bleeding symptoms in VWD occur when VWF is sufficiently decreased OR when a qualitative defect in VWF impairs one of its functions.
• VWD mostly affects primary hemostasis, so clinical manifestations are similar to those seen in platelet disorders (easy bruising, prolonged bleeding from mucosal surfaces, petechiae).
• However, in some types of VWD, there is a qualitative defect in VWF that affects its binding site for factor VIII, mimicking the findings seen in classical hemophilia (soft tissue and joint bleeding) This occurs in a rare inherited forms of VWD (types 2N and 3) and can occur in acquired VWD
• Acquired VWD can be associated with hematologic malignancies (including CLL, Multiple Myeloma, MGUS, Waldenstrom’s, lymphoma), autoimmune diseases, and some drugs
• The pathophysiology of acquired VWD is thought to be due to several different mechanisms, including: antibody formation to VWF, proteolysis, non-immune binding of paraproteins to cells resulting in increased clearance or sequestration of VWF

(Victoria Kelly MD, 12/4/10)