Clinical Information

von Willebrand factor (VWF) is a large multimeric plasma glycoprotein that has essential roles in primary hemostasis. Wild-type VWF molecules are series of multimers varying in size from dimers to multimers over 40 subunits (>10-million Daltons). The largest multimers provide multiple binding sites that can interact with both platelet receptors and subendothelial matrix sites of injury and are the most hemostatically active form of VWF. The biological functions of VWF are as follows:

1. VWF is a ligand and mediates platelet adhesion to the subendothelial collagen at the site of vessel wall injury by binding to the platelet receptor glycoprotein (GP)-Ib, V, IX complex and subendothelial collagen.

2. VWF binds and stabilizes procoagulant factor VIII in the circulation.

3. Under conditions of high shear, VWF also mediates platelet-platelet cohesion by binding to the platelet receptor GP-IIb/IIIa (integrin alpha IIb beta3)

von Willebrand disease (VWD) is the most common hereditary bleeding disorder that is caused by quantitative or qualitative VWF defect. VWD manifests clinically as easy bruising, mucocutaneous bleeding (eg, epistaxis, menorrhagia), and bleeding after trauma or surgery.

VWD has been classified into 3 major types:

-Type 1, typically an autosomal dominant disease, is the most common, accounting for approximately 70% of VWD patients. It represents a quantitative deficiency of VWF of variable severity.

-Type 2, which is usually an autosomal dominant disease, is characterized by several qualitative abnormalities of VWF. Four subtypes have been identified: 2A, 2B, 2M, and 2N.

-Type 3, an autosomal recessive disorder, leads to severe disease with virtually undetectable levels of VWF, as well as very low levels of factor VIII.

Acquired von Willebrand syndrome (AVWS) is associated with a number of different disease states and is caused by several different pathophysiological mechanisms, including antibody formation, proteolysis, binding to tumor cells with increased clearance, and decreased synthesis. AVWS is most frequently described in patients with dysproteinemias (including monoclonal gammopathy of undetermined significance [MGUS], multiple myeloma, and macroglobulinemia), lymphoproliferative disorders, myeloproliferative disorders (eg, essential thrombocythemia), autoimmune diseases (eg, systemic lupus erythematosus), high-shear stress cardiovascular conditions such as severe aortic stenosis, gastrointestinal angiodysplasia, and hypothyroidism.