Clinical Information

von Willebrand factor (VWF) is a large multimeric plasma glycoprotein that performs 2 critical functions in hemostasis:

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

-VWF is a carrier molecule for procoagulant factor VIII in the circulation, increasing the factor VIII half-life 5-fold. Under conditions of high shear, VWF also mediates platelet-platelet cohesion by binding to the platelet receptor GP-IIb/IIIa (integrin alpha IIb beta3)

A bleeding disorder, von Willebrand disease (VWD), occurs when VWF is quantitatively deficient or qualitatively abnormal. VWD manifests clinically as easy bruising, mucocutaneous bleeding (eg, epistaxis, menorrhagia), and bleeding after trauma or surgery. VWD is the most common of the inherited bleeding disorders, and can also occur on an acquired basis.

Plasma VWF consists of a 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.

Inherited VvWD  has been classified into 3 types:

-Type 1, typically an autosomal dominant disease, is the most common, accounting for approximately 70% of VvWD 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 vFWVFW . Four subtypes have been identified: 2A, 2B, 2M, and 2N.

-Type 3, an autosomal recessive disorder, leads to severe disease with extremely reduced or 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), severe aortic stenosis, gastrointestinal angiodysplasia, and hypothyroidism.