hematology and oncology
Von Willebrand Disease
Introduction
Von Willebrand disease (VWD) is a hereditary quantitative deficiency or functional abnormality ofvon Willebrand factor(VWF), which causes platelet dysfunction. Bleeding tendency is usually mild. Screening tests usually show a normal platelet count and, possibly, a slightly prolonged partial thromboplastin time (PTT). Diagnosis is based on low levels ofvon Willebrand factorantigen andvon Willebrand factoractivity (ristocetin cofactor activity). Treatment involves control of bleeding with replacement therapy (virally inactivated, intermediate-purity factor VIII concentrate) ordesmopressin. (See also Overview of Platelet Disorders .) promotes the platelet adhesion phase of Overview of Hemostasis by binding with a receptor on the platelet surface membrane (glycoprotein Ib/IX), thus connecting the platelets to the vessel wall. VWF is also required to maintain normal plasma factor VIII levels. Levels of VWF can temporarily increase in response to stress, exercise, pregnancy, inflammation, or infection. Von Willebrand disease is classified into 3 main types: Type 1: A quantitative deficiency of VWF, which is the most common form and is an autosomal dominant disorder. VWD concentration and activity are both reduced proportionally. Type 2: A qualitative impairment in synthesis and function of VWF that can result from various genetic abnormalities and is an autosomal dominant disorder. Type 3: A rare autosomal recessive disorder in which homozygotes have no detectable VWF Four different type 2 subtypes are recognized, distinguished by different functional abnormalities of the VWF molecule: In type 2A, VWF fails to bind to platelets and there is a reduction in high molecular weight VWF multimers. In Type 2B, platelets avidly bind high molecular weight VWF resulting in increased clearance of platelets and high molecular weight multimers. VWF In type 2M, there is decreased platelet binding of VWF and VWF levels are reduced. VWF multimer distribution is preserved, but the ratio of VWF activity to concentration is reduced. In type 2 N, there is impaired binding of VWF to factor VIII and significant reduction in factor VIII levels (ie, to 1 to 5%) similar to that seen in hemophilia A. Although VWD, like Hemophilia , is a hereditary disorder that may cause factor VIII deficiency, the factor VIII deficiency in VWD is usually only moderate (ie, to 20 to 40%). Acquired von Willebrand diseaseis rare and is characterized by low levels of VWF due to decreased production or increased clearance of VWF from the circulation but is not inherited. It occurs in patients with lymphoproliferative, myeloproliferative and autoimmune disorders. 