Von Willebrand Disease Laboratory Diagnosis

Abstract

von Willebrand disease (vWD) is an autosomal disorder characterized by episodic mucocutaneous bleeding.1 vWD may be the most common inherited bleeding disorder; however, estimates of its prevalence range from 0.01% to 1.0%, depending on the definition and population basis.2 The clinical diagnosis of vWD is complex because symptoms vary within kindred and over time. Furthermore, the most common symptoms, epistaxis, menorrhagia, ecchymoses, and bleeding after dental extraction, occur nearly as frequently in healthy people as in people diagnosed with vWD identified by laboratory detection of known mutations.3 Owing to the difficulties associated with the diagnosis of vWD, the National Heart, Lung, and Blood Institute (NHLBI) sponsored an expert panel that started to plan clinical practice guidelines in the spring of 2004. The panel sought expert consultation and review by several professional organizations such as the American Society of Hematology, the Centers for Disease Control and Prevention, the Food and Drug Administration, and the North American Specialized Coagulation Laboratory Association (NASCOLA). Their final recommendations became available in 2007.1 von Willebrand factor (vWF) is a compound plasma protein that circulates as small (∼2 million Da) to large (∼20 million Da) multimers. vWF, particularly its large multimers, coats the exposed fibrillar collagen of damaged adventitia. The bound vWF expands (“unrolls”) and binds platelet membrane receptor glycoprotein (GP) Ib/V/IX, enabling platelets to adhere to vascular injury sites in arterioles and capillaries. vWD researchers consider the level of vWF activity to be directly proportional to the availability of large vWF multimers, a consideration supported by their presence in plasma samples from healthy subjects and their partial absence from some patients with vWD, as demonstrated using vWF multimeric electrophoresis.4 vWF also binds and stabilizes coagulation factor VIII (FVIII). Binding to collagen, platelets, and FVIII relies on ligand-specific receptors confined to specific …