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Clinical presentation and diagnosis of von Willebrand disease

Margaret E Rick, MD
Section Editor
Lawrence LK Leung, MD
Deputy Editor
Jennifer S Tirnauer, MD


Von Willebrand disease (VWD) is the most common inherited bleeding disorder, affecting up to 1 percent of the population as assessed by random laboratory screening, although only approximately 1 percent of these individuals are appreciably symptomatic [1]. It is characterized by mutations that lead to a decrease in the level or impairment in the action of von Willebrand factor (VWF) (table 1). Most cases are transmitted as an autosomal dominant trait that affects males and females equally [2]. There are also acquired forms of VWD that are caused by several different pathophysiologic mechanisms. (See "Classification and pathophysiology of von Willebrand disease" and "Biology and normal function of von Willebrand factor".)

The clinical presentation and diagnosis of VWD will be reviewed here. Treatment of VWD is discussed separately. (See "Treatment of von Willebrand disease".)


Von Willebrand factor (VWF) plays an important role in primary hemostasis by binding to both platelets and endothelial components, forming an adhesive bridge between platelets and vascular subendothelial structures at sites of endothelial injury (figure 1) and between adjacent platelets in areas with high shear [3,4]. It 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 [5].

Von Willebrand factor circulates as a series of multimers formed from a basic dimer subunit. (See "Biology and normal function of von Willebrand factor".) High molecular weight VWF multimers are the most active form of VWF [3,4], providing multiple binding sites that can interact with both platelet receptors and subendothelial structures at sites of injury. Plasma VWF is synthesized by megakaryocytes and endothelial cells and undergoes extensive post-synthetic processing. When released acutely from these cells, VWF contains even larger multimers than are normally observed in the circulation. These "unusually large" forms are prothrombotic [6]; they are rapidly proteolyzed by the VWF cleaving protease (ADAMTS13) to the "normal" multimer size distribution as defined by a normal plasma pool [7]. (See "Biology and normal function of von Willebrand factor".)


Although decreased levels of von Willebrand factor (VWF) are relatively common, only a fraction of patients come to medical attention because of bleeding symptoms and are diagnosed as having von Willebrand disease (VWD). This low incidence of bleeding is due to the mild nature of the disease in many patients and to the lack of bleeding challenges and/or lack of recognition of minor excessive bleeding (eg, heavy menstrual bleeding) in others.


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Literature review current through: Sep 2016. | This topic last updated: May 6, 2016.
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