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Classification and pathophysiology 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 caused by mutations that lead to an impairment in the synthesis or function of von Willebrand factor (VWF). There are also acquired forms of VWD that are caused by several different pathophysiologic mechanisms.

The classification and pathophysiology of VWD will be reviewed here. The clinical manifestations, diagnosis, and treatment of this disorder are discussed separately. (See "Clinical presentation and diagnosis of von Willebrand disease" and "Treatment of von Willebrand disease".)


In 1926, Erik von Willebrand described the first patient with the disease that now bears his name. The patient and her family members, many of whom were also affected, lived on the Åland Islands in the Gulf of Bothnia (in the Baltic Sea, between Finland and Sweden). The proband was severely affected and had multiple episodes of mucosal bleeding that led to her death at the age of 13 years; 4 of her 11 siblings were also severely affected. The patients' platelet counts were normal.

Von Willebrand named the disorder "hereditary pseudohemophilia" because he recognized the autosomal inheritance pattern in his study of 66 other family members (in contrast to the sex-linked recessive pattern seen in the hemophilias) [1]. After an assay for factor VIII became available in the 1950s, it was demonstrated that patients with VWD had decreased plasma levels of factor VIII [2] and that the bleeding could be corrected with transfusion of plasma or partially purified preparations of "factor VIII" (using preparations that we now know also contained VWF) [3].

Considerable debate remained about the nature of the protein(s), and there was uncertainty as to whether one or two proteins carried out the platelet-related functions and the factor VIII procoagulant functions. These concerns were resolved when factor VIII and VWF were cloned in the 1980s [4-8]. These observations, followed by improved understanding of the molecular genetics of VWF and VWD, led to the current classification of the different types of VWD. Despite new information, only minor additions have provided new information about the types of VWD.


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Literature review current through: Sep 2016. | This topic last updated: May 25, 2016.
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