von Willebrand disease (VWD)


VWD is a congenital bleeding disorder which results from quantitative or qualitative defects of von Willebrand factor (VWF). It is the most common inherited bleeding disorder in humans with a prevalence ranging from 3-4 per 100,000 to 1.3% of the population (Keeney & Cumming, 2001). The current classification of VWD consists of 6 distinct types (Sadler et al., 2006). Types 1 and 3 result in a quantitative VWF deficiency, whilst the four type 2 variants cause qualitative VWF defects.

VWD Classification
Description
Type 1 Partial quantitative deficiency of VWF. Multimers may be abnormal, but the proportion of large multimers is not significantly decreased. Typically autosomal dominant in inheritance although diagnosis is complicated by reduced penetrance and variable expressivity.
Type 2A Qualitative VWF defect resulting in a reduction of VWF-dependent platelet adhesion. Associated with absence of the largest multimers. Generally autosomal dominant.
Type 2B Qualitative VWF defect resulting in increased VWF-dependent platelet adhesion. Associated with (usually) reduced high molecular weight multimers. Inheritance is autosomal dominant.
Type 2M Qualitative VWF defect associated with specific defects in platelet/VWF interaction but with a normal range of multimers. Inheritance is autosomal dominant.
Type 2N Qualitative VWF defect resulting from defective VWF binding to coagulation factor VIII (FVIII) and consequently low levels of circulating FVIII. Inheritance is autosomal recessive.
Type 3 Clinically severe quantitative disorder resulting from a markedly reduced or absent platelet and plasma VWF (less than 5 IU/dL). Consequently, FVIII activity is also reduced. Inheritance is autosomal recessive.
Adapted from Keeney & Cumming, 2001 and Sadler et al., 2006.


This page is maintained by Dan Hampshire
Department of Cardiovascular Science, University of Sheffield