Authors' recommendations: Von Willebrand disease (VWD), the most common inherited bleeding disorder, results from a deficiency of and/or defects in von Willebrand factor (VWF). VWF is a large multimeric glycoprotein that functions in primary hemostasis, promoting platelet adhesion following vascular injury. In addition, VWF binds and stabilizes the coagulation factor VIII (FVIII), protecting it from degradation. The majority of VWD cases result from variants in the VWF gene, located on chromosome 12 at band p13.3. However, VWF gene testing may be complicated by the large size of the gene, its highly polymorphic nature, and the presence of a pseudogene (an inactive gene containing sequences highly homologous to VWF exons 23 through 34) on chromosome 22. With an estimated prevalence of up to 1% in the general population, VWD is characterized by a life-long propensity for mucocutaneous bleeding (bleeding of the mucous membranes and skin), easy bruising, epistaxis (nose bleeds), menorrhagia (heavy menstrual bleeding), and increased postoperative and postpartum bleeding. In addition, soft tissue and joint bleeding may occur in severe cases. VWD is classified into six different types: type 1, type 2A, type 2B, type 2M, type 2N, and type 3. Type 1 VWD results from a partial quantitative deficiency of VWF and may be associated with variable degrees of bleeding severity, typically in the mild to moderate range. It is usually inherited in an autosomal dominant manner with variable expressivity and incomplete penetrance. The four type 2 subtypes of VWD result from qualitative defects in VWF. Type 2A VWD, an autosomal dominant condition, is characterized by a loss of high-molecular-weight VWF multimers, and impaired VWF-platelet interactions. Type 2B VWD is characterized by an increased affinity for the platelet glycoprotein Ib (GPIb), and may be difficult to distinguish from a condition known as pseudo-VWD (or platelet type VWD), which is caused by variants in the GP1BA gene encoding the GPIb protein. It is also inherited in an autosomal dominant manner. Type 2M VWD is similar to type 2A in that it is an autosomal dominant condition characterized by decreased platelet adhesion, but differs in that there is no deficiency of high-molecular-weight VWF multimers. Type 2N VWD is characterized by a markedly decreased affinity for FVIII binding, which results in increased proteolysis of the FVIII protein. As a result, type 2N VWD, which is inherited in an autosomal recessive manner, may be difficult to distinguish from mild hemophilia A caused by variants in the X-linked FVIII gene. Type 3 VWD, which is also inherited in an autosomal recessive manner, is characterized by an essentially complete absence of VWF protein and a risk of severe bleeding problems (including bleeding in the soft tissue and joints). The diagnosis and classification of VWD is based on clinical history and the results of several phenotypic assays, including measurements of plasma VWF levels, VWF activity, FVIII binding, platelet aggregation studies, and analysis of multimer distribution. The management of VWD-related bleeds may involve treatment with desmopressin (which stimulates the release of endogenous VWF), or treatment with VWF/FVIII concentrates in patients with inadequate responses to desmopressin.

Project Status: Completed

Year Published: 2011

URL for published report: http://www.hayesinc.com/hayes/crd/?crd=13150

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: HAYES, Inc.

Contact Address: 157 S. Broad Street, Suite 200, Lansdale, PA 19446, USA. Tel: 215 855 0615; Fax: 215 855 5218

Contact Name: saleinfo@hayesinc.com

Contact Email: saleinfo@hayesinc.com

Copyright: 2011 Winifred S. Hayes, Inc