von Willebrand Disease (VWD) is one of the most common inherited bleeding disorders worldwide with a prevalence of ~1% of the normal population (Werner et al. 1993) . VWD is caused by defective or deficient von Willebrand Factor (VWF) (Ginsburg et al. 1985). VWF is a large, multimeric glycoprotein that is released into the blood from endothelial cells and platelets and plays a key role in hemostasis through binding with the platelet GP1Bα receptors (See Bernard Soulier Syndrome) and by transporting factor VIII to sites of vascular damage (Goodeve 2010). Symptoms of VWD are present from birth, but may become more severe with hemostatic challenge and with increasing age. There are three main types of VWD and several subtypes (Sadler et al. 2006):

Type 1 VWD--accounts for ~70% of cases. Mutations are identified in ~65% of cases. Autosomal dominant inheritance with mild mucocutaneous bleeding and quantitative deficiency of VWF.
Type 2 VWD--accounts for ~25% of cases. Characterized by qualitatively defective VWF and is divided into four subgroups based upon the defective function of VWF:
Type 2A-- mainly autosomal dominant, some recessive inheritance with mild to moderate mucocutaneous bleeding due to reduced platelet interactions.
Type 2B-- autosomal dominant inheritance with mild to moderate mucocutaneous bleeding and potential thrombocytopenia; type 2B is associated with enhanced platelet interactions.
Type 2M-- autosomal dominant inheritance with mild to moderate mucocutaneous bleeding due to reduced platelet interactions.
Type 2N-- autosomal recessive inheritance, mimics mild hemophilia A and is characterized by excessive bleeding with hemostatic challenge (e.g. surgery); type 2N is associated with impaired binding of VWF to factor VIII.
Type 3 VWD-- accounts for ~5% of cases. Mutations are identified in up to 90% of cases. Autosomal recessive inheritance with severe mucocutaneous and musculoskeletal bleeding due to nearly complete quantitative deficiency of VWF.

See also Goodeve and James 2011.

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