Because VWF plays an important role in binding platelets to each other and to collagen, a lack of VWF will cause a coagulopathy in which patients bleed spontaneously or excessively. VWD is the most common hereditary blood clotting disorder in humans. A deficiency in the quality or quantity of VWF can cause VWD. VWD is usually hereditary but can be acquired if a person develops antibodies against VWF.
There are several hereditary types of VWD:
Type I is the most common (75-80%). It is autosomal-dominant with variable expressivity. It is the result of a quantitative loss of VWF expression. VWF levels are 20-50% of normal. Clinical symptoms are usually mild to moderate, sometimes asymptomatic. Mild cases respond to the drug DDAVP.
Type II is autosomal dominant, much less common, and has several variants. In this type, VWF is made, but the protein is dysfunctional. The drug DDAVP is ineffective.
Type III is rare (1-3%). It is a very severe form. It is autosomal recessive, usually found in the offspring of two parents with type I. These patients have no detectable VWF or factor VIII activity. Type III causes severe and spontaneous mucosal bleeding and does not respond to DDAVP.
Another type of VWD is called 'Platelet-Type' or ‘pseudo VWD.’ These patients have no problem making VWF but have a mutation in the GPIb receptor. The mutation actually enhances VWF binding affinity. This means that circulating platelets bind VWF, even when not activated. This results in large platelet aggregates with VWF multimers that are cleared from the circulation. This pseudo-type VWD presents as thrombocytopenia and diminished levels of VWF.
