ABSTRACT
Given the complexity o f vWF, it make sense that there are several forms of vWD (Table 5.1). The most common form of vWD is a reduction in protein concentra tion. This is know as vWD type 1. In the type 2 variants the vWF itself is abnormal. In type 2A the vWF concentration is not reduced but its function is impaired. This most often leads to loss o f the high molecular weight multimers of vWF. Type 2B is a fascinating sub-type in which there is a “gain in function” mutation rendering the vWF capable of binding to Gp lb even without collagen binding. Therefore the protein can bind to platelets even while circulating in the blood stream. This leads to clearance and reduction of the higher molecular weight forms. In addition there is often mild thrombocytopenia. Type 2M vWD have reduced function of vWF without obvious change in the size o f multimers. Patients with type 3 vWD have a homozygous defect with no vWF circulating and no factor VIII. These patients will often present with severe bleeding including joint bleeds. Type Normandy (2N) is often mistaken for classic hemophilia. Here, the vWF is unable to bind factor VIII. This leads to low factor VIII levels but normal vWF levels. Unlike in classic hemo philia, the inheritance of Normandy type is autosomal dominant with men and women equally effected. Finally, in “platelet-type” or “pseudo” vWD it is the platelet receptor that has the “gain of function mutation” that reduces both the number of platelets and the number of high molecular weight multimers.
