Von Willebrand disease (VWD) arises from a qualitative or quantitative deficiency of Von Willebrand factor (VWF), a multimeric protein that is required for platelet adhesion. Type 2 VWD (20-30% of all VWD cases) is a qualitative defect and the bleeding tendency can vary between individuals. There are normal levels of VWF, but the multimers are structurally abnormal or subgroups of large or small multimers are absent.
VWD Type 2B is a "gain of function" autosomal dominant defect leading to spontaneous binding of the A1 domain to platelet glycoprotein 1b (GP1b) and subsequent rapid clearance of the platelets and high molecular weight VWF multimers (HMWM). A mild thrombocytopenia may occur. The large VWF multimers are absent in the circulation and the factor VIII binding is normal.
VWD Type 2A causes a deficiency of HMWM, resulting in a decrease in the affinity of VWF for platelets and the subendothelium. The platelets are therefore unable to attach together in order to form a clot.
VWD Type 2M results in reduced affinity of the A1 domain for GP1b without deficiency of HMWM, which decreases the ability of platelets to form a clot when an injury occurs.
Genetics - Molecular Pathology
MOLP
4 weeks