Laboratory Diagnosis of von Willebrand Disease

The von Willebrand Factor protein showing various functional domains that have been mapped to regions of the cDNA. These show sites of interaction with FVIII, GPIb, GPIIb/IIIa, collagen, and heparin. Various genetic mutations have been mapped to specific regions of the cDNA as shown above, and mutations within these domains result in different clinical expressions of VWD. A mutation in the D’ domain results in type 2N VWD where there is a loss of the FVIII binding ability of VWF. A mutation in the D3 domain results in types 2A and 2N VWD where there is a loss in the platelet binding ability of VWF or the ability to bind to FVIII. A mutation in the A1 domain results in types 2B and 2M VWD where there is either a gain-of-function mutation in the VWF molecule or a loss of the platelet binding ability of VWF. A mutation in the A2 domain results in type 2A VWD where there is a loss of the platelet binding ability of VWF.