Contribution of genetical analysis for diagnosis of von Willebrand’s disease type 2B

Structure and function of von Willebrand factor

“…VWD is a congenital extrinsic platelet defect resulting in platelet dysfunction [108] and is commonly reported in dogs, swine, horses, cattle, and cats. This autosomally inherited disorder is caused by either qualitative (type II) or quantitative (types I and III) deficiency of VWF.…”

High-resolution imaging of multimers can detect von Willebrand’s disease type 2A even if ristocetin cofactor is higher than von Willebrand antigen

“…Generally, a ratio below 0.7 indicates the type 2A and also the type 2B VWD [3], which requires further testing for discrimination. The clinically important exclusion of the much rarer type 2B can be achieved by normal platelet count and a platelet aggregation response below 10% to a diminished dose of ristocetin (0.6 mg mL −1 ) or by genetical analysis [4]. These considerations could lead to the statement that the VWD type 2A can be always diagnosed without MA.…”

Laboratory Testing for von Willebrand Disease: Toward a Mechanism-Based Classification

“…Mutations in the A1 and proximal A2 domain may cause increased binding to GPIbα. 63 The mutant vWF, especially the largest multimers, bind platelets without the need for shear stresses that normally unravel vWF at sites of injury. Coated platelets may get cleared, presumably by the reticuloendothelial system, which reduces the availability of large multimers and periodically causes thrombocytopenia, particularly in response to conditions that increase circulating vWF (eg, pregnancy, trauma).…”