von Willebrand factor inhibitor

von Willebrand factor (VWF) is a large adhesive glycoprotein synthesised in endothelial cells and megakaryocytes. Unlike the activated coagulation factors of secondary haemostasis it is not an enzyme and its functions involve binding to cells and molecules. Upon vessel injury, VWF binds directly to exposed sub-endothelial collagen and remains anchored. Blood flow unravels anchored VWF to expose the binding site for the constitutively expressed platelet surface receptor glycoprotein Ib. VWF captures and tethers platelets arriving at the scene which promotes subsequent events of primary haemostasis towards formation of a platelet plug. VWF also serves as the plasma carrier of FVIII to protect it from proteolytic degradation and also to ‘deliver’ it to sites of injury and clot formation. von Willebrand disease (VWD) is the most common hereditary bleeding disorder and the deficiency can be quantitative, involving reduced levels of normally functioning VWF, or qualitative, involving dysfunctional molecules. Laboratory investigation of VWD encompasses a battery of assays that assess different aspects of the molecule which inform sub-classification and clinical management:

Unlike haemophilia A, inhibitor development in patients with VWD is a rare complication of treatment and mainly occurs in patients with severe inherited type 3 VWD. Acquired VWD in patients previously haemostatically normal can be due to autoantibodies, adsorption of VWF onto malignant cell clones, hypothyroidism or the high shear forces in aortic valve stenosis leading to loss of high molecular weight multimers via ADAMTS13.