Chapter 14 - Von Willebrand Factor and Thrombosis

Abstract

Von Willebrand factor (VWF) contributes to the pathogenesis of atherosclerosis, the development of arterial and venous thrombosis, and thromboembolic risks in people with atrial fibrillation. Experimental studies demonstrate that VWF mediates critical platelet-endothelial cell interactions involved in atherogenesis. Epidemiological investigations report that elevated levels of VWF in conjunction with other risk factors predict cardiovascular events; for example, in patients with angina, hospitalization for acute coronary syndromes and 1-year all-cause mortality. Furthermore, high VWF levels are associated with subclinical brain infarcts and ischemic strokes in children and adults. People with genetic polymorphisms that increase the release of VWF from endothelial cells are at risk for venous thrombosis, and VTE is associated with elevated VWF levels in patients with cancer, hyperthyroidism, and chronic renal disease. In addition, VWF is increased in the left atrial blood of patients with atrial fibrillation and predicts stroke and vascular events in these individuals. Decreases in ADAMTS13 relative to VWF are associated with ischemic stroke, myocardial infarction, venous thrombosis, and cardiovascular events in patients with atrial fibrillation. Currently under development are ADAMTS13 concentrates and drugs that modify the binding of VWF to collagen, but whether these approaches will be safe and effective for the treatment of patients with thrombotic disorders requires further investigation.