Genetic Variations of the Hemostatic System as Risk Factors for Venous and Arterial Thrombotic Disease

R.   F.   Franco; M.   D.   Trip; P.   H.   Reitsma

Abstract

Arterial thrombosis (manifested as myocardial infarction, ischaemic stroke, or peripheral occlusive artery disease) and venous thrombosis (main clinical presentations include deep vein thrombosis and pulmonary embolism) represent major health problems that are associated with high rates of morbidity and mortality, particularly in Western societies. Several lines of evidence point to a role of novel hemostatic genetic risk factors in influencing thrombotic risk. In fact, it is becoming increasingly clear that the analysis of genetic risk factors and plasmatic factors, together with private life style and environmental factors may contribute significantly to our understanding of the genetic predisposition to vascular thrombosis. The most significant breakthrough was the confirmation of the notion that inherited hypercoagulable conditions are present in a large proportion of patients with venous thromboembolism. These include mutations in the genes encoding antithrombin, protein C, protein S, factor V, and prothrombin. Moreover, plasmatic risk indicators like hyperhomocysteinemia and elevated concentrations of factors II, VIII, IX, XI and fibrinogen have also been documented. Plasma levels of proteins of the hemostatic system also predict the onset and outcome of arterial thrombosis. Several studies examined the relationship between genetic markers of the hemostatic system (platelet receptors, endothelial receptors, anticoagulant proteins, coagulation factors and proteins of the fibrinolytic system) and arterial disease. The results from these studies are frequently conflicting and often are not concordant with plasmatic studies. Therefore, large prospective studies remain needed in order to evaluate the significance of hemostatic plasma levels and gene variations in arterial thrombotic diseases.

Keywords: Genetic Variations, Hemostatic System, Risk Factors, Arterial Thrombotic Disease, platelet, fibrinolytic system

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