engleski

Coagulation factor gene polymorphisms – role in thrombosis

Hypercoagulability, a state of hightened activation of the coagulation system plays a major role in pathogenesis of venous thromboembolism (VTE). Hypercoagulability also likely plays some less clearly defined role in the pathogenesis of various forms of arterial thrombosis. The inherited hypercoagulable states are associated with venous rather than arterial thrombosis. It is well known today that mutations in genes that code for regulatory proteins in the process of coagulation and fibrinolysis have an impact on structure and function of these proteins. Until recently, genetic defects could be identified in about 10% of patients with hereditary thrombophilia with antithrombin, protein C and protein S genes considered relevant for venous thrombosis. The discovery of important genetic predisposition factors for VTE ten years ago - FV R506Q and the prothrombin G20210A variant - explain the cause of about 60 percent of familial thrombophilia. The role of other genetic polymorphisms among coagulation factors genes as possible risk factors for VTE has not yet been proven. Various studies have stressed the importance of genetic factors for the development of arterial thrombosis with myocardial infarction and ishemic stroke as complication. Coagulation factors contribute to the generation of arteriosclerosis by formation of blood clots that oclude arteries but the data on mutations and polymorphisms in genes that code for these factors gave inconclusive results. Protective effect on the development of myocardial infarction was shown in several studies for FXIIIVal34Leu polymorphism only. FV R506Q, FVII GR353Q and VWF Thr789Ala polymorphisms are candidates that can contribute a certain percentage to the total risk of this complex process.

coagulation factors; genetic polymorphism; regulatory proteins

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