Genetic risk factors of venous thrombosis

Venous thrombosis, whose main clinical presentations include deep vein thro mbosis and pulmonary embolism, represents a major health problem worldwide. Numerous conditions are known to predispose to venous thrombosis and these conditions are commonly referred to as risk indicators or risk factors. Ge nerally accepted or "classically" acquired risk factors for venous thromboe mbolism include advanced age, prolonged immobilisation, surgery, fractures, use of oral contraceptives and hormone replacement therapy, pregnancy, pue rperium, cancer and antiphospholipid syndrome. In addition to these well-es tablished risk factors for venous thrombosis, several lines of evidence tha t have emerged over the past few decades indicate a role of novel genetic r isk factors, mainly related to the haemostatic system, in influencing throm botic risk. The most significant breakthrough has been the confirmation of the concept that inherited hypercoagulable conditions are present in a larg e proportion of patients with venous thromboembolic disease. These include mutations in the genes that encode antithrombin, protein C and protein S, a nd the factor V Leiden and factor II G20210 A mutations. Moreover, plasmati c risk indicators, such as hyper-homocysteinemia and elevated concentration s of factors II, VIII, IX, XI and fibrinogen, have also been documented. Th is extensive list of genetic and acquired factors serves to illustrate that a single cause of venous thrombosis does not exist and that this condition should be considered as a complex or multifactorial trait. Complex traits can be understood by assuming an interaction between different mutations in candidate susceptibility genes. The risk that is associated with each gene tic defect may be relatively low in isolation but the simultaneous presence of several mutations may dramatically increase disease susceptibility. Mor eover, environmental factors may interact with one or more genetic variatio ns to add further to the risk. The analysis of genetic risk factors and pla smatic factors, together with private life style and environmental factors, has contributed significantly to our understanding of the genetic predispo sition to venous thrombosis.