Venous thrombosis, whose main clinical presentations include
deep vein thrombosis 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. Generally accepted or "classically" acquired risk factors for
venous thromboembolism include advanced age, prolonged immobilisation, surgery, fractures, use of
oral contraceptives and
hormone replacement therapy, pregnancy, puerperium,
cancer and
antiphospholipid syndrome. In addition to these well-established risk factors for
venous thrombosis, several lines of evidence that have emerged over the past few decades indicate a role of novel genetic risk factors, mainly related to the haemostatic system, in influencing thrombotic risk. The most significant breakthrough has been the confirmation of the concept that inherited hypercoagulable conditions are present in a large proportion of patients with venous thromboembolic disease. These include mutations in the genes that encode
antithrombin,
protein C and
protein S, and the
factor V Leiden and
factor II G20210 A mutations. Moreover, plasmatic risk indicators, such as
hyperhomocysteinemia and elevated concentrations of factors II, VIII, IX, XI and
fibrinogen, have also been documented. This 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 genetic defect may be relatively low in isolation but the simultaneous presence of several mutations may dramatically increase
disease susceptibility. Moreover, environmental factors may interact with one or more genetic variations to add further to the risk. The analysis of genetic risk factors and plasmatic factors, together with private life style and environmental factors, has contributed significantly to our understanding of the
genetic predisposition to
venous thrombosis.