Genetic risk factors of venous thrombosis

Hum Genet. 2001 Oct;109(4):369-84. doi: 10.1007/s004390100593.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antithrombins / deficiency
  • Blood Coagulation Factors / metabolism
  • Factor V / genetics
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing
  • Humans
  • Hyperhomocysteinemia / genetics
  • Hyperhomocysteinemia / metabolism
  • Mutation
  • Protein C / metabolism
  • Protein S / metabolism
  • Prothrombin / genetics
  • Risk Factors
  • Venous Thrombosis / diagnosis
  • Venous Thrombosis / genetics*
  • Venous Thrombosis / metabolism
  • Venous Thrombosis / physiopathology


  • Antithrombins
  • Blood Coagulation Factors
  • Protein C
  • Protein S
  • Factor V
  • Prothrombin