Review ArticleHomocysteine and venous thromboembolism-Is there any link?

Homocysteine is an intermediary product of methionine metabolism. The level of homocysteine is controlled by two pathways-remethylation and transsulphuration. Elevated homocysteine level may result from deficiency or impaired function of enzymes and cofactors in these pathways. Homocystinuria is a rare genetic disease with extreme hyperhomocysteinemia and is associated with the occurrence of arterial and venous thrombotic events at young age. Therefore, homocysteine has been considered a risk factor for vascular diseases.Plasma homocysteine level is influenced by many factors, genetic as well as environmental. Mild hyperhomocysteinemia is quite common. The role of homocysteine in venous thrombosis has been studied less extensively than its role in arterial diseases and nowadays it seems quite controversial. In vitro, it is possible to demonstrate multiple prothrombotic action of homocysteine. However, the results of epidemiologic studies are not so clear. Most of them found an association of hyperhomocysteinemia with venous thromboembolism (VTE) but the association was quite weak and moreover, it was much weaker in prospective than in retrospective studies. It is not quite clear whether elevated homocysteine level is the cause of thromboembolic event or the consequence of it. It is also possible that hyperhomocysteinemia plays a role in the pathogenesis of VTE only as an additional risk factor in the presence of other thrombophilic disorders.However, some data confirm hyperhomocysteinemia as a risk factor for recurrent VTE. Some smaller studies have also found association of hyperhomocysteinemia with venous thrombosis at unusual sites.Homocysteine level can be lowered by vitamin supplementation, especially with folic acid and vitamin B12. So far, the benefit of lowering homocysteine level in primary and secondary VTE prevention has not been clearly proven.Currently, there is not enough evidence to support the necessity of testing homocysteine level in VTE patients, neither is sufficient evidence of the benefit of vitamin supplementation in mild or moderate hyperhomocysteinemia. Therefore, such testing and supplementation should be performed only in selected cases.