Hyperhomocysteinemia: clinical and therapeutical involvement in venous thrombosis

Hyperhomocysteinemia, considered "the cholesterol of nineties", is an established risk factor for cardiovascular diseases and premature atherosclerosis. Hyperhomocysteinemia is due to genetic and acquired factors (unhealthy lifestyle with poor diet in folate and vitamin B, elderly, renal impairment, thyroid diseases, malignancies). More recently, hyperhomocysteinemia was associated with venous thrombosis. Several studies found a correlation with a usual site of thrombosis (central retinal vein, mesenterical level, cerebral veins, Budd-Chiari syndrome). Other studies showed the association between hyperhomocysteinemia and recurrent venous thrombosis. This condition is of high interest because homocysteine may represent a potentially reversible cause of thrombophilia. Although methylenetetrahydrofolate reductase (MTHFR) C677T genotype and deficits of folic acid, vitamin B12 lead to hyperhomocysteinemia, in cases with a thrombotic event the correlations between homocysteine level and folic acid as well as between homocysteinemia and vitamin B12 were found to be weak and no significant correlation between homocysteinemia and MTHFR was identified. Recently, some authors reported an independent association between low levels of folic acid or vitamin B12 and venous thrombosis. Regarding the MTHFR genotype, the risk for venous thrombosis is increased only in patients with factor V Leiden. A recent meta-analysis of 24 retrospective and 3 prospective studies published in electronic literature showed that a 5 micromol/L higher homocysteine level was associated with a 27% (95% CI: 1-59) higher risk of venous thrombosis in prospective studies and a 60% (95% CI: 10-134) higher risk in retrospective studies. A meta-analysis of the short-term trials of therapy with folic acid showed a reduction of 25% of homocysteinemia and a further reduction of 7% when vitamin B12 was associated. This situation may be associated with a 10% to 20% decreased risk of venous thrombosis. Further trials are required to estimate if this is worthwhile from the clinical point of view. In medical practice the measurement of homocysteinemia may be indicated in unexplained idiopathic venous thrombosis, or recurrent episodes or venous thrombosis occurred at an early age or at an uncommon site.