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Homocysteine and Risk of Recurrent Venous Thromboembolism

The measurement of plasma homocysteine is included in many thrombophilia panels for venous thromboembolism (VTE). Previous observational studies have shown that hyperhomocysteinemia is associated with an increased risk of first-time and recurrent VTE. Randomized trials, however, showed no benefit of homocysteine lowering therapy on the risk of first or recurrent VTE.

Recently, the results of the Multiple Environmental and Genetic Assessment (MEGA) case-control follow-up study were published. The study enrolled 4956 patients aged 18 to 17 years who had an objectively diagnosed first episode of deep vein thrombosis (DVT) of the leg or pulmonary embolism (PE) between March 1999 and August 2004. Patients were treated with anticoagulant for a mean of 6.9 months. A total of 2210 patients with a first episode of VTE were followed for a recurrent event, starting at the date of discontinuation of anticoagulant therapy, for a median follow- up of 6.9 years. Homocysteine, methionine and cysteine were measured approximately three months following discontinuation of anticoagulation. During follow-up, 340 patients had a VTE recurrence.

The mean level of homocysteine at baseline in patients who developed a recurrence was 13.6μmol/L and in patients without recurrence was 13.1 μmol/L. The mean level of methionine in patients with recurrence was 24.6 μmol/L and in patients without recurrence was 24.0 μmol/L. Cysteine values were 239.7μmol/L and 235.5 μmol/L in patients with and without recurrence, respectively.

This study found no association between elevated levels of homocysteine and cysteine or decreased levels of methionine with increased risk of recurrent VTE. The authors concluded that measurement of homocysteine or the MTHFR 677T mutation should not be included in the routine thrombophilia workup.


Annefleur DO et al. Hyperhomocysteinaemia and the risk of recurrent venous thrombosis: results from the MEGA follow-up study. Brit J Haematol. 2019; doi: 10.1111/bjh.16075

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