Hyperhomocysteinemia as a risk factor for deep-vein thrombosis

N Engl J Med. 1996 Mar 21;334(12):759-62. doi: 10.1056/NEJM199603213341203.


Background: Previous studies have suggested that hyperhomocysteinemia may be a risk factor for venous thrombosis. To assess the risk of venous thrombosis associated with hyperhomocysteinemia, we studied plasma homocysteine levels in patients with a first episode of deep-vein thrombosis and in normal control subjects.

Methods: We measured plasma homocysteine levels in 269 patients with a first, objectively diagnosed episode of deep-vein thrombosis and in 269 healthy controls matched to the patients according to age and sex. Hyperhomocysteinemia was defined as a plasma homocysteine level above the 95th percentile in the control group (18.5 micromol per liter).

Results: Of the 269 patients, 28 (10 percent) had plasma homocysteine levels above the 95th percentile for the controls, as compared with 13 of the controls (matched odds ratio, 2.5; 95 percent confidence interval, 1.2 to 5.2). The association between elevated homocysteine levels and venous thrombosis was stronger among women than among men and increased with age. The exclusion of subjects with other established risk factors for thrombosis (e.g., a deficiency of protein C, protein S, or antithrombin; resistance to activated protein C; pregnancy or recent childbirth; or oral-contraceptive use) did not materially affect the risk estimates.

Conclusions: High plasma homocysteine levels are a risk factor for deep-vein thrombosis in the general population.

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Case-Control Studies
  • Female
  • Homocysteine / blood*
  • Homocystine
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio
  • Protein C Deficiency
  • Protein S Deficiency
  • Risk Factors
  • Sex Factors
  • Thrombophlebitis / blood
  • Thrombophlebitis / etiology*


  • Homocysteine
  • Homocystine