Hereditary thrombophilia / hypercoagulopathies

Topic Completed: 1 June 2012

Revised: 7 January 2019, last major update June 2012

Copyright: (c) 2002-2016,, Inc.

PubMed Search: Hyperhomocysteinemia [title]

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Cite this page: Parsons J. Hyperhomocysteinemia . website. Accessed June 7th, 2020.
Definition / general
  • Homocysteine is an amino acid, derived from methionine, may be converted to cysteine
  • Its metabolic pathways require vitamins B12, B6 and folate
  • Elevated levels may be hereditary (due to mutations in these pathways) or acquired (due to deficiencies of vitamins B12, B6 or folate, renal failure, carcinoma, hypothyroidism or medications)
  • Elevations in homocysteine are associated with increased risk of arterial and venous thrombosis and atherosclerosis, based on retrospective case control studies
  • Prospective studies show a weak positive association with arterial thrombosis, and no definite association for venous thrombosis
  • Homozygosity or heterozygosity for the C677T mutation in MTHFR gene (methylene tetrahydrofolate reductase), which is involved in homocysteine metabolic pathway, does not appear to be a risk factor for thrombosis, but may be significant in folate - deficient patients
  • Although MTHFR was previously thought to be associated with thrombosis, newer data suggests this test is not useful in the first - line evaluation of thrombosis
  • Mutation in the methioninesynthetase gene (MTR) also can lead to increased homocystein levels but, as with MTHFR mutations, are not thought to be associated with thrombosis
  • Consider testing patients with documented coronary artery disease, cerebrovascular disease or peripheral vascular disease for homocysteine
  • High levels can be treated with vitamins B6, B12, folic acid, trimethylglycine, although they may not reduce the risk of future cardiovascular events
  • Homocysteinemia is usually associated with a moderately elevated plasma homocysteine, while homocysteinuria is a specific genetic entity with very high plasma homocysteine levels
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Folate metabolism

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