Hyperhomocysteinemia and thrombosis: an overview.
BACKGROUND
Homocysteine, a sulfur-containing amino acid, absent in natural diets, is a metabolic intermediary in transmethylation and transsulfuration reactions. Such reactions are essential to normal cellular growth, differentiation, and function. Excess homocysteine is associated with vascular disease and related disorders.


OBJECTIVE
To review homocysteine metabolism, the pathogenesis and classification of hyperhomocysteinemia, and the published literature investigating the association of homocysteine and methylenetetrahydrofolate reductase defects with arterial and venous thromboembolism and related disorders. The role of vitamin supplementation in patients with hyperhomocysteinemia is addressed.


METHODS
Published medical and scientific literature. Articles addressing the objectives were selected and reviewed. Pertinent studies and conclusions were summarized, grouped, and contrasted.


CONCLUSIONS
The association of hyperhomocysteinemia and arterial and venous thrombosis is controversial. Severe hyperhomocysteinemia is associated with atherosclerosis. The effect of mild hyperhomocysteinemia is less certain. Coinheritance of methylenetetrahydrofolate reductase defects and factor V Leiden is likely to increase the risk of venous thromboembolism. The association of methylenetetrahydrofolate reductase defects combined with no additional thrombophilic risk factors with venous thrombosis is less clear. High doses of folic acid to lower homocysteine levels might not be necessary.
Eldibany
Mohamed M
MM
Department of Pathology and Laboratory Medicine, Evanston Northwestern Healthcare, Northwestern University Feinberg School of Medicine, Evanston, IL 60201, USA. meldibany@enh.org
Caprini
Joseph A
JA
D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications* / Q000628:therapy; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000097:blood; D013923:Thromboembolism / Q000097:blood / Q000209:etiology* / Q000473:pathology
D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2)