Hyperhomocysteinemia may predispose to arterial and venous thrombosis.
(See also Overview of Thrombotic Disorders.)
Hyperhomocysteinemia may predispose to arterial thrombosis and venous thromboembolism (VTE) by injuring vascular endothelial cells (1), possibly due to increased free radical generation. . However, some studies have found that the association is no longer significant when confounding variables are fully accounted for (2). Furthermore, randomized trials of vitamin supplementation in patients with VTE and heart disease (3) and patients with VTE without major risk factors (4) were not associated with reduced event rates. Therefore, routine measurement of homocysteine levels in patients with venous and arterial thromboembolism is discouraged.
Plasma homocysteine levels are elevated ≥ 10-fold in homozygous cystathionine beta-synthase deficiency. Milder elevations occur in heterozygous deficiency and in other abnormalities of folate metabolism, including methyltetrahydrofolate reductase deficiency. The most common causes of hyperhomocysteinemia are acquired
Folate deficiency is rare where folate fortification of wheat flour occurs.
The abnormality is established by measuring fasting plasma homocysteine levels in patients with cardiovascular disease or thromboembolism who are suspected of having the disorder.
General references
1. Undas A, Brozek J, Szczeklik A. Homocysteine and thrombosis: from basic science to clinical evidence. Thromb Haemost 2005;94(5):907-915. doi:10.1160/TH05-05-0313
2. Ospina-Romero M, Cannegieter SC, den Heijer M, Doggen CJM, Rosendaal FR, Lijfering WM. Hyperhomocysteinemia and Risk of First Venous Thrombosis: The Influence of (Unmeasured) Confounding Factors. Am J Epidemiol 2018;187(7):1392-1400. doi:10.1093/aje/kwy004
3. Ray JG, Kearon C, Yi Q, Sheridan P, Lonn E; Heart Outcomes Prevention Evaluation 2 (HOPE-2) Investigators. Homocysteine-lowering therapy and risk for venous thromboembolism: a randomized trial. Ann Intern Med 2007;146(11):761-767. doi:10.7326/0003-4819-146-11-200706050-00157
4. den Heijer M, Willems HP, Blom HJ, et al. Homocysteine lowering by B vitamins and the secondary prevention of deep vein thrombosis and pulmonary embolism: A randomized, placebo-controlled, double-blind trial. Blood 2007;109(1):139-144. doi:10.1182/blood-2006-04-014654
Treatment of Hyperhomocysteinemia
Dietary supplementation
Plasma homocysteine levels may be normalized by dietary supplementation with folate, vitamin B12, or vitamin B6 alone or in combination; however, it is not been shown that this therapy reduces the risk of arterial or venous thrombosis.
