Pharmacotherapy of hyperhomocysteinaemia in patients with thrombophilia.
Hyperhomocysteinaemia is often the result of inherited abnormalities of the enzymes involved in homocysteine metabolism or vitamin deficiencies (vitamins B12, B6 or folate) and is present in approximately 5% of the general population. High homocysteine levels in these individuals are associated with a significant increase in relative risk for both arterial and venous thromboembolic disease. Consequently, effective homocysteine-lowering therapeutic strategies have been extensively investigated. Folic acid represents the cornerstone of treatment. In daily doses of at least 0.4 mg, it effectively reduces homocysteine levels, even in non-folate-deficient patients. The addition of vitamins B12 and/or B6, to folic acid supplementation may provide a small further reduction in homocysteine levels in certain groups of patients. Renal impairment is an important cause of hyperhomocysteinaemia. Individuals with hyperhomocysteinaemia secondary to renal disease commonly require significantly higher doses of folic acid (5-40 mg) to achieve maximal therapeutic effect. The important question of whether effective homocysteine-lowering therapy translates into a reduction in vascular disease remains unknown but is being addressed in a series of ongoing prospective trials.
O'Donnell
James
J
Katherine Dormandy Haemophilia Centre and Haemostasis Unit, Department of Haematology, Royal Free Hospital School of Medicine, Pond Street, London NW3 2QG, UK.
Perry
David J
DJ
D005492:Folic Acid / Q000008:administration & dosage / Q000627:therapeutic use; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D008715:Methionine / Q000097:blood; D011736:Pyridoxine / Q000008:administration & dosage / Q000627:therapeutic use; D051437:Renal Insufficiency / Q000150:complications / Q000188:drug therapy; D019851:Thrombophilia / Q000209:etiology*; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000627:therapeutic use; D014815:Vitamins / Q000008:administration & dosage / Q000627:therapeutic use*
D014815:Vitamins; D006710:Homocysteine; D005492:Folic Acid; D008715:Methionine; D011736:Pyridoxine; D014805:Vitamin B 12