Treatable high homocysteine alone or in concert with five other thrombophilias in 1014 patients with thrombotic events.

In 1014 patients with thrombotic events, we determined how often treatable high serum homocysteine alone, or in concert with five other thrombophilias, was associated with thrombotic events. We studied 1014 outpatients sequentially referred for evaluation of thrombotic events, all having six measures of thrombophilia--three PCR (methylenetetrahydrofolate reductase C677T-A1298C, factor V Leiden G506A, prothrombin G20210A), and three serologic (factors VIII, XI, homocysteine). Of the 1014 patients, 198 (20%) had atherothrombosis, 199 (20%) ocular vascular thrombosis, 211 (21%) osteonecrosis, 180 (18%) pseudotumor cerebri, and 123 (12%) recurrent miscarriage. In 434 of 1014 (43%) patients, all six thrombophilic measures were normal. High homocysteine, present in 126 of 1014 patients (12.4%), was the sole thrombophilia in 50 (5%), accompanied only by methylenetetrahydrofolate reductase homozygosity-compound heterozygosity in 22 (2.2%), and accompanied by other thrombophilias in 54 (5%). Patients were more likely than 110 healthy controls to have high homocysteine (12 vs. 5%; P = 0.02) and high factor VIII (21 vs. 7%; P = 0.0003). On treatment for a median of 18 months with L-methyl folate (5 mg), vitamin B6 (100 mg), and vitamin B12 (2 mg/day), in 74 homocysteinemic patients, median homocysteine fell from 15.6 to 10.0 μmol/l (P < 0.0001), and in 56 (76%), homocysteine fell to normal on treatment. When homocysteinemia was the sole thrombophilia, normalization of homocysteine was accompanied by freedom from new thrombotic events in 38 of 41 patients (93%). In evaluation of 1014 patients with thrombotic events, 126 (12%) had treatable high serum homocysteine, and in 50 (5%), high homocysteine was the sole treatable thrombophilia.