COEXISTENCE OF ANTITHROMBIN DEFICIENCY, FACTOR-V-LEIDEN AND HYPERHOMOCYSTEINEMIA IN A THROMBOTIC FAMILY

We report a thrombotic family with combined type I antithrombin defici ency and factor V Leiden (factor V-R506Q) in which the proposita, affe cted by recurrent venous and arterial thrombosis, was also characteriz ed by mild hyperhomocysteinemia (28 mu mol/l; normal <18.5 mu mol/l). Her two thrombotic sisters, with normal antithrombin levels and factor V molecules, showed hyperhomocysteinemia (51 and 30 mu mol/l, respect ively). Four other members of the family had the combined antithrombin /factor V Leiden defect and two of them had thrombosis. The common A22 3V mutation in the methylenetetrahydrofolate reductase gene, responsib le for the thermolabile variant of the enzyme, was found to be heteroz ygous in the proposita; the two sisters were homozygous and heterozygo us, respectively. The heterozygous sister also had a high titre of ant iphospholipid antibodies (85 units of immunoglobulin G antiphospholipi d antibody/ml). Furthermore, low plasma folate levels were found in th e three hyperhomocysteinemic subjects of the family. This family with several prothrombotic defects is a clear example of the polyfactorial nature of thrombophilia. (C) 1998 Lippincott-Raven Publishers.