HIGH ANTIBODY-LEVELS TO PROTHROMBIN IMPLY A RISK OF DEEP VENOUS THROMBOSIS AND PULMONARY-EMBOLISM IN MIDDLE-AGED MEN - A NESTED CASE-CONTROL STUDY

Antibodies against phospholipid-binding plasma proteins, such as beta( 2)-glycoprotein I (beta(2)-GPI) and prothrombin, are associated with t hromboembolic events in patients with systemic lupus erythematosus and also in subjects with no evident underlying diseases. We wanted to ex amine whether increased levels of antibodies to negatively-charged pho spholipids (cardiolipin), to phospholipid-binding plasma proteins beta (2)-GPI and prothrombin and to oxidised low-density lipoprotein (LDL) were associated with risk of deep venous thrombosis or pulmonary embol ism in subjects with no previous thrombosis. The antibodies were measu red in stored serum samples from 265 cases of deep venous thrombosis o f the lower extremity or pulmonary embolism occurring during a median follow-up of about 7 years and from 265 individually matched controls. The study subjects were middle-aged men participating in a cancer pre vention trial of alpha-tocopherol and beta-carotene and the cases of t hromboembolic events were identified from nationwide Hospital Discharg e Register. The risk for thrombotic events was significantly increased only in relation to antiprothrombin antibodies. As adjusted for body mass index, number of daily cigarettes and history of chronic bronchit is, myocardial infarction and heart failure al baseline, the odds rati o per one unit of antibody was 6.56 (95% confidence interval 1.73-25.0 ). The seven highest individual optical density-unit values of antipro thrombin antibodies were all confined to subjects with thromboembolic episodes. In conclusion, the present nested case-control study showed that high autoantibody levels against prothrombin implied a risk of de ep venous thrombosis and pulmonary embolism and could be involved in t he development of the thrombotic processes.