Risk of venous thrombosis in carriers of the prothrombin G20210A variant and factor V Leiden and their interaction with oral contraceptives

Background and Objectives. The prothrombin G20210A mutation and factor V Le iden have been found to be associated with an increased risk of venous thro mbosis, but the reported prevalences of Be prothrombin gene variant both in the normal population and in patients with deep venous thrombosis (DVT) va ry greatly in the literature, Moreover, the influence of oral contraceptive s (OC) on thrombotic events In patients with the prothrombin G20210A varian t has not been well established. In this study we evaluate both circumstanc es. Design and Methods. A case-control study was run on 229 patients with DVT a nd 246 healthy controls. The patients' history of thrombosis and acquired t hrombotic risk factors, especially OC, were recorded Prothrombin G20210A mu tation, factor V Leiden, antithrombin, heparin II cofactor, plasminogen and proteins C and S were evaluated. Results. Seven and a half percent of the patients and 2.9% of the controls were carriers of the prothrombin mutation, while 12.2% of the patients and 1.6% of the controls had factor V Leiden. Among the 229 DVT patients there were 130 patients with clinically suspected thrombophilia (first thrombotic event occurring before the age of 45 years or positive family history of t hrombosis or recurrent venous thrombosis). Ten percent of these 130 patient s were carriers of the prothrombin G20210A mutation and 18.5% had the facto r V Leiden mutation. The odds ratios (OR) for DVT risk were: 2.4 (95% CI, 1 .0-6.3) for the total DVT patients and 5.2 (95% CI, 1.4-19.5) for the patie nts with clinically suspected thrombophilia with the prothrombin mutation. The risk of thrombosis was 6.9 (95% CI, 2.3-20.6) for the DVT patients and 14.3 (95% CI, 3.3-64.6) for the patients with clinically suspected thrombop hilia with factor V Leiden. Fifty-five percent of the patients with combine d congenital defects (prothrombin mutation G20210A plus another congenital defect) had recurrent thrombosis. In women receiving OC the risk of DVT was 3.5 (95% CI,, 1.5-8.2) that of the patients not receiving OC. When women w ith combined defects were also taking OC, the risk of thrombosis increased significantly. Interpretation and Conclusions. The prevalence of the prothrombin G20210A m utation in the healthy population in our study is similar to that observed in other southern European countries. The prothrombin G20210A mutation does not by itself seem to be a high thrombotic risk factor. However, when it i s present together with other thrombotic risk factors, the predicted risk o f thrombotic events increases. The use of OC by women with the prothrombin G20210A variant or RI Leiden, either alone or combined with other thromboti c risk factors, was associated with a significant Increase in the risk of v enous thrombosis. (C) 2000; Ferrata Storti Foundation.