Different circumstances of the first venous thromboembolism among younger or older heterozygous carriers of the G20210A polymorphism in the prothrombin gene

Abstract

BACKGROUND AND OBJECTIVES: The G20210A polymorphism in the prothrombin gene is a common cause of inherited thrombophilia. Scarce information is available about the circumstances of the heralding thrombotic manifestation at different ages. The aim of this study was to determine the risk of spontaneous or secondary venous thromboembolism (VTE) among younger and older carriers of the G20210A prothrombin polymorphism. DESIGN AND METHODS: We performed a case-control study, investigating 650 patients with a first objectively documented deep venous thrombosis of the legs or pulmonary embolism and 703 individuals with no history of vascular disease. In all of them we carried out laboratory screening for antithrombin III, protein C and protein S deficiencies, and for the presence of the factor V Leiden and the G20210A prothrombin polymorphisms. RESULTS. After adjustment for other inherited causes of thrombophilia (deficiency of antithrombin III, protein C or S, factor V Leiden) the overall risk for VTE associated with the prothrombin polymorphism was 3.4 times higher than in the controls (95% CI, 2.0 to 5.8). Stratification according to the age and to the circumstances of the first event revealed an increased risk of spontaneous VTE only among the patients older than 45 years in comparison with age-matched controls (odds ratio 4.4, 95% CI 1.8 to 10.6); among the younger individuals the risk was increased for secondary VTE (odds ratio 4.8, 95% CI, 2.3 to 9.8) but not for spontaneous VTE. INTERPRETATION AND CONCLUSIONS: The clinical penetrance of the thrombotic tendency associated with the G20210A prothrombin polymorphism is more expressed in the presence of a circumstantial risk factor (oral contraceptives, pregnancy, surgery, trauma) and in the presence of older age, which acts as an additional circumstantial risk factor. Accordingly, such situations should not discourage from carrying out laboratory screening.