Inherited thrombophilic risk factors and venous thromboembolism: distinct role in peripheral deep venous thrombosis and pulmonary embolism

STUDY OBJECTIVES: To investigate whether the FII A(20210) mutation is associated with isolated pulmonary embolism (PE). DESIGN: Case-control study. SETTING: Five thrombosis centers in southern Italy. PATIENTS: Six hundred forty-seven consecutive referred patients with objectively documented venous thrombosis and 1,329 control subjects. Measurements and results: Medical histories were collected. The G-to-A transition at nucleotide 1691 within the factor V gene (FV Leiden) and the G-to-A transition at nucleotide position 20210 within the prothrombin gene locus (FII A(20210)), levels of anticoagulant factors, and levels of antiphospholipid antibodies were determined by standard techniques. Patients with deep venous thrombosis (DVT) of the lower extremities (n = 346) or with additional PEs (n = 175) showed similar prevalences of FV Leiden mutation (24.3% and 16.6%, respectively) and FII A(20210) mutation (14.2% and 12.6%, respectively), and similar deficiencies of natural anticoagulants (4.9% and 2.3%, respectively). In both groups, the frequencies of FV Leiden and/or FII A(20210) mutation were higher than those observed among 1,329 apparently healthy control subjects (4.8% and 4.4%, respectively; p < 0.0001). Among patients with isolated PE (n = 126), prevalences of FV Leiden (7.1%) and FII A(20210) mutation (8.7%) were similar to those of control subjects. Inherited thrombophilic abnormalities were less frequent among patients with PE only (15.6%) than among those with DVT only (37.0%; p < 0.001) or whose conditions were complicated by PE (28. 0%; p = 0.020). Adjusting for age and sex, FV Leiden mutation, FII A(20210) mutation, or both mutations were associated with DVT with PE (FV Leiden mutation: odds ratio OR], 3.0; 95% confidence interval CI], 1.6 to 5.5; FII A(20210) mutation: OR, 2.6; 95% CI, 1. 3 to 5.2; and both mutations: OR, 82.1; 95% CI, 7.5 to 901.2) or without PE (FV Leiden mutation: OR, 6.1; 95% CI, 4.0 to 9.3; FII A(20210) mutation: OR, 2.8; 95% CI, 1.7 to 4.8; and both mutations: OR, 167.5; 95% CI, 21.6 to 1,297.7), but not with isolated PE (FV Leiden mutation: OR, 1.2; 95% CI, 0.5 to 2.8; FII A(20210) mutation: OR, 1.2; 95% CI, 0.5 to 3.1; and both mutations: OR, 22.1; 95% CI, 1. 3 to 370.2). CONCLUSIONS: FII A(20210) mutation is associated with DVT in the lower extremities alone or when complicated by PE, but it is not associated with isolated PE.