Inherited thrombophilic risk factors and venous thromboembolism - Distinctrole in peripheral deep venous thrombosis and pulmonary embolism

Study objectives: To investigate whether the FII A(20210) mutation is assoc iated 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 object ively documented venous thrombosis and 1,329 control subjects. Measurements and results: Medical histories were collected. The G-to-A tran sition at nucleotide 1691 within the factor V gene (FV Leiden) and the G-to -A transition at nucleotide position 20210 within the prothrombin gene locu s (FII A20210), levels of anticoagulant factors, and levels of antiphosphol ipid antibodies were determined by standard techniques. Patients with deep venous thrombosis (DVT) of the lower extremities (n = 346) or with addition al PEs (n = 175) showed similar prevalences of FV Leiden mutation (24.3% an d 16.6%, respectively) and FII A20210 mutation (14.2% and 12.6%, respective ly), and similar deficiencies of natural anticoagulants (4.9% and 2.3%, res pectively). In both groups, the frequencies of FV Leiden and/or FII A(20210 ) mutation were higher than those observed among 1,329 apparently healthy c ontrol subjects (4.8% and 4.4%, respectively; p < 0.0001). Among patients w ith 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 throm bophilic 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 we re complicated by PE (28.0%; p = 0.020). Adjusting for age and sex, FV Leid en mutation, FII A20210 mutation, or both mutations were associated with DV T with PE (FV Leiden mutation: odds ratio [OR], 3.0; 95% confidence interva l [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 m utation: 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), bu t not with isolated PE (FV Leiden mutation: OR, 1.2; 95% CI, 0.5 to 2.8; FI I A(20210) mutation: OR, 1.2; 95% CI, 0.5 to 3.1; and both mutations: OR, 2 2.1; 95% CI, 1.3 to 370.2). Conclusions: FII A(20210) mutation is associated with DVT in the lower extr emities alone or when complicated by PE, but it is not associated with isol ated PE.