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Increased Risk for Venous Thrombosis in Carriers of the Prothrombin G→A20210 Gene Variant

Maurizio Margaglione, MD; Vincenzo Brancaccio, MD; Nicola Giuliani, MD; Giovanna D'Andrea, BS; Giuseppe Cappucci, BS; Luigi Iannaccone, BS; Gennaro Vecchione, BS; Elvira Grandone, MD; and Giovanni Di Minno, MD
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From IRCCS, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy; Ospedale A. Cardarelli, Napoli, Italy; and Universita di Palermo, Palermo, Italy. Requests for Reprints: Maurizio Margaglione, MD, Unita di Aterosclerosi e Trombosi, IRCCS, Casa Sollievo della Sofferenza, viale Cappuccini, San Giovanni Rotondo (FG) 71013, Italy. Current Author Addresses: Drs. Margaglione, Giuliani, and Grandone and Mrs. D'Andrea, Mr. Cappucci, and Mr. Vecchione: Unita di Aterosclerosi e Trombosi, IRCCS, Casa Sollievo della Sofferenza, viale Cappuccini, San Giovanni Rotondo (FG) 71013, Italy.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1998;129(2):89-93. doi:10.7326/0003-4819-129-2-199807150-00003
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Background: A mutation in the prothrombin gene (G→A20210) has been associated with higher plasma prothrombin levels and an increased tendency for venous thrombosis.

Objective: To determine whether the prothrombin A20210 allele is independently associated with the occurrence of venous thrombosis.

Design: Case-control study.

Setting: Two thrombosis centers in southern Italy.

Patients: 281 consecutive patients with venous thrombosis confirmed by objective tests and 850 controls.

Measurements: Medical history was collected on standardized questionnaires. The presence of prothrombin G→A20210 and factor V Leiden mutations was determined by polymerase chain reaction. The presence of anticoagulant factors and prothrombin activity was determined by tests of function.

Results: In 150 controls, increased prothrombin activity (P < 0.001) was associated with the prothrombin A20210 allele. This allele was more frequent in patients than in controls (8.01% compared with 2.29%; P < 0.001) and was associated with an increased risk for thrombosis (odds ratio, 3.88 [95% CI, 2.23 to 6.74]). The increased prevalence of this allele was independent of the presence of the factor V Leiden mutation. After adjustment for sex, age, arterial thrombosis, and factor V Leiden mutation, the risk was still significantly elevated (odds ratio, 3.13 [CI, 1.89 to 5.21]). Moreover, the overall prevalence of inherited coagulation abnormalities was significantly higher in patients with thrombosis of the lower extremities than in patients with thrombosis of the upper extremities (odds ratio, 3.77 [CI, 1.10 to 12.93]). Fourteen patients carried both the prothrombin G→A20210 and factor V Leiden mutations.

Conclusions: The prothrombin A20210 allele is independently associated with the occurrence of venous thrombosis, particularly in patients with a history of thrombosis of the lower extremities.





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