G20210A mutation in the prothrombin gene and the risk of recurrent venous thromboembolism

OBJECTIVES The study was done to determine whether the G20210A mutation in the prothrombin gene increases the risk of recurrent venous thromboembolism (VTE), both alone and in combination with factor V Leiden. BACKGROUND Several inherited defects of coagulation are associated with increased risk of first VTE, including a recently identified G20210A mutation in the prothrombin gene. However, whether the presence of this mutation confers an increased risk of recurrent venous thromboembolism is controversial. METHODS A total of 218 men with incident venous thromboembolism were genotyped for the prothrombin mutation and for factor V Leiden and were followed prospectively for recurrent VTE over a follow-up period of 7.3 years. RESULTS A total of 29 men (13.3%) suffered recurrent VTE. Five of the 14 carriers of the prothrombin mutation developed recurrent VTE (35.7%; incidence RATE = 8.70 per 100 person-years), while 24 of 204 individuals who did not carry the prothrombin mutation developed recurrent VTE (11.8%; incidence RATE = 1.76 per 100 person-years). Thus, presence of the G20210A mutation was associated with an approximate fivefold increased risk for recurrent VTE (crude relative risk [RR] 4.93; 95% confidence interval [CI] 1.9–12.9; P = 0.001; age-, smoking-, and body mass index-adjusted RR 5.28; 95% CI 2.0–14.0; P = 0.001). In these data, recurrence rates were similar among those with an isolated mutation in the prothrombin gene (18.2%) as compared to those with an isolated factor V Leiden mutation (19.2%). However, all three study participants who carried both mutations (100%) suffered a recurrent event during follow-up. CONCLUSIONS In a prospective evaluation of 218 men, the presence of prothrombin mutation was associated with a significantly increased risk of recurrent VTE, particularly among those who co-inherited factor V Leiden.