Venous thromboembolism, oral contraceptives and high prothrombin levels

The G20210A prothrombin mutation, associated with elevated prothrombin levels, is a risk factor for venous thromboembolism (VTE) and displays a strong interaction with oral contraceptives (OC). No data are available on VTE risk of OC use in women with high prothrombin levels, either associated or not with the mutation. The aim of this study was to evaluate the risk of VTE in OC users with high prothrombin levels, either including or excluding carriers of the prothrombin mutation. Prothrombin levels were measured by a chromogenic assay in 152 women who suffered from VTE in reproductive age and in 296 healthy women. Subjects carrying thrombophilic alterations other than the G20210A prothrombin mutation were excluded. Prothrombin levels were stratified into quartiles. The OR of subjects in the upper quartile were 3.10 [95% confidence interval (CI) 1.73-5.55] and 2.07 (95% CI 1.11-3.85) in all women and in those not carrying the prothrombin mutation, respectively. Among the 152 patients, 88 had experienced VTE during OC; in the control group we considered as OC users the women who had used OC for at least 6 months in the 2 years before presentation but had stopped the treatment at least 3 months before the time of blood sampling (n = 127). For the interaction between OC and prothrombin levels only the two extreme strata of prothrombin were considered. Women with the lowest prothrombin levels and who did not use OC were used as reference category. The VTE risk of using OC in subjects with prothrombin levels in the upper quartile was increased 5.4-fold (95% CI 2.38-12.3) and 3.5-fold (95% CI 1.48-8.22) in all women and in those not carrying the prothrombin mutation, respectively. We conclude that elevated prothrombin levels, even in women without the G20210A prothrombin mutation, are associated with an increased risk for venous thromboembolism and that oral contraceptive use potentiates such association.