PB0956 - Venous thrombosis associated with combined oral contraceptives: role of intrinsic thrombin generation potential

Background: Ideally, women at high risk of venous thromboembolism (VT) when using combined oral contraceptives (COC), should be identified prior to starting.

Aims: To assess if TG-potential (estimated prior starting COC) can identify women at high risk of VT

Methods: TG-potential was evaluated in 1072 premenopausal women (444 cases; 628 controls from the MEGA study) with the assumption that measurements performed in cases (who all discontinuated COC use) late after thrombosis was mimicking their intrinsic TG-potential. In controls using COC at the time of the blood draw, we estimated their intrinsic TG-potential in the absence of use COC by substracting the mean COC effect from their measured TG-potential. To assess the risk of VT, odds ratios (ORs) were calculated for TG-potential (peak-height or activated protein C sensitivity ratio [APCsr]) after stratification in quartiles. Using the 75th-percentile of TG-potential in controls as cut-off, the effect of COC use, elevated TG-potential, and combination on VT risk was assessed with adjustment on age, body mass index and family history of VT (using women with neither risk factor as reference ). Analyses were also stratified on progestogen type.

Results: The ORs of VT for TG-potential in the top quartile (compared with the lowest quartile) were 11.6 (95% confidence interval [CI]: 6.3-21) for peak-height, 2.3 (95%CI: 1.6-3.4) for APCsr. The combination of elevated TG-potential and subsequent COC use (OR(peak-height)=16.7 [95%CI: 10.5-26], OR(APCsr)=13.3 [95%CI: 8.4-21]) was higher than expected from individual risks. After exclusion of FV-Leiden and prothrombin-G20210A carriers, women with elevated peak-height levels were still the most vulnerable to COC (Table 1). This synergistic effect on VT risk was higher in women using third-generation COC than levonorgestrel-ones, even after exclusion of of FV-Leiden and prothrombin-G20210A mutations.

Conclusion(s): High TG-potential is associated with an increased risk for VT and COC use potentiates such association