Normal pregnancy is associated with an increase in thrombin generation from the very early stages of the first trimester

Background: Pregnancy is a hypercoagulable state associated with an increased risk of venous thrombosis, which begins during the first trimester, but the exact time of onset is unknown. Thrombin generation, a laboratory marker of thrombosis risk, increases during normal pregnancy but it is unclear exactly how early this increase occurs. Methods: We assessed thrombin generation by Calibrated Automated Thrombography in women undergoing natural cycle in vitro fertilization, who subsequently gave birth at term following a normal pregnancy (n = 22). Blood samples were taken just prior to conception and repeated five times during very early pregnancy, up to Day 59 estimated gestation. Results: Mean Endogenous Thrombin Potential (ETP), peak thrombin generation and Velocity Index (VI) increased significantly from pre-pregnancy to Day 43 gestation (p = 0.024–0.0004). This change persisted to Day 59 gestation. The mean of the percentage change from baseline, accounting for inter-individual variation, in ETP, peak thrombin and VI increased significantly from pre-pregnancy to Day 32 gestation (p = 0.0351–<0.0001) with the mean increase from baseline persisting to Day 59 gestation. Conclusion: Thrombin generation increases significantly during the very early stages of normal pregnancy when compared to the pre-pregnancy state. The increased risk of venous thrombosis therefore likely begins very early in a woman's pregnancy, suggesting that women considered clinically to be at high thrombotic risk should start thromboprophylaxis as early as possible after a positive pregnancy test