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

Changes in laboratory markers of thrombotic risk early in the first trimester of pregnancy may be linked to an increase in estradiol and progesterone

Background: Pregnant women are at increased risk of venous thrombosis compared to non-pregnant women. Epidemiological and laboratory data suggest that hypercoagulability begins in the first trimester but it is unknown exactly how early in pregnancy this develops. The mechanisms that result in a prothrombotic state may involve oestrogens and progestogens. Methods: Plasma samples were taken prior to conception and five times in early pregnancy, up to Day 59 gestation, from 22 women undergoing natural cycle in vitro fertilization, who subsequently gave birth at term following a normal pregnancy. Thrombin generation, free Protein S, Ddimer, Fibrinogen, factor VIII, estradiol and progesterone were measured. To counter inter-individual variability, the change in laboratory measurements between the pre-pregnant and pregnant state were measured over time. Results: Peak thrombin, Endogenous Thrombin Potential, Velocity Index and fibrinogen significantly increased, and free Protein S significantly decreased, from pre-pregnancy levels, by 32 days gestation. Ddimer and VIII significantly increased from pre-pregnancy levels by 59 days gestation. Estradiol significantly increased by Day 32 gestation with a non-significant increase of 67% by Day 24 gestation. Progesterone significantly increased by Day 32 gestation. Almost all laboratory markers of thrombosis correlated significantly with estradiol and progesterone. Conclusion: Our work is the first to demonstrate that the prothrombotic state develops very early in the first trimester. Laboratory markers of hypercoagulability correlate significantly with estradiol and progesterone suggesting these are linked to the prothrombotic state of pregnancy. Clinicians should consider commencing thromboprophylaxis early in the first trimester in women at high thrombotic risk