Prothrombin fragment F1+2 in pregnancy is associated with thrombophilic risk factors and a history of venous thromboembolism (VTE)

R. B. Zotz1, R. E. Scharf1, A. Gerhardt2,1 (1Duesseldorf, Germany, 2Ulm, Germany)

Pediatric and Women Issues
Date: 17.02.2017,
Time: 11:00 - 12:00

Objective: Since the positive predictive value of factor V Leiden (FVL) and other genetic risk determinants for a pregnancy-associated VTE is low, additional indicators of hypercoagulability are needed to identify women at risk of VTE during pregnancy. An increased level of prothrombin fragment 1+2 is a potential indicator of hypercoagulation in normal pregnancy. We hypothesized that women with previous VTE and FVL or prothrombin G20210A mutation are at a higher hypercoagulable state during pregnancy than women without prior thrombotic complications and without genetic thrombophilic risk factors.

Methods: In a prospective study, we determined prothrombin fragment F1+2 over pregnancy (818 measurements) among 131 women with previous VTE, 109 women with previous fetal loss (1 late or 3 early fetal losses), 51 women with previous severe preeclampsia, and 93 healthy pregnant women. Evaluation of thrombophilia included factor V Leiden and prothrombin G20210A mutation. The prothrombin fragment F1+2 levels were statistically analyzed over the course of pregnancy using a multivariate mixed model.

Results: Among women with a previous history of VTE, prothrombin fragment F1+2 values were significantly higher during the course of pregnancy than among pregnant women without VTE (p<0.0001) (p=0.63 for preeclampsia vs. no preeclampsia, p=0.40 for fetal loss vs. no fetal loss). The results were adjusted for the physiological increase of prothrombin fragment F1+2 over pregnancy (p<0.0001) and independent of heparin prophylaxis (prothrombin fragment F1+2 reduced, p=0.004). In addition, FVL (p=0.004) and prothrombin G20210A mutation (p=0.011) were independently associated with increased levels of prothrombin fragment F1+2.

Conclusion: Increased prothrombin fragment F1+2 in pregnancy are associated with thrombophilic risk factors (FVL and prothrombin G20210A mutation) and a history of VTE. Determination of indicators of hypercoagulation such as prothrombin fragment F1+2 can represent a supplementary approach to identifying women at risk of VTE during pregnancy, independent of known and unknown risk determinants of VTE.