Changes in blood coagulation and fibrinolysis during pregnancy create a state of hypercoagulability. This phenomenon predisposes to venous thromboembolism. Indicators of hypercoagulation in normal pregnancy are circulating thrombin-antithrombin complexes and increased levels of prothrombin fragment 1+2. A significant positive correlation between gestational age and elevated prothrombin fragment 1+2 has been shown. We hypothesized that women with previous venous thromboembolism are at a higher hypercoagulable state during subsequent pregnancies than women without prior thrombotic complications.

In a prospective study, we determined prothrombin fragment F1+2 over pregnancy among 109 women (175 measurements) with previous venous thromboembolism, and among 75 pregnant women (75 measurements) without previous venous thromboembolism. The prothrombin fragment F1+2 levels were statistically analyzed over time using a Mixed Model. This model allows a longitudinal analysis of the influence of a between-subjects factor (e.g. history of thrombosis) on prothrombin fragment F1+2 levels, the influence of a within-subjects factor (weeks of gestation) on prothrombin fragment F1+2 levels, and the interaction of the history of thrombosis and weeks of gestation representing a change of risk factor-dependent differences over time (weeks of gestation).

Among women with a previous history of venous thrombosis, prothrombin fragment F1+2 values were significantly higher during the course of pregnancy than among pregnant women without venous thromboembolism (p=0.0014). The results were adjusted for the physiological increase of prothrombin fragment F1+2 over pregnancy and were independent of heparin prophylaxis. Thus, determination of indicators of hypercoagulation like prothrombin fragment F1+2 represent an additional approach independent of known and unknown risk determinants of thrombosis to identify women at risk for venous thromboembolism during pregnancy.

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