Plasma levels of thrombin-antithrombin complexes predict preterm premature rupture of the fetal membranes

Objective: Decidual hemorrhage (abruption) is strongly associated with preterm premature rupture of fetal membranes (PPROM). Moreover, thrombin enhances decidual matrix metalloproteinase (MMP) expression, and MMP has been strongly linked to PPROM. The current study sought to determine whether increased thrombin activation, as assessed by circulating maternal plasma thrombin-antithrombin (TAT) complexes, predicted subsequent PPROM. Study design: We conducted a nested, case-control study of plasma TAT levels, measured by sensitive immunoassay, among 27 women with a singleton preterm birth preceded by PPROM and 54 matched, term controls. Receiver operating characteristic curve analysis was performed to identify the optimal TAT cut-off level predicting PPROM. Results: Mean gestational age at delivery in cases was 33.3 weeks, compared to 39.7 weeks in controls (p <0.001). Compared with controls, women with PPROM had increased median plasma TAT levels in both the second trimester (5.1 μg/l (range 2.2-26.3 μg/l) vs. 3.2 μg/l (range 1.3-7.3 μg/l); p = 0.001) and third trimester (7.0 μg/l (range 2.6-85.8 μg/dl) vs. 4.8 μg/l (range 1.7-15.4 μg/dl); p = 0.01). In the PPROM group, 16.0% of the women exhibited bleeding during the pregnancy, while the corresponding value among controls was 3.6% (p = 0.07). In the second trimester, the odds ratio for PPROM with a TAT level of > 3.9 μg/l was 6.0 (95% Cl 1.67-21.1). This value predicted PPROM with a sensitivity of 88%, specificity of 68% and positive and negative predictive values of 82% and 97%, respectively. Conclusion: Second-trimester elevated plasma TAT concentrations are predictive of subsequent PPROM. These data provide further evidence that PPROM is associated with decidual thrombin activation.