Activation of coagulation system in preterm labor and preterm premature rupture of membranes

Objective: Thrombin, originally discovered as a coagulation factor, is a multifunctional protease capable of inducing myometrial contractions in vitro and in vivo. This enzyme has been implicated in the mechanisms of premature labor. Plasma concentrations of thrombin-antithrombin (TAT) complexes are an index of in vivo thrombin generation. The purpose of this study was to determine whether patients with premature labor and preterm premature rupture of membranes (PROM) have evidence of increased thrombin generation in maternal blood, as determined by the TAT complex concentrations. Methods: A cross-sectional study was designed to determine plasma concentrations of TAT complexes in 110 women in the following groups: non-pregnant women (n = 20); normal pregnant women (n = 30); women in preterm labor with intact membranes (n = 30); and women with preterm PROM (n = 30). TAT complex concentrations were determined with a sensitive and specific immunoassay. Statistical analysis was conducted with non-parametric statistics. Results: Patients with preterm labor and intact membranes had a significantly higher median plasma TAT complex concentration than normal pregnant women (women in preterm labor, median 19.1 μg/l; range 7.4-406 vs. normal pregnant women, median 15 μg/l; range 6.8-32.5; p = 0.03). Patients with preterm PROM had a higher median TAT complex concentration than normal pregnant women (preterm PROM, median 19.1 μg/l; range 4.7-738.6 vs. normal pregnant women, median 15 μg/l; range 6.8-32.5; p = 0.03). Normal pregnancy was associated with a higher median plasma TAT complex concentration than the non-pregnant state (normal pregnant women, median 15 μg/l; range 6.8-32.5 vs. non-pregnant women, median 2.7 μg/l; range 0.9-14.2; p < 0.001). Conclusion: Preterm labor and preterm PROM are associated with an excess generation of thrombin.