Changes in amniotic fluid concentration of thrombinantithrombin III complexes in patients with preterm labor: Evidence of an increased thrombin generation

Offer Erez, Roberto Romer, Edi Vaisbuch, Tinnakorn Chaiworapongsa, Juan Pedro Kusanovic, Shali Mazaki-Tovi, Francesca Gotsch, Ricardo Gomez, Eli Maymon, Percy Pacora, Samuel S. Edwin, Chong Jai Kim, Nandor Gabor Than, Pooja Mittal, Lami Yeo, Zhong Dong, Bo Hyun Yoon, Sonia S. Hassan, Moshe Mazor

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Abstract

Objective.Preterm labor is associated with excessive maternal thrombin generation, as evidenced by increased circulating thrombinantithrombin (TAT) III complexes concentration. In addition to its hemostatic functions, thrombin has uterotonic properties that may participate in the mechanism leading to preterm birth in cases of intrauterine bleeding. Thrombin also has a proinflammatory role, and inflammation is associated with increased thrombin generation. The aim of this study was to determine whether intra-amniotic infectioninflammation (IAI) is associated with increased amniotic fluid AF thrombin generation in women with preterm and term deliveries. Study design.This cross-sectional study included the following groups: (1) mid-trimester (n=74); (2) term not in labor (n=39); (3) term in labor (n=25); (4) term in labor with IAI (n=22); (5) spontaneous preterm labor (PTL) who delivered at term (n=62); (6) PTL without IAI who delivered preterm (n=59); (7) PTL with IAI (n=71). The AF TAT III complexes concentration was measured by enzyme linked immunosorbent assay (ELISA). Non-parametric statistics were used for analysis. Results. (1) TAT III complexes were identified in all AF samples; (2) patients with PTL who delivered preterm, with and without IAI, had a higher median AF TAT III complexes concentration than those with an episode of PTL who delivered at term (p < 0.001, p=0.03, respectively); (3) among patients with PTL without IAI, elevated AF TAT III complexes concentration were independently associated with a shorter mniocentesis-to-delivery interval hazard ratio, 1.5; (95% CI, 1.072.1); (4) among patients at term, those with IAI had a higher median AF TAT III complexes concentration than those without IAI, whether in labor or not in labor (p=0.02); (5) there was no significant difference between the median AF TAT III complexes concentration of patients at term with and without labor; (6) patients who had a mid-trimester mniocentesis had a lower median AF TAT III complexes concentration than that of patients at term not in labor (p < 0.001). Conclusions.We present herein a distinct difference in the pattern of intra-amniotic thrombin generation between term and preterm parturition. PTL leading to preterm delivery is associated with an increased intra-amniotic thrombin generation regardless of the presence of IAI. In contrast, term delivery is associated with an increased intra-amniotic thrombin generation only in patients with IAI.

Original languageEnglish
Pages (from-to)971-982
Number of pages12
JournalJournal of Maternal-Fetal and Neonatal Medicine
Volume22
Issue number11
DOIs
StatePublished - 1 Nov 2009

Keywords

  • Delivery
  • Inflammation
  • Preterm parturition
  • Protease-activated receptors
  • Survival curvel

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