A link between a hemostatic disorder and preterm PROM: a role for tissue factor and tissue factor pathway inhibitor

Abstract

Objective-Vaginal bleeding is a risk factor for preterm PROM (PPROM). A disorder of decidual hemostasis has been implicated in the genesis of PROM. Indeed, excessive thrombin generation has been demonstrated in PPROM both before and at the time of diagnosis. Decidua is a potent source of tissue factor (TF), the most powerful natural pro-coagulant. A decidual hemostatic disorder may link vaginal bleeding, PPROM, and placental abruption. This study was conducted to determine the behavior of maternal TF and its natural inhibitor, the tissue factor pathway inhibitor (TFPI) in PPROM.Methods-This cross-sectional study included women with PPROM (n=123) and women with normal pregnancies (n=86). Plasma concentrations of TF and TFPI were measured by a sensitive immunoassay. Non-parametric statistics were used for analysis. Results-1)The median maternal plasma TF concentration was significantly higher in patients with PPROM than in women with normal pregnancies (median: 369.5 pg/ml; range: 3.27-2551 pg/ ml vs. median: 291.5 pg/ml; range: 6.3-2662.2 pg/ml, respectively; p=0.001,); 2) the median maternal TFPI plasma concentration was significantly lower in patients with PPROM than in women with a normal pregnancies (median: 58.7 ng/ml; range: 26.3-116 ng/ml vs. median: 66.1 ng/ml; range: 14.3-86.5 ng/ml, respectively; p=0.019); 3) there was no correlation between the plasma concentration of TF and TFPI and the gestational age at sample collection; and 4) among patients with PPROM there was no association between the presence of intra-amniotic infection or inflammation and median plasma concentrations of TF and TFPI. Conclusions-1) Patients with PPROM have a higher median plasma concentration of TF and a lower median plasma concentration of TFPI than women with normal pregnancies. 2) These findings suggest that PPROM is associated with specific changes in the hemostatic/coagulation system. NIH Public Access

Placental vascular pathology and increased thrombin generation as mechanisms of disease in obstetrical syndromes

“…Indeed, although preterm labor was not associated with a significant change in the median maternal plasma TF concentration, the TFPI/TF ratio of these patients was lower than that of normal pregnant women, mainly due to decreased TFPI concentrations. This observation was also reported in patients with preterm PROM 77 , and those with preeclampsia 53 . The lower TFPI/TF ratio in patients with preeclampsia occurs despite the increase in the median maternal plasma TFPI concentration observed in these patients.…”

“…However, the increase in the median maternal TF plasma concentration is such that the overall balance between TF and its inhibitor is affected leading to increased thrombin generation in this syndrome. In contrast to preeclampsia, maternal plasma TFPI concentration decreases in patients with PTL 52 and preterm PROM 77 regardless to the presence of intra-amniotic infection/inflammation, as well as in women with fetal demise 54 , and does not change in mothers with SGA fetuses 53 . Overall these findings suggest that the increased thrombin generation observed among these patients may derive not only from an increased activation of the hemostatic system, but also from insufficient anti-coagulation, as reflected by the lower TFPI concentrations (Fig.…”

Maternal and neonatal epidemiological features in clinical subtypes of preterm birth

“…PTB-PPROM was characterized by a higher frequency of vaginal bleeding and anemia during pregnancy, two risk factors already reported in the literature[23,30]. When the comparisons were matched for maternal age, significant differences were observed with high frequencies of use of corticosteroids during pregnancy and increased frequency of vaginal bleeding.…”

Weakening and Rupture of Human Fetal Membranes – Biochemistry and Biomechanics

“…Decidual cells have been shown to have abundant tissue factor thus facilitating the production of Thrombin after hemorrhage (Lockwood et al, 1993(Lockwood et al, & 2001. PPROM patients have increased tissue factor (Erez et al, 2008). Thrombin is known to have many actions not related to coagulation.…”