High tissue factor activity and low tissue factor pathway inhibitor concentrations in patients with preterm labor

Abstract

Objective Preterm labor (PTL) has been associated with an increased thrombin generation in the maternal circulation and amniotic fluid. Tissue factor (TF) is a potent initiator of the coagulation cascade, which can trigger the hemostatic system to generate thrombin. The aims of this study were to determine whether spontaneous PTL with intact membranes is associated with changes in the maternal plasma concentrations and activity of TF and tissue factor pathway inhibitor (TFPI). Methods This cross-sectional study included women in the following groups: 1) normal pregnancies (n=86); 2) term pregnancies in spontaneous labor (TIL) (n=67) and not in labor (TNL) (n=88); and 3) patients with spontaneous PTL and intact membranes (n=136) that were classified into three sub-groups: a) PTL without intra-amniotic infection and/or inflammation (IAI) who delivered at term (n=49), b) PTL without IAI who delivered preterm (n=54), and c) PTL with IAI who delivered preterm (n=33). Plasma concentrations of TF and TFPI were measured by ELISA, and their activity was measured by chromogenic assays. Non-parametric statistics were used for analysis. Results 1) Among women at term, those with spontaneous labor had a higher median maternal plasma TF and a lower median TFPI concentrations than that of those without labor. 2) Patients with PTL had a significantly lower median maternal plasma TFPI concentration than that of normal pregnant women, regardless of the presence of IAI. 3) There was no significant differences in the median maternal plasma TF concentrations between patients with a normal pregnancy and those with PTL. 4) In contrast, the median TF activity was higher among patients with PTL than in women with normal pregnancies, regardless of the presence of IAI or preterm delivery. 5) However, maternal plasma TFPI activity did not differ among the study groups. Conclusion Women with preterm parturition, in contrast to those in labor at term, have a higher TF activity and a lower TFPI concentration, without a significant change in the median maternal plasma TF concentration. These observations suggest that the increased thrombin generation reported in patients with PTL may be the result of activation of the extrinsic pathway of the coagulation cascade. In addition, the increased thrombin generation reported in patients with PTL could be due to insufficient anti-coagulation, as reflected by the low maternal plasma TFPI concentration.

The Dynamics of the Hemostatic Parameters in Physiological Pregnancy and After Delivery

“…Meanwhile, in comparison with the values of pregnant women, the mean concentration of TF in mother's plasma is higher in patients with preeclampsia or with preterm prelabor rupture of membranes [45,46]. An interesting suggestion was made about the connection of excessive expression of TF to bloodstream and the onset of preterm labor [47] that we share completely.…”

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

“…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.…”

“…There is evidence to support that the extrinsic pathway of coagulation is activated in many of these pregnancy complications and it is the source of the increased thrombin generation 51 . Indeed, increased immunoreactive TF concentrations were reported in women with preeclampsia and those with preterm PROM 52 . Moreover, the contribution of preeclampsia to elevated maternal immunoreactive TF persisted also among patients with fetal demise, while those with fetal death who were normotensive did not have higher median TF concentration than normal pregnant women.…”

ИНИЦИАЦИЯ СвертывАНИЯ КровИ В РАЗНые СрокИ ФИЗИологИческИ ПротекАющей БеремеННостИ

“…Важно учитывать и то, что при значительном изменении количества и/или активности многих участников гемостатических реакций этот пери-од жизни женщины, как правило, не сопровожда-ется тромбозом или кровотечениями благодаря УДК 616. 15 Цель исследования -анализ пусковых механизмов активации свертывания крови на разных сроках физиологи-чески протекающей беременности и оценка возможной роли их нарушений для возникновения репродуктивных потерь и преждевременных родов. МАТЕРИАЛ И МЕТОДЫ.…”

“…Допускается, что избыточная активация на раннних этапах гемоко-агуляции может приводить как к тромбозам, так и к клиническим осложнениям во время беремен-ности [14,15,29].…”