Tissue factor and its natural inhibitor in pre-eclampsia and SGA

Abstract

Objective Tissue factor (TF), the major activator of the extrinsic pathway of coagulation, is abundant in the placenta and decidua. The aim of this study was to determine the maternal plasma concentrations of TF and its primary inhibitor, tissue factor pathway inhibitor (TFPI), in women who delivered small for gestational age (SGA) neonates, and in preeclampsia. Study Design A cross-sectional study included the following groups: 1) women with normal pregnancies (n=86); 2) patients who delivered SGA neonates (n=61); and 3) women with preeclampsia (n=133). Maternal plasma concentrations of TF and TFPI were measured by a sensitive immunoassay. Non-parametric statistics were used for analysis. Results 1)Women with preeclampsia had a significantly higher median plasma concentration of TF than patients with a normal pregnancy (median: 1187 pg/ml; range: 69–11675 vs. median: 291.5 pg/ml; range: 6.3–2662.2; p<0.0001, respectively); 2) Similarly, TFPI concentrations were higher in preeclampsia than in normal pregnancy (median: 87.5ng/ml; range 25.4–165.1 vs. median: 66.1 ng/ml; range: 14.3–86.5; p<0.0001, respectively); 3) Surprisingly, mothers with SGA neonates had a lower median maternal plasma concentration of TF (median: 112.2 pg/ml; range: 25.6–1225.3) than women with a normal pregnancy (p<0.0001). Conclusion 1) Maternal plasma concentrations of TF in patients with preeclampsia, but not in those who delivered an SGA neonate, were higher than in women with normal pregnancies; 2) While the role of immunoreactive plasma TF in coagulation remains controversial, our observations suggest that changes are present in the context of complications of pregnancy.

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

“…Moreover, the median TF concentration of patients with preeclampsia was also higher than in patients with fetal demise without hypertension. These findings are consistent with previous studies 3,53 , suggesting that elevated TF immunoreactivity and activity may be associated with the pathophysiologic process leading to preeclampsia, rather than being a consequence of the fetal death. In some of the obstetrical syndromes there was elevated tissue factor activity in the maternal circulation without a concomitant increase in the plasma concentration of this factor.…”

“…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.…”

“…In the normal state, the immunoreactive concentrations of TFPI in the plasma are 500 to 1000 times higher than that of TF 75 , suggesting that an excess of anti-coagulant proteins closely controls the coagulation cascade activity. The median maternal plasma TFPI concentration increases during preeclampsia 53,76 , which is associated with an exaggerated maternal systemic inflammatory response. 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.…”

Pravastatin prevents miscarriages in mice: role of tissue factor in placental and fetal injury

“…38 Although TF is required for uterine hemostasis and maintenance of the placental labyrinth during gestation, 39 increased placental TF expression can result in pregnancy complications such as preeclampsia (PE). 40,41 We previously demonstrated that pregnancy loss induced by antiphospholipid antibodies in mice is associated with increased TF expression. 16,20 In this study, we found increased TF expression and activity in placentas from CBA/J ϫ DBA/2 matings compared with control matings with normal pregnancies.…”