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 behaviour 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 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.

Figure 1

The correlations between maternal plasma tissue factor (TF)(1a) and tissue factor pathway inhibitor (TFPI) (1b) concentrations and gestational age at blood collection.

Figure 2

Comparison of maternal plasma tissue factor (TF) concentrations between women with normal pregnancy (n=79) and patients with preterm PROM (n=123). Tissue factor plasma concentrations were significantly higher in patients with preterm PROM than in women with a normal pregnancy (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).

Figure 3

Comparison of maternal plasma tissue factor pathway inhibitor (TFPI) concentrations between women with normal pregnancy (n=86) and patients with preterm PROM (n=123). TFPI plasma concentrations were significantly lower in patients with preterm PROM than in women with a normal pregnancy (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).