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Objective: Pyelonephritis has a more severe course during pregnancy than in the non-pregnant state. This has been attributed to the increased susceptibility of pregnant women to microbial products. An acquired protein Z deficiency has been reported when there is excessive thrombin activity. The aim of this study was to determine whether pyelonephritis during pregnancy is associated with changes in maternal plasma protein Z concentrations., Study Design: A cross-sectional study was conducted to compare plasma protein Z concentrations between normal pregnant women (N = 71) and pregnant women with pyelonephritis (N = 42). Protein Z concentrations were measured by enzyme-linked immunosorbent assay. Parametric and non-parametric statistics were used for analysis., Results: Patients with pyelonephritis had a significantly lower median plasma concentration of protein Z than did patients with normal pregnancies (median 2.14 microg/mL (0.4-3.4) vs. median 2.36 microg/mL (1.09-3.36); p = 0.03). There was no difference in the median plasma concentration of anti-protein Z antibodies between patients with pyelonephritis and those with normal pregnancies., Conclusion: The median maternal plasma protein Z concentration was significantly lower in patients with pyelonephritis during pregnancy than in patients with normal pregnancies.

Objective: Preeclampsia (PE) is characterized by excessive thrombin generation, which has been implicated in the multiple organ damage associated with the disease. The biological effects of thrombin on coagulation and inflammation are mediated by protease-activated receptor-1 (PAR-1), a G protein-coupled receptor. The aim of this study was to determine whether preterm PE is associated with changes in placental expression of PAR-1., Study Design: This cross-sectional study included two groups matched for gestational age at delivery: (1) patients with preterm PE (<37 weeks of gestation; n = 26) and (2) a control group of patients with preterm labor without intra-amniotic infection (n = 26). Placental tissue microarrays were immunostained for PAR-1. Immunoreactivity of PAR-1 in the villous trophoblasts was graded as negative, weak-positive, or strong-positive., Results: (1) The proportion of cases with strong PAR-1 immunoreactivity was significantly higher in placentas of patients with PE than in placentas from the control group (37.5% (9/24) vs. 8.7% (2/23); p = 0.036, respectively). (2) PAR-1 immunoreactivity was found in the cellular compartments of the placental villous tree, mainly in villous trophoblasts and stromal endothelial cells. (3) PAR-1 was detected in 92.3% (24/26) of the placentas of women with PE and in 88.5% (23/26) of the placentas from the control group., Conclusion: Placentas from pregnancies complicated by preterm PE had a significantly higher frequency of strong PAR-1 expression than placentas from women with spontaneous preterm labor. This observation is consistent with a role for PAR-1 as a mediator of the effect of thrombin on coagulation and inflammation in PE. We propose that the effects of thrombin in PE are due to increased thrombin generation and higher expression of PAR-1, the major receptor for this enzyme.

Objective: Protein Z, a vitamin K-dependent plasma protein, has an important role in the regulation of the coagulation cascade. Protein Z deficiency has been associated with unexplained pregnancy loss and adverse pregnancy outcome in patients with thrombophilia. This study was conducted to determine if preeclampsia (PE), small for gestational age (SGA), and fetal demise are associated with changes in maternal plasma concentrations of protein Z., Study Design: This cross-sectional study included normal pregnant women (N = 71), patients with PE (N = 130), patients who delivered an SGA neonate (N = 58), and patients with fetal demise (N = 58). Maternal plasma protein Z concentrations were measured by a sensitive and specific immunoassay. Protein Z deficiency was defined as maternal plasma concentrations 0.05); and (3) women in the PE and fetal demise groups had significantly higher rates of protein Z deficiency than those with normal pregnancy outcome., Conclusions: (1) PE, but not SGA or fetal demise, is associated with a significantly lower maternal median plasma concentration of protein Z than normal pregnancy, and (2) a high rate of protein Z deficiency is observed in patients with PE and fetal demise.