Perturbed (procoagulant) endothelium and deviations within the fibrinolytic system during the third trimester of normal pregnancy

Sørensen, Jannie Dalby; Secher, Niels Jørgen; Jespersen, Jørgen

doi:10.3109/00016349509024445

Cited by 26 publications

(10 citation statements)

References 27 publications

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“…During pregnancy, the changes in the coagulation system are considered to be an adaptive mechanism for the prevention of bleeding at the time of delivery [1][2][3][4][5]. Indeed, normal pregnancy is associated with excessive thrombin generation [5,6] and a tendency for platelets to aggregate in response to agonists [7,8].…”

Section: Introductionmentioning

confidence: 99%

Preeclampsia is associated with low concentrations of protein Z

Erez

Hoppensteadt

Romero

et al. 2007

The Journal of Maternal-Fetal & Neonatal Medicine

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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 ¼ 71), patients with PE (N ¼ 130), patients who delivered an SGA neonate (N ¼ 58), and patients with fetal demise (N ¼ 58). Maternal plasma protein Z concentrations were measured by a sensitive and specific immunoassay. Protein Z deficiency was defined as maternal plasma concentrations 5 th percentile of the normal pregnancy group (1.59 mg/mL). Non-parametric statistics were used for analysis.Results.(1) Patients with PE had a lower median plasma concentration of protein Z than normal pregnant women (PE: median 1.6 mg/mL, range 0.2-3.3 mg/mL vs. normal pregnancy: median 2.4 mg/mL, range 1.1-3.4 mg/mL; p 5 0.0001); (2) patients with an SGA neonate (median 2.3 mg/mL, range 0.2-3.8 mg/mL) and fetal demise (median 2.6 mg/mL, range 0.2-4.3 g/mL) did not have significantly different median protein Z concentrations from normal pregnant women (p 4 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.

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Section: Introductionmentioning

confidence: 99%

Preeclampsia is associated with low concentrations of protein Z

Erez

Hoppensteadt

Romero

et al. 2007

The Journal of Maternal-Fetal & Neonatal Medicine

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“…These results suggest that, during pregnancy, the presence of thrombin in the intervillous space does not promote significant placental inflammation, thereby ensuring fetal well‐being. This is important since pregnancy is considered to be a thrombophilic state based on the elevation of several plasma coagulation factors in maternal blood including thrombin 22,23. Conversely, the finding that LPS at extremely low concentrations enhanced IL‐8 expression in SCTs suggests that the placenta plays a critical role in cytokine production and leukocyte infiltration in pregnancies complicated by intrauterine infection.…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of Lipopolysaccharide and Thrombin on Interleukin‐8 Expression in Syncytiotrophoblasts and Endothelial Cells: Implications for Fetal Survival

Kadner

Guller

2004

Annals of the New York Academy of Sciences

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Syncytiotrophoblasts (SCTs) are directly bathed by maternal blood and, as such, are in direct contact with proinflammatory stimuli present in the maternal circulation. The extent and nature of cytokine responses induced in SCTs play a central role in the maintenance of pregnancy. Thrombin is a critical mediator of tissue factor-initiated blood coagulation. Thrombin has been more recently demonstrated to induce cytokine expression and inflammation in several cell types. To dissect the patterns of regulation of cytokine production in the placental villus, we compared the effects of thrombin and lipopolysaccharide (LPS) treatments on cytokine expression in SCTs and endothelial cells. For studies, primary cultures of cytotrophoblasts from human term placentas were differentiated to SCTs. We observed that the presence of thrombin only modestly enhanced interleukin-8 (IL-8) levels in SCTs in a manner that was not dose-dependent. Conversely, SCTs were exquisitely sensitive to LPS, the presence of which induced approximately a 10-fold increase in IL-8 levels with an EC(50) approximately 1 ng/mL. Northern blotting and real-time PCR results indicated that LPS (but not thrombin) treatment induced a >4-fold increase in levels of IL-8 mRNA. The addition of the anti-inflammatory steroid, dexamethasone, significantly reduced the LPS-mediated increase in levels of IL-8 in SCTs. Conversely, in human umbilical vein endothelial cells, thrombin and LPS treatments induced 10- and 20-fold increases in IL-8 expression, respectively. These results indicate that LPS, but not thrombin, promotes proinflammatory processes in SCTs, with cell-type specificity. The inability of thrombin in the intervillous space to evoke inflammatory responses in SCTs may constitute an important aspect of fetal survival. Conversely, our results suggest that SCTs do play a key role in infection-associated changes in placental cytokine expression.

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“…In term of the coagulation and hemostatic systems there are several major compartments: the maternal circulation, the fetal maternal interface (the placenta, and membranes), amniotic fluid and the fetus that each has a specific behavior during gestation. The changes in the coagulation system during gestation are considered to be adaptive mechanisms and are aimed to: 1) the prevention of bleeding at the time of trophoblast implantation and the delivery of the fetus; 2) allow the laminar flow and the intervillous space; and 3) seal amniotic fluid leak and reduce obstetrical bleeding [3][4][5][6][7] . Of interest, the fetus is somewhat less involved and its coagulation system develops during gestation, and this subject is beyond the scope of this review.…”

Section: What Are the Changes In The Coagulation System During Normalmentioning

confidence: 99%

Peer Review #1 of "Placental vascular pathology and increased thrombin generation as mechanisms of disease in obstetrical syndromes (v0.1)"

2014

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Placental vascular pathology and increased thrombin generation as mechanisms of disease in obstetrical syndromes Obstetrical complications including preeclampsia, fetal growth restriction, preterm labor, preterm prelabor rupture of membranes and fetal demise are all the clinical endpoint of several underlying mechanisms (i.e. infection inflammation, thrombosis, endocrine disorder, immunologic rejection, genetic, and environmental), therefore, they may be regarded as syndromes. Placental vascular pathology and increased thrombin generation were reported in all of these obstetrical syndromes. Moreover, elevated concentrations of thrombin-anti-thrombin III complexes and changes in the coagulation as well as anticoagulation factors can be detected in the maternal circulation prior to the clinical development of the disease in some of these syndromes. In this review, we will assess the changes in the hemostatic system during normal and complicated pregnancy in maternal blood, maternal-fetal interface and amniotic fluid, and describe the contribution of thrombosis and vascular pathology to the development of the great obstetrical syndromes.

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Perturbed (procoagulant) endothelium and deviations within the fibrinolytic system during the third trimester of normal pregnancy

Cited by 26 publications

References 27 publications

Preeclampsia is associated with low concentrations of protein Z

Preeclampsia is associated with low concentrations of protein Z

Differential Effects of Lipopolysaccharide and Thrombin on Interleukin‐8 Expression in Syncytiotrophoblasts and Endothelial Cells: Implications for Fetal Survival

Peer Review #1 of "Placental vascular pathology and increased thrombin generation as mechanisms of disease in obstetrical syndromes (v0.1)"

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