子痫前期和凝血功能异常

子痫前期孕妇表现为病理性高凝状态,凝血功能的监测对妊娠期高血压疾病及其并发症的预防和治疗具有一定的临床意义.随着对子痫前期凝血机制的深入研究,阿司匹林、低分子肝素等抗凝剂在改善子痫前期母胎预后方面的作用受到了更多关注.     

Prediction of Maternal Predisposition to Preeclampsia

Objective: To derive a prediction index based on the most salient patient history, laboratory, and clinical parameters for identifying women at high risk for developing preeclampsia (PE). Methods: Nonpregnant women with a history of PE (n?=?101) were compared with nonpregnant parous women with a history of one or more successful normotensive pregnancies (n?=?50) but with comparable age, gestation, and parity profiles. The parameters included a medical examination (demographics, patient history, family history, and clinical and obstetrical findings), laboratory investigations (hemostasis, coagulation, and vitamins), and morphological and functional tests (cardiovascular and renal functions). Stepwise logistic regression analysis was applied to develop a three-step PE prediction index based on the most discriminant parameters. Results: Patients with and without PE differed significantly (p?<?0.05) with respect to 1) maternal history of chronic hypertension, body mass index, and blood pressure; 2) APTT, PT, activated factor VIII, homocystein, free protein S and vitamin B1; and 3) relative plasma volume. Based on these three sets of parameters, a three-step PE prediction index was developed. The likelihood ratio of a positive index score was equal to 3.4, 7.3, and 8.8, respectively. Thus, assuming a PE prevalence (or prior probability) of 5%, a patient's chances of developing PE when presenting with a positive score on the three-step prediction index were 15%, 28%, and 32%, respectively. Discussion: In the absence of welldefined pre-pregnancy screening guidelines for PE, the present study attempts to proceed in a stepwise fashion by looking at medical examination data first, requesting, if necessary, specific hemostasis and coagulation tests next, and finally measuring the relative plasma volume for confirmatory purposes. This approach offers a satisfactory positive predictive value and cost efficiency ratio.     

Decreased Maternal Plasma Apelin Concentrations in Preeclampsia

Background. Preeclampsia is a hypertensive disorder that complicates 3–7% of pregnancies. The development of preeclampsia has not been completely elucidated and current therapies are not broadly efficacious. The apelinergic system appears to be involved in hypertensive disorders and experimental studies indicate a role of this system in preeclampsia. Thus, an epidemiological evaluation of apelin protein concentration in plasma was conducted in case–control study of pregnant women. Methods. Data and maternal plasma samples were collected from pregnant women with confirmed preeclampsia (n = 76) or normotensive controls (n = 79). Concentrations of apelin peptides were blindly measured using enzyme-linked immunosorbent assay. Data were subjected to statistical analyses. Results. Plasma apelin concentrations, measured at delivery, were lower in preeclampsia cases compared with controls (mean ± standard deviation: 0.66 ± 0.29 vs. 0.78 ± 0.31 ng/mL, p = 0.02). After controlling for confounding by maternal age, smoking status, and pre-pregnancy body mass index, odds of preeclampsia were 48% lower for women with high versus low plasma apelin (≥0.73 vs. <0.73 ng/mL) concentrations. Conclusion. Reduced circulating apelin peptides may be associated with preeclampsia. The apelinergic system should be further investigated to elucidate its role in preclampsia and other hypertensive maternal disorders.     

Alternations of Maternal and Cord Plasma Hemostasis in Preeclampsia Before and After Delivery

Objective: The aim of this study was to investigate the role of hemostatic factors in the pathogenesis of preeclampsia. Materials and Methods: Maternal and cord plasma concentrations of tissue factor (TF), tissue factor pathway inhibitor (TFPI), von willebrand factor (vWF), soluble P-selectin (sP-selectin), fibrinopeptide A (FPA), D-dimer, and antithrombin III (AT-III) were measured by enzyme-linked immunosorbent assay (ELISA) in 46 women with preeclampsia and 40 normotensive pregnant women before and after delivery. Results: The maternal plasma concentrations of TF, vWF, and sP‐selectin were higher, but lower concentrations of TFPI, AT-III, and D-dimer were observed in women with preeclampsia compared to normotensive pregnant women before and after delivery. Compared with maternal plasma, fetal plasma concentrations of TF concentrations were increased significantly in both groups, whereas vWF, FPA, TFPI, AT-III, and D-dimer were decreased. Compared with normotensive pregnancy, fetal plasma concentrations of TF were markedly increased in preeclampsia, accompanied with a higher vWF and a lower sP-selectin and D-dimer levels. Furthermore, fetal plasma TF concentrations were more significantly increased in women with high blood pressure and severe proteinuria. Conclusions: Imbalance in the coagulation/fibrinolysis equilibrium, especially alterations in the extrinsic pathway of coagulation and anticoagulation, may play an important role in the pathogenesis of preeclampsia. In addition, fetal alteration of TF may be involved in the pathogenesis of fetal complications of preeclampsia.     

Maternal Serum Chlamydia Pneumoniae Antibodies and CRP Levels in Women with Preeclampsia and Gestational Hypertension

Objective. To determine whether Chlamydia pneumoniae antibodies and highly sensitive C-reactive protein (hsCRP) levels in maternal sera are associated with preeclampsia or gestational hypertension. Methods. C. pneumoniae antibodies and hsCRP levels were measured in maternal serum during first trimester (mean, 10.4 weeks of gestation) using the microimmunofluorescence (MIF) test and a highly sensitive immunoenzymometric assay, respectively. Results. No differences in the IgG antibody levels against C. pneumoniae or hsCRP levels were seen between the women with preeclampsia or gestational hypertension and those in the reference group. However, the women with preeclampsia and preterm delivery had serum IgG antibodies to C. pneumoniae (IgG titre ≥32) significantly more often in their first trimester sera compared with women having preeclampsia and full-term deliveries (p = 0.03). In addition, the proportion of subjects with C. pneumoniae IgG antibodies (IgG titre ≥32) and/or elevated CRP levels (≥3.8 mg/L, upper quartile) was double among the women with preeclampsia and elective preterm delivery compared with the women with preeclampsia who delivered at term (p = 0.01). Conclusion. Our results suggest that chronic C. pneumoniae infection and systemic low-grade inflammation may be associated with preeclampsia requiring elective delivery before 37 weeks gestation.     

Preeclampsia Due to Fetal Non-immune Hydrops: Mirror Syndrome and Review of Literature

Objective.?Mirror syndrome (Ballantyne's syndrome) refers to the association of fetal hydrops and maternal preeclampsia. The aim of this study was to determine the relation and incidence between fetal hydrops and preeclampsia in our clinic.?Methods.?A retrospective review of patients associated with fetal hydrops and findings with preeclampsia was used. Seventy-five cases with single pregnancy and diagnoses with nonimmune hydrops fetalis were found. According to the data 4 cases were found related with preeclampsia.?Results.?Mirror syndrome is rarely encountered and underdiagnosed. We found a frequency of 5.3% (4 cases in 75 affected pregnancies) for single non-immune hydrops cases in which maternal hypertension occurred. Fetal outcome is depending on etiology and prognosis is mainly very low. Maternal symptoms and laboratory findings are resolving after intrauterine fetal death or delivery. Conclusion. Hydrops fetalis must be considered as a potential risk factor for preeclampsia. It is important that this clinical condition has a potential of about 5% for proceeding preeclampsia.     

Detection of Circulating Trophoblast Particles in Peripheral Maternal Blood in Preeclampsia Complicated Pregnancies

Objective. Data on trophoblast particles in peripheral maternal circulation are rare. Applying a new enrichment technique, Oncoquick®, we evaluated the number of trophoblast particles in maternal blood in preeclamptic and non-preeclamptic pregnancies. Methods. After isolation of trophoblast particles using Oncoquick®, trophoblast particles were detected by immunocytochemistry, applying a monoclonal pan cytokeratin (CK) antibody. Fetal origin of the detected particles was verified by XY- fish analysis in women delivering male infants. Results. Trophoblast particles were identified in 25/52 (48%) of preeclamptic and 1/20 (5%) of non-preeclamptic pregnancies. Conclusion. The number of trophoblast particles in peripheral maternal blood of preeclamptic pregnancies was significantly higher than in non-preeclamptic pregnancies.     

Preeclampsia is Associated with Lower Percentages of Regulatory T Cells in Maternal Blood

Objective: Immunological mechanisms are involved in the pathophysiology of preeclampsia. During pregnancy there is an increase in regulatory T (Treg) cells, which has an important role in regulating tolerance to the immunologically distinct fetus. We hypothesised that percentages of Treg cells are decreased in preeclamptic patients. Methods: Peripheral blood was obtained from 26 healthy pregnant controls and 18 preeclamptic patients. Treg cells were measured using flow-cytometry. Results: Women with pregnancies complicated by preeclampsia had significantly lower percentages of CD4⁺FOXP3⁺ Treg cells. Conclusion: We conclude that a deficiency of regulatory T cells may play a role in the pathophysiology of preeclampsia.     

Preeclampsia: an imbalance in placental prostacyclin and thromboxane production

Preeclampsia is characterized by increased vasoconstriction frequently associated with increased platelet aggregation, reduced uteroplacental blood flow, and premature delivery. Because prostacyclin antagonizes the vasoconstrictor, platelet-aggregating, and uterine-activating actions of thromboxane, we considered the hypothesis that placental production of thromboxane was increased coincident with decreased production of prostacyclin in preeclampsia. Fresh human term placentas were obtained immediately after delivery from 11 normal and 10 preeclamptic pregnancies (blood pressure greater than or equal to 140/90 mm Hg, urinary protein greater than 0.3 gm/24 hr). Tissues (350 mg) were incubated sterilely in 6 ml of Dulbecco's Modified Eagle's Medium for 48 hours at 37 degrees C with 95% oxygen and 5% carbon dioxide in a metabolic shaker. Samples were collected at 8, 20, 32, and 48 hours and analyzed for thromboxane by radioimmunoassay of its stable metabolite, thromboxane B2, and for prostacyclin by radioimmunoassay of its stable metabolite, 6-keto prostaglandin F1 alpha. The production of thromboxane was significantly increased in preeclamptic versus normal placental tissue (22.9 +/- 4.7 versus 6.3 +/- 1.5 pg/mg/hr, mean +/- SE, p less than 0.01), whereas the production of prostacyclin was significantly decreased (3.0 +/- 0.3 versus 6.7 +/- 0.5 pg/mg/hr, p less than 0.001). In both normal and preeclamptic placentas, the production rates of thromboxane and prostacyclin were inhibited by indomethacin (5 mumol/L) and not affected (p greater than 0.50) by arachidonic acid (100 mumol/L). Therefore, during normal pregnancy, the placenta produces equivalent amounts of thromboxane and prostacyclin, so that their biologic actions on vascular tone, platelet aggregation, and uterine activity will be balanced. In preeclamptic pregnancy, however, the placenta produces seven times more thromboxane than prostacyclin.     

Renal Angiotensin-II Receptors Expression Changes in a Model of Preeclampsia

The blunted response to angiotensin II (Ang II) during pregnancy is lost in patients by preeclampsia. This impaired response has been attributed to a change in one or both of the Ang II receptors, type 1 (AT₁R) and type 2 (AT₂R). The ratio of the Ang II receptor types in the kidney has not been studied. We postulated that an imbalance exists between AT₁R/AT₂R receptors in the renal cortex from rats subjected to an experimental model of preeclampsia, and that this altered ratio can modify the characteristic blunted pressor response to Ang II during pregnancy. The feto-placental units of Wistar rats were made ischemic by subrenal aortic coarctation, thus creating an experimental model of preeclampsia. We measured the AT₁R and AT₂R protein expression and the presence of the heterodimer AT₁R/AT₂R in the renal cortex and evaluated the pressor response to Ang II in an isolated kidney preparation from non-pregnant, healthy pregnant, and preeclampsia model rats. Pregnancy increased AT₂R and AT₁R/AT₂R heterodimer expression and decreased the pressor response to Ang II. In contrast, AT₁R increased, while AT₂R and AT₁R/AT₂R heterodimer decreased in the preeclampsia model group. Thus, Ang II hypersensitivity observed in preeclampsia might be related to an increased expression of AT₁R over AT₂R and to a decreased presence of the AT₁R/AT₂R heterodimer in renal cortex.     

Neutrophils,but Not Lymphocytes or Monocytes,Infiltrate Maternal Systemic Vasculature in Women with Preeclampsia

Objective: Leukocytes are activated in women with preeclampsia, but the class of leukocytes that infiltrates the maternal vasculature and, therefore, is most likely to cause vascular dysfunction is not known. Methods: Subcutaneous fat biopsies were obtained at Cesarean section or abdominal surgery from 7 normal non-pregnant women, 7 women with normal pregnancies, and 7 women with preeclampsia. Tissues were immunohistochemically stained for CD14, a monocyte/macrophage antigen, CD99, a lymphocyte antigen, and CD66b, a neutrophil antigen. Results: CD14 stained cells were found infiltrated into fat tissue but were not present in vessels for any of the groups. CD99-stained cells were present in approximately 20% to 30% of vessels with no difference among groups. CD66b-stained cells were present in all groups with a significantly greater percentage of vessels stained for preeclamptic than normal pregnant or normal non-pregnant women (70 ± 6 vs. 43 ± 9 vs. 21 ± 5%, respectively, p < 0.01). CD66b cells were the most abundant cell type that infiltrated vessels of preeclamptic women. Conclusions: 1) A significantly greater number of neutrophils adhered to endothelium and infiltrated into the intimal space in the maternal systemic vasculature of preeclamptic women than in that of normal pregnant women or normal non-pregnant women; 2) No significant difference in lymphocyte infiltration was observed among the patient groups, and lymphocytes were present in much lower numbers than-neutrophils; 3) Monocytes/macrophages were found in fat tissue but not in vessels. We speculate that neutrophils are the class of leukocytes that cause the majority of vascular cell dysfunction in women with preeclampsia.     

Plasma Hemopexin Activity in Pregnancy and Preeclampsia

Objective: Plasma hemopexin activity, associated with increased vascular permeability, was evaluated in healthy pregnant and non-pregnant women and in pre-eclamptic women. Methods: Hemopexin activity and the hemopexin inhibitor, extracellular ATP, were assayed in plasma from pregnant (n?=?10), preeclamptic (n?=?9), and non-pregnant women (n?=?10) using standard methods. Abdominal fascia tissue fragments from preeclamptic and pregnant women were immunohistochemically stained for vascular ecto-apyrase or ecto-5′nucleotidase. Results: The data show significantly enhanced Hx activity exclusively in plasma from pregnant women and significantly enhanced plasma ATP in pre-eclamptic women compared with the other groups. Dephosphorylation of preeclamptic plasma resulted in reactivation of Hx activity. Fascia tissue-samples from preeclamptic women showed reduced ecto-apyrase activity and enhanced ecto-5′nucleotidase activity compared to pregnant women. Conclusion: Enhanced hemopexin activity may be associated with normal pregnancy, but not with preeclampsia. Decreased hemopexin in pre-eclamptic patients may be due to enhanced plasma ATP, which is possibly promoted by diminished activity of vascular ecto-apyrase.     

Metalloprotease (ADAM12-S) as a Predictor of Preeclampsia: Correlation with Severity,Maternal Complications,Fetal Outcome,and Doppler Parameters

Objectives. To compare the first trimesteric serum level of ADAM12-S in women who developed mild and severe preeclampsia and in healthy gravidas and to correlate these changes with the severity of the disease, maternal complications, fetal outcome, and Doppler cerebroplacental ratio (CPR). Design. Comparative prospective observational study. Setting: University hospital. Methods: Serum samples were obtained from 414 women in their first trimester, of which 259 women completed their pregnancy without complications and 155 women developed preeclampsia later in their pregnancies. All were subjected to history taking, examination, laboratory investigations, obstetric ultrasound, and Doppler CPR. Results. ADAM12-S was significantly decreased in patients with severe and in mild preeclampsia compared with the controls. Moreover, there was strong negative correlation with disseminated intravascular coagulopathy (DIC) and HELLP syndrome, cesarean delivery, postpartum hemorrhage, and neonatal intensive care unit admission. ADAM12-S had medium negative correlation with systolic blood pressure and diastolic blood pressure, accidental hemorrhage, cesarean hysterectomy, prematurity, and low birth weight. In addition, it had a weak negative correlation with intracranial hemorrhage, residual hypertension, and intrauterine fetal death. ADAM12-S had strong positive correlation with CPR. There were no correlation with eclampsia, intrauterine growth retardation, acute pulmonary edema, and acute renal failure. Conclusion. ADAM12-S is significantly decreased in severe and mild preeclampsia and is correlated with CPR, severity of preeclampsia, maternal complications, and fetal outcome. It is recommended to measure ADAM12-S in the first trimester to predict maternal complications and fetal outcome in pregnancies complicated by preeclampsia.     

Estimation of Lipid Profile in Subjects of Preeclampsia

Objectives

To evaluate lipid profiles in subjects with preeclampsia. To determine if there is any change in lipid profiles in subject of preeclampsia as compared to normal antenatal females, non-pregnant females and post partum females.

Methods

Study was carried out on pregnant women and non pregnant women attending or admitted in the Obstetrics and Gynecology Department of SSG Hospital, Baroda between 1st June 2007 to 31st May 2008. Each serum sample from different groups was evaluated for Total cholesterol(mg/dl), Triglyceride (mg/dl), HDL-cholesterol (mg/dl), LDL-cholesterol (mg/dl) and VLDL-cholesterol (mg/dl) using diagnostic kits and a comparison drawn and analyzed using t-test and chi-square test.

Results

Dyslipidemia in the form of significantly decreased HDL concentration and significantly increased total cholesterol, LDL, VLDL &; Triglycerides concentration is conspicuously evident in subjects of preeclampsia as compared to non pregnant, normotensive pregnant and postpartum subjects.

Conclusion

Dyslipidemia is significantly evident in preeclampsia and plays an important pathological role. The various causative factors for dyslipidemia and its prevention need to be further studied and evaluated.     

Resibufogenin Administration Prevents Oxidative Stress in a Rat Model of Human Preeclampsia

Background and Objectives. Marinobufagenin (MBG) is a cardiotonic steroid that is increased in preeclampsia. An analog of MBG, resibufogenin (RBG), prevents the development of preeclampsia in a rat model. Oxidative stress is a concomitant of endothelial dysfunction in the latter disorder. The objective of the current studies was to evaluate the status of oxidative stress in a rat model of preeclampsia. Methods. We measured the aortic AT₁ receptor expression and urinary excretion of 8-isoprostane (8IP) in rats rendered “preeclamptic” and compared the findings to those obtained in normal pregnant animals, pregnant rats injected with MBG, and preeclamptic rats treated with RBG. Results. Aortic AT₁ receptor expression and the urinary excretion of 8IP were significantly augmented in “preeclamptic” and MBG-injected pregnant rats compared to normal pregnant animals. RBG prevented evidence of oxidative stress in “preeclamptic” rats. Conclusion. MBG is involved in the causation of oxidative stress in our rat model and RBG attenuates this change.     

Maternal Leptin Concentrations are Similar in African Americans and Caucasians in Normal Pregnancy,Preeclampsia and Small-for-Gestational-Age Infants

Leptin concentrations were measured in African American women in order to assess leptin's role in the increased frequency and severity of preeclampsia. In addition, leptin concentrations were measured in women who delivered small-for-gestational-age (SGA) infants. A case-control study of African American and Caucasian women with normal pregnancies, preeclampsia, or SGA infants was done. Plasma leptin was quantitated by radio-immunoassay. The previously recognized pattern of increased leptin concentrations in preeclampsia was replicated. Leptin concentrations did not differ by race in any diagnostic category, and concentrations in women with SGA infants were not higher than those in healthy women. Differences in the frequency and severity of preeclampsia in African Americans cannot be explained by higher leptin concentrations.     

子(癎)前期孕妇中性粒细胞相关因子与胎儿的关系

目的:了解中性粒细胞在子前期胎儿中的状态,探讨其在胎儿患病中的作用。方法:采用流式细胞术检测20例子前期患者和20例正常妊娠孕妇肘静脉血和脐静脉血中中性粒细胞粘附分子CD11b的表达,同时采用酶联免疫吸附实验检测两组血浆IL-8和弹性蛋白酶的浓度。结果:①子前期组母体静脉血CD11b的平均对数荧光强度指数、血浆IL-8和弹性蛋白酶的浓度均高于正常妊娠组(P<0.05);②子前期组脐静脉血CD11b的平均对数荧光强度指数高于正常妊娠组(P<0.05),但血浆IL-8和弹性蛋白酶的浓度与正常妊娠组比较无统计学差异(P>0.05);③胎儿脐静脉血中的中性粒细胞CD11b平均对数荧光强度指数与母体静脉血中的中性粒细胞CD11b平均对数荧光强度指数有正相关关系(r=0.590,P<0.01)。结论:子前期胎儿中性粒细胞的激活与母体中性粒细胞的激活相关,胎儿循环中存在中性粒细胞的激活,推测中性粒细胞在子前期胎儿病率中有一定作用。