Predictivity of mean platelet volume in severe preeclamptic women

Introduction: To evaluate the predictive and clinical utilization of the mean platelet volume (MPV) in severe preeclamptic women. MPV is known as platelet size and associated with platelet activation or new platelet synthesis. Platelet count is decreased by vascular endothelial damage in cases of severe preeclampsia. It leads to increased turnover of platelets. Methods: The severe preeclamptic women with and without preeclampsia during pregnancy were divided into subgroups depending on the gestational birth week early, (<34), late (34–37) preterm birth and term (≥37) gestational weeks. Their MPV was measured 24 hours prior to birth and compared with all subgroups according to the gestational week. Result: The study subgroups were performed from early (n = 87), late (n = 48) preterm and term (n = 76) birth with severe preeclampsia, whereas early (n = 69), late (n = 63) and term (n = 228) without gestational hypertensive disorders were recruited in the control subgroups. The MPV of the early, late preterm and term preeclamptic subgroups was statistically higher than that of the control subgroups (9.4 ± 1.3fL vs 8.6 ± 1.2 fL, p < 0.001; 9.5 ± 1.0 fL vs 8.5 ± 0.9 fL, p < 0.001 and 10.2 ± 1.1 fL vs 8.9 ± 1.2 fL, p < 0.001), whereas the mean platelet count of all the study subgroups was significantly lower (237.3 ± 81.3 × 10⁹ /L, 270.0 ± 83.9 × 10⁹/L, p = 0.015; 232.3 ± 80.1 × 10⁹/L vs 268.8 ± 92.7 × 10⁹/L, p < 0.001 and 221.8 ± 70.3.9 × 10⁹/L vs 232.9 ± 82.3 × 10⁹/L, p = 0.03). The sensitivity and specificity of the cut-off MPV for all the subgroups were each less than 80%. Conclusion: The MPV may be a predictive marker of severe preeclampsia.     

Combined Doppler ultrasound and platelet indices for prediction of preeclampsia in high-risk pregnancies

Abstract

Objectives: To evaluate Doppler ultrasound and platelet indices for the prediction of preeclampsia (PE).

Design: Prospective observational study.

Methods: The study included 270 normal pregnancy primigravida <20?years at 20–24-week gestation. Doppler ultrasound was done to detect uterine artery diastolic notch and to measure the pulsation index (PI) and the resistance index (RI). The platelet count (PC), mean platelet volume (MPV), platelet distribution width (PDW) and platelet large cell ratio (Plcr) was measured by automated blood picture.

Outcome: Validity of combined tests in prediction of PE.

Results: Patients who developed PE had significant higher percentage of diastolic notch, higher mean PI, RI, and significant increase of MPV and PDW than normotensive women (p?<?.001). Patients with abnormal Doppler and abnormal platelet indices had significant higher incidence of severe PE (p?<?.001).

Conclusion: Abnormal platelet indices combined with abnormal Doppler is a predictor of severity rather than the rate of development of PE.     

Micropartículas plaquetarias en preeclampsia y eclampsia

Objective

To compare platelet microparticle values in eclamptic, preeclamptic and normotensive pregnant women.

Material and methods

Patients attending the Dr. Urquinaona Central Hospital in Maracaibo, Venezuela, were selected. Thirty patients with mild preeclampsia (group A), 30 with severe preeclampsia (group B) and 30 with eclampsia (group C) were included. Thirty-five healthy women with a similar age and body mass index to those in the study groups were selected as controls (group D). Only nuliparous patients were included. Blood samples were collected before delivery from all patients and immediately after diagnosis for platelet microparticle determination in the study groups.

Results

Statistically significant differences were found in gestational age between groups B and C compared with the control group (P < .05). Higher platelet microparticle values were found in eclamptic patients and severe preeclamptic patients. Lower values were found in mild preeclamptic patients. Significantly higher platelet microparticle values were found in the study groups than in controls (P < .05). When linear regression was performed, the factors significantly affecting platelet microparticle values were 24-hour proteinuria, transaminase and uric acid levels and platelet count (P < .05).

Conclusions

Our findings indicate that platelet microparticle values are higher in eclamptic and preeclamptic women than in normotensive pregnant women.     

Is there any relationship between adipocytokines and angiogenesis factors to address endothelial dysfunction and platelet aggregation in untreated patients with preeclampsia?

Purpose

Preeclampsia is a multisystem disorder and its etiology remains still unclear. Recent hypotheses rely on imbalance between angiogenic and antiangiogenic factors and disruption of endothelial function of spiral arteries. In addition; increased VTE (venous thromboembolism) risk is still unclear in preeclampsia. Our aim was to investigate the relationship between endothelial dysfunction, adipocytokines, platelet function, and vasculogenesis in preeclampsia.

Methods

Plasma angiogenic (PlGF, VEGF), antiangiogenic factors (sflt-1, endoglin) with adipocytokines (leptin, adiponectin, ghrelin), endothelial dysfunction markers (vWF, NO), and platelet function markers (ADP and collagen induced platelet aggregation, P-selectin) were examined in 30 early-onset, 22 late-onset preeclampsia, and 27 healthy pregnants. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum biomarker levels except NO. NO levels were determined using colorimetric method.

Results

Endoglin, leptin, and vWF levels were increased in preeclampsia (P < 0.001), whereas PlGF, P-selectin (P < 0.001), and col-induced platelet aggregation slope (P < 0.05) were decreased in the same counterpart as compared to healthy pregnants. Endoglin also correlated with sflt-1 in preeclamptic patients.

Conclusion

Increase in the levels of antiangiogenic factors and leptin herewith decline in the level of other angiogenic factor PlGF, did not affect nitric oxide and platelet aggregation markers significantly. Increased levels of vWF and endoglin might be result of endothelial dysfunction, so our findings suggest that an impaired angiogenesis may address endothelial dysfunction, but not platelet aggregation for preeclampsia.

     

Preeclampsia, delivery, and the hemostatic system

To determine the effects of preeclampsia and delivery, the hemostatic system was evaluated before and 24 to 48 hours after delivery in 59 nulliparous patients without clinical signs of disseminated intravascular coagulation. Fifteen patients with mild preeclampsia and 18 with severe preeclampsia were compared with 26 pregnant control patients. Preeclampsia was associated with high fibronectin (p less than 0.001), low antithrombin III (p less than 0.001), and low alpha 2-antiplasmin (p less than 0.005), suggesting endothelial injury, clotting, and fibrinolysis, respectively. After delivery, fibronectin decreased only in preeclamptic patients (p less than 0.005); alpha 2-antiplasmin increased in all groups (p less than 0.001). Endothelial injury in preeclampsia appeared to resolve soon after delivery, which could contribute to the rapid clinical improvement noted in the early puerperium.     

不同类型重度子痫前期血小板参数变化的研究

目的探讨不同类型的重度子痫前期患者血小板参数的变化规律及其临床意义。方法将早发型重度子痫前期93例、晚发型重度子痫前期126例作为研究对象,对两组孕妇从妊娠12+1～16周起,每4周1次的血小板计数(platelet count,PLT)、血小板平均体积(mean platelet volume,MPV)、血小板分布宽度(platelet distributing width,PDW)、血小板压积(plateletcrit,PCT)进行对比分析,并与作为对照组的200例正常孕妇相比较。结果①早发型重度子痫前期患者PLT自孕24+1～28周起低于正常对照组及晚发型组患者,晚发型组患者自孕28+1～32周起PLT低于正常对照组孕妇,差异有统计学意义(P<0.05);②早发型重度子痫前期患者在PLT发生变化前4周即出现MVP及PDW高于正常对照组及晚发型组患者,晚发型组患者自孕24+1～28周起MPV、PDW高于正常对照组孕妇,差异有统计学意义(P<0.05)。③早发型重度子痫前期患者自孕28+1～32周起PCT低于正常对照组孕妇,差异有统计学意义(P<0.05)。晚发型组患者PCT与对照组孕妇相比差异无统计学意义。结论早发型重度子痫前期患者较晚发型患者血小板减少更为严重,连续监测血小板参数对于子痫前期的预测、治疗、病情的监测,都有重要的意义。     

In Vitro Plasma-Induced Endothelial Oxidative Stress and Circulating Markers of Endothelial Dysfunction in Preeclampsia: An Observational Study

Objective:?To investigate plasma-induced endothelial reactive oxygen species (ROS) production in vitro and its relation to endothelial dysfunction in preeclampsia (PE).?Methods:?Plasma was drawn from 17 PE patients, 17 matched healthy pregnant (HP) women, 17 matched non-pregnant healthy volunteers (NP), and 10 septic shock (SC) patients. In vitro plasma-induced ROS production was assessed in cultured human endothelial cells. In vivo endothelial activation and injury were assessed through measurements of plasma von Willebrand factor (vWF) and soluble thrombomodulin (sTM) concentrations, respectively.?Results:?Endothelial ROS production was not induced by PE, HP, and NP plasmas. However, it was significantly increased in SC compared to other groups (p < .005). Pregnancy (PE and HP) was associated with higher vWF compared to NP. Among pregnancies, vWF was higher in PE compared to HP women (p < .05). sTM was unchanged between PE, HP and NP. In SC, vWF and sTM were significantly increased compared to other groups (p < .01). Simultaneously, endothelial ROS production and sTM concentration were correlated (p = .673; p < .05).?Conclusion.?Plasma does not induce in vitro endothelial ROS production in PE women for which endothelial dysfunction is limited to activation but not injury. By contrast, SC patients demonstrate both endothelial activation and injury, closely related to plasma-induced endothelial oxidative stress.     

Homocysteine and Cellular Fibronectin are Increased in Preeclampsia,not Transient Hypertension of Pregnancy

Objective. The objective of this study was to confirm that endothelial dysfunction is present in preeclampsia and absent in transient hypertension of pregnancy, and to determine whether the cardiovascular risk factor homocysteine is associated with the degree of endothelial dysfunction.

Methods. We measured cellular fibronectin (as a marker of endothelial injury) and total plasma homocysteine in samples collected at the time of admittance to labor and delivery in 17 women with preeclampsia (increased blood pressure, proteinuria, and hyperuricemia), 16 women with transient hypertension of pregnancy (only increased blood pressure), and 34 normal pregnant women. Each subject with preeclampsia was matched by prepregnancy body mass index, race, and gestational age at delivery to one subject with transient hypertension of pregnancy and two controls.

Results. Cellular fibronectin was found to be significantly increased in women with preeclampsia compared to subjects with transient hypertension of pregnancy or normal pregnant women (22.9±14.1 μg/mL versus 10.9±5.4 and 10.1±6.2 μg/mL, respectively, p<0.0001). Similarly, total plasma homocysteine was also significantly increased in the women with preeclampsia compared to subjects with transient hypertension of pregnancy or normal pregnant women (8.3±2.5 μM versus 5.5±2.2 and 5.4±3.4 μM respectively, p<0.01). However, contrary to our hypothesis, there was no apparent association between cellular fibronectin and homocysteine.

Conclusions. The increased concentrations of homocysteine observed in preeclampsia are not a general feature of all hypertensive complications of pregnancy. Furthermore, endothelial dysfunction is present in preeclampsia and is not evident in transient hypertension of pregnancy. However, the apparent endothelial dysfunction in preeclampsia is not explained by the increase in homocysteine concentrations observed.     

The maternal plasma soluble vascular endothelial growth factor receptor-1 concentration is elevated in SGA and the magnitude of the increase relates to Doppler abnormalities in the maternal and fetal circulation

Objectives. The soluble form of vascular endothelial growth factor receptor-1 (sVEGFR-1), an antagonist to vascular endothelial growth factor and placental growth factor, has been implicated in the pathophysiology of preeclampsia. Preeclampsia and pregnancy complicated with small for gestational age (SGA) fetuses share some pathophysiologic derangements, such as failure of physiologic transformation of the spiral arteries, endothelial cell dysfunction, and leukocyte activation. The objectives of this study were to: (1) determine whether plasma concentrations of sVEGFR-1 in mothers with SGA fetuses without preeclampsia at the time of diagnosis are different from those in patients with preeclampsia or normal pregnant women, and (2) examine the relationship between plasma concentrations of sVEGFR-1 and Doppler velocimetry in uterine and umbilical arteries in patients with preeclampsia and those with SGA.

Study design. A cross-sectional study was conducted to determine the concentrations of the soluble form of VEGFR-1 in plasma obtained from normal pregnant women (n = 135), women with SGA fetuses (n = 53), and patients with preeclampsia (n = 112). Patients with SGA fetuses and those with preeclampsia were sub-classified according to the results of uterine and umbilical artery Doppler velocimetry examinations. Plasma concentrations of sVEGFR-1 were determined by an ELISA. Since these concentrations change with gestational age, differences among various subgroups were statistically estimated with the delta value, defined as the difference between the observed and expected plasma sVEGFR-1 concentration. The expected values were derived from regression analysis of plasma sVEGFR-1 concentrations in normal pregnancy. Regression analysis and univariate and multivariate analysis were employed.

Results. (1) Mothers with SGA fetuses had a mean plasma concentration of sVEGFR-1 higher than normal pregnant women (p < 0.001), but lower than patients with preeclampsia (p < 0.001). (2) Among patients with SGA fetuses, only those with abnormal uterine artery Doppler velocimetry had a mean plasma sVEGFR-1 concentration significantly higher than normal pregnant women (p < 0.001). (3) Among mothers with SGA fetuses in whom Doppler velocimetry was performed (n = 41), those with abnormalities in both the uterine and umbilical artery velocimetry had the highest mean delta of sVEGFR-1 plasma concentration (mean ± standard deviation (SD): 0.69 ± 0.29). Conversely, patients who had normal Doppler velocimetry in both uterine and umbilical arteries had the lowest mean delta (mean ± SD: 0.09 ± 0.29) of sVEGFR-1 plasma concentrations (ANOVA; p < 0.001). (4) Among patients with preeclampsia in whom Doppler velocimetry was performed (n = 69), those with abnormalities in both the uterine and umbilical artery velocimetry had the highest mean delta sVEGFR-1 plasma concentration (mean ± SD: 1.01 ± 0.22) among all groups classified (ANOVA; p < 0.001). (5) Among patients with SGA and those with preeclampsia, there was a relationship (Chi-square for trend p < 0.001 for both) between the severity of Doppler velocimetry abnormalities and the proportion of patients who had high delta sVEGFR-1 plasma concentrations (defined as a concentration two standard deviations (2SD) above the mean delta of normal pregnant women). (6) Multiple regression analysis suggested that the diagnostic category (e.g., SGA or preeclampsia), Doppler abnormalities, and gestational age at blood sampling were associated with an increase in plasma sVEGFR-1 concentrations (p < 0.001).

Conclusions. These observations provide support for the participation of the soluble receptor of vascular endothelial growth factor in the pathophysiology of SGA with abnormal uterine artery Doppler velocimetry and preeclampsia. An excess of sVEGFR-1 is released into the maternal circulation of patients with preeclampsia and those with SGA fetuses, as abnormalities of impedance to blood flow involve uterine and umbilical circulation.     

Serum sFlt-1, cystatin C and cathepsin B are potential severity markers in preeclampsia: a pilot study

Preeclampsia is associated with abnormal invasion of the trophoblast through decidua and subsequently altered remodeling of the maternal spiral arteries and endothelial dysfunction. This phenomenon is explained by the dysregulation of various kinds of vascular factors and proteases. The purpose of this study was to compare the circulating levels of sFlt-1, cathepsin B, and cystatin C in preeclamptic and normotensive pregnancies. Sixty-two pregnant women were enrolled in this prospective study. Twenty women were preeclamptic and 42 were normotensive. Serum levels of sFlt-1, cathepsin B, and cystatin C were measured using an enzyme-linked immunosorbent assay kit. Circulating levels of sFlt-1, cathepsin B, and cystatin C were significantly higher in preeclamptic than in normotensive pregnant women (p < 0.001; p = 0.017; p = 0.003). Preeclamptic women with severe features demonstrated significantly higher levels of cathepsin B (p = 0.05). Serum sFlt-1 and cystatin C levels were positively correlated with elevated systolic and diastolic blood pressure. The levels of cathepsin B were positively correlated with alanine and aspartate aminotransferase. The amount of 24 h proteinuria was positively, but non-significantly correlated with sFlt-1 and cystatin C. In addition to sFlt-1 levels, the serum levels of cathepsin B and cystatin C significantly change when preeclampsia develops. These markers are associated with severity markers of elevated blood pressure and liver injury in preeclampsia.     

Utility of a Single Plasma Fibronectin Level for the Prediction of Preeclampsia

Previous studies have indicated that repeated maternal plasma fibronectin (FN) levels may aid in the prediction of preeclampsia. To investigate the development of a preeclampsia screening test, avoiding the requirement for repeated maternal blood samples throughout pregnancy, we examined the efficacy of a single screening plasma FN level for the prediction of preeclampsia. Total plasma FN levels were determined between 24 and 32 weeks' gestation in 115 normotensive patients, and cellular FN was determined in a subgroup of 81 of these patients. Among nulliparas (n = 76) total plasma FN values were significantly (P = 0.007) greater in patients (n = 13) who subsequently developed preeclampsia (median = 370, range 130-1104 μg/ml) than among those who remained nonpreeclamptic (median = 283, range 80-490 μg/ml). Based on maximization of the receiver/operator curve, a cut-off plasma FN value of 300 μg/ml was selected as a positive screen in the nulliparous group, resulting in a sensitivity of 85%, specificity of 60%, positive predictive value of 31% and a negative predictive value of 95%. Eleven of the thirteen nulliparous preeclamptics had positive plasma FN screens prior to onset of disease, with increased plasma FN occurring 8-14 weeks prior to the clinical onset of preeclampsia. There were no significant differences in cellular FN values between the nulliparous preeclamptics (median = 3.40, range 2.80–4-20 μg/ml) and nonpreeclamptics (median = 3.30, range 2.40-5.20 μg/ml; P = 0.41). Due to the low incidence of preeclampsia in the multiparous patients in our study (2.6%), measurements of neither total plasma nor cellular FN were found to be of value as a screening test in this group. These results indicate the potential value of a single maternal plasma FN screen at 24-32 weeks' gestation for predicting preeclampsia in nulliparous women.     

血浆纤维结合蛋白对胎儿生长受限和妊娠高血压综合征的早期预测价值

目的探讨孕妇血浆纤维结合蛋白(FN)水平变化对胎儿生长受限(FGR)和妊娠高血压综合征(妊高征)的早期预测价值.方法用免疫速率比浊法测定130例孕妇血浆FN水平,并随访其妊娠结局.比较用FN水平预测FGR、妊高征、FGR合并妊高征3种妊娠结局的预测价值.结果 (1)妊娠结局130例孕妇中发生FGR 10例(FGR组)、妊高征10例(妊高征组)、FGR合并妊高征4例(FGR+妊高征组)、无合并症的正常妊娠妇女106例(正常妊娠组).4组孕妇间平均年龄、孕次、取样孕周、分娩孕周比较,差异无显著性(P＞0.05).(2)FGR组、妊高征组、FGR+妊高征组FN水平分别为(486.45±122.69) mg/L、 (428.38±118.71) mg/L、(443.66±68.13) mg/L,均显著高于正常妊娠组(284.41±93.83) mg/L(P＜0.001).(3) FN水平预测FGR 、妊高征、FGR+妊高征3种妊娠结局的受试者工作曲线(ROC曲线)下面积,分别为0.893、0.818、0.867. (4)以FN≥460 mg/L为最佳切点预测3种妊娠结局的敏感性、特异性、阳性预测值、阴性预测值及Kappa指数,FGR组为57.14%、95.69%、61.54%、94.87%、0.545 5;妊高征组为42.86%、91.38%、37.50%、92.98%、0.322 1;FGR+妊高征组为91.27%、50.00%、15.38%、98.29%、0.197 5. 结论晚孕早期妇女血浆FN水平可作为FGR或妊高征的早期预测指标之一,最佳切点为≥460 mg/L,尤其对FGR的预测价值优于对妊高征的预测.     

Mean Platelet Volume,a Novel Biomarker in Adolescents with Severe Primary Dysmenorrhea

Study ObjectiveTo evaluate whether mean platelet volume (MPV) would be a profitable marker in predicting disease severity in adolescents with severe primary dysmenorrhea (PD).Design, Setting, Participants, Interventions, and Main Outcome MeasuresA total of 67 patients diagnosed with PD and 37 healthy adolescents with regular menstrual cycles were included in the study. Hemoglobin, MPV, and white blood cell, platelet, lymphocyte, and neutrophil counts were measured as part of the automated complete blood examination. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio were obtained from the absolute neutrophil or platelet count, respectively, divided by the absolute lymphocyte count. The visual analog scale was used to assess the level of pain, as mild (<40 mm), moderate (40-60 mm) and severe (>60 mm) PD.ResultsThe MPV level of the combined severity of PD and control groups were similar. However, the MPV was significantly lower in the severe PD group compared with the control group (P = .04). There were no significant differences in the other hematological parameters between the groups. The mean visual analog scale score of the PD and control subjects were 7.35 ± 2.25 and 1.07 ± 1.96, respectively (P < .01). There was a poor negative correlation, which was statistically insignificant, between MPV and white blood cell count.ConclusionThe present study showed that MPV is decreased in adolescents with severe PD. Further studies with larger numbers of subjects are necessary to clarify the roles of platelets in the pathogenesis of severe PD and evaluate the changes in MPV value in response to treatment.     

Intrahepatic cholestasis of pregnancy as a risk factor for preeclampsia

Intrahepatic cholestasis of pregnancy and preeclampsia are two major pregnancy complications. We aimed to investigate the association between intrahepatic cholestasis of pregnancy (ICP) and preeclampsia. Single-center retrospective study. Study group included 180 women (162 singletons and 18 twin gestations) who were diagnosed with ICP based on clinical presentation, elevated liver enzymes and bile acids. The reference group included 1618 women (1507 singletons and 111 twin gestations) who delivered during the study period, and were matched according to age, gravidity, parity and singleton or twin gestation. The incidence of ICP was 0.36%. The incidence of preeclampsia was higher in women with ICP compared to reference group (7.78% vs 2.41%, aOR, 3.74 95% CI 12.0–7.02, p < 0.0001), for either without—(3.89% vs 1.61%, aOR 2.83, 95% CI 1.23–6.5, p = 0.145) or with severe features (3.89% vs 0.80%, aOR 5.17 95% CI 2.14–12.50, p = 0.0003). For both singleton and twin pregnancies, overall preeclampsia rates were higher in the ICP group (5.56% vs 2.19%, aOR 2.91 95% CI 1.39–6.07 p = 0.0045; and 27.78% vs 5.41%, aOR 10.9 95% CI 2.16–47.19, p = 0.0033, respectively). Earlier diagnosis of ICP was associated with higher incidence of preeclampsia (31.1 ± 3.8 vs 34.86 ± 6.2 gestational weeks, p = 0.0259). The average time between ICP diagnosis and to the onset of preeclampsia was 29.7 ± 24 days. ICP is associated with an increased risk for preeclampsia. We suggest intensified follow-up for preeclampsia in women with ICP, especially among those with early ICP presentation and twins’ gestations.     

Hemostasis in hypertensive disorders of pregnancy

We studied parameters of hemostasis reported to be altered with "pure" preeclampsia in hypertensive disorders of pregnancy. Plasma fibronectin, antithrombin, and alpha-2 antiplasmin were measured in normal pregnancies (N = 26) and in pregnancies complicated by preeclampsia (N = 19), hypertension (N = 11), and chronic hypertension with superimposed preeclampsia (N = 11). Preeclampsia, both pure and superimposed, was associated with high fibronectin (P less than .001), low antithrombin III (P less than .001), and low alpha-2 antiplasmin (P less than .05) levels, suggesting endothelial injury, clotting, and fibrinolysis, respectively. Alpha-2 antiplasmin was increased with chronic hypertension (P less than .001), regardless of whether there was superimposed preeclampsia. Fibronectin appeared to be more closely linked with preeclampsia than antithrombin III or alpha-2 antiplasmin and may prove valuable in detecting preeclampsia when evaluating hypertension in pregnancy.     

Evidence supporting a role for blockade of the vascular endothelial growth factor system in the pathophysiology of preeclampsia : Young Investigator Award

Objective

Soluble vascular endothelial growth factor receptor 1 (sVEGFR-1), which antagonizes VEGF functions, has been implicated in the pathophysiology of preeclampsia. The purpose of this study was to determine whether preeclampsia is associated with a change in the plasma concentration of sVEGFR-1, and, if so, whether such a change is correlated with the severity of the disease.

Methods

A cross-sectional study was conducted to determine the concentrations of sVEGFR-1 in plasma obtained from normal pregnant women (n = 61) and patients with preeclampsia (n = 61). Plasma concentrations of sVEGFR-1 were determined by enzyme-linked immunoassay.

Results

Preeclampsia had a higher median plasma concentration of sVEGFR-1 than normal pregnancy (P < .001). The median plasma concentration of sVEGFR-1 was higher in early-onset (≤34 weeks) than late-onset (>34 weeks) preeclampsia (P = .005), and higher in severe than in mild preeclampsia (P = .002). In normal pregnancy, there was a correlation between plasma concentration of sVEGFR-1 and gestational age (r = 0.5; P < .001). In contrast, there was a negative correlation between plasma concentration of sVEGFR-1 and gestational age at the onset of preeclampsia (r = -0.5; P < .001).

Conclusion

Preeclampsia is associated with an increased plasma sVEGFR-1 concentration. The elevation of sVEGFR-1 concentration is correlated with the severity of the disease. These observations suggest the participation of VEGF and its soluble receptor in the pathophysiology of preeclampsia.     

Reduction in the severity of early onset severe preeclampsia during gestation may be associated with changes in endothelial cell activation: A pathological case report

Early severe preeclampsia with changes consistent with the Hemolysis elevated liver enzymes low platelet count (HELLP) variant and severe fetal growth restriction rarely resolves prior to delivery. Established clinical disease is preceded by endothelial dysfunction and inflammation. Endothelial activation is reported in vitro to be raised in the presence of necrotic trophoblastic debris which is deported into the maternal circulation in preeclampsia. We report on an early severe preeclamptic patient admitted at 24 weeks gestation. Maternal serum was taken at day 2, 16, 30 of admission and 45 days postpartum. 20% maternal serum or trophoblastic debris from first trimester placental explants that had been cultured with 10% maternal serum was exposed to endothelial cells. Endothelial cell activation was quantified by the cell surface ICAM-1 expression and U937 monocyte adhesion assay. The clinical condition of this patient improved including the blood pressure, liver function, and platelet count by the 3rd day after antihypertensive treatment and remained normal until delivery at 37 weeks. ICAM-1 expression and U937 moncyte adhesion assay of endothelial cells was significantly increased following exposure of the endothelial cells to the maternal serum or trophoblastic debris from placentae treated with maternal serum drawn on day 2. However, ICAM-1 expression and the monocyte adhesion assay were significantly reduced following exposure of endothelial cells to maternal serum or trophoblastic debris from placenta treated with maternal serum drawn on day 16 or 30. Our data suggest unknown factor(s) in the maternal serum triggered endothelial cell activation when the clinical symptoms were present. The improvement in the clinical condition occurred along with the changes in endothelial cell activation.     

Transcranial Doppler Findings of Cerebral Vasospasm in Preeclampsia

The objective of this study was to evaluate the effect of preeclampsia and its severity on maternal mean middle cerebral artery blood flow velocity (mean MCA-CBFV) using transcranial doppler sonography (TCD), as well as the effect of magnesium on mean MCA-CBFV in preeclampsia.

This study used a prospective, comparative design. TCD was used to examine maternal mean MCA-CBFV in both healthy subjects (controls) and preeclamptic subjects (cases). The two groups were similar in age, gestational age, and parity. Healthy subjects were categorized into three groups: Group I, 6–14 weeks, n = 10; Group 11, 24–40 weeks, n = 27; Group HI, postpartum n = 15, 12–36 h. Serial TCD examinations of the middle cerebral artery were completed in 21 preeclamptic subjects at four different points in time: Time I is an initial measurement before delivery; Time 2 is also before delivery but after magnesium had been administered; Time 3 is postpartum while on magnesium (12–24 h), Time 4 is postpartum off magnesium, (24–48 h).

Preeclamptic subjects had significantly increased mean MCA-CBFV when compared to healthy subjects: antepartum (mean 78.2 vs. 55.1 cm/sec, P < 0.0005); postpartum (mean 101.3 vs. 69.8 cm/sec, P < 0.0001). Severe preeclamptics had significantly higher mean MCA-CBFV than mild preeclamptics at each point in time: Time 1: P < 0.016; Time 2: P < 0.040; Time 3: P < 0.002; and Time 4: P < 0.028. These data support the theory that cerebral vasospasm of the smaller diameter vessels is a major component of preeclampsia.     

Predictors of severe and febrile neutropenia during primary chemotherapy for ovarian cancer

Objective

To identify factors that increase the risk of neutropenic events in women with advanced ovarian carcinoma receiving initial chemotherapy.

Methods

Multi-center retrospective study of women with FIGO stage III-IV epithelial ovarian cancer treated postoperatively with multi-agent intravenous chemotherapy from 1995 to 2008. Outcomes were severe (SN; absolute neutrophil count [ANC] < 500/mm³) and febrile neutropenia (FN; ANC < 1000/mm³ and temperature > 38.1 °C). Cumulative risk of neutropenic events was estimated by Kaplan Meier method. Multivariate analysis was by Cox proportional hazard regression.

Results

Three hundred twenty-six patients met inclusion criteria. There were 251 SN events among 140 (43%) patients and 24 FN events among 22 (7%) patients. Univariate predictors of SN were body surface area < 2.0 m² (p = 0.03), body mass index (BMI) < 30 kg/m² (p < 0.01), Caucasian race (p < 0.01), treatment on research protocols (p < 0.01), non-carboplatin-containing regimens (p < 0.01), and planned relative dose intensity (RDI) > 85% of standard (p = 0.02). Women over age 60 were more likely to develop FN (p = 0.05). Multivariate predictors of SN were treatment on research protocols (hazard ratio [HR] 1.93; p < 0.01), Caucasian race (HR 2.13; p = 0.01), and planned RDI > 85% (HR 1.69; p = 0.05); predictors of FN were age > 60 (HR 2.84; p = 0.05) and non-carboplatin containing regimens (HR 4.06; p < 0.01).

Conclusion

While SN is fairly common, FN occurs infrequently in women with EOC undergoing taxane and platin-based chemotherapy and primary prophylactic growth factor support is not indicated. However, women older than 60 years of age receiving non-carboplatin containing regimens are at higher risk for FN and warrant closer surveillance.     

Hemorheological studies on platelet counts and size in normal pregnancy and pregnancies with preeclampsia and intrauterine growth retardation

It has been reported that preeclampsia and pregnancy resulting in intrauterine growth retardation (IUGR) are associated with high hematocrits. The relations between hematocrits (Ht) and platelet volumes in normal and abnormal pregnancies were investigated to clarify a hemorheological effect on formation of microthrombus. 1) In normal pregnancy, Ht was decreased from 12-19 weeks gestation and reached its lowest level at 28-31 weeks gestation. The mean platelet volume (MPV) was decreased from 20 to 31 weeks gestation but markedly increased from 38 to 41 weeks gestation. The platelet count (Pl) remained unchanged during pregnancy. 2) In severe type of preeclampsia, at 28-37 weeks gestation Ht and MPV were markedly increased and Pl was markedly decreased at 38-41 weeks gestation as compared with normal pregnancies. 3) Mothers who delivered IUGR had a much higher level of Ht at 28-35 weeks gestation and MPV level from 38 weeks gestation than in normal mothers. As the volume of young platelets is large, increased MPV is suggestive of the occurrence of platelet consumption. From these results, it was suggested that microcirculatory disturbances such as higher blood viscosity due to hemoconcentration and microthrombus formation were related to the onset of preeclampsia or IUGR.