Hemolysis, Elevated Liver Enzymes, Low Platelets Research Articles

Dexamethasone compared with betamethasone for glucocorticoid treatment of postpartum HELLP syndrome

Objectives: To compare the efficacy of dexamethasone and betamethasone to ameliorate the course of postpartum hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. Methods: A prospective, mixed randomized/non-randomized clinical investigation of patients with postpartum HELLP syndrome. Treatment with either dexamethasone or betamethasone was continued until there was evidence of disease recovery. Results: Baseline characteristics of both the dexamethasone ( n=18) and betamethasone ( n=18) groups were similar. Although the time to discharge from the obstetrical recovery room was not statistically significant between groups, reduction in mean arterial blood pressure was more pronounced in the dexamethasone group as compared with the betamethasone group (−15.3±1.4 mmHg vs. −7.5±1.4 mmHg, respectively, P<0.01). Patients in the dexamethasone group required less antihypertensive treatment than the betamethasone group (6% vs. 50%, P=0.01) and also had a decreased need for readmission to the obstetrical recovery room (0% vs. 22%, P=0.03). Conclusion: This investigation supports the use of dexamethasone as the superior glucocorticoid to use for patients with postpartum HELLP syndrome.

Soluble HLA-DR levels in the maternal circulation of normal and pathologic pregnancy

Objective: The purpose of this study was to determine that circulating HLA-DR molecules are important candidates for the monitoring of maternal immunostimulation and immunosuppression. Study design: Concentrations of soluble HLA-DR molecules were estimated in EDTA plasma samples of 61 nonpregnant women, 123 healthy pregnant women in the second trimester, 66 healthy women who were delivered at term, and 136 women who were delivered because of complications such as uncontrollable preterm intrauterine activation, abruptio placentae, intrauterine growth retardation, preeclampsia, and HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome. Results: In comparison to nonpregnant women, the normal course of pregnancy was associated with strongly increasing levels of soluble HLA-DR from second trimester on until term. In comparison to women who were delivered preterm because of uncontrollable intrauterine activation, increased soluble HLA-DR concentrations were detected in case of HELLP syndrome (P < .05), although decreased levels were detected in the case of intrauterine growth retardation, preeclampsia (P < .01), and abruptio placentae (P < .01). Conclusion: Dysregulation of the maternal immune response to pregnancy may play an important role in the cause of complicated pregnancies. (Am J Obstet Gynecol 2003;188:473-9.)

Magnesium Sulfate in Women With Mild Preeclampsia

In Brief OBJECTIVE To determine whether magnesium sulfate prevents disease progression in women with mild preeclampsia. METHODS A total of 222 women with mild preeclampsia were randomized to receive intravenous magnesium sulfate (n = 109) or matched placebo (n = 113). Mild preeclampsia was defined as blood pressure of at least 140/90 mm Hg taken on two occasions in the presence of newonset proteinuria. Patients with chronic hypertension or severe preeclampsia were excluded. Patients were considered to have disease progression if they developed signs or symptoms of severe preeclampsia, eclampsia, or laboratory abnormalities of full or partial HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome. RESULTS The groups were similar with respect to maternal age, ethnicity, gestational age, parity, and maternal weight at enrollment. Fourteen women (12.8%) in the magnesium group and 19 (16.8%) in the placebo group developed severe preeclampsia after randomization (relative risk = 0.8, 95% confidence interval 0.4, 1.5, P = .41). None in either group developed eclampsia or thrombocytopenia. Women assigned magnesium had similar rates of cesarean delivery (30% versus 25%), chorioamnionitis (3% versus 2.7%), endometritis (5.3% versus 4.3%), and postpartum hemorrhage (1% versus 0.9%), compared to those assigned placebo. Neonates born to women assigned magnesium had similar mean Apgar scores at 1 and 5 minutes as those born to women assigned placebo (7.7 ± 1.5 versus 7.8 ± 1.6 and 8.7 ± 0.7 versus 8.8 ± 0.6, respectively). CONCLUSION Magnesium sulfate does not have a major impact on disease progression in women with mild preeclampsia. Magnesium use does not seem to increase rates of cesarean delivery, infectious morbidity, obstetric hemorrhage, or neonatal depression. Compared to a placebo, intravenous magnesium sulfate does not have a major impact on disease progression in women with mild preeclampsia.

Magnesium sulfate in women with mild preeclampsia: a randomized controlled trial

Objective To determine whether magnesium sulfate prevents disease progression in women with mild preeclampsia. Methods A total of 222 women with mild preeclampsia were randomized to receive intravenous magnesium sulfate ( n = 109) or matched placebo ( n = 113). Mild preeclampsia was defined as blood pressure of at least 140/90 mm Hg taken on two occasions in the presence of new-onset proteinuria. Patients with chronic hypertension or severe preeclampsia were excluded. Patients were considered to have disease progression if they developed signs or symptoms of severe preeclampsia, eclampsia, or laboratory abnormalities of full or partial HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome. Results The groups were similar with respect to maternal age, ethnicity, gestational age, parity, and maternal weight at enrollment. Fourteen women (12.8%) in the magnesium group and 19 (16.8%) in the placebo group developed severe preeclampsia after randomization (relative risk = 0.8, 95% confidence interval 0.4, 1.5, P = .41). None in either group developed eclampsia or thrombocytopenia. Women assigned magnesium had similar rates of cesarean delivery (30% versus 25%), chorioamnionitis (3% versus 2.7%), endometritis (5.3% versus 4.3%), and postpartum hemorrhage (1% versus 0.9%), compared to those assigned placebo. Neonates born to women assigned magnesium had similar mean Apgar scores at 1 and 5 minutes as those born to women assigned placebo (7.7 ± 1.5 versus 7.8 ± 1.6 and 8.7 ± 0.7 versus 8.8 ± 0.6, respectively). Conclusion Magnesium sulfate does not have a major impact on disease progression in women with mild preeclampsia. Magnesium use does not seem to increase rates of cesarean delivery, infectious morbidity, obstetric hemorrhage, or neonatal depression.

The evaluation of maternal parameters at diagnosis may predict HELLP syndrome severity

Objective: Hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, a severe manifestation of pre-eclampsia and/or intrauterine growth restriction (IUGR) of the fetoplacental unit, is classifiedinto three classes, according to the lowest platelet count observed during the course of the disease. The aim of our work was to analyze the levels of lactate dehydrogenase (LDH), aspartate transferase(AST), alanine transferase (ALT) and platelets at the time of HELLP syndrome diagnosis, to find possible cut-off values that could predict the severity of the syndrome from its early onset.Methods:A retrospective analysis of the clinical records of 26 patients consecutively diagnosed with classes 1 and 2 HELLP syndrome was performed. Platelet count (× 1000/ml), LDH (IU/l), AST (IU/l), ALT (IU/l),hemoglobin (g/dl), hematocrit (%) and D-dimer (log of titer) were determined at admission and compared with the most severe peak values. Receiver operating characteristic (ROC) curves were used to calculatethe best cut-off value at admission which correlated with the development of class 1 HELLP syndrome (the most severe condition). The post-test probability of developing class 1 severity was calculated.Results: Mean gestational age at diagnosis was 33.4 weeks (range 23-40 weeks). Peak values of LDH, AST and ALT were significantly higher in class 1 HELLP syndrome patients. The platelet count atadmission was not informative in differentiating patients who would later develop class 1 or class 2 HELLP syndrome. According to the best cut-off values at admission for LDH, AST and ALT, the post-testprobability to predict patients with class 1 HELLP syndrome was 74%, 71% and 78%, respectively. If all the three parameters were above the cut-off value, the probability increased to 90%.Conclusions:The LDH, AST and ALT values at admission blood test, and to a greater extent the combination of all three abnormal tests, could predict the severity of HELLP syndrome.

Distribution of ABO and Rh blood groups in patients with HELLP syndrome.

The aim of this retrospective study was to evaluate the relationship between HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome and the maternal blood groups. Five hundred and forty-seven women with severe preeclampsia were included and divided into eight groups according to their blood groups: A Rh-positive (n=203), A Rh-negative (n=38), B Rh-positive (n=83), B Rh-negative (n=10), 0 Rh-positive (n=148), 0 Rh-negative (n=21), AB Rh-positive (n=39), and AB Rh-negative (n=5). The groups were controlled by analysis of variance and found to be homogeneous with respect to parity, gestational age, blood pressure, hemoglobin, hematocrit, platelet values, prothrombin time, partial thromboplastin time, fibrinogen, creatinine, alanine aminotransferase, aspartate aminotransferase, bilirubin, uric acid, and proteinuria. Incidence of HELLP syndrome was 24% in the overall study population whereas 48% of the patients with the blood group O Rh-negative had HELLP syndrome associated with an increase in risk by a factor of 3.1. To our knowledge this is the first report of such an association.

The Role of Serum Uric Acid as a Prognostic Indicator of the Severity of Maternal and Fetal Complications in Hypertensive Pregnancies

Objective: To examine whether an elevated serum uric acid level in hypertensive pregnant women is a useful prognostic indicator of severe hypertension; hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome; and small for gestational age (SGA) infants.Methods: A total of 459 women newly diagnosed with hypertension in pregnancy were categorized into “gestational hypertension” and “hypertension with proteinuria (preeclampsia)” groups. Their serum uric acid levels were correlated with the development of HELLP syndrome, severity of hypertension, and incidence of SGA newborns (< 10th percentile birth weight). HELLP syndrome was divided into 3 classes depending on the severity of the thrombocytopenia. Prior to this study, serum uric acid levels had been measured in a group of normotensive women. Mean and standard deviation of serum uric acid levels for each group were compared using analysis of variance and student t-tests, where necessary.Results: Significant elevation in serum uric acid levels over normotensive pregnant women (285 ± 72 μmol/L) was observed in both the gestational hypertensive group (341 ± 83 μmol/L) and the preeclamptic group (384 ± 93 μmol/L) of women (p < 0.001 and p < 0.05 respectively). Serum uric acid levels were also significantly elevated (p < 0.001) in women with gestational hypertension with HELLP syndrome (382 ± 78 μmol/L) compared to those without HELLP syndrome (330 ± 80 μmol/L). Preeclamptic women with HELLP syndrome (412 ± 99 μmol/L) also demonstrated elevated uric acid levels (p < 0.05) over those without HELLP syndrome (374 ± 87 μmol/L). However, the level of uric acid did not predict the severity of HELLP syndrome. The presence of SGA infants in the gestational hypertensive group was not associated with increased uric acid levels.Conclusion: Uric acid levels, although significantly elevated in women with gestational hypertension and preeclampsia as compared to normotensive pregnant women, are not good prognostic indicators of the severity of the maternal or fetal complications.

Acute complications of preeclampsia.

Preeclampsia is an idiopathic multisystem disorder specific to human pregnancy and the puerperium. More precisely, it is a disease of the placenta, because it has also been described in pregnancies where there is trophoblast but no fetal tissue (complete molar pregnancies). Although the pathophysiology of preeclampsia is poorly understood, it is clear that the blueprint for its development is laid down early in pregnancy. It has been suggested that the pathologic hallmark is a complete or partial failure of the second wave of trophoblast invasion from 16 to 20 weeks’ gestation, which is responsible in normal pregnancies for destruction of the muscularis layer of the spiral arterioles. As pregnancy progresses, the metabolic demands of the fetoplacental unit increase. However, because of the abnormally shallow invasion of the placenta, the spiral arterioles are unable to dilate to accommodate the required increase in blood flow, resulting in “placental dysfunction” that manifests clinically as preeclampsia. Although attractive, this hypothesis remains to be validated. Preeclampsia is a clinical diagnosis. The classic definition of preeclampsia encompasses three elements: new-onset hypertension (defined as a sustained sitting blood pressure !140/90 mm Hg in a previously normotensive woman); new-onset proteinuria (defined as >300 mg/24 hours or !2+ on a clean-catch urinalysis in the absence of urinary tract infection); and new-onset significant nondependent edema. However, more recent consensus reports have suggested eliminating edema as a criterion for the diagnosis. A more extensive synopsis of preeclampsia is beyond the scope of this discussion. This monograph serves to review in detail the diagnosis and management of several acute maternal complications of preeclampsia: eclampsia, HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome, liver rupture, pulmonary edema, renal failure, disseminated intravascular coagulopathy (DIC), hypertensive emergency, and hypertensive encephalopathy and cortical blindness. Correspondence: Errol R. Norwitz, MD, PhD, Department of Obstetrics & Gynecology, Brigham & Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115. E-mail: enorwitz@partners.org PROD. # GRF20214

Evidence for Fatty Acid Oxidation in Human Placenta, and the Relationship of Fatty Acid Oxidation Enzyme Activities with Gestational Age

Fetal disorders of mitochondrial fatty acid oxidation have recently been associated with obstetric complications including pre-eclampsia, Hemolysis, Elevated Liver enzymes, Low Platelets (HELLP) syndrome, placental floor infarct, and Acute Fatty Liver of Pregnancy (AFLP). These diseases occur in about a third of the mothers who are heterozygous for a defect in long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) enzyme and who bear a fetus homozygous for the defect. The mechanism of this association is not clearly understood. In this study, we provide evidence that the placenta may be the site of production of toxic intermediates of fatty acid metabolism, which accumulate to cause liver damage in the mother. We show that two critical enzymes of long chain fatty acid metabolism, long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and short chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD), are active in the normal human placenta. There is an inverse correlation between the enzyme activity of both the enzymes and maternal gestational age during the second and third trimesters. We believe that the demonstration of fatty acid oxidation enzyme activity by the placenta is the first step towards assessing a possible role for fetal/placental fatty acid oxidation defects in the pathogenesis of a subset of pregnancy complications.

Incidence and Predictors of Severe Obstetric Morbidity: Case-Control Study

Records at 25 maternity units in London covering a 1-year period during 1997-1998 were reviewed to determine the frequency of severe obstetrical morbidity and to identify predictors. The study population of 48,865 women delivering infants during this period included 588 who met criteria for severe obstetrical morbidity. Four conditions were considered: severe bleeding; severe preeclampsia, including hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome and eclampsia; severe sepsis: and uterine rupture. Four control subjects were chosen for each case subject to better detect differences in predictive factors. The incidence of severe obstetrical morbidity in this review was 12 per 1000 deliveries (95% confidence interval, 11.2-13.2). Five maternal deaths were ascribed directly to the study conditions: three to sepsis and one each to bleeding and HELLP syndrome. The ratio of severe morbidity to mortality was 118:1. Disease-specific morbidity rates per 1000 deliveries were 6.7 for severe hemorrhage, 3.9 for severe preeclampsia, ().2 for eclampsia, 0.5 for HELLP syndrome. 0.4 for severe sepsis, and 0.2 for uterine rupture. After adjustment for confounding factors, characteristics independently associated with severe obstetrical morbidity as a whole included age greater than 34 years, nonwhite ethnicity, past or current hypertension, previous postpartum bleeding, emergency cesarean delivery, antenatal hospital admission, multiple pregnancy, and taking iron or an antidepressant before delivery. Few risk factors were independently and significantly associated with the occurrence of severe sepsis or uterine rupture. These findings suggest that severe obstetrical morbidity may be a more sensitive measure of pregnancy outcomes than mortality by itself. Most of these events are related to obstetrical bleeding and severe preeclampsia, and lowering the risk will require attention to the best ways of managing these complications.

Syncytin, a novel human endogenous retroviral gene in human placenta: Evidence for its dysregulation in preeclampsia and HELLP syndrome

Objective: A novel human endogenous retroviral element, designated as syncytin, has been suggested as a contributor to normal placental architecture, especially in the fusion processes of cytotrophoblasts to syncytiotrophoblasts. We tested the hypothesis of whether the gene expression of syncytin may be altered in cases with placental dysfunction such as preeclampsia or HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome. Study Design: We included 30 women with normal pregnancies, 16 with preeclampsia, and 6 with HELLP syndrome. After delivery, messenger ribonucleic acids (mRNA) of syncytin, glyceraldehyde-3-phosphate dehydrogenase and β-actin were analyzed in placental villi with use of quantitative real-time polymerase chain reaction. Results: In placental villi, syncytin mRNA/β-actin mRNA and syncytin mRNA/glyceraldehyde-3-phosphate dehydrogenase mRNA ratios were lower in patients with preeclampsia (P <.05) or HELLP syndrome than in healthy control subjects. Conclusion: A reduced placental expression of syncytin may contribute to altered cell fusion processes in placentogenesis and disturbed placental function in hypertensive disorders of pregnancy. (Am J Obstet Gynecol 2002;186:210-3.)

LINKAGE AND ASSOCIATION STUDIES OF IL1B AND IL1RN GENE POLYMORPHISMS IN PREECLAMPSIA

Objective: To determine whether preeclampsia is either associated with or linked to two polymorphisms in the IL1B gene (IL1B- TaqI and IL1B- 511) and one polymorphism in the IL1RN gene (IL1RN- IVS2). Methods: Genotyping was performed in 150 affected sib-pair families and 104 healthy Dutch blood donors. Genotype and allele frequencies as well as allelic associations were assessed in three groups of unrelated women from these 150 families; 133 with either eclampsia, preeclampsia or the haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, 101 with preeclampsia only, and 63 with HELLP syndrome only. These frequencies were compared to those in controls. Frequencies of transmitted and nontransmitted haplotypes, inferred from the three polymorphisms, were compared. Allele sharing between affected siblings from all 150 families was assessed by means of multipoint nonparametric affected sib-pair analyses. Results: No significant differences in genotype and allele frequencies were found between the unrelated study groups and controls. No allelic associations were apparent, nor were there differences in frequencies of transmitted and nontransmitted haplotypes within affected families. Excess allele sharing for any of the three polymorphic markers was absent in affected sib-pairs. Conclusions: None of the IL1B and IL1RN polymorphisms provided evidence for either association or linkage with the risk for (pre)eclampsia/HELLP syndrome, preeclampsia only or HELLP syndrome only.

Outcome of pregnancy with severe liver disease

Objectives: To study the incidence, presentation, and outcome of patients with severe liver disease in an urban Indian population. Method: 26 patients with severe liver disease were identified in the study period of one year at a teaching tertiary care institute in Mumbai. Investigations included bedside Bleeding and Clotting Time (BT/CT), coagulation profiles and liver and renal function tests. Management was directed towards initial stabilization followed by early delivery in an intensive care setting. Result: 80.71% of the patients had HELLP (Hemolysis, Elevated Liver enzymes, Low Platelets) syndrome. The remaining were cases of acute fulminant hepatitis and acute fatty liver of pregnancy. The most consistent finding was thrombocytopenia (88.46%). Disseminated Intravascular Coagulopathy (DIC) was the most common complication (65%). BT/CT were 100% sensitive for the diagnosis of DIC. Maternal and perinatal mortality were 42.3% and 61.5% respectively. Conclusion: Intensive care facilities and an early diagnosis are essential for the management of mothers with severe liver disease. Prognosis is poor for patients with fulminant hepatitis and acute fatty liver. Screening for DIC is a must. Delay in recovery of biochemical parameters may indicate atypical disease. Patient education is essential at discharge.

Neutrophil oxygen radical production in pre-eclampsia with HELLP syndrome

Objective: To determine whether severe pre-eclampsia complicated by hemolysis, elevated liver enzymes, low platelets (HELLP) -syndrome alters neutrophil oxygen radical production. Materials and Methods: Neutrophils were obtained from 10 healthy non-pregnant, 9 normal pregnant and 9 women with severe pre-eclampsia with concurrently HELLP syndrome. Oxygen radical production was evaluated using luminol-enhanced chemiluminescence and measured by cytochrome C reduction. Furthermore we incubated sera from cases and controls with isolated healthy neutrophils and measured their capacity to generate oxygen radicals. Results: Unstimulated neutrophil oxygen radical production was significantly lower in severe pre-eclamptics compared with healthy non-pregnant and pregnant subjects, whereas phorbol ester-induced oxygen radical production did not differ among categories. Cytochrome C reduction of unstimulated neutrophils showed similar results. Healthy neutrophils incubated with sera from pre-eclamptics enhanced the oxygen radical production significantly more than neutrophils incubated with sera from the healthy subjects. Conclusions: Severe pre-eclampsia is characterised by decreased unstimulated neutrophil oxygen radical production. This may be the result of an exhausted cellular response due to stimulation by a factor present in the serum of these patients.

Polymorphisms in the tumor necrosis factor and lymphotoxin-α gene region and preeclampsia

OBJECTIVE: To investigate potential association or linkage among nine polymorphisms in the genes encoding tumor necrosis factor (TNF) α or lymphotoxin (LT) α and preeclampsia. METHODS: Four di-allelic polymorphisms and five microsatellite markers in the genes encoding TNF-α ( TNF) and LTα ( LTA) and their haplotypes were studied in 150 Dutch families. These families contained sib-pairs of women affected with preeclampsia; eclampsia; the hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome (strict criteria); or pregnancy-induced hypertension (mild criteria). Frequencies were compared with 98 healthy controls. Nonparametric affected sib-pair analyses for allele sharing among siblings were carried out for all nine markers. Each sibship was composed of an affected index woman and one or more affected sisters. RESULTS: Although we found a striking association with the TNF-I haplotype in 30 index women with (pre-)eclampsia or HELLP syndrome compared with controls (odds ratio [OR] 3.8; 95% confidence interval [CI] 1.6, 8.9), this association was not found in their 30 sisters meeting similar disease criteria. Analyses in all 150 families showed a similar TNF-I association in 122 index women meeting the strict criteria compared with controls (OR 1.9; 95% CI 1.1, 3.3), but, again, not in their 91 sisters meeting similar disease criteria. This association was stronger in a subgroup of 75 index women with preeclampsia only (OR 2.3; 95% CI 1.2, 4.2). No excess allele sharing for any marker was seen between the siblings. CONCLUSION: The nine polymorphisms studied in the TNF-LTA region did not show evidence for association or linkage with familial preeclampsia.

Preeclampsia, a pregnancy-specific disease, is associated with fetal monocyte activation.

The maternal syndrome of preeclampsia is an exclusively pregnancy-related illness involving multiple organs and severe forms may be complicated by HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome. Recently, it has been proposed that both normal pregnancy and preeclampsia are associated with a systemic activation of the nonspecific maternal immune system and that, in particular, monocytes have a central role in the adjustment of maternal immune functions in pregnancy. Here we have investigated the role of the fetal nonadaptive immune system in normal term delivery, uncontrollable preterm labor, and preeclampsia. We demonstrate that spontaneous delivery at term as well as preterm occurrence of preeclampsia or HELLP syndrome are accompanied by an increased intracellular production of IL-6 in fetal monocytes, indicating strong activation of this cell type. In contrast, we show that elective cesarean delivery at term in the absence of labor or preterm delivery due to uncontrollable labor are not accompanied by an increased production of IL-6 in these cells. These results suggest that increased IL-6 synthesis in fetal monocytes may be a process occurring in association with normal spontaneous term delivery and that this process obviously occurs in early pregnancy in case of preeclampsia. Therefore, we propose that the activation of fetal monocytes as effectors of the innate immunity may be involved in mechanisms inducing spontaneous term delivery and that the occurrence of preeclampsia may be based on dysfunctions of probably both the maternal and the fetal innate immune system.

Uterine Artery Doppler Flow and Uteroplacental Vascular Pathology in Normal Pregnancies and Pregnancies Complicated by Pre-eclampsia and Small for Gestational Age Fetuses

This study was conducted to investigate the association between uterine artery Doppler flow patterns and uteroplacental vascular pathology in normal and complicated pregnancies in view of the recently described concept of heterogeneous causes of hypertensive pregnancy complications. Forty-three women whose pregnancies were complicated by pre-eclampsia, the HELLP (Haemolysis, Elevated Liver enzymes, Low Platelets) syndrome and/or small for gestational age (SGA) fetuses and 27 women with normal pregnancies undergoing elective caesarean section were included. We obtained uterine artery Doppler waveforms at a mean of 4 days before delivery. Placental bed biopsies were obtained at caesarean section and analysed for physiological changes and pathological changes.We found that abnormal uterine artery Doppler flow was strongly associated with pregnancy complications. Absence of physiological changes was seen in 58 per cent of complicated pregnancies and 40 per cent of normal pregnancies. Pathological changes were seen in 58 per cent of complicated pregnancies and 53 per cent of normal pregnancies; they occurred in spiral arteries with and without physiological changes, and there was no significant correlation to Doppler results. In conclusion, absence of physiological changes is associated with abnormal uterine artery Doppler flow and pregnancy complications. However, there is a gradient in the severity of uteroplacental vascular pathology and the correlation with pregnancy complications is not as strong as previously thought. There is also a significant degree of uteroplacental vascular pathology in normal pregnancies with normal uterine artery Doppler flow. This variation may be partly due to sampling error, as a typical biopsy contains only one or two spiral arteries. We hypothesize that additional factors might be necessary to induce the clinical syndrome of pre-eclampsia.

HELLP syndrome and factor V Leiden

The association of thrombophilia and obstetrical complications is documented and well consistent with the hypothesis of an insufficient placental perfusion due to fibrin deposition as a major underlying pathophysiological mechanism. Factor V Leiden is one of the most frequent thrombophilic mutations. A high prevalence of this mutation has recently been reported in a group of 21 German women with haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. In this respect, we studied the prevalence of factor V Leiden in 18 women who were consecutively diagnosed at our Department of Obstetrics and Gynaecology as having HELLP syndrome, between 1995 and 1999. Women were tested either at the time of diagnosis or months or years after delivery for coagulation parameters, protein C (PC), protein S (PS), antithrombin III, lupus-like anticoagulant, anticardiolipin antibodies (ACA), activated protein C (APC) resistance and detection of the G1691A mutation (factor V Leiden). In all women, the parameters studied were normal and in none of the investigated cases was the G1691A mutation found. HELLP being a severe form of preeclampsia, we think that the reported association between factor V Leiden and HELLP may reflect the well-known association with preeclampsia.

Oxidized and free whole blood thiols in preeclampsia

Objective: To measure levels of oxidized and free thiols in whole blood of normotensive pregnant and preeclamptic women and evaluate the role of oxidative stress. Methods: We measured whole blood oxidized and free levels of cysteine, homocysteine, cysteinylglycine, and glutathione by high performance liquid chromatography in women with normotensive pregnancies ( n = 50), preeclampsia ( n = 29), and preeclampsia complicated by the hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome ( n = 16). Results: Oxidized and free levels (median [range], μmol/L) of cysteine and homocysteine were higher in women with preeclampsia than normotensive pregnancies (45 [27–81] versus 29 [9–91], P < .001, and 98 [57–193] versus 69 [33–215], P < .001; 0.8 [0.2–4.4] versus 0.4 [0.01–1.6], P < .001, and 2.1 [0.7–9.4] versus 1.2 [0.2–21.2], P < .01; respectively). The ratios of free to oxidized cysteine, homocysteine, and cysteinylglycine were lower in preeclampsia than normotensive pregnancy (2.2 [1.3–3.0] versus 2.4 [1.7–4.3], P < .001; 2.3 [0.5–5.4] versus 2.9 [1.1–24], P < .001; 4.1 [2.3–11.6] versus 5.4 [2.6–24.3], P < .02, respectively), indicating a shift in favor of the oxidized form of those thiols. In HELLP syndrome, levels of oxidized and free cysteine and levels of oxidized homocysteine were higher than normal (44 [33–63] versus 29 [9–91], P < .001, and 102 [82–133] versus 69 [33–215], P < .001; 1.0 [0.3–2.9] versus 0.4 [0.01–1.6], P < .001, respectively). No significant differences were found in oxidized glutathione levels in women with preeclampsia (22 [5–49] versus 17 [2– 60], P = .06) or free levels in preeclamptic women with HELLP syndrome (757 [624–993] versus 842 [539–1516], P = .09) as compared with normotensive pregnant women. The ratios of free to oxidized cysteinylglycine and glutathione were higher in women with HELLP syndrome than in those with preeclampsia (5.4 [3.3–12.7] versus 4.1 [2.3–11.6], P = .02, and 56 [28–124] versus 45 [16–166], P = .02, respectively). Conclusion: Significantly lower ratios of free to oxidized cysteine, homocysteine, and cysteinylglycine in preeclampsia might indicate oxidative stress.

Oxidized and Free Whole Blood Thiols in Preeclampsia

In Brief Objective To measure levels of oxidized and free thiols in whole blood of normotensive pregnant and preeclamptic women and evaluate the role of oxidative stress. Methods We measured whole blood oxidized and free levels of cysteine, homocysteine, cysteinylglycine, and glutathione by high performance liquid chromatography in women with normotensive pregnancies (n = 50), preeclampsia (n = 29), and preeclampsia complicated by the hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome (n = 16). Results Oxidized and free levels (median [range], μmol/L) of cysteine and homocysteine were higher in women with preeclampsia than normotensive pregnancies (45 [27–81] versus 29 [9–91], P < .001, and 98 [57–193] versus 69 [33–215], P < .001; 0.8 [0.2–4.4] versus 0.4 [0.01–1.6], P < .001, and 2.1 [0.7–9.4] versus 1.2 [0.2–21.2], P < .01; respectively). The ratios of free to oxidized cysteine, homocysteine, and cysteinylglycine were lower in preeclampsia than normotensive pregnancy (2.2 [1.3–3.0] versus 2.4 [1.7–4.3], P < .001; 2.3 [0.5–5.4] versus 2.9 [1.1–24], P < .001; 4.1 [2.3–11.6] versus 5.4 [2.6–24.3], P < .02, respectively), indicating a shift in favor of the oxidized form of those thiols. In HELLP syndrome, levels of oxidized and free cysteine and levels of oxidized homocysteine were higher than normal (44 [33–63] versus 29 [9–91], P < .001, and 102 [82–133] versus 69 [33–215], P < .001; 1.0 [0.3–2.9] versus 0.4 [0.01–1.6], P < .001, respectively). No significant differences were found in oxidized glutathione levels in women with preeclampsia (22 [5–49] versus 17 [2–60], P = .06) or free levels in preeclamptic women with HELLP syndrome (757 [624–993] versus 842 [539–1516], P = .09) as compared with normotensive pregnant women. The ratios of free to oxidized cysteinylglycine and glutathione were higher in women with HELLP syndrome than in those with preeclampsia (5.4 [3.3–12.7] versus 4.1 [2.3–11.6], P = .02, and 56 [28–124] versus 45 [16–166], P = .02, respectively). Conclusion Significantly lower ratios of free to oxidized cysteine, homocysteine, and cysteinylglycine in preeclampsia might indicate oxidative stress. Low whole blood ratios of free and oxidized thiol levels for cysteine, homocysteine, and cysteinylglycine in preeclampsia reflect oxidative stress.