Hemolysis, Elevated Liver Enzymes, And Low Platelets Syndrome Research Articles

Total bile acids in the maternal and fetal compartment in relation to placental ABCG2 expression in preeclamptic pregnancies complicated by HELLP syndrome

ObjectiveTo investigate total bile acid (TBA) levels in maternal (MB) and umbilical cord blood (UCB) in normotensive, preeclamptic (PE), and PE pregnancies complicated by hemolysis elevated liver enzymes and low platelets (HELLP) syndrome in the context of ABCG2 placental gene expression levels, a recently reported placental bile acid transporter. MethodsTBA levels were determined in 83 paired MB and UCB samples of normotensive, PE and PE/HELLP pregnancies and in 22 paired arterial and venous UCB samples from uncomplicated term pregnancies. ABCG2 gene expression was measured in 104 human placentas by reverse transcriptase quantitative polymerase chain reaction. ResultsOverall, TBA levels in MB are higher compared to levels in UCB (p<0.0001), but this comparison looses statistical significance for the 11 PE/HELLP cases. TBA levels in maternal blood are increased in PE/HELLP compared to PE pregnancies (p=0.016). TBA levels in arterial and venous UCB from 22 normotensive pregnancies are not statistically different. ABCG2 expression is reduced in pregnancies where preeclampsia is further complicated by HELLP syndrome. ABCG2 expression in human placenta is not correlated with TBA levels in either the maternal or fetal compartment. ConclusionIncreased maternal TBA levels in PE/HELLP pregnancies indicate a relation between bile acids in the maternal circulation and HELLP syndrome. As overall TBA levels in maternal blood are increased compared to UCB, we conclude that the placenta partly protects the fetus from increased maternal TBA levels. This consistent difference in TBA levels between the maternal and fetal compartment is unrelated to the placental expression of ABCG2.

Maternal near-miss audits to improve quality of care.

Department of SocialMedicine, Ribeir~ao Preto Medical School, University of S ~ao Paulo, Ribeir ~ao Preto, SP, BrazilCorrespondence: O Tunc€ alp, HRP—UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and ResearchTraining in Human Reproduction, Department of Reproductive Health and Research, World Health Organization, 20 Avenue Appia, Geneva,Switzerland. Email tuncalpo@who.intAccepted 11 March 2014.

Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems.

Pre-eclampsia and eclampsia are common causes of serious morbidity and death. Calcium supplementation may reduce the risk of pre-eclampsia, and may help to prevent preterm birth. To assess the effects of calcium supplementation during pregnancy on hypertensive disorders of pregnancy and related maternal and child outcomes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 March 2013) and contacted study authors for more data where possible. We updated the search in May 2014 and added the results to the 'Awaiting Classification' section of the review. Randomised controlled trials (RCTs) comparing high-dose (at least 1 g daily of calcium) or low-dose calcium supplementation during pregnancy with placebo or no calcium. We assessed eligibility and trial quality, extracted and double-entered data. High-dose calcium supplementation (≥1 g/day)We included 14 studies in the review, however one study contributed no data. We included 13 high-quality studies in our meta-analyses (15,730 women). The average risk of high blood pressure (BP) was reduced with calcium supplementation compared with placebo (12 trials, 15,470 women: risk ratio (RR) 0.65, 95% confidence interval (CI) 0.53 to 0.81; I² = 74%). There was also a significant reduction in the risk of pre-eclampsia associated with calcium supplementation (13 trials, 15,730 women: RR 0.45, 95% CI 0.31 to 0.65; I² = 70%). The effect was greatest for women with low calcium diets (eight trials, 10,678 women: average RR 0.36, 95% CI 0.20 to 0.65; I² = 76%) and women at high risk of pre-eclampsia (five trials, 587 women: average RR 0.22, 95% CI 0.12 to 0.42; I² = 0%). These data should be interpreted with caution because of the possibility of small-study effect or publication bias.The composite outcome maternal death or serious morbidity was reduced (four trials, 9732 women; RR 0.80, 95% CI 0.65 to 0.97; I² = 0%). Maternal deaths were not significantly different (one trial of 8312 women: calcium group one death versus placebo group six deaths). There was an anomalous increase in the risk of HELLP (haemolysis, elevated liver enzymes and low platelets) syndrome (two trials, 12,901 women: RR 2.67, 95% CI 1.05 to 6.82; I² = 0%) in the calcium group, however, the absolute number of events was low (16 versus six).The average risk of preterm birth was reduced in the calcium group (11 trials, 15,275 women: RR 0.76, 95% CI 0.60 to 0.97; I² = 60%) and amongst women at high risk of developing pre-eclampsia (four trials, 568 women: average RR 0.45, 95% CI 0.24 to 0.83; I² = 60%), but no significant reduction in neonatal high care admission. There was no overall effect on the risk of stillbirth or infant death before discharge from hospital (11 trials 15,665 babies: RR 0.90, 95% CI 0.74 to 1.09; I² = 0%).One study showed a reduction in childhood systolic BP greater than 95th percentile among children exposed to calcium supplementation in utero (514 children: RR 0.59, 95% CI 0.39 to 0.91). In a subset of these children, dental caries at 12 years old was also reduced (195 children, RR 0.73, 95% CI 0.62 to 0.87). Low-dose calcium supplementation (< 1 g/day)We included 10 trials (2234 women) that evaluated low-dose supplementation with calcium alone (4) or in association with vitamin D (3), linoleic acid (2), or antioxidants (1). Most studies recruited women at high risk for pre-eclampsia, and were at high risk of bias, thus the results should be interpreted with caution. Supplementation with low doses of calcium significantly reduced the risk of pre-eclampsia (RR 0.38, 95% CI 0.28 to 0.52; I² = 0%). There was also a reduction in hypertension, low birthweight and neonatal intensive care unit admission. Calcium supplementation (≥ 1 g/day) is associated with a significant reduction in the risk of pre-eclampsia, particularly for women with low calcium diets. The treatment effect may be overestimated due to small-study effects or publication bias. It also reduces preterm birth and the occurrence of the composite outcome 'maternal death or serious morbidity'. We considered these benefits to outweigh the increased risk of HELLP syndrome, which was small in absolute numbers. The World Health Organization recommends calcium 1.5 g to 2 g daily for pregnant women with low dietary calcium intake.The limited evidence on low-dose calcium supplementation suggests a reduction in pre-eclampsia, but needs to be confirmed by larger, high-quality trials. Pending such results, in settings of low dietary calcium where high-dose supplementation is not feasible, the option of lower-dose supplements (500 to 600 mg/day) might be considered in preference to no supplementation.

Laboratory Evaluation in the Workup of Preeclampsia

INTRODUCTION: Preeclampsia occurs in 6–8% of pregnancies and is the second leading cause of maternal mortality in the United States. Preeclampsia is associated with HELLP (Hemolysis, Elevated Liver enzymes and Low Platelet count) syndrome and it has become a common practice to evaluate for the syndrome with laboratory testing in all women who present with hypertension. Our objective is to investigate the rate of abnormal laboratory values in our population and identify the associated risk factors. METHODS: This is a retrospective analysis of women who presented to Stony Brook University Hospital between January and December 2010 for evaluation of hypertension in pregnancy. The charts were reviewed for demographics, signs and symptoms, blood pressure ranges, and laboratory results. Student's t test, χ2, Pearson, and Spearman correlation tests were used for analysis. RESULTS: Six hundred thirty-three encounters were reviewed and 20 abnormal laboratory tests were identified (3.2%). The abnormalities were elevated liver function tests (14), low platelets (eight), and elevated lactate dehydrogenase (one). Women with abnormal results were more likely to have right upper quadrant pain and twin gestation (P<.001 and P=.03). There was also a small positive correlation between right upper quadrant pain, twin gestation, and elevated 24-hour urine protein with abnormal values. CONCLUSIONS: Only a small percentage of women who were evaluated had abnormal laboratory findings. Three risk factors were identified: right upper quadrant pain, twin gestation, and elevated 24-hour urine protein. These findings call into question their routine use in the evaluation of hypertension in pregnancy. A selective approach based on risk factors may be a more cost-effective approach to the evaluation of these women.

Rats with hypertension, hemolysis, elevated liver enzymes and low platelets (HELLP) have increased placental and circulating FASL (LB713)

The CD95L or FASL system of apoptosis is part of the tumor necrosis factor family that contributes to cell death. Placental CD95L is up‐regulated in women with HELLP syndrome and has been proposed to contribute to the liver damage seen in these patients. The objective of the current study was to determine if animals with HELLP have increased CD95L similar to women with HELLP. Additionally, as the anti‐inflammatory drug dexamethasone has been found to decrease inflammation in women with HELLP we also examined its’ effects on circulating CD95L in women with HELLP. Whole blood was collected from women with HELLP before and 24hrs after dexamethasone administration (10mg per 12hr intravenously). On gestational day (GD) 12, sEndoglin (7ug/kg/day) and sFlt‐1 (4.7ug/kg/day) infusion began via mini‐osmotic pump into normal pregnant (NP) rats. On GD18 carotid catheters were inserted, GD19 plasma and tissue were collected and CD95L was measured via western blot or enzyme linked immunosorbent assay. Women with HELLP had significantly higher levels of circulating CD95L compared to NP women (132.7+35 vs. 29.11+16; n=6;P=0.02). HELLP rats had significantly more circulating CD95L compared to NP rats (179.6+24 vs. 117.1+13pg; n=5; P=0.05). HELLP rats also had increased production of placental CD95L as measured via western blot (17.97+3 vs. 9.45+2.7 O.D.). These data suggest that similar to women with HELLP syndrome, rats with HELLP syndrome have increased circulating CD95L. Future studies will examine the effects of dexamethasone on decreasing CD95L production.

Risk Factors, Management, and Outcomes of Hemolysis, Elevated Liver Enzymes, and Low Platelets Syndrome and Elevated Liver Enzymes, Low Platelets Syndrome

To describe the risk factors, management and outcomes of hemolysis, elevated liver enzymes, and low platelets (HELLP) and elevated liver enzymes, low platelets (ELLP) syndrome in the United Kingdom. A case-control study was conducted using the U.K. Obstetric Surveillance System between June 2011 and May 2012, including 129 women diagnosed with HELLP, 81 diagnosed with ELLP, and 476 control women. Women with HELLP were more likely than those in the control group to be 35+ years old (33% compared with 22%, adjusted odds ratio [OR] 1.85, 95% confidence interval [CI] 1.12-3.06), nulliparous (67% compared with 43%, adjusted OR 4.16, 95% CI 2.48-6.98), have had a previous gestational hypertensive disorder (9% compared with 7%, adjusted OR 3.47, 95% CI 1.49-8.09), and have a multiple pregnancy (7% compared with 2%, adjusted OR 4.51, 95% CI 1.45-14.06). Women with ELLP were more likely than those in the control group to be nulliparous (79% compared with 43%, adjusted OR 8.35, 95% CI 3.88-17.95), and have had a previous gestational hypertensive disorder (7% compared with 7%, adjusted OR 4.66, 95% CI 1.37-15.89). Of the women diagnosed antenatally with HELLP or ELLP, 51% (71/138) had planned management of immediate delivery, 43% (60/138) had delivery planned within 48 hours, and 5% (7/138) had planned expectant (conservative) management. No differences were found between women who had delivery planned within 48 hours and those who had planned immediate delivery in terms of the proportion who received blood products (37% compared with 33%, P=.681); were admitted to the intensive care unit (57% compared with 61%, P=.652); experienced severe morbidity (10% compared with 4%, P=.300); or had a neonate with major complications (6% compared with 11%, P=.342). A short delay in the delivery of women diagnosed antenatally with HELLP or ELLP syndrome may be considered. However, the rarity of the condition limits study power.

MiRNA expression profiles determined in maternal sera of patients with HELLP syndrome

Objective: Syndrome of hemolysis, elevated liver enzymes and low platelets (HELLP) represents a distinct subgroup of severe preeclampsia. The aim of our study was to identify differentially expressed miRNAs in sera of patients with HELLP syndrome in comparison to unaffected controls. Study design: Blood samples were obtained from patients with manifest HELLP syndrome and matched unaffected controls. The expression of 754 mature miRNAs was assessed using the TaqMan Array format (n = 12). Results of seven differentially expressed miRNAs were further validated by single quantitative real-time polymerase chain reaction (qPCR) assays. Results: Serum miRNA analysis allowed detection of maternal and fetal miRNAs. Distinct miRNA expressions were confirmed for miR-122, miR-758 and miR-133a represented by a median up-regulation ≥two-fold in the HELLP group. The liver specific miR-122 was 11.5-fold increased with an area under curve (AUC) of 0.82 in the receiver operating characteristic (ROC) analysis. Cluster analyses of our data uncovered subgroups of HELLP patients were associated with clinical subtypes and differences in organ manifestation. Conclusion: In our proof of principle study, we demonstrated that patients with HELLP syndrome showed alterations of serum miRNA expression patterns. Data analysis goes along with the hypothesis that HELLP syndrome is regarded to be a heterogeneous disease.

Development of maternal and neonatal composite outcomes for trials evaluating timing of delivery in women with pre-eclampsia

Composite outcomes comprising more than one clinically relevant end point are used in clinical trials where there is no single important outcome or the outcome is very rare. Pre-eclampsia is associated with significant maternal and neonatal complications and delivery is often expedited to minimise complications. There is a need for a randomised trial to evaluate the timing of delivery in women with mild to moderate pre-eclampsia at late preterm gestation. No single outcome has been identified to be the most clinically important, reflecting the multisystemic nature of pre-eclampsia. We developed composite maternal and neonatal outcomes to be considered as the primary outcome measure for a clinical trial in this area. A two-generational Delphi method was used to identify these clinically important maternal and neonatal outcomes. Composite outcomes were developed based on biological plausibility, independence from each other, equal importance and frequency of occurrence. The final maternal composite outcome included maternal death, eclampsia, stroke or reversible ischaemic neurological deficit, pulmonary oedema, major obstetric haemorrhage, infusion of a third anti-hypertensive or need for positive ionotropic support, HELLP (haemolysis, elevated liver enzymes and low platelets) syndrome and placental abruption; and the neonatal composite outcome included neonatal death, respiratory distress syndrome needing ventilator support and neurological outcomes as cystic periventricular leukomalacia and grade III/IV intraventricular haemorrhage. The composite outcomes developed will enable clinical trials on the timing of delivery in women with mild to moderate pre-eclampsia to provide robust estimates for the intervention to be implemented in clinical practice.

Absence of G1528C mutation in long-chain 3-hydroxyacyl-CoA dehydrogenase in four Indian patients with pregnancy-related liver disease

Sir, Acute fatty liver of pregnancy (AFLP) is a rare pregnancyrelated liver disorder manifesting in late pregnancy with acute liver failure [1], while the hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome is a microangiopathy affecting the liver and other organs in late pregnancy [2]. Long-chain 3-hydroxyacyl-coenzyme-A dehydrogenase (LCHAD) deficiency in the fetus has been associated with these hepatic disorders of the mother during pregnancy [3]. The commonest mutation is G1528C in exon 15 of the mitochondrial trifunctional protein (MTP) α subunit, which leads to a substitution of a glutamine for glutamate, which selectively decreases LCHAD activity [4]. Though the occurrence of the G1528C mutation has been studied in Western populations [4, 5], where it is common, the information on this from other populations is scarce. We studied the presence of the G1528C mutation in three patients with AFLP (all fulfilled “Swansea” criteria for diagnosis, none had liver biopsy, two had coexistent HELLP, and one had coexistent pre-eclampsia and partial HELLP) [6] and one patient with HELLP syndrome (coexistent preeclampsia). All patients (age: 23; 19–28 years, median; range) presented in third trimester (36; 32–38 weeks of gestation). Three were primigravida while one patient had a previous uneventful pregnancy. All patients were eventually discharged in stable condition, and the immediate fetal outcome was favorable in all. The placenta is known to carry out mitochondrial β oxidation, and its genetic make up is identical to the fetus [7], and hence, we used placental DNA for our genetic analysis by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) analysis. This study was approved by the Institutional Review Board, and consent was obtained from the patient for the study. As required by the criteria, all patients had an unyielding make up for the etiology of acute liver disease, including serology tests for acute viral hepatitis A, B, and E. Controls were placenta from normal deliveries of equal gestational age. The blood was drained, and the placental tissue was rinsed thrice with saline and stored at −80 °C. Baseline laboratory parameters in the four patients analyzed are summarized in Table 1. DNAwas isolated from 100 mg placenta and amplified using forward (5′-CCCTTGCCAGGTGATTGGC-3′) and reverse (5′-GTATAGAAGCCAGGTCCATCCTGCCAAG-3 ′) primers [8]. The PCR products were purified, digested with Pst1, and separated by agarose gel electrophoresis to identify the G1528C mutation. Purified PCR products were bidirectionally sequenced using the BigDye Terminator V3.1 kit in a 3130 genetic analyzer (Applied Biosystems, Carlsbad, USA) and analyzed using NovoSNP software (http://www.molgen. ua.ac.be/bioinfo/novosnp/). PCR was used to amplify the whole of exon 15 of the α subunit, which codes for LCHAD activity of the MTP (Fig. 1a, first lane on left). All healthy controls as well as AFLP and HELLP patients showed two characteristic fragments after Pst1 digestion (465 and 175 bp), indicating an absence of the G1528C mutation [8]. V. Raghupathy :K. R. Thangaraj :K. A. Balasubramanian : A. Ramachandran (*) The Wellcome Trust Research Laboratory, Division of Gastrointestinal Sciences, Christian Medical College, Vellore 632 004, India e-mail: anup@cmcvellore.ac.in

Placental Syncytiotrophoblast Maintains a Specific Type of Glycocalyx at the Fetomaternal Border: The Glycocalyx at the Fetomaternal Interface in Healthy Women and Patients With HELLP Syndrome

Recent studies showed that considerable amounts of glycosaminoglycans are released into maternal blood during normal pregnancy and in hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. Maternal endothelia and the syncytiotrophoblast layer have been discussed as a possible origin of these glycocalyx components. Our study aimed to visualize the glycocalyx on the syncytiotrophoblast by electron microscopy, to analyze its structure and composition by immunohistochemistry, and to determine potential differences between healthy women and women with HELLP syndrome. For electron microscopy, a cotyledon was fixed by perfusion of the intervillous space with a 2% lanthanum-nitrate glutaraldehyde solution followed by immersion fixation in the same fixative. For immunohistochemistry, sections of 16 placentas (HELLP patients/healthy women, n = 8 each) were stained with monoclonal antibodies against the main glycocalyx constituents syndecan 1, hyaluronic acid, and heparan sulfate. Semiquantitative evaluation of staining intensity focused on the apical surface of the syncytiotrophoblast and fetal intravillous endothelia as possible localizations of a placental glycocalyx. Electron microscopy revealed a glycocalyx of approximately 250 nm, covering the syncytiotrophoblast layer. This was found to contain large amounts of syndecan 1, but neither hyaluronic acid nor heparan sulfate as major components. Intravillous fetal endothelium did not express any of the investigated glycosaminoglycans. Healthy women and patients with HELLP showed no differences concerning glycocalyx composition and thickness of the syncytiotrophoblast. The composition of the "placental" glycocalyx differs from the adult and fetal vascular glycocalyx. Obviously, the human placental syncytiotrophoblast maintains a special kind of glycocalyx at the fetomaternal interface.

ENOSI4 and EPHX1 polymorphisms affect maternal susceptibility to preeclampsia: analysis of five polymorphisms predisposing to cardiovascular disease in 279 Caucasian and 241 African women

The aim of this study was to evaluate possible associations of genetic polymorphisms predisposing to cardiovascular disease with the development and/or the severity of preeclampsia. A two hospital-based prospective case-control study was performed in Germany and Ghana. 470 blood samples of 250 Caucasian and 220 black African have been genotyped by pyrosequencing and fragment length analysis. We evaluated the distribution of the epoxide hydrolase 1 (EPHX1) polymorphism on exon 3, the endothelial nitric oxide synthase (eNOS) polymorphisms on exon 7 and on intron 4, the angiotensinogen polymorphism on exon 2 and the estrogen receptor 1 polymorphism in intron 1. 74 Caucasian and 84 African were classified as preeclampsia with 27 Caucasian developing a hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome and 17 African women experiencing eclampsia. Multivariate logistic regression analysis adjusting for ethnicity, age and parity revealed for carriers of eNOSI4 VNTR4a a 1.7-fold increased (95% CI 1.10-2.711, p = 0.016) risk to develop preeclampsia and a 3.6-fold increase for carriers of the EPHX1 113Tyr (95% CI 1.366-8.750, p = 0.009) to develop severest preeclampsia. Our finding of eNOSI4 polymorphism predisposing to preeclampsia independently of ethnicity, age and parity supports the concept of NO being involved in the endothelial disorder preeclampsia. Since EPHX1 is highly expressed in the liver, can interact with various signaling pathways and is involved in central nervous system disorders, the association of EPHX1 polymorphism with the HELLP syndrome and eclampsia may hint to EPHX being a further key player in the pathogenesis of preeclampsia.

Beware of delayed severe brain swelling after intracerebral haematoma in HELLP syndrome.

Haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome is a condition associated with increased risk of adverse outcomes during pregnancy and peripartum, including neurological complications. We report the third case in the world literature of delayed brain swelling following cerebral haemorrhage as a complication of HELLP syndrome. A 36-year-old woman in labour developed HELLP, which was complicated with intracerebral haematoma. This was evacuated, but motor impairment persisted after surgery and unfortunately the patient died unexpectedly during the 11th postoperative day. Computer tomographic brain scans documented diffuse cerebral swelling, which we think may have been caused by cerebral vasospasm. Cerebral vasospasm should always be considered when managing patients who suffered from stroke complicating HELLP syndrome. Close monitoring is advised even in later stages of recovery.

Bell's palsy in pregnancy: underlying HELLP syndrome or pre-eclampsia?

Bell's palsy is not uncommon during pregnancy. An association with pre-eclampsia (PE) has been reported previously. Furthermore, it has even been suggested that Bell's palsy could be a predictor of PE. We report three cases illustrating various possible aspects of this association, one of them including the features of HELLP (haemolysis, elevated liver enzymes, and low platelets) syndrome.

Anxiety and depression following preeclampsia or hemolysis, elevated liver enzymes, and low platelets syndrome. A systematic review

Women who suffered from pregnancy complications are at increased risk for anxiety and depression. The aim of this study was to evaluate whether having suffered from preeclampsia (PE) or HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome is associated with anxiety and depression, and whether PE/HELLP is an independent risk factor for developing anxiety and depression. Systematic search on PubMed and PsycInfo with no time limit. Studies presenting original data, including women with a history of PE/HELLP and at least one comparison group of women without PE/HELLP, reporting the results for each group separately or in a multivariate regression analysis with PE/HELLP as an independent variable. Study characteristics and outcomes were extracted using a prespecified form. If necessary, additional calculations were performed. The search yielded 267 articles, with only six being suitable for inclusion in this review. Studies on depression (six studies) showed generally positive associations between PE/HELLP and the prevalence of depression or severity of depressive symptoms. However, the results of three studies were not statistically significant. Studies addressing anxiety (two studies) did not show significant associations between PE/HELLP and anxiety scores. Associations between post-traumatic stress and PE/HELLP, investigated in four studies, were often nonsignificant. Due to heterogeneity of study methods, a meta-analysis of the results was not possible. In most studies, confounder control was poor. Evidence is mixed but generally points to positive associations between various forms of psychopathology and previous PE/HELLP. Causality of the associations can, however, not be judged adequately.

Deficiência da desidrogenase de 3‐hidroxi‐acil‐coa de cadeia longa no feto e fígado gordo agudo da gravidez

Maternal‐foetal interactions are critical determinants of maternal health and perinatal outcome. Liver diseases uniquely related to pregnancy may develop, including acute fatty liver of pregnancy and HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome. Although the etiopathogenesis has not been completely elucidated, these diseases have been associated with foetal fatty oxidation disorders, particularly correlated with foetal defects of long‐chain fatty oxidation. We report a clinical case of a complicated pregnancy with an acute fatty liver of pregnancy and the detection of mutation 1528G>C in the newborn's and both parents’ homozygote. Screening for fatty acid oxidation disorders and specifically long‐chain 3‐hidroxyacyl‐coenzyme‐A‐ dehydrogenase deficiency (LCHAD) should be carried out with newborns from mothers with hepatic complications during pregnancy such as acute fatty liver of pregnancy or severe or recurrent HELLP syndrome.

Focused ultrasound is the next step in perioperative care

In this issue of the Journal, two different investigators report the use of bedside ultrasound for focused cardiac examination as well as for focused thoracic and abdominal examinations in patients undergoing non-cardiac surgery. These ultrasound observations led to a change in patient management, and it is expected that more widespread use of this tool in our practice will likely have a significant impact on perioperative care. This paradigm change implies that consideration should be given to incorporating an ultrasound curriculum within our anesthesiology training programs. The first case involves a previously healthy 29-yr-old pregnant woman who developed preeclampsia complicated by HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Following Cesarean delivery, the patient remained anuric and was transferred to the intensive care unit. A bedside cardiac ultrasound was performed using a validated pulsed wave tissue Doppler technique to estimate filling pressures and evaluate cardiac function. The patient was found to be responsive to passive leg raising and fluid therapy, and ultrasound confirmed the absence of fluid overload; however, a few hours later, she was found to be anemic. At that point, abdominal ultrasound was used to diagnose an intra-abdominal hematoma. Based on these findings, a decision was made to transfuse blood and explore the abdomen surgically. Postoperatively, the patient became hypoxic, and a repeated lung ultrasound showed comet-tail artifacts of B-lines, which is suggestive of an alveolar-interstitial syndrome. The absence of elevated filling pressure on cardiac ultrasound suggested non-cardiogenic pulmonary edema and the possibility of acute respiratory distress syndrome. The other case involves a 58-yr-old man who was scheduled for elective nasal polyp excision. The patient was known to have aortic stenosis and was ‘‘cleared’’ preoperatively by a cardiologist and a cardiac surgeon. A preoperative anesthesia evaluation of cardiac function with bedside ultrasound revealed an unsuspected large pericardial effusion with signs of pericardial tamponade and right atrial and right ventricular collapse. The case was cancelled and the patient underwent percutaneous pericardial drainage. The clinical presentation and pericardial fluid analysis led to the diagnosis of ChurgStrauss syndrome complicated by progressive pericardial effusion. The patient was discharged from hospital several days later, and his nasal polyps were treated medically. These two cases effectively illustrate the gradual integration of bedside ultrasound as a point-of-care examination performed by the anesthesiologist for conditions that are not uncommon in the perioperative setting. Ultrasound was used in a goal-oriented approach to answer a specific question, and it involved more than solely examination of the heart. As anesthesiologists and critical care physicians, we strive to maintain adequate oxygen delivery; ultrasound can play a role in identifying A. Denault, MD, PhD (&) Department of Anesthesia, Montreal Heart Institute, 5000 Belanger Street, Montreal, QC H1S 1T8, Canada e-mail: andre.denault@gmail.com

Perfil clínico y epidemiológico de pacientes con preeclampsia atendidas en una clínica privada de Medellín, Colombia (2005-2010)

Preeclampsia is a syndrome that affects the cardiovascular, renal, and hepatic systems and is associated with increased maternal and fetal morbidity and mortality. ObjectiveTo describe the epidemiological profile of patients with a diagnosis of preeclampsia who were treated in a private clinic in Medellin between 2005 and 2010. MethodologyWe performed a descriptive and retrospective study that reviewed the medical records of patients treated for preeclampsia. The SPSS program was used for the statistical analysis. The means, standard deviation and ranges were calculated for quantitative variables. Proportions were calculated for qualitative variables. ResultsA total of 707 women with a diagnosis of preeclampsia were studied. Among the most frequent characteristics were first pregnancy (50.3%), a history of hypertension (12.4%), and blood pressure at admission exceeding 140/90mmHg (50.4%). The symptoms most frequently associated with preeclampsia were edema (56.2%) and headache (47.6%). Maternal complications consisted of HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome in 10.9% and eclampsia (1.8%). A total of 38.7% of the neonates had low birth weight and 1.7% were stillborn. ConclusionPreeclampsia was most common in patients with a first pregnancy. The main complication was HELLP syndrome, and eclampsia was rare. Therefore, strategies for early diagnosis and for the management of at-risk patients should be developed, thus avoiding the development of severe complications and maternal-fetal morbidity and mortality.

PM.01 Management and Outcomes of HELLP Syndrome in the UK

ObjectiveTo describe the current management and outcomes of HELLP (haemolysis, elevated liver enzymes and low platelet count) syndrome in the UK.MethodsA national descriptive study using the UK Obstetric Surveillance System,...

Outcomes in hypertensive disorders of pregnancy in the North Indian population

Introduction:Hypertensive disorders complicating pregnancy seriously endanger the safety of the mother and fetus during pregnancy. Very few studies have explored hypertensive disorders of pregnancy in India, even though this disease has been associated with adverse maternal and perinatal outcomes. This study aimed to analyze the disease pattern and risk factors associated with the disorder and assess the maternal and fetal outcomes in cases of hypertensive disorders of pregnancy.Subjects and methods:This case-control study was carried out over 1 year from 2011 to 2012 at the Department of Obstetrics and Gynecology, King George’s Medical University, Lucknow, Uttar Pradesh, India. A total of 149 patients were enrolled in the study. As seven were lost to follow-up, analysis was carried out on 142 cases. Patients were further classified according to the National High Blood Pressure Education Program Working Group (2000) as having mild preeclampsia (65 cases), severe preeclampsia (32 cases), or eclampsia (45 cases). Thirty-one healthy pregnant non-hypertensive women were enrolled into the study as controls.Results:The most common manifestation was edema, seen in 90% of cases. Proteinuria was also relatively common, 26.76% of patients with proteinuria of ≥300 mg/24 hours, 47.88% with proteinuria of ≥2 g/24 hours, and 25.35% with a urinary protein excretion of 3–5 g/24 hours. Central nervous system involvement was observed in 42.2% of cases, elevated bilirubin levels in 47.0%, visual symptoms in 6.4%, vaginal bleeding in 11.3%, and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome was reported in 2.80%. Maternal deaths occurred in 2.8% of cases, all of which were from the eclampsia group. Stillbirths occurred in 16.9% of cases, and overall neonatal death observed in 4.23% of cases.Conclusion:Women with hypertensive disorders of pregnancy were more prone to adverse maternal and fetal outcomes than normotensive pregnant women, but we observed a decreasing trend in the present study compared with that reported in other studies, which might be due to the increased number of hospital deliveries that occurred in our study.

Increased Serum Concentrations of Circulating Glycocalyx Components in HELLP Syndrome Compared to Healthy Pregnancy: An Observational Study

Severe inflammation has been shown to induce a shedding of the endothelial glycocalyx (EGX). Inflammatory cytokines, such as tumor necrosis factor α (TNF-α), impede the thickness of the EGX. While a controlled inflammatory reaction occurs already in normal pregnancy, women with hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome had an exaggerated inflammatory response. This study investigates the shedding of the glycocalyx during normal pregnancy and in women with HELLP syndrome. Glycocalyx components (syndecan 1, heparan sulfate, and hyaluronic acid) were measured in serum of healthy women throughout pregnancy (4 time points, n = 26), in women with HELLP syndrome (n = 17) before delivery and in nonpregnant volunteers (n = 10). Serum concentrations of TNF-α and soluble TNF-α receptors (sTNF-Rs) were assessed once in all 3 groups. Syndecan 1 serum concentrations constantly rose throughout normal pregnancy. Immediately before delivery, a 159-fold increase was measured compared to nonpregnant controls (P < .01). Even higher amounts were observed in patients with HELLP prior to delivery (median 12252 ng/mL) compared to healthy women matched by gestational age (median 5943 ng/mL; P < .01). Relevantly, increased serum levels of heparan sulfate, hyaluronic acid, and sTNF-Rs were only detected in patients with HELLP (P < .01). These findings suggest that considerable amounts of syndecan 1 are released into maternal blood during uncomplicated pregnancy. The HELLP syndrome is associated with an even more pronounced shedding of glycocalyx components. The maternal vasculature as well as the placenta has to be discussed as a possible origin of circulating glycocalyx components.