Complement activation and regulation in preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome.

The complement system is critical to human health owing to its central role in host defense and innate immunity. During pregnancy, the complement system must be appropriately regulated to allow for immunologic tolerance to the developing fetus and placenta. Although some degree of complement activation can be seen in normal pregnancy, the fetus seems to be protected in part through the placental expression of complement regulatory proteins, which inhibit complement activation at different steps along the complement activation cascade. In women who develop preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome, there is a shift toward increased complement activation and decreased complement regulation. There is an increase in placental deposition of C5b-9, which is the terminal effector of classical, lectin, and alternative complement pathways. C5b-9 deposition stimulates trophoblasts to secrete soluble fms-like tyrosine kinase-1, which sequesters vascular endothelial growth factor and placental growth factor. Pathogenic mutations or deletions in complement regulatory genes, which predispose to increased complement activation, have been detected in women with preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome. Before the disease, biomarkers of alternative complement pathway activation are increased; during active disease, biomarkers of terminal complement pathway activation are increased. Urinary excretion of C5b-9 is associated with preeclampsia with severe features and distinguishes it from other hypertensive disorders of pregnancy. Taken together, existing data link preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome with increased activation of the terminal complement pathway that, in some cases, may be influenced by genetic alterations in complement regulators. These findings suggest that the inhibition of the terminal complement pathway, possibly through C5 blockade, may be an effective strategy to treat preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome, but this strategy warrants further evaluation in clinical trials.

Real-world data on the clinical use of angiogenic factors in pregnancies with placental dysfunction.

BACKGROUND: In routine clinical practice, angiogenic factor measurement can facilitate prediction and diagnosis of preeclampsia and other manifestations of placental dysfunction (eg, intrauterine growth restriction). OBJECTIVE: This real-world data analysis investigated the utility of soluble fms-like tyrosine kinase-1 and placental growth factor for preeclampsia and placental dysfunction. STUDY DESIGN: Blood serum soluble fms-like tyrosine kinase-1 and placental growth factor were measured using Elecsys soluble fms-like tyrosine kinase-1 and placental growth factor immunoassays (cobas e analyzer; Roche Diagnostics). Overall, 283 unselected singleton pregnancies with ≥1 determination of soluble fms-like tyrosine kinase-1-to-placental growth factor ratio were included. Distribution of the ratio at admission was normal (<38 [58.7%]), intermediate (38-85/110 [19.1%]), or pathologic (>85/110 [22.3%]). Overall, 15.5% had preeclampsia or hemolysis, elevated liver enzyme levels, and low platelet count, and 15.5% of women had intrauterine growth restriction. RESULTS: Increasing soluble fms-like tyrosine kinase-1-to-placental growth factor ratio was associated with an increase in priority of delivery (r=0.38; P<.001). The percentage of patients who developed preeclampsia by soluble fms-like tyrosine kinase-1-to-placental growth factor ratio at admission was 5.4% (normal), 7.4% (intermediate), and 49.2% (pathologic). The greatest difference in soluble fms-like tyrosine kinase-1-to-placental growth factor ratio from admission to birth occurred in pathologic pregnancies (171.12 vs 39.84 for normal pregnancies). Soluble fms-like tyrosine kinase-1-to-placental growth factor ratio correlated inversely with gestational age at delivery, birthweight, and prolongation time. There was no significant relation between the prolongation period or the gestational age at first determination to the increase of soluble fms-like tyrosine kinase-1 and placental growth factor between admission and delivery (ΔQ). This analysis used a real-world approach to investigate the clinical utility of the soluble fms-like tyrosine kinase-1-to-placental growth factor ratio in placental dysfunction. CONCLUSIONS: Confirming the results of prospective studies, we observed a positive correlation between soluble fms-like tyrosine kinase-1-to-placental growth factor ratio and severity of placental dysfunction and a negative association with time to delivery. In a real-world setting, the soluble fms-like tyrosine kinase-1-placental growth factor ratio stratifies patients with normal outcome and outcome complicated by placental dysfunction.

Dysregulation of complement system in HELLP syndrome.

OBJECTIVE: To investigate the expression of complement system's activation factors in patients with HELLP syndrome. METHODS: A case-control study was performed. Sixteen HELLP syndrome patients, 32 severe preeclampsia patients, and 48 normal pregnancy women were involved in this studyELISA was used to test C1q, C4d, MBL, Bb, C3a, C5a, sC5b-9, s-Endoglin, and sflt-1 in the plasma. RESULTS: The levels of C5a (P < 0.01) and sC5b-9 (P = 0.014) in HELLP syndrome were higher than those in severe preeclampsia patients. CONCLUSIONS: The abnormal activation of the complement system is more significant in the pathogenesis of HELLP syndrome than in severe preeclampsia.

Differentiating Hemolysis, Elevated Liver Enzymes, and Low Platelet Count Syndrome and Atypical Hemolytic Uremic Syndrome in the Postpartum Period.

[Figure: see text].

Thrombotic microangiopathy during pregnancy.

Pregnancy is a high-risk time for the development of different kinds of thrombotic microangiopathy (TMA). Three major syndromes including TTP (thrombotic thrombocytopenic purpura), PE/HELLP (preeclampsia/hemolysis, elevated liver function tests, low platelets), and aHUS (atypical hemolytic- uremic syndrome) should be sought in pregnancy-TMA. These severe disorders share multiple clinical features and overlaps and even the coexistence of more than one pathologic mechanism. Each of these disorders finally ends in endothelial damage and fibrin thrombi formation within the microcirculation that fragments RBCs (schystocytes), aggregates platelets, and creates ischemic injury in the targeted organs i.e.; kidney and brain. Although the mechanisms of these severe disorders have been revealed, pregnancy-related TMA still interfaces with diagnostic and therapeutic challenges. Here, we highlight the current knowledge of diagnosis and management of these complications during pregnancy.

Hemolysis, Elevated Liver Enzymes, and Low Platelet Count Syndrome With Severe Thrombocytopenia and Severe ADAMTS13 Activity Deficiency.

BACKGROUND: Differentiating preeclampsia with hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome from thrombotic thrombocytopenic purpura (TTP) can present a diagnostic dilemma. CASE: We report the case of a 34-year-old woman, G1P0, with monochorionic diamniotic twins who presented with new-onset blurry vision, hypertension, and a platelet count of 4×109/L. After a multidisciplinary discussion, a diagnosis of atypical HELLP syndrome was made, despite overlapping features concerning for TTP. Her platelet count and ADAMTS13 activity testing showed appropriate recovery after delivery, without plasma exchange therapy, supporting the diagnosis of HELLP syndrome. CONCLUSION: Hemolysis, elevated liver enzymes, and low platelet count syndrome may present with severe thrombocytopenia and severe ADAMTS13 activity deficiency in ranges otherwise known to be more common with TTP.

Unfolding the pathophysiology of congenital thrombotic thrombocytopenic purpura in pregnancy: lessons from a cluster of familial cases.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP), a rare, potentially life-threatening thrombotic microangiopathy, manifests either as congenital TTP or acquired forms. It is caused by the absence or severe depletion of a disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13) protease, leading to the accumulation of ultra large von Willebrand factor multimers as well as extensive platelet adhesion and clumping, which can ultimately cause severe secondary end-organ damage. Pregnancy can provoke or exacerbate TTP, leading to maternal and fetal complications. OBJECTIVE: In this report, we focused on pregnancy outcomes in a recently recognized cohort of congenital TTP patients of Bedouin Arab descent in southern Israel who were all homozygous for a novel c.3772delA variant of the ADAMTS13 gene, leading to the clinical manifestations of TTP largely during pregnancy. STUDY DESIGN: All patients presented in this study belong to 2 closely related families of Arab Bedouin descent and were found to be homozygous for a novel ADAMTS13-c.3772delA variant. The cohort consisted of 19 females; 16 of them had congenital TTP and had been pregnant and were thus included. Patient data were collected from electronic medical records. RESULTS: Of note, 13 women from our cohort, who delivered 14 fetuses (owing to 1 twin pregnancy), were diagnosed with congenital TTP following complicated pregnancies, which included recurrent pregnancy loss, stillbirth, early onset preeclampsia (both mild and severe), hemolysis, elevated liver enzymes and low platelet count syndrome, intrauterine growth restriction with abnormal Doppler flow, preterm premature rupture of membranes, and a total perinatal mortality rate of 30.7% (4/13). An additional 3 women, who were diagnosed owing to complications outside of pregnancy and at older ages, experienced TTP during their pregnancies, which occurred before diagnosis. Subsequent pregnancies were treated with fresh frozen plasma leading to a 100% fetal survival rate in the pregnancies that reached fetal viability. All placentas had lesions consistent with maternal vascular underperfusion. However, the severity and frequency of these lesions were lower in the 8 placentas from pregnancies treated with fresh frozen plasma. CONCLUSION: This case series details a distinctive cohort of congenital TTP patients, all homozygous for the same, novel ADAMTS13 variant, who presented with clinical complications during pregnancy and maternal vascular lesions of underperfusion in the placenta. Our findings imply that the variant identified in the ADAMTS13 gene in our cohort may have a specific functional impact on the placenta, and that treatment with fresh frozen plasma during pregnancy ameliorates the course of the disease, leading to a milder phenotype or a normal pregnancy in the majority of cases.

Plasma CD59 concentrations are increased in preeclampsia with severe features and correlate with laboratory measures of end-organ injury.

OBJECTIVES: Dysregulation of CD59 may lead to increased complement-mediated end-organ injury in preeclampsia. We sought to determine if soluble CD59 concentrations are altered in preeclampsia with severe features. STUDY DESIGN: Observational case-control study, which enrolled subjects prospectively from six centers in Colombia from 2015 to 2016. Cases had preeclampsia with severe features and controls were either healthy or had chronic hypertension, gestational hypertension, or preeclampsia without severe features. Trained coordinators collected clinical data, blood and urine. Analyses were by test of medians and Spearman's correlation. MAIN OUTCOME MEASURES: Soluble CD59 concentration in plasma and urine, using enzyme linked immunosorbent assays. RESULTS: In total, 352 subjects were enrolled (104 cases; 248 controls). Compared to healthy women or those with other hypertensive disorders of pregnancy, women with preeclampsia with severe features had increased concentration of CD59 in plasma (P < 0.001) and decreased CD59 in urine (P = 0.01). In sub-group analyses, plasma CD59 concentrations were increased in preeclampsia with severe features compared to healthy controls (P < 0.001) or controls with either chronic hypertension (P = 0.002) or gestational hypertension (P = 0.02). Increased plasma CD59 concentrations correlated with decreased platelet count and increased lactate dehydrogenase, creatinine, aspartate transaminase, urine protein/creatinine ratio, systolic blood pressure and diastolic blood pressure (P < 0.01, all correlations). CONCLUSION: In women with preeclampsia with severe features, soluble CD59 concentrations were increased in plasma and decreased in urine, and plasma levels correlated with increased blood pressure and end-organ injury. Soluble CD59 concentrations may help identify a subset of women with preeclampsia that have altered regulation of terminal complement proteins.

Identifying new potential genetic biomarkers for HELLP syndrome using massive parallel sequencing.

BACKGROUND: Preeclampsia (PE) is a frequently occurring multisystemic disease affecting ~5% of pregnancies. PE patients may develop HELLP syndrome (haemolysis, elevated liver enzymes, and low platelet), a mother and foetus life-threatening condition. Research into HELLP's genetic origin has been relatively unsuccessful, mainly because normal placental function and blood pressure regulation involve the fine-regulation of hundreds of genes. OBJECTIVE: To identify new genes and mutations constituting potential biomarkers for HELLP syndrome. STUDY DESIGN: The present case-control study involved whole-exome sequencing of 79 unrelated HELLP women. Candidate variants were screened in a control population constituted by 176 individuals. Stringent bioinformatics filters were used for selecting potentially etiological sequence variants in a subset of 487 genes. We used robust in silico mutation modelling for predicting the potential effect on protein structure. RESULTS: We identified numerous sequence variants in genes related to angiogenesis/coagulation/blood pressure regulation, cell differentiation/communication/adhesion, cell cycle and transcriptional gene regulation, extracellular matrix biology, lipid metabolism and immunological response. Five sequence variants generated premature stop codons in genes playing an essential role in placental physiology (STOX1, PDGFD, IGF2, MMP1 and DNAH11). Six variants (ERAP1- p.Ile915Thr, ERAP2- p.Leu837Ser, COMT-p.His192Gln, CSAD-p.Pro418Ser, CDH1- p.Ala298Thr and CCR2-p.Met249Lys) led to destabilisation of protein structure as they had significant energy and residue interaction-related changes. We identified at least two mutations in 57% of patients, arguing in favour of a polygenic origin for the HELLP syndrome. CONCLUSION: Our results provide novel evidence regarding PE/HELLP's genetic origin, leading to new biomarkers, having potential clinical usefulness, being proposed.

Role of sFlt-1/PIGF ratio and uterine Doppler in pregnancies with chronic kidney disease suspected with Pre-eclampsia or HELLP syndrome.

PURPOSE: Pregnancies of women with chronic kidney disease (CKD) are at higher risk of experiencing adverse perinatal (APO) and maternal outcome (AMO). Mean uterine artery pulsatility index (mUtA-PI) as well as the ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are helpful tools in diagnosing pre-eclampsia (PE) in women with CKD. The aim of the study was to evaluate the role of sFlt-1/PIGF ratio and mUtA-PI as predictors for APO, AMO, preterm delivery and decline of kidney function in CKD pregnancies. METHODS: A total of 28 CKD pregnancies with suspected PE/HELLP syndrome were retrospectively included, in whom both sFlt-1/PIGF and mUtA-PI were determined during the third trimester. APO was defined as fetal growth restriction, respiratory distress syndrome, intubation, admission to NICU, 5 min Apgar <7 and intracerebral hemorrhage. AMO was defined as the development of PE, HELLP syndrome or resistant hypertension. Decline of kidney function was defined as a 25% increase of creatinine level after delivery. RESULTS: Of all included women, eight (28.6%) developed a PE/HELLP syndrome. AMO (28.6%) and APO (32.1%) were frequently observed. ROC analyses revealed a predictive value for AMO and sFlt-1/PIGF or mUtA-PI. Neither sFlt-1/PIGF nor mUtA-PI could predict APO or decline of postnatal kidney function. mUtA-PI was a predictor for preterm delivery. CONCLUSION: Uterine Doppler and sFlt-1/PIGF are predictors of AMO in CKD pregnancies. Therefore, both markers might be helpful for an improved risk assessment. However, neither sFlt-1/PIGF nor mUtA-PI were able to predict a decline of postnatal kidney function or APO.

Severe pre-eclampsia complicated by acute fatty liver disease of pregnancy, HELLP syndrome and acute kidney injury following SARS-CoV-2 infection.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has presented many diagnostic challenges and uncertainties. Little is known about common pathologies complicating pregnancy and how their behaviour is modified by the presence of SARS-CoV-2. Pregnancy itself can alter the body's response to viral infection, which can cause more severe symptoms. We report the first case of a patient affected with sudden-onset severe pre-eclampsia complicated by acute fatty liver disease of pregnancy, HELLP (haemolysis, elevated liver enzymes and low platelet) syndrome and acute kidney injury following SARS-CoV-2 infection. Although an initial diagnostic dilemma, a multidisciplinary team approach was required to ensure a favourable outcome for both the mother and the baby. Our case report highlights the need for health professionals caring for pregnant women to be aware of the complex interplay between SARS-CoV-2 infection and hypertensive disorders of pregnancy.

Fas ligand neutralization attenuates hypertension, endothelin-1, and placental inflammation in an animal model of HELLP syndrome.

Neutralization of FasL is linked to suppression of hypertension, placental inflammation, and endothelin system activation in an animal model of hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. During HELLP syndrome the placenta has been reported to serve as the primary source of Fas ligand (FasL), which has an impact on inflammation and hypertension during pregnancy and is dysregulated in women with severe preeclampsia and HELLP syndrome. We hypothesize that neutralization of FasL during pregnancy in an animal model of HELLP syndrome decreases inflammation and placental apoptosis, improves endothelial damage, and improves hypertension. On gestational day (GD) 12, rats were chronically infused with placental antiangiogenic factors sFlt-1 and sEng to induce HELLP syndrome. To neutralize FasL, MFL4 or FasL antibody was infused into a subset of HELLP or normal pregnant rats on GD13. IgG infusion into another group of NP and HELLP rats on GD13 was used as a control for FasL antibody, and all rats were euthanized on GD19 after blood pressure measurement. Plasma and placentas were collected to assess inflammation, apoptosis, and the degree of placental debris activation of endothelial cells. Administration of MFL4 to HELLP rats significantly decreased blood pressure compared with untreated HELLP rats and HELLP rats infused with IgG and improved the biochemistry of HELLP syndrome. Both circulating and placental FasL were significantly attenuated in response to MFL4 infusion, as were levels of placental and circulating TNFα when compared with untreated HELLP rats and HELLP rats infused with IgG. Endothelial cells exposed to placental debris and media from HP + MFL4 rats secreted significantly less endothelin-1 compared with stimulated endothelial cells from HELLP placentas. Neutralization of FasL is associated with decreased MAP and improvement in placental inflammation and endothelial damage in an animal model of HELLP syndrome.

Pentraxin-3 is a candidate biomarker on the spectrum of severity from pre-eclampsia to HELLP syndrome: GenPE study.

Pentraxin-3 has been reported as a promising biomarker of pre-eclampsia and its severity; however, available studies have small sample sizes, and analyses are not always adjusted for confounders. The aim of this study is to establish the strength of the association between maternal Pentraxin-3 level and pre-eclampsia or HELLP syndrome. It was a case-control study. Women with pre-eclampsia or HELLP syndrome were defined as cases, and women with healthy pregnancies at term (>37 weeks) were classified as controls. Plasma concentrations of Pentraxin-3 were determined at the time of delivery by quantitative enzyme immunoassay. Associations between Pentraxin-3 and pre-eclampsia and HELLP syndrome were assessed by multinomial logistic regression. Subsidiary analysis for the time of disease onset was also carried out. Odds ratios and 95% confidence intervals are reported. A total of 1024 pregnant women were included (461 controls, 368 pre-eclampsia, 195 HELLP). A positive log-linear relationship was found between the top pentraxin-3 quintile and HELLP syndrome. After adjustment for confounders (maternal age, ethnicity, socioeconomic position, date and place of recruitment, family history of pre-eclampsia, smoking, body mass index at beginning of pregnancy, gestational age and multiple pregnancy), the strength of the association was higher for HELLP syndrome [OR 1.13 (95% CI 1.08; 1.18)] than for pre-eclampsia [OR 1.03 (95% CI 1.03; 1.10)]. No difference according to time of onset or pentraxin-3 level was found. In summary, pentraxin-3 level was associated with pre-eclampsia, but it was more strongly associated with HELLP syndrome. Longitudinal studies with a lower probability of residual confounding are necessary to improve our knowledge about the role of pentraxin-3 in pre-eclampsia.

Prenatal Plasma Fibrinogen Level Predicts Postpartum Hemorrhage of Patients With HELLP Syndrome.

Hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome is a serious complication of pregnancy. Postpartum hemorrhage indicates poor prognosis of pregnant women with HELLP syndrome. The aim of our study is to investigate the predictive value of coagulation markers for postpartum hemorrhage of pregnant women with HELLP syndrome. In a retrospective cohort study, 106 patients who were diagnosed as pregnant women with HELLP syndrome in Peking University Third Hospital from August 2010 to January 2017 were analyzed. The demographic characters of maternal and fetus, days of hospital stay, postpartum complications, and the laboratory tests of coagulation markers within 3 days before delivery were collected. In addition, 100 healthy pregnant women were collected as a control group. The result showed that the incidence of preeclampsia in pregnant women with postpartum hemorrhage was higher than that in pregnant women without hemorrhage (P = .011). The level of fibrinogen (FIB) in postpartum hemorrhage pregnant women with HELLP syndrome was lower than that in nonpostpartum hemorrhage pregnant women with HELLP syndrome and healthy pregnant women (2.3 [1.68-2.81] vs 3.64 ± 0.95, P = .000; 2.3 [1.68-2.81] vs 4.48 ± 0.62, P = .000). Multivariate analysis showed that decreased FIB levels independently predicted the postpartum hemorrhage of pregnant women with HELLP syndrome (odds ratio = 7.374, 95% confidence interval [CI], 1.551-35.05, P = .012). The receiver operating characteristic curve showed that the area under the curve of FIB level when predicting postpartum hemorrhage is 0.841 (95% CI, 0.708-0.976). When the cutoff value of FIB was 3.04 g/L, the sensitivity was 90.90% and the specificity was75.80%. Therefore, the low level of prenatal FIB is a reliable biomarker to predict postpartum hemorrhage of pregnant women with HELLP syndrome, which make it useful for pregnant women with HELLP syndrome in guiding surveillance therapy and prognosis assessment.

Plasma ceramide is increased and associated with proteinuria in women with pre-eclampsia and HELLP syndrome.

OBJECTIVES: Ceramide is a sphingolipid with anti-angiogenic and pro-apoptotic properties that has shown to be increased in plasma of women with pre-eclampsia. We aimed to compare plasma and placental sphingolipid content among normotensive pregnant women and pre-eclamptic women with and without HELLP syndrome and we aimed to assess whether ceramide is related to hypertension and proteinuria in pre-eclampsia. STUDY DESIGN: Case-control study. Participants were recruited from the Department of Obstetrics at the Academic Medical Center in Amsterdam, The Netherlands. In total 48 pregnant women were included: 24 with pre-eclampsia and 24 normotensive controls. Of the 24 pre-eclamptic women, 11 had HELLP syndrome. MAIN OUTCOME MEASURES: Plasma and placental ceramide content and correlation with blood pressure and protein excretion in pre-eclampsia. RESULTS: Total plasma, but not placental, ceramide was higher in pre-eclamptic women with HELLP syndrome (11200 95% CI 9531-12870 nmol/ml, n = 11) compared to pre-eclamptic women without HELLP (7413 95% CI 5928-8898 nmol/ml, n = 13, p < 0.001) and normotensive pregnant women (7404 95% CI 6695-8112 nmol/ml, n = 24, p < 0.001). Maternal circulating ceramide levels were strongly associated with proteinuria (r = 0.621, n = 24, p = 0.001) in pre-eclamptic women and inversely correlated with gestational age at delivery (r = 0.771, p < 0.01) in pre-eclamptic women with HELLP syndrome. Plasma ceramide was not correlated with blood pressure. CONCLUSION: Plasma but not placental ceramide content is increased in women with pre-eclampsia and HELLP syndrome. The strong positive correlation with proteinuria and the inverse correlation with gestational age at delivery indicate that excess plasma ceramide may contribute to the pathophysiology of pre-eclampsia and HELLP.

Aspartate-aminotransferase to platelet ratio index score for predicting HELLP syndrome.

INTRODUCTION: HELLP (hemolysis, elevated liver enzyme levels, low platelet counts)-syndrome is a rare but dramatic pregnancy-related illness. The difficult part of this syndrome is the lack of standardised diagnostic criterias and tests to be used to predict it. The aim of this study is determining the role of APRI score in the diagnosis of HELLP syndrome. MATERIAL AND METHODS: In this cross sectional, retrospective study, patients with HELLP syndrome as case group and age-matched healthy pregnants at the similar pregnancy trimester as control group were included between January 12,017 and May 31, 2018. Data including sex, age, laboratory values, prognosis were recorded from the computerized system of the hospital. The p-value <0.05 was considered statistically significant. RESULTS: 40 patients with HELLP syndrome and 124 age-matched healthy pregnants included in the study. There was a statistically significant difference between control group and HELLP patients in terms of the mean urinary protein, platelet count, ALT, AST, creatinin, D dimer levels and also the mean APRI score. In the multivariate regression analysis, APRI score was found a better predictor than AST and both were in a good significant in predicting HELLP. On the ROC curve in order to distinguish the patients with HELLP from the control group for AST and APRI score, the sensitivity was found to be 71.7% and 82.6%, specificity to be 91.2% and 87.6% respectively. Maternal mortality rate of HELLP syndrome was 10%. CONCLUSION: We concluded that the APRI score was robustly predicted HELLP syndrome than AST alone in this study. Further studies are needed to support our data with prospective, multicentre, larger patient groups.

Copper and ceruloplasmin levels are closely related to the severity of preeclampsia.

Objective: The aim of this study was to investigate the maternal serum concentrations of copper (Cu) and ceruloplasmin (CP) in patients with mild preeclampsia, severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome, and to determine their association with the severity of the disease.Methods: This study was carried out at the largest tertiary care health center in the southeast region in Turkey and Department of Obstetrics and Gynecology, Dicle University Hospital. A total of 179 pregnant women, including 58 healthy pregnant women and 71 mild preeclampsia, 26 severe preeclampsia, and 24 HELLP syndrome cases classified according to the American College of Obstetricians and Gynecologists' 2013 guidelines were included in this prospective study. Blood samples were taken from all the pregnant women to evaluate the serum Cu and CP levels. The Cu level was determined via atomic absorption/emission spectroscopy, while the serum CP level was assessed with a nephelometric assay using an automatic image analyzer. Spearman's rank correlation tests were used to determine the correlations between the serum levels of the antioxidative markers and the preeclampsia severity.Results: The mean ± SD of the Cu was 81.2 ± 11.84 µg/dl in the mild preeclampsia cases and 160.2 ± 20.89 µg/dl in the severe preeclampsia cases (p < .001). The mean ± SD of the CP was 33.0 ± 4.81 mg/dl in the mild preeclampsia cases and 65.3 ± 9.17 mg/dl in the severe preeclampsia cases (p < .001). The Cu and CP levels were significantly higher in the patients with HELLP syndrome, which is an advanced and more severe form of severe preeclampsia, than in the mild and severe preeclampsia patients (p < .001 and p < .001, respectively). Therefore, the serum Cu and CP levels were correlated with the severity of preeclampsia (r = 859, p < .001 and r = 786, p < .001, respectively). In addition, there was a positive correlation between the serum Cu and CP levels and the systolic and diastolic blood pressure values and aspartate amino transferase levels (AST), and a negative correlation between the serum Cu and CP levels and the platelet count.Conclusion: This was the first study in which the ceruloplasmin and Cu levels were investigated in HELLP syndrome patients. When considering the results obtained in the present study, there were significant relationships between the Cu, CP levels which are the markers of oxidative stress and the preeclampsia severity.

Early-Pregnancy Circulating Antioxidant Capacity and Hemodynamic Adaptation in Recurrent Placental Syndrome: An Exploratory Study.

BACKGROUND/AIMS: Placental syndromes (PS) refer to pregnancy complications that include gestational hypertension, (pre)eclampsia, HELLP syndrome, and/or placental insufficiency-induced fetal growth restriction. These disorders are characterized by increased oxidative stress. This study aims to test the hypothesis that the abnormal hemodynamic adaptation to pregnancy, typical for early PS pregnancy, is accompanied by abnormal maternal levels of antioxidants relative to those in normal pregnancy. METHODS: Before, and at 12, 16, and 20 weeks pregnancy, we measured trolox equivalent antioxidant capacity (TEAC), uric acid (UA), and TEACC (TEAC corrected for UA) in maternal serum of former PS patients, who either developed recurrent PS (rPS; n = 16) or had a normal next pregnancy (non-rPS; n = 23). Concomitantly, we also measured various hemodynamic variables. RESULTS: rPS differed from non-rPS by higher TEACC levels before pregnancy (178 vs. 152 µM; p = 0.02) and at 20 weeks pregnancy (180 vs. 160 µM; p = 0.04). Only non-rPS responded to pregnancy by significant rises in hemodynamic measures. CONCLUSION: These data indicate that rPS pregnancies are preceded by an increase in antioxidant capacity, presumably induced by subclinical vascular injury and low-grade chronic inflammation.