Administration of corticosteroid therapy for HELLP syndrome in pregnant women: evidences from seven randomized controlled trials.

BACKGROUND: HELLP syndrome, featuring hemolysis, elevated liver enzymes, and thrombocytopenia, is life-threatening disease of pregnancy that triggers comorbidities in both pregnant women and the fetus/newborn. This study provides an updated systematic review and meta-analysis of relevant studies to assess the therapeutic efficacy of corticosteroids in maternal and neonatal outcomes. METHODS: Randomized control trials (RCTs) regarding the use of corticosteroids in the HELLP population from three electronic databases, including Ovid MEDLINE, Ovid EMBASE, andCochrane Central Register of Controlled Trials, were searched from database inception to 23 March 202323 March 2023. RESULTS: A total of 485 patients treated with corticosteroids from 7 RCTs were included. Compared to placebo, corticosteroids therapy failed to significantly improve the maternal outcomes regard to maternal morbidity (RR = 1.36, 95%CI [0.45, 4.10]), eclampsia (RR = 1.16, 95%CI [0.76, 1.77]), acute renal failure (RR = 0.71, 95%CI [0.41, 1.22]), pulmonary edema (RR = 0.34, 95%CI [0.10, 1.15]) and oliguria (RR = 1.08, 95%CI [0.75, 1.54]). In addition, pooled data showed that it wasn't significant differences between corticosteroids therapy and placebo regarding neonatal outcomes. CONCLUSIONS: This study compared the efficacy of corticosteroids in patients with HELLP syndrome, revealing that corticosteroids did not provide any significant benefit in clinical outcomes for pregnant women and newborns with HELLP. The conclusions of this study must be verified by a larger sample of high-quality RCTs.

Immunosuppressive therapy with tacrolimus is a potential drug candidate for the prevention of unexplained or preeclamptic stillbirths with Th1-dominant immune states: a case series of five patients.

Some of obstetrical complications such as unexplained pregnancy loss and preeclampsia (PE) are associated with maternal-fetal immune abnormalities, leading to uteroplacental dysfunction, insufficient fetal immune tolerance, or fetal rejection. Immunosuppressants with calcineurin inhibitors could be useful for the prevention of these complications by modulating the cellular immune balance by directly inhibiting activated T-helper (Th) 1 and natural killer (NK)/NKT cells. We present our experience with the immunosuppressant tacrolimus in five pregnant women who had a previous pregnancy history of unexplained or preeclamptic stillbirth. Th1 and Th2 cell populations and NK cell activities in peripheral blood were measured as clinical parameters during pregnancy. Case 1-3 achieved suppressions of predominant Th1 immunity and live births without pregnancy-related complications. In case 4, increased tacrolimus dose after a miscarriage resulted in her first live birth; however, she developed PE and severe fetal growth restriction with elevated Th1/Th2 cell ratios at 26 weeks of gestation. Case 5 had a previous history of early onset PE and the hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome, and an emergency cesarean section was needed for maternal safety at 20 weeks of gestation. The course of the next pregnancy was stable under tacrolimus treatment; however, the HELLP syndrome recurred after PE at 33 weeks of gestation. Although an imbalance in the Th1/Th2 cell ratio was not observed during pregnancy, NK cell activity was markedly elevated before delivery. In conclusion, tacrolimus is a potential drug candidate for the prevention of unexplained or preeclamptic stillbirth with Th1-dominant immune states.

Ruptured subcapsular liver hematoma as a rare complication of HELLP syndrome. A therapeutic challenge.

HELLP syndrome (HS), a low-incidence condition of uncertain pathogenesis associated with pregnancy hypertensive syndromes, is characterized by hemolysis, elevated liver enzymes and low platelet count. Ruptured subcapsular liver hematoma complicated with hemoperitoneum is an uncommon but very serious condition where early recognition and multidisciplinary management are key to reduce its associated maternal, infant mortality rate. Symptoms are nonspecific, characterized by por epigastric pain, nausea and vomiting; clinical suspicion and appropriate imaging studies are of crucial importance. We report the case of a 36-year-old primiparous woman at 39 weeks of gestation. She was admitted for early membrane rupture, with delivery complicated by retained placenta. During the immediate puerperium she had blood pressure > 140/90 mmHg, epigastric pain and vomiting, which required respiratory and hemodynamic support. An exploratory laparotomy was performed that revealed a massive hemoperitoneum as well as CR in the RLL with multifocal active bleeding. The left liver lobe was macroscopically normal. The patient underwent hemoperitoneum drainage and hepatic packing (HP); biopsy findings were consistent with necrosis. Polytransfusion was initiated with blood products and antihemorrhagic agents.

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.

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.

The Application of ROTEM in a Parturient With Antiphospholipid Syndrome in the Setting of Anticoagulation for Cesarean Delivery: A Case Report.

A 35-year-old parturient with antiphospholipid syndrome and a working diagnosis of hemolysis, elevated liver enzyme, and low platelets (HELLP) underwent a cesarean delivery 9 hours after receiving heparin. Her preoperative activated partial thromboplastin time and rotational thromboelastometry (ROTEM) intrinsic pathway (INTEM) clotting time were 120 and 1870 seconds, respectively. Fresh frozen plasma was administered for heparin neutralization. The ROTEM INTEM/heparinase assay (HEPTEM) ratio can help confirm heparin neutralization and guide intraoperative transfusion management.

Eculizumab Treatment for Postpartum HELLP Syndrome and aHUS-Case Report.

Preeclampsia is a pregnancy-specific disorder affecting ca 3% of all pregnant women. Preeclampsia is the source of severe pregnancy complications. Later life consequences for mother and infant include increased risk of cardiovascular disease. Preeclampsia is caused by the dysfunction of the endothelium with subsequent activation of complement and coagulation systems. HELLP syndrome is considered to be an extreme complication of preeclampsia but it can also present independently. Diagnostic symptoms in HELLP syndrome are Hemolysis, Elevated Liver enzymes, and Low Platelets. Similar phenotype is present in thrombotic microangiopathies (TMAs) and HELLP syndrome is considered part of the TMA spectrum. Here, we present a case of severe preeclampsia and HELLP syndrome, which exacerbated rapidly and eventually led to need of intensive care, plasma exchange, and hemodialysis. The patient showed signs of hemolysis, disturbance in the coagulation, and organ damage in liver and kidneys. After comprehensive laboratory testing and supportive care, the symptoms did not subside and treatment with complement C5 inhibitor eculizumab was started. Thereafter, the patient started to recover. The patient had pregnancy-induced aHUS. Earlier initiation of eculizumab treatment may potentially shorten and mitigate the disease and hypothetically decrease future health risks of preeclamptic women.

Dexamethasone in HELLP syndrome: experience in Bolivia.

Objective: To demonstrate the utility of dexamethasone, used according to the criteria of the attending physician, in patients with HELLP syndrome.Methods: This cross-sectional study was conducted in patients with HELLP syndrome and was based on the daily, real-life management of HELLP syndrome. Patients who received dexamethasone had it administered immediately after giving birth at a dosage of 8 mg every 8 hours for 72 hours, for a total of 72 mg. The analysis was conducted between patients who received corticosteroids and those who did not, with complete or partial HELLP.Results: There were 97 women who suffered complications from HELLP syndrome, there were 43 (44.3%) received dexamethasone. The groups were comparable except for the initial platelet count because this was the criterion used to divide the groups. In addition, the group without corticosteroids comprised more patients with partial HELLP. The platelet count shows that on the third day was similar in both groups, following a difference of more than 40,000 at the beginning of the study. The average platelet increase was 27,448 in the group without corticosteroids and 88,408 in the corticosteroid group; p = .001.Conclusions: This study demonstrates that the administration of postpartum dexamethasone at a dosage of 8 mg every 8 hours for 72 hours in HELLP syndrome is associated with a significant increase in platelet count.

Managing pregnancy-associated clinical emergencies in systemic lupus erythematosus: a case-based approach.

Introduction: Systemic lupus erythematosus (SLE)-related thrombocytopenia during pregnancy and the postpartum period have been associated with adverse pregnancy outcomes and perinatal complications. In this case report, we present two SLE patients with thrombocytopenia emergencies secondary to HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome and thrombotic thrombocytopenic purpura (TTP).Areas covered: The first case involved a 26-year-old woman, G1P0 at 26 weeks gestation (GA), with high-titer antiphospholipid antibodies (aPL) (positive lupus anticoagulant, anti-beta 2 glycoprotein-1 (aß2GP1), anti-cardiolipin) and non-criteria aPL to phosphatidylserine/prothrombin complex and anti-domain 1 ß2GP1. This case highlights the risks associated with aPL in pregnancy, considers management issues relating to anticoagulation during pregnancy and highlights the importance of maintaining a high index of suspicion for diagnosis of HELLP in SLE patients. The second case was a 36-year-old female, G3P2 at 32 weeks GA, with class III lupus nephritis (LN) who developed severe pre-eclampsia, which included mild thrombocytopenia. This case illustrates the challenges in identifying and differentiating between three pregnancy emergencies that can be seen in SLE patients (pre-eclampsia, LN, and TTP) and presents the management of TTP in peripartum SLE.Expert opinion: These two cases remind us of the importance of timely diagnosis and management of thrombocytopenia in this population.

Diagnosis of HELLP Syndrome: A 10-Year Survey in a Perinatology Centre.

HELLP (Hemolysis, Elevated Liver enzymes, Low Platelet count) syndrome is a severe and rapidly progressing condition that requires distinct diagnostic considerations. The aim of this study was to evaluate the impact of the Mississippi triple-class system on the HELLP syndrome diagnosis, treatment, and outcomes in a perinatology centre during a 10-year period, and consider its effectiveness and necessity in everyday practice. A retrospective observational cohort study was carried out using the medical records of a tertiary perinatology centre with the diagnosis of HELLP syndrome from the period of time between 2005 and 2014. The patients who fit the HELLP syndrome diagnosis were grouped by the Mississippi triple-class system. The means of diagnosis and treatment outcomes within those groups were analysed statistically. There was insufficient statistical evidence of the blood pressure levels corresponding to the severity of patients' condition (p > 0.05 in all of the groups). The clinical presentation varied within all of the classes, and the only objective means of diagnosis and evaluation of progression of the condition were laboratory tests. Even though HELLP syndrome is considered a hypertensive multi-organ disorder of pregnancy, the level of hypertension does not correlate to the severity of the condition; hence, the diagnosis should be based on biochemical laboratory evidence. Vigilance in suspicion and the recognition of HELLP syndrome and appropriate treatment are essential in order to ensure better maternal and neonatal outcomes.

Delayed hemolysis, elevated liver enzymes, low platelet count syndrome in succession of switches of preventive anticoagulant treatment in a 41-year-old patient with a history of recurrent assisted implantation failures: a case report.

BACKGROUND: For the past decades the mean age of primiparae in Western societies is constantly increasing. At the same time, there is a growing demand for assisted reproductive technologies such as in vitro fertilization and intracytoplasmic sperm injection. Subsequently, a higher prevalence of pregnancy-associated diseases such as gestational hypertension and preeclampsia is observed. To improve pregnancy rates after in vitro fertilization/intracytoplasmic sperm injection and to reduce the risk of pregnancy-associated diseases with a cardiovascular pathophysiology, two anticoagulants are the focus of current research: low molecular weight heparin and acetylsalicylic acid (aspirin). CASE PRESENTATION: A 41-year-old white woman, gravida 3, para 0, received low molecular weight heparin to reduce the risk of abortion after five unsuccessful intracytoplasmic sperm injections and two miscarriages. She autonomously discontinued the medication with low molecular weight heparin at 12 weeks and 2 days of gestation and took aspirin instead until 24 weeks and 2 days of gestation as preeclampsia prophylaxis. However, the pregnancy ended with an urgent cesarean section at 27 weeks and 4 days of gestation due to a fast progressing hemolysis, elevated liver enzyme levels, and low blood platelet count syndrome, a potentially life-threatening variant of preeclampsia. CONCLUSION: Based on the current demographic trend toward late-in-life pregnancy it is mandatory to establish clear guidelines concerning preventive treatment options of preeclampsia for patients with risk factors. The establishment of a special first-trimester screening for these women should be discussed. Moreover, it is necessary to raise the awareness among physicians of these contemporary issues to guarantee the best possible medical care.

Eculizumab in pregnancy: a narrative overview.

Pregnancy can be a dangerous trigger for patients with paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), or hemolysis, elevated liver enzymes and low platelet (HELLP) syndrome. Due to the possibility of several serious complications, pregnancy is somewhat discouraged in the presence of the above diseases. Eculizumab is a humanized antibody that may dramatically change the clinical course of PNH, aHUS and HELLP syndrome. However, data on the safety of eculizumab in pregnancy are scarce. In this narrative overview, we summarize current evidence on the use of eculizumab during pregnancy in women with PNH, aHUS and HELLP syndrome. Eculizumab is not present in breast milk, and the levels observed in umbilical cord blood samples are not sufficient to affect the concentrations of complement in newborns. Therefore, eculizumab may be regarded as safe in pregnancy. Nonetheless, given that data on eculizumab in pregnancy are limited, it is not possible to completely exclude risks for both mother and fetus in treating PNH, aHUS and HELLP syndrome.

Effectiveness of high-dose glucocorticoids on hemolysis, elevating liver enzymes, and reducing platelets syndrome.

OBJECTIVE: To investigate the effectiveness of high-dose glucocorticoids on hemolysis, elevating liver enzymes, and reducing platelets (HELLP) syndrome. METHODS: A total of 151 patients with HELLP syndrome were analyzed and divided into two groups. Six subgroups of treatment and control groups were divided into three grades in accordance with the American Mississippi Diagnostic Criteria. RESULTS: There were no differences in general characteristics of the patients, primipara rate, minimum platelet recovery time, postpartum hemorrhage volume, postpartum hemorrhage rate, cumulative average of maternal damage, intensive care unit admission rate, perinatal mortality rate, and overall incidence rate of adverse outcomes in fetuses among the groups. The primipara rate in the control group of the third grade was significantly higher than that in the treatment group of the third grade. The treatment group of the second grade (88.7%) had a significantly higher preterm delivery rate than that in the control group of the second grade (66.7%). There were no differences in minimum hemoglobin, and maximum lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase levels among the groups and subgroups. CONCLUSION: High-dose glucocorticoids cannot significantly improve maternal and fetal prognoses and laboratory indices. However, our results might offer some clinical evidence for HELLP syndrome therapy.

Effects of high-dose dexamethasone in postpartum women with class 1 haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome.

This study was performed to investigate the effectiveness of dexamethasone in the management of postpartum women with class 1 haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome. This retrospective study was conducted on 18 women with class 1 HELLP syndrome at the Shiga University of Medical Science. They were divided into two groups: Group A comprised participants who did not receive dexamethasone, and Group B comprised participants that intravenously received dexamethasone. The main outcomes were the serum laboratory values, mortality and morbidity. The only significant difference between the two groups in baseline characteristics was the aspartate aminotransferase levels. The linear regression analysis showed a significant difference between the two groups in the recovery of platelet counts (p = .046) and aspartate aminotransferase (p = .009). These findings support the use of high-dose dexamethasone to promote recovery of the platelet counts and aspartate aminotransferase levels in postpartum women with class 1 HELLP syndrome. Impact statement What is already known on this subject? Haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome is one of the most dangerous complications that can occur during pregnancy and is considered a particularly serious variant of severe preeclampsia. Several clinical trials have been performed since 1994 because it was expected that corticosteroid therapy, primarily with dexamethasone, accelerates recovery after delivery. However, the effect of dexamethasone therapy on class 1 HELLP syndrome is unclear. What do the results of this study add? In this retrospective study, we demonstrated that dexamethasone administration significantly improved the recovery of the platelet count in postpartum women with class 1 HELLP syndrome, and did not increase the rate of maternal postpartum complications. What are the implications of these findings for clinical practice and/or further research? The use of high-dose dexamethasone in postpartum women with class 1 HELLP syndrome might be effective to promote recovery of the platelet count, and contributes a shorter duration of hospitalisation. Because the number of patients with class 1 HELLP syndrome is small, it is important to confirm these findings with well-designed multicentre prospective studies.

Preterm Labor Caused by Hemolysis, Elevated Liver Enzymes, Low Platelet Count (HELLP) Syndrome and Postpartum Infection Complicated with Actinomyces Species: A Case Report.

BACKGROUND Actinomyces species are normal flora of the upper respiratory, female genital, and gastrointestinal tract. Actinomyces species are generally considered to have a low virulence potential. Here we report one case of Actinomyces viscosus isolated from a neonatal blood culture as a consequence of extreme prematurity in the presence of HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome. CASE REPORT A 23-week gestational age female infant was born to a 32-year-old mother. The pregnancy was complicated by severe HELLP syndrome leading to cesarean section at 23-week gestation. The initial blood culture grew anaerobic gram-positive branching rods consistent with Actinomyces species. Due to patient instability, antibiotic was started and continued for a total of 13 days. On day of life 26, the reference laboratory identified the organism as A. viscosus by 16S ribosomal RNA. CONCLUSIONS In this case, Actinomyces species was a consequence of HELLP syndrome and consecutive extreme prematurity. Further research to look more closely at Actinomyces species isolated from neonatal blood culture will help to elucidate the true significance of these isolates.

Hypertensive Disorders in Pregnancy Current Practice Review.

BACKGROUND: Hypertensive disorders (preeclampsia, eclampsia, gestational hypertension, and chronic hypertension with superimposed preeclampsia) complicate 3-5% of all pregnancies and are a significant cause of maternal mortality and morbidity. Preeclampsia is a multi-system disorder characterised by new onset hypertension after the 20th week of pregnancy with proteinuria. Proteinuria is defined as 300 mg or more of protein in a 24-hour urine collection or a protein: creatinine ratio of 0.3 mg/dL using a spot urine specimen. Hypertensive disorders have a complex pathophysiology that results from abnormal placen- tation and a maternal response that develops into a clinicalsyndrome for which there is no single test or "cure". In high income countries, low rates of maternal mortality from hy- pertensive disease in pregnancy illustrate the importance of pregnant women being able to readily access antenatal care. CONCLUSION: There remains the need to develop evidence-based clinical guidelines for detection, prophylaxis and management worldwide.

Importance of correctly interpreting magnetic resonance imaging to diagnose posterior reversible encephalopathy syndrome associated with HELLP syndrome: a case report.

BACKGROUND: Severe haemolysis, elevated liver enzyme levels, and low platelet count (HELLP) syndrome in pregnancy are possible underlying trigger factors for posterior reversible encephalopathy syndrome (PRES). Magnetic resonance imaging (MRI) shows diffuse signal abnormalities involving the subcortical white matter in the parieto-occipital lobes. Although the diagnosis of RPES was clearly established by the distinctive reversibility of clinical and radiological abnormalities, it is difficult to distinguish from differential diagnosis. Thus, it is important to correctly interpret MRI. CASE PRESENTATION: We describe a case of HELLP syndrome with PRES. A 38-year-old pregnant woman was admitted to our hospital as an emergency case with a complaint of upper abdominal pain and headache at 29 weeks of pregnancy and the development of HELLP syndrome. An emergency caesarean section was immediately performed. After the operation, the patient received intravenous corticosteroids, and her blood pressure was controlled. Thereafter, she showed an altered mental status. MRI showed hypersignal intense lesions in the cortical and subcortical white matter in the occipital lobes, basal ganglia and callosal splenium in both the fluid-attenuated inversion recovery (FLAIR) sequence and apparent diffusion coefficient (ADC), but these lesions were not recognized in diffusion-weighted imaging (DWI). These images were suggestive of PRES. The patient was kept in the hospital and received the appropriate treatment, after which the patient's level of consciousness improved and all laboratory tests and imaging examinations returned normal. CONCLUSION: The MRI findings were useful for the prompt diagnosis of PRES, characterized by hypersignals in FLAIR and ADC, but not in DWI. Additionally, there was an "atypical" MRI appearance of basal ganglial and callosal splenial involvement in this case, which may mistakenly lead clinicians to diagnose other aetiologies than typical PRES. It is considered that vasogenic oedema is the main pathology of PRES according to the MRI image findings. MRI is the gold standard for diagnosing PRES because it can provide information about cerebral involvement earlier than CT; further, it can be a useful tool in the differential diagnosis. This technique facilitated the prompt diagnosis and treatment of the said patient, ultimately resulting in a good outcome.