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

Comparative Analysis Between Invalidated Biochemical Markers and the Well-established Markers of HELLP Syndrome

<i>Background</i>: The use of the well-established markers of the Hemolysis, Elevated Liver enzymes and Low Platelet (HELLP) syndrome is very limited in the resource-poor settings of the developing populations. This study aimed to compare the readily available but invalidated biochemical markers with the well-established markers of HELLP syndrome. <i>Methods</i>: This was a retrospective cross-sectional study conducted among women diagnosed with HELLP syndrome in the University of Port Harcourt Teaching Hospital (UPTH) from 2011 to 2020. Data of each eligible case was acquired from the laboratory and medical records using a well-structured template and analyzed by standardized protocols. <i>Results</i>: A total of 230 cases of HELLP syndrome was identified; 200 complete HELLP (cHELLP) and 30 partial HELLP (pHELLP) variants. The cHELLP variants presented at an older age, higher gestational age, and had higher plasma bilirubin (PB), lactate dehydrogenase (LDH), creatinine, and uric acid (UA) but lower albumin concentration compared to those with pHELLP variant (p<0.05). With worsening severity, there was an increasing trend of plasma creatinine and UA but a decreasing trend of albumin among the cHELLP variants (p<0.05). UA level exhibited the strongest positive correlation with PB, LDH, aspartate, and alanine aminotransferases and maintained the strongest negative correlation with platelet count among those with cHELLP variants (p<0.05). At a cut-off value of 1.5 mmol/L, plasma UA (AUC:0.968; 95%CI:0.913-1.000;p<0.001) level had the most robust ROC values compared to those of plasma creatinine and albumin among the cHELLP variants. <i>Conclusion</i>: From the foregoing, plasma UA should be considered as an adjunct marker of cHELLP syndrome. However, further studies are highly recommended to evaluate conclusions from this study.

APPROACHING PREGNANCY-ASSOCIATED THROMBOTIC MICROANGIOPATHIES IN THE FACE OF DIAGNOSTIC UNCERTAINTY

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Critical illness is infrequently encountered in pregnant patients though remains a prominent concern due to potential maternal and fetal morbidity and mortality. We report a case of a female in her second trimester with severe microangiopathic hemolytic anemia, thrombocytopenia, and end organ damage to highlight the emergent measures and multidisciplinary action necessary to avoid adverse outcomes when the ultimate diagnosis is not immediately clear. CASE PRESENTATION: A 26-year-old female, gravida 4, para 1, with a medical history of chronic kidney disease due to focal segmental glomerulosclerosis presented at 21 weeks and 2 days gestation with abdominal pain, nausea, and headaches. On initial evaluation the patient was found to have hypertensive emergency, acute kidney injury (AKI), acute liver injury, and intrauterine fetal demise. Within 48 hours of presentation the patient required transfusions for worsening thrombocytopenia and acute anemia with a markedly elevated lactate dehydrogenase (LDH), undetectable haptoglobin and 5% schistocytes. The patient underwent an urgent dilation and evacuation and plasma exchange (PE) for a suspected thrombotic microangiopathy (TMA). She was found to have normal level of ADAMTS13 ruling out thrombotic thrombocytopenic purpura (TTP) and PE was stopped. Cell counts and liver function gradually improved; however, the patient had progression of her AKI with a creatinine peak of 10.9mg/dL one week after initial presentation. Autoimmune and complement studies were obtained revealing a significant elevation in the alternative pathway BB complement level concerning for atypical hemolytic uremic syndrome (aHUS). A renal biopsy was obtained to confirm the presence of TMA. The patient had gradual improvement in renal function and was ultimately discharged with specialty follow up to review the biopsy and make definitive decisions on therapeutic management. Unfortunately the renal biopsy was non-diagnostic due to inadequate tissue sampling and the patient failed to return for outpatient appointments. DISCUSSION: Thrombotic microangiopathies are a rare and devastating group of disorders carrying high morbidity and mortality and pose a diagnostic challenge due to the overlapping clinical and laboratory findings. Pregnancy-specific conditions such as HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome must be differentiated from other causes of TMA including TTP and aHUS. Certain clinical features such as the degree of laboratory derangements and timing during pregnancy may suggest an etiology; however, definite diagnosis often takes several days. CONCLUSIONS: This case demonstrates the necessity for rapid intervention, such as PE for TTP and aHUS, as well as emergent delivery for HELLP Syndrome, even amidst relative diagnostic uncertainty as delay in therapy contributes to worse outcomes. Reference #1: Fakhouri F, Vercel C, Fremeaux-Bacchi V. Obstetric nephrology: AKI and thrombotic microangiopathies in pregnancy. Clin J Am Soc Nephrol. (2012) 7:2100–6. 10.2215/CJN.13121211. 10.2215/CJN.13121211 Reference #2: Gupta M, Feinberg B, Burwick R. Thrombotic microangiopathies of pregnancy: differential diagnosis. Pregnancy Hypertens. (2018) 12:29–34. 10.1016/j.preghy.2018.02.007 Reference #3: Pishko A, Levine L, Cines C, . Thrombocytopenia in pregnancy: diagnosis and approach to management. Blood Rev (2020) 40. 0.1016/j.blre.2019.100638 DISCLOSURES: No relevant relationships by Kelsey Black, source=Web Response No relevant relationships by Megan Conroy, source=Web Response No relevant relationships by Adam Shaver, source=Web Response

Placental abruption as a trigger of DIC in women with HELLP syndrome: a population-based study

Background Disseminated Intravascular Coagulation (DIC) is a life-threatening condition. Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) syndrome is one of the obstetrical syndromes mostly associated with DIC and thus, high rates of fatal complications. There is a lack of information regarding epidemiologic and clinical characteristics of women who developed HELLP syndrome with and without DIC. Additionally, until now, there is no adapted and widely accepted way to diagnose DIC among pregnant women presenting with HELLP syndrome, despite the evident maternal mortality linked to the disease. Objectives: (1) Address the gaps in knowledge regarding the prevalence, epidemiologic and clinical characteristics of women with HELLP syndrome who develop DIC; and (2) determine the risk factors for the development of DIC among women with HELLP syndrome. Study design This was a population-based retrospective cohort study, including all women who delivered at the Soroka University Medical Center between the years 2001–2017. The study population was divided into three groups: (1) comparison group (n = 207,266 deliveries); (2) HELLP syndrome without DIC (n = 320); (3) HELLP syndrome with DIC (n = 21). The diagnosis of DIC was based on the ICD-9 code as recorded in the obstetrical database of the Soroka University Medical Center. The coding is based on the diagnosis made by the attending physician during hospitalization. Results (1) The rate of HELLP syndrome in the study population was 0.16% (341/207,607), of them 6.16% (21/341) had DIC; (2) among patients with HELLP syndrome, those with DIC had a higher median gravidity and parity; (3) a higher rate of severe maternal morbidity including blood product transfusion, placental abruption, eclampsia, acute renal failure and maternal death was observed in those who had HELLP syndrome and DIC compared to those with HELLP syndrome without DIC and the comparison group (p-value <.001 for comparison among the three groups); (4) among women with HELLP syndrome, those with DIC had a longer median PT difference, higher serum creatinine and lower AST as well as ALT median concentrations than those without DIC; (5) patients with HELLP syndrome and DIC had a higher rate of stillbirth and postpartum death than patients in the other groups (p-value <.001 for comparison among the three groups); and (6) placental abruption was an independent risk factor for the development of DIC in women with HELLP syndrome (p-value <.001). Conclusions (1) Among women with HELLP syndrome, those who developed DIC had a higher rate of maternal and neonatal morbidity and mortality than those without DIC; and (2) placental abruption, but not abnormal liver function, was an independent risk factor for the development of DIC in women with HELLP syndrome.

The NLRP3 Inflammasome Role in the Pathogenesis of Pregnancy Induced Hypertension and Preeclampsia.

Pregnancy-induced hypertension and preeclampsia are associated with significant maternal and fetal mortality. A better understanding of these diseases, delineation of molecular pathomechanism, and efficient treatment development are some of the most urgent tasks in obstetrics and gynecology. Recent findings indicate the crucial role of inflammation in the development of hypertension and preeclampsia. Although the mechanism is very complex and needs further explanation, it appears that high levels of cholesterol, urate, and glucose activates NLRP3 inflammasome, which produces IL-1β, IL-18, and gasdermin D. Production of these proinflammatory chemokines is the beginning of a local and general inflammation, which results in sympathetic outflow, angiotensin II production, proteinuria, hemolysis, liver damage, immunothrombosis, and coagulopathy. The NLRP3 inflammasome is a critical complex in the mediation of the inflammatory response, which makes it crucial for the development of pregnancy-induced hypertension and preeclampsia, as well as its complications, such as placental abruption and HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Herein, the presented article delineates molecular mechanisms of these processes, indicating directions of future advance.

Comparing acute fatty liver of pregnancy from hemolysis, elevated liver enzymes, and low platelets syndrome

Acute fatty liver of pregnancy (AFLP) and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome are both associated with significant maternal and perinatal morbidity and mortality. Because of the overlap of several clinical and laboratory findings differentiation can sometimes be difficult. Both disorders have been of interest for more than 100 years, however they were not completely characterized until the early 1980s. It was not until the 1980s that AFLP and HELLP syndrome, and more specifically their clinical, laboratory, and pathologic findings, were further differentiated in the literature. More recently, the pathophysiologic mechanisms have been elucidated. In this review, we outline the similarities and differences in the clinical presentation, laboratory findings, maternal and perinatal outcomes, and clinical recovery for women diagnosed with these two syndromes. From our observations, we suggest that levels of fibrinogen, creatinine, cholesterol, and total bilirubin be used to assist with differentiating AFLP from HELLP syndrome upon admission in women presenting with either suspected disease. The rationale for identifying the specific conditions is that clinical consequences for recovery vary considerably. Specifically, AFLP is associated with significantly more hepatic and renal dysfunction as well as coagulopathy. Fortunately, both conditions can be managed with supportive measures with overall improved perinatal outcomes including morbidity and mortality.

Innate and Adaptive Immune Responses in HELLP Syndrome.

Innate and adaptive immune involvement in hemolysis, elevated liver enzymes and low platelet (HELLP) syndrome is an understudied field, although it is of high clinical importance. This syndrome implies a risk of serious morbidity and mortality to both the mother and the fetus during pregnancy. It was proposed that HELLP syndrome occurs in a circulatory inflammatory milieu, that might in turn participate in a complex interplay between the secreted inflammatory immunomodulators and immune cell surface receptors. Meanwhile, reported immune cell attenuation during HELLP may consequently lead to a prolonged immunoactivation and tissue damage. In this regard, learning more about the immune components of this syndrome should widen the understanding of the HELLP pathophysiology and eventually enable development of novel immune-based therapeutics. This review aims to summarize and discuss the recent and previous findings of the innate and adaptive immune responses during HELLP in order to update the current knowledge of the immune involvement in HELLP pathogenesis.

High-altitude residence alters blood-pressure course and increases hypertensive disorders of pregnancy

Objectives To determine whether the full spectrum of hypertensive disorders of pregnancy (HDP) – comprising gestational hypertension; preeclampsia with or without severe features; eclampsia; and Hemolysis, Elevated Liver enzymes, and Low Platelets (HELLP) Syndrome – is increased at high (≥2500 m, 8250 ft) compared with lower altitudes in Colorado independent of maternal background characteristics, and if so their relationship to neonatal well-being. Methods A retrospective cohort study was conducted using statewide birth-certificate data to compare the frequency of gestational hypertension, preeclampsia (with or without severe features), eclampsia, HELLP Syndrome, or all HDP combined in 617,958 Colorado women who lived at high vs. low altitude (<2500 m) and delivered during the 10-year period, 2007–2016. We also compared blood-pressure changes longitudinally during pregnancy and the frequency of HDP in 454 high (>2500 m)- vs. low (<1700 m)-altitude Colorado residents delivering in 2013 and 2014, and matched for maternal risk factors. Data were compared between altitudes using t-tests or chi-square, and by multiple or logistic regression analyses to adjust for risk factors and predict specific hypertensive or neonatal complications. Results Statewide, high-altitude residence increased the frequency of each HDP disorder separately or all combined by 33%. High-altitude women studied longitudinally also had more HDP accompanied by higher blood pressures throughout pregnancy. The frequency of low birth weight infants (<2500 g), 5-min Apgar scores <7, and NICU admissions were also greater at high than low altitudes statewide, with the latter being accounted for by the increased incidence of HDP. Conclusions Residence at high altitude constitutes a risk factor for HDP and recommends increased clinical surveillance. The increased incidence also makes high altitude a natural laboratory for evaluating the efficacy of predictive biomarkers or new therapies for HDP.

Diagnosis and management of pregnancies complicated by haemolysis, elevated liver enzymes and low platelets syndrome in the tertiary setting.

Haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome occurs in one to six per 1000 pregnancies; maternal death has been reported in 1-24% of cases. Vague presentation is common; hypertension and proteinuria which characterise pre eclampsia are often absent when HELLP syndrome presents. Physicians are often called on to review gravid patients with unexplained symptoms or abnormal laboratory results, and it is vital that these clinicians are aware of the myriad of ways in which HELLP syndrome may present and evolve. To describe the natural history of HELLP syndrome by providing contemporary data from our 8-year experience at The Royal Women's Hospital in Melbourne. A retrospective analysis of the clinical and biochemical changes presentation, natural history and outcomes for 43 women whose delivery was complicated by HELLP syndrome according to Sibai criteria. There were two stillbirths and no neonatal or maternal deaths. Most (79%) women delivered by caesarean section. Fourteen per cent were asymptomatic at diagnosis; epigastric pain was the most common presenting symptom. Hypertension was absent at presentation for more than one-third of patients. Laboratory tests showed improvement after delivery, with platelet count showing most rapid recovery postpartum. Misdiagnosis and delayed recognition of HELLP syndrome are common due to vague and varying presentation. When HELLP syndrome is identified delivery is required to avoid catastrophic maternal and neonatal outcomes. We hope to provide guidance for general and obstetric physicians by providing contemporary evidence of the presentation and clinical course of pregnancies complicated by HELLP syndrome.

Transfer of Hemolysis, Elevated Liver Enzymes, and Low Platelets Syndrome by a Liver Graft From a Pregnant Female Donor to a Male Recipient: A Case Report

Eclampsia with hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome is a rare complication of pregnancy. HELLP syndrome may occur up to a week postpartum in women with eclampsia. Case reportWe report a case of liver transplantation with the organ procured from a pregnant (gestation week 28) female donor who suffered brain death after cerebellar hemorrhage owing to eclampsia. Liver function tests were normal at the time of liver procurement. The liver graft was matched to a 62-year-old man with primary sclerosing cholangitis. On day 7 after an uneventful transplantation, the recipient presented with increased aminotransferases and severe thrombocytopenia. The recipient also developed hypertension and hyperthermia and a clinical picture of HELLP syndrome. The patient underwent emergency liver retransplantation on day 12 after the first transplantation. Intraoperatively, massive necrosis of the liver graft with diffuse subcapsular hematomas was seen. ConclusionsIt appears that in our case, HELLP syndrome was transferred to and occurred in a male recipient. Eclampsia in the donor without overt HELLP syndrome may persist and be transferred by liver graft, developing into HELLP syndrome even in a male recipient. Therefore, liver grafts from female donors with eclampsia should be used with caution. Emergency retransplantation may be necessary.

Multivitamin use and risk of preeclampsia in a high-income population: A cohort study

ObjectiveThe objective of this study was to examine the association between multivitamin use in the periconceptional period and the risk of preeclampsia. Study designThe association was investigated in a prospective cohort study. 15,154 deliveries in women followed at a large university hospital in Denmark were included between 16 September 2012 and 31 October 2016. Pregnant women were sent a questionnaire containing items related to socio-demographic-, lifestyle- and health factors. The responses on multivitamin use were merged with the preeclampsia diagnosis from the Danish Medical Birth Registry. We used multiple logistic regression analyses to assess the association and to adjust for potential confounders. Main outcome measuresThe outcome of interest, preeclampsia, included the preeclampsia subtypes eclampsia and HELLP (Haemolysis, Elevated Liver enzymes, and Low Platelets) syndrome. ResultsIn total 12,954 women (85%) reported multivitamin use. A diagnosis of preeclampsia was found in 397 women (2.6%). We found a similar risk of preeclampsia in multivitamin user and non-users, adjusted odds ratio (AOR) for periconceptional multivitamin use = 0.97 (95% CI: 0.70 to 1.36) and AOR for early pregnancy multivitamin use = 0.97 (95% CI: 0.71 to 1.32). Subgroup analyses stratified on body mass index showed that among women with overweight, both periconceptional and early pregnancy multivitamin use were associated with a statistically significant lower risk of preeclampsia (AOR = 0.49, 95% CI: 0.24 to 0.99 and AOR = 0.35, 95% CI: 0.18 to 0.69, respectively). ConclusionPericonceptional- and early pregnancy multivitamin use was found to be associated with a similar risk of preeclampsia compared to non-users.

Hepatic Complications in Preeclampsia.

In cases of preeclampsia with severe features and hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome, hepatic complications portend significant short-term and long-term maternal health implications. In this section, we will discuss the physiology of normal hepatic function in pregnancy, the pathophysiology of the abnormalities noted in hepatic function during the process of preeclampsia development, the diagnosis and management of preeclampsia, imitators of HELLP syndrome, the utility of various biomarkers in the diagnosis and prognosis of the preeclampsia disease spectrum, possible underlying genetic factors predisposing women to developing hepatic abnormalities with preeclampsia, and finally prognosis and management of a subcapsular hematoma.

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

ABSTRACTIntroduction: 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 (aβ2GP1), anti-cardiolipin) and non-criteria aPL to phosphatidylserine/prothrombin complex and anti-domain 1 β2GP1. 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.

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.

Frequency of Various Bleeding Disorders Among Gynecological and Obstetric Patients Presenting with Bleeding

Introduction: Bleeding issues specific to women and adolescent females are common across the world. These issues can present either due to gynecological causes or obstetric one; however these can result in significant morbidity and work up needs to be done to rule out any underlying bleeding diathesis. Aims &amp; Objectives: To determine frequency of various bleeding disorders among gynecological and obstetric patients presenting with bleeding. Place and duration of study: It is a cross sectional study which was conducted in the Hematology Department, Services Institute of Medical Sciences, Lahore. The duration of study was 6 months i.e from 21st Oct, 2018 to 30th April, 2019. Material &amp; Methods: Females with age range of 15 to 50 years irrespective of pregnancy presenting as menorrhagia, metrorrhagia or obstetrical bleeding were included. Results: In the present study there were total 140 cases with mean age of 30.14±9.59 years. There were 98 (70%) cases that were pregnant. There were 35 (25%) cases presented with PPH (Post Partum Hemorrhage), 42 (30%) with IPH (Intra Partum Hemorrhage), 49 (35%) with menorrhagia and 14 (10%) with metrorrhagia. HELLP (Hemolysis, Elevated Liver enzymes and Low Platelet count) syndrome was seen in 13 (9.29%) cases, DIC (Disseminated Intravascular Coagulation) in 2 (1.43%), gestational thrombocytopenia in 7 (5%), while factor deficiency in 34 (24.29%) cases; and 84 (60%) of cases revealed none of the bleeding disorder. Out of total 34 cases of factor deficiencies, vWD was the most common, seen in 20 (58.82%) cases. There was none of the cases seen having deficiency of factor II, VII, VIII, XI, XII. HELLP syndrome was seen in 11 (84.62%) of the cases with age group 15 to 32 years and similarly both cases of DIC were seen in same age group; but the difference in both the age groups regarding these bleeding disorders was not statistically significant with p= 0.38. There was no significant difference in terms of pregnancy; however, both cases of DIC were seen in pregnancy with insignificant p value of 0.51. HELLP syndrome was more seen in IPH affecting 5 (38.40%), factor deficiency in menorrhagia affecting 13 (38.2%) with p value of 0.61. vWD and factor V Leiden presented in 44.4% cases each with PPH, and vWD affected 87.5% of cases in IPH without any significant difference with p= 0.42. Conclusion: Bleeding disorders are not uncommon in gynecological and obstetric conditions. Factor deficiency were the most common causes and amongst these vWD was the most deficient factor. There was no significant association with any confounding variable; however, DIC was only seen in obstetrical conditions. Key words: Bleeding, menorrhagia, HELLP, DIC, IPH, PPH

HOspital care versus TELemonitoring in high-risk pregnancy (HOTEL): study protocol for a multicentre non-inferiority randomised controlled trial

IntroductionPregnant women faced with complications of pregnancy often require long-term hospital admission for maternal and/or fetal monitoring. Antenatal admissions cause a burden to patients as well as hospital resources and...

A case of immune thrombocytopenic purpura complicated by HELLP syndrome

The combination of immune thrombocytopenic purpura and haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome is rare, with only two previous case reports published. Management of the two conditions is vastly different, and the diagnosis of HELLP syndrome superimposed on immune thrombocytopenic purpura may be difficult, resulting in delayed management.

Placenta derived factors involved in the pathogenesis of the liver in the syndrome of haemolysis, elevated liver enzymes and low platelets (HELLP): A review.

With this review we try to unravel if placenta-derived factors are able to initiate liver sinusoidal endothelial cells (LSEC) decay in HELLP syndrome and eventually cause the development of sinusoidal obstruction syndrome (SOS). Haemolysis, Elevated Liver enzymes and Low Platelets (HELLP) syndrome is a severe complication of pregnancy. It is characterized by elevated liver enzymes, low platelet count and haemolytic anaemia. The risk of developing HELLP syndrome within a pregnancy is 0.1-0.8%. The mortality rate among women with HELLP syndrome is 0-24% and the perinatal death goes up to 37%. The aetiology of HELLP syndrome is not fully understood but the pathogenesis of the liver pathology in the HELLP syndrome resembles that of a SOS with endothelial damage of the LSECs which ultimately leads to liver failure. We hypothesize that placenta derived factors cause LSEC damage and thereby liver dysfunction. We searched in the PubMed database for relevant articles about placenta derived factors involved in endothelial activation especially in the liver. We yielded eventually 55 relevant articles. Based on this literature search we associate that in HELLP syndrome there is an increase of soluble fms-like tyrosine kinase (sFlt1), vascular endothelial growth factor (VEGFR), soluble endoglin (sEng), galectin-1 (Gal-1), endothelin-1 (ET-1), Angiopoietin 2 (Angs-2), Asymmetric dimethylarginine (ADMA), activin B, inhibin A, Fas ligand (FasL) and heat shock protein 70 (Hsp70). We assume that these eleven increased placenta derived factors are responsible for LSEC damage which eventually leads to liver failure. This concept shows a possible design of the complicated pathophysiology in HELLP syndrome. However further research is required.

Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio and Complete Blood Count Components in the First Trimester Do Not Predict HELLP Syndrome.

Background and Objectives: Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), and other components of the routine complete blood count (CBC) were found to be sensitive biomarkers of preeclampsia and other inflammatory obstetric conditions in previous studies, with conflicting results. We speculated that the same associations existed with hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome in the first trimester of pregnancy. Materials and Methods: We conducted a retrospective case–control study at a tertiary care hospital in NY (USA), in the time frame between January 2016 and December 2018. Our population consisted of pregnant women in the first trimester: We compared patients with HELLP syndrome (cases) with healthy patients (controls) matched by age, body mass index (BMI), parity, and race. Patients with preeclampsia, infection, and fever were excluded. Venous blood samples were obtained as part of the routine work-up during the first prenatal visit in the first trimester, which includes a CBC. The main outcomes were NLR and PLR, and the secondary outcomes were hemoglobin, RDW, platelet count, MPV, neutrophils, and lymphocytes. Results: There were 10 patients in each group. There were no differences in NLR and PLR levels and other CBC components between the two groups. Conclusions: In our study NLR, PLR, and other CBC components did not predict HELLP syndrome. We speculate that HELLP syndrome has a sudden increase of tissue inflammation in the third trimester that is not manifested during the early phases of placentation. Larger studies are needed to evaluate the true ability of NLR, PLR, and CBC components to predict HELLP syndrome in the first trimester.

Elastic properties of ascending aorta and ventricular–arterial coupling in women with previous pregnancy complicated by HELLP syndrome

To compare the elastic properties of the ascending aorta and ventricular-arterial coupling (VAC) in women with a previous pregnancy complicated by hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, women who experienced preeclampsia, and healthy controls. Women with a history of preeclampsia (n = 60) or HELLP syndrome (n = 49) and matched healthy controls (n = 60) underwent transthoracic echocardiography at 6 months to 4 years after delivery. Aortic M-mode and tissue Doppler imaging (TDI) parameters were measured. Aortic diameters were assessed at end-diastole at four levels: Valsalva sinuses, sinotubular junction, tubular tract, and aortic arch. Aortic compliance, distensibility, stiffness index, Peterson's elastic modulus, pulse-wave velocity, and M-mode strain were calculated using standard formulae. Aortic expansion velocity, early and late diastolic retraction velocities, and peak systolic tissue strain (TDI-ε) were determined. VAC was defined as the ratio between aortic elastance (Ea) and left ventricular end-systolic elastance (Ees). All women were free from cardiovascular risk factors. Women with a history of HELLP syndrome showed larger aortas than those with previous preeclampsia or controls, probably related to a higher blood pressure. Aortic elastic properties, including Ea, were similar between HELLP and preeclampsia groups, even comparing cases with early-onset preeclampsia and HELLP. In contrast, Ees was more impaired in the HELLP group than in the other two. Consequently, about one-quarter of women who experienced HELLP syndrome had a pathological VAC, whereas only 5% of previously preeclamptic patients did. Multivariate analysis confirmed the association between HELLP syndrome and VAC, whereas other parameters including aortic compliance, distensibility, stiffness index, and elastic modulus are linked only to gestational age at preeclampsia onset, ad also Ea and Ees did. We found a significant overlap between the aortic elastic properties in women with a history of preeclampsia and those with a previous HELLP syndrome, suggesting a common pathophysiologic pathway. However, women who experienced HELLP syndrome showed a higher blood pressure than other cases and controls, probably determining larger aortas. In addition, VAC was more altered in the HELLP group than in the others because of a higher Ea and a lower Ees.

Maternal-Fetal Outcomes of Pregnancies with Thrombocytopenia-One Center Experience

Objective: To investigate the etiology, obstetric risk factors, complications, and outcomes of pregnancies affected by thrombocytopenia. Material and Methods: A retrospective surveillance study was conducted based on the hospital records of 1286 women that gave birth during the period between 1st January 2017 and 31st December 2018 at the Department of Gynecology and Obstetrics of the Trakya University's School of Medicine. Clinical data including basic history, physical examination, and investigations of women with thrombocytopenia were evaluated. We randomly selected 154 patients without thrombocytopenia that delivered in our clinic during the same period, as the control group, and compared the maternal and fetal outcomes with the thrombocytopenic patient group. Results: A total of 154 out of 1286 women (11.9%) had thrombocytopenia of varying severity. Gestational thrombocytopenia (GT) was the most common cause, being identified in 76.2% of the cases with thrombocytopenia. This was followed by preeclampsia (15.5%). About 4.5% of pregnant women with thrombocytopenia were accounted for by idiopathic thrombocytopenic purpura (ITP), 2.5% of the patients by eclampsia, while HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome was observed in 1.3% of the pregnant women with thrombocytopenia. An increased rate of IUGR (Intrauterine growth restriction), fetal distress, and adverse neonatal outcomes were recorded among patients that had thrombocytopenia with preeclampsia, eclampsia, and HELLP syndrome. Furthermore, we observed higher rates of fetal distress and adverse neonatal outcomes in patients with thrombocytopenia compared to the control group. Conclusion: GT was the most common cause of thrombocytopenia in pregnancy, followed by preeclampsia. Eclampsia, HELLP syndrome, and ITP were rare causes of this disorder during pregnancy. Early detection and treatment of expected complications are critical for the effective management of such cases.