Hemolysis, Elevated Liver Enzymes, Low Platelets Syndrome Research Articles

ORIGINAL ARTICLE: Distribution and Maturity of Dendritic Cells in Diseases of Insufficient Placentation

Problem The immunological equilibrium at the feto‐maternal interphase contributes towards late gestational diseases like growth restriction (IUGR) pre‐eclampsia (PE) and hemolysis, elevated liver enzymes, low platelets (HELLP)‐syndrome. The state of activation of decidual dendritic cells (DC) has emerged as one of the central players influencing this immunological equilibrium.Method of study Paraffin‐embedded tissue sections from 27 pregnancies were immunostained for DC markers DEC‐205, DC‐SIGN, DC‐LAMP and costained for DC‐SIGN/CD56 and DC‐SIGN/ vascular endothelial growth factor receptor (VEGFR) ‐1 and ‐2. We investigated placental tissue of IUGR fetuses and of patients who developed PE or HELLP‐syndrome as well as placental tissue derived from normal pregnancies.Results We found that expression of DEC‐205 and DC‐SIGN was significantly upregulated in HELLP placentas, whereas expression of DC‐LAMP was abrogated almost entirely. Costaining showed an interaction between DC‐SIGN+ DC and natural killer cells as well as costaining of VEGFR‐1 and ‐2 and DC‐SIGN. Pre‐eclamptic and IUGR placentas showed no significant change in any of the investigated markers compared to normal controls.Conclusion Our data suggest a participation of DC‐mediated immunological mechanisms in HELLP syndrome.

Maternal factor V Leiden mutation is associated with HELLP syndrome in Caucasian women

There is growing evidence that hypertensive pregnancy complications and other adverse pregnancy outcomes are associated with the presence of inherited or acquired thrombophilias. As hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome is one of the most severe forms of pre-eclampsia we aimed to assess the prevalence of the factor V Leiden, the prothrombin 20210G >A mutation and the methylenetetrahydrofolate reductase (MTHFR) 677C >T polymorphism in women with HELLP syndrome and in their fetuses from the same index pregnancy. The study was performed retrospectively in a case-control design. Seventy-one mother-child pairs with HELLP syndrome and 79 control mother-child pairs with uncomplicated pregnancies were included in the study. Genotyping of the three thrombophilic mutations was performed using the LightCycler technology. The chi-squared test was used for statistical analysis. Main outcome measures were maternal and fetal genotypes and their correlation with clinical parameters. Maternal heterozygosity for factor V Leiden was significantly more prevalent in the HELLP group than in controls (OR 4.45, 95% CI 1.31-15.31). No significant association was observed for maternal prothrombin mutation or MTHFR polymorphism (p=0.894, p=0.189, respectively). The fetal genotype was not associated with HELLP syndrome for any of the three mutations investigated. Analysis of gene-gene interactions and genotype-phenotype correlation with respect to clinical parameters and perinatal outcome revealed no further differences. Our study confirms that women heterozygous for factor V Leiden have an increased risk of developing HELLP syndrome, while the most frequent mutations of the prothrombin and MTHFR gene do not play a major role in the pathogenesis of HELLP syndrome.

The Hematologic Manifestations of the Antiphospholipid Syndrome

Various hematological pathologies have been described in association with antiphospholipid syndrome (APS). Thrombocytopenia is frequently found in APS patients, its incidence has ranged from 22-42% in different series, it is usually moderate (>50x10(9)/L) without clinical manifestation and requires no intervention. A high percentage of patients with isolated idiopathic thrombocytopenic purpura have antiphospholipid antibodies, however the pathogenetic role and the clinical importance of these antibodies in this condition is still not clear. Other hematological manifestations reported in association with APS include: bone marrow necrosis, and various thrombotic microangiopathic syndromes such as: thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, HELLP (hemolysis, elevated liver enzymes, low platelet) syndrome, and catastrophic APS. A high index of suspicion is needed for the early recognition and treatment of these conditions.

Liver diseases unique to pregnancy

The aim of this review article is to improve knowledge of the liver disease in pregnancy. The article summarizes the results of own experience and the recent reviews of liver disorders unique to pregnancy. Abnormalities in liver tests occur in 3% of pregnancies with causes ranging from self-limiting to rapidly fatal. In Kaunas University of Medicine Hospital, a retrospective analysis disclosed a rate of 0.52% of liver diseases in 16252 pregnant women over a 5-year period. Several liver diseases occur only during pregnancy and are considered to be associated with the pregnant state. The liver disorders unique to pregnancy have characteristic clinical features and timing of onset. Hyperemesis gravidarum occurs in the first trimester, intrahepatic cholestasis of pregnancy in the second or third trimester, preeclampsia, HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome, and acute fatty liver of pregnancy usually in the third trimester. The disorders of late pregnancy - preeclampsia, HELLP syndrome, and acute fatty liver of pregnancy - may progress to severe liver dysfunction. The correct diagnosis is critical, as any delay can result in morbidity or mortality of both the mother and fetus. Early delivery and advances in supportive management are the only available option for improving the prognosis.

Oxidative Stress and Proinflammatory Cytokine Levels are Increased in Premature Neonates of Preeclamptic Mothers with HELLP Syndrome

Background: Respiratory distress syndrome (RDS) incidence is increased in infants of preeclamptic mothers with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. RDS and HELLP syndrome have been associated with oxidative stress and inflammatory processes. Objectives: We hypothesize that end-tidal carbon monoxide corrected for inhaled CO (ETCOc), malondialdehyde (MDA) (markers of oxidative stress) and proinflammatory cytokine (IL-6, IL-8) production are higher in infants of preeclamptic mothers with HELLP syndrome than in those of preeclamptic mothers without HELLP syndrome. Methods: Prospective study of 36 infants of preeclamptic mothers (GA <32 weeks) admitted to the Neonatal Intensive Care Unit. ETCOc was measured at 0–12, 48–72 and 168 h postnatally using the CO-Stat™ End-Tidal Breath Analyzer. Simultaneously, blood was sampled for MDA, IL-8 and IL-6. Results: At 0–12 h, ETCOc, MDA and IL-8 values (median[range]) were significantly higher in HELLP infants than in infants from preeclamptic mothers without HELLP (ETCOc 2.2 [1.5–3.9] vs. 1.8 [0.5–2.9] ppm; MDA 2.3 [1.3–4.1] vs. 1.5 [0.4–3.1] µmol/l; IL-8 145 [24–606] vs. 62 [26–397] pg/ml; all p <0.05). MDA remained significantly higher during the first 168 h of life (2.3 [0.8–5.8] vs. 1.1 [0.8–3.7] µmol/l, p = 0.02). Conclusion: Oxidative stress and proinflammatory cytokine levels are increased in infants of preeclamptic mothers with HELLP syndrome. These processes may cause inactivation of surfactant explaining the increased RDS incidence in these infants.

Atypical case of reversible posterior leucoencephalopathy syndrome associated with puerperal HELLP syndrome

Reversible posterior lekoencephalopathy syndrome (RPLS) is usually reversible. However, permanent cerebral damage may result if diagnosis is delayed. White matter edema in the posterior cerebral hemispheres is typical on neuroimaging. A 36-year-old primigravid woman underwent induction of labor due to mild pregnancy-induced hypertension. At 5 h after delivery, she developed eclampsia seizures complicated by hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. Magnetic resonance imaging showed high-density lesions in anterior regions without any abnormalities in posterior cerebral regions. Cases of postpartum RPLS without involvement of posterior brain regions after eclampsia complicated by HELLP syndrome are very rare. Patients with RPLS do not always show typical manifestations.

Lung maturation in small for gestational age fetuses from pregnancies complicated by placental insufficiency or maternal hypertension

Background Clinical studies suggest that respiratory outcome of infants born preterm may be influenced by placental insufficiency and hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. If so, one could expect to see differences in lung maturation indices (lecithin/sphingomyelin (L/S) ratio and lamellar body count (LBC)) in the amniotic fluid. The present study investigates lung maturation indices of preterm small for gestational age (SGA) fetuses with or without abnormal Doppler ultrasound examination and with or without maternal hypertension/HELLP syndrome. Study design Retrospective cohort study of 76 neonates born in our center between 1997 and 2003 with gestational age (GA) < 34 weeks, birth weight < p10 for GA and available results from amniocentesis. All analyses were corrected for potential confounders. Results The L/S ratio was significantly higher in the abnormal Doppler group as compared to the normal Doppler group ( p = 0.02). The L/S ratio was significantly lower in hypertensive pregnancies as compared to normotensive pregnancies ( p = 0.02). Subdivision of the maternal hypertension group showed a significantly lower L/S ratio in the HELLP syndrome group as compared to the normotension group ( p = 0.04). Conclusion The L/S ratio of SGA fetuses is significantly higher in cases with presumed placental insufficiency and significantly lower when pregnancies are complicated by HELLP syndrome. These observations are in line with the hypothesis that placental insufficiency accelerates lung maturation and with recent reports of poorer respiratory outcome in infants from mothers with HELLP syndrome.

The 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene is not associated with HELLP syndrome

Plasminogen activator inhibitor-1 (PAI-1) is a major inhibitor of fibrinolysis, and a single nucleotide insertion/deletion (4G/5G) polymorphism in the promoter region of the PAI-1 gene has been identified. Subjects homozygous for the 4G allele have the highest PAI-levels due to increased PAI-1 gene transcription. Pre-eclampsia, and one of its most severe forms, the HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome, are characterized by increased placental thrombosis based on a procoagulatory state in the mother. Several studies have investigated the role of the PAI-1 4G/5G polymorphism in pre-eclampsia, but no study has focused especially on HELLP syndrome. Therefore we aimed to assess the association between HELLP syndrome and the 4G/5G polymorphism in the PAI-1 gene. Genotyping of the PAI-1 4G/5G promoter polymorphism was performed in 102 Caucasian women with HELLP syndrome and 102 Caucasian women with uncomplicated pregnancies. The 4G/4G genotype was more frequent in women with HELLP syndrome than in controls (35.3% vs. 22.5%, respectively) but this difference was not significantly different (P = 0.129). The frequency of the 4G allele was 0.588 in patients and 0.515 in controls. These data suggest that women carrying a 4G/4G genotype of the PAI-1 gene are not at increased risk for developing HELLP syndrome and are thus in line with the majority of previous studies on the association between the PAI-1 4G/5G polymorphism and pre-eclampsia.

Maternal outcome in eclamptic patients in Abuja, Nigeria--a 5 year review.

To assess the outcome ofwomen admitted with eclampsia in the National Hospital, Abuja, Nigeria. A retrospective analysis. The medical records register in the accident and emergency department, labour ward, maternity ward and the intensive care unit were searched to identify cases of eclampsia admitted at the National Hospital,Abuja (NHA) between 1st March 2000 and 28th February 2005. The incidence of eclampsia was 7.8 per 1000 deliveries. Eclampsia significantly occured in nulliparous and unbooked mothers (p < 0.001 & p < 0.0001 respectively). Most (71.5%) of mothers delivered by Caesarean section and the most common indication for this was an unfavourable cervix (cervix thick, firm and closed when assessed at presentation in the labour ward). Nineteen (41.3%) of mothers developed complications with HELLP (hemolysis, elevated liver enzymes, low platelets) occurring in six patients (31.6%). There were 13 maternal deaths giving a case fatality rate of 28.3% and a maternal mortality ratio for eclampsia of222/100,000. HELLP syndrome was responsible for 46.2% of deaths in the study. The maternal outcome of eclamptics in Abuja, Nigeria is poor and HELLP syndrome is a major contributor to the high fatality rate. Emphasis should be on primary preventive measures such as early, continuous, good antenatal care and improvement of intensive care facilities. More widespread use of Magnesium sulphate for anticonvulsant prophylaxis is advocated.

Are Clinical Symptoms More Predictive Than Laboratory Parameters for Adverse Maternal Outcome in HELLP Syndrome?

Controversy continues about the diagnosis, management, and prognosis of HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome, in large part because of a lack of standardized diagnostic criteria. The investigators reviewed 61 pregnancies associated with HELLP syndrome that were diagnosed antenatally in the years 2003–2005. All participants had features of preeclampsia/eclampsia as well as evidence of hemolysis (a typical peripheral blood smear, a lactate dehydrogenase level of at least 600 IU/liter, or elevated indirect bilirubin), thrombocytopenia (a platelet count less than 150,000/mm3), and hepatic dysfunction (aspartate aminotransferase [AST] of at least 40 IU/liter and/or an alanine transaminase of 40 IU/liter or greater). The overall incidence of adverse maternal outcomes in this series was 73%. Three women, 5% of the total, died of intracranial bleeding or disseminated intravascular coagulation (DIC). About half the women had eclampsia, and nearly 60% of them had an eclamptic seizure before hospital admission. Compared to women without seizures, eclamptic women had significantly higher rates of headache, visual changes, epigastric pain, and nausea and vomiting. Women whose platelet counts were less than 50,000/mm3 were nearly 4-fold likelier to have eclampsia, but this was not a statistically significant association. Abruption occurred in 7 (11%), acute renal failure in 9 (15%), and DIC in 5 (8%), but neither laboratory nor clinical abnormalities distinguished between women with and those without these complications. The transfusion rate was significantly increased in women whose platelet counts were 50,000/mm3 or less. Adverse outcomes were similar in women whose peak AST was more or less than 150 U/liter. In this population of women diagnosed with HELLP syndrome before delivery, clinical symptoms predicted adverse maternal outcomes more accurately than did abnormal laboratory findings.

Urinary Podocyte Excretion as a Marker for Preeclampsia

The proteinuria of preeclampsia is associated with glomerular endotheliosis, and a role for damaged and lost podocytes (glomerular epithelial cells) in the development of proteinuria has received support from studies of patients with glomerular diseases. This study asked whether urinary excretion of viable podocytes, quantified by the expression of podocin and other podocyte-specific proteins, is observed in pregnant women with clinically confirmed preeclampsia. In addition, levels of angiogenic factors implicated in the pathogenesis of preeclampsia were estimated. They included soluble receptor for vascular endothelial growth factor, also called fms-like tyrosine kinase receptor-1 (sFlt-1); placental growth factor (PIGF); and serum soluble endoglin. The cross-sectional study recruited 33 pregnant women with preeclampsia, 11 with HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome, and 23 normotensive pregnant women. All of the 15 preeclamptic women evaluated and also those with HELLP syndrome, but not normotensive control subjects, had podocin-positive cells in their urine. Podocyturia was 100% sensitive and 100% specific for the diagnosis of preeclampsia, and the degree of proteinuria correlated positively with podocyturia. The positive predictive value of urinary podocyte excretion for the presence of preeclampsia was greater than that of sFlt-1, PIGF, or endoglin. Nevertheless, serum levels of sFlt-1 were significantly higher in women with preeclampsia or HELLP syndrome than in normotensive control women, and the same was the case for serum levels of soluble endoglin. Women with preeclampsia or HELLP syndrome had lower serum levels of free PlGF than did normotensive pregnant women. Urine levels of PlGF did not differ from those in normal women. Podocyturia is a very sensitive and specific marker for preeclampsia, and it may contribute to the development of proteinuria in affected women. Further studies may clarify the effects of dysregulated vascular endothelial growth factor on mechanisms regulating podocyte attachment.

HELLP Syndrome

The occurrence of hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome before 20 weeks of gestation is extremely rare. This condition has been reported in only few cases, and always in conjunction with other comorbidities such as fetal triploidy and the antiphospholipid syndrome. A 24-year-old woman was admitted at 15 weeks and 3 days of gestation with uncontrollable hypertension and proteinuria. An extensive workup did not reveal any underlying medical or obstetric conditions. Within 11 days of admission her condition deteriorated and the diagnosis of severe HELLP syndrome was supported by the findings of hemolysis, elevated liver enzymes, and severe thrombocytopenia, all of which resolved after termination of the pregnancy. Clinicians should consider the diagnosis of HELLP syndrome in women presenting with clinical manifestations or laboratory abnormalities consistent with this diagnosis, even before 20 weeks of gestation.

Purtscher-like Retinopathy in a Patient with HELLP Syndrome

To report the antepartum presentation of Purtscher-like retinopathy and hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome that resulted in severe permanent visual loss. Interventional case report. A 25-year-old primigravida patient at 38.5 weeks gestation presented with severe bilateral loss of vision. Immediate hospitalization with complete evaluation, urgent medical treatment, and cesarean section was performed. Ophthalmoscopic evaluation showed bilateral Purtscher-like retinopathy. Laboratory studies revealed elevated liver enzymes, thrombocytopenia, and evidence of intravascular coagulation consistent with HELLP syndrome. Despite the successful delivery of a healthy baby, the patient developed permanent visual loss. Purtscher-like retinopathy with permanent visual loss can occur antepartum in patients with HELLP syndrome.

Maternal Plasma Concentrations of Soluble Endoglin in Pregnancies with Intrauterine Growth Restriction

Soluble endoglin (sEng), a coreceptor for TGF with antiangiogenic properties, acts synergistically with soluble fms-like tyrosine kinase 1 (sFlt1) to induce symptoms of HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome in animal models and to promote a preeclamptic phenotype. Pregnant women with preeclampsia show increased sEng concentrations in circulation, whereas the sEng increase is detectable months before the clinical onset of the disease. The aim of the study was to determine whether maternal sEng is altered in pregnancies with normotensive intrauterine growth restriction (IUGR). sEng and sFlt1 were retrospectively determined by a commercial ELISA. The study included 11 normotensive pregnancies with IUGR, 18 pregnancies with manifest preeclampsia, and 15 gestational-age-matched controls. Patients with preeclampsia showed significantly higher sEng concentrations compared with controls (57.0 ng/ml vs. 5.3 ng/ml; P < 0.001). Also IUGR pregnancies showed significantly elevated sEng concentrations (25.9 ng/ml; P < 0.001), but the levels were lower compared with the preeclamptic patients. There was a strong positive correlation between the sEng and sFlt1 concentration (Pearson 0.552; P < 0.01). Similar to sEng, the maternal sFlt1 concentration is highest in the preeclamptic patients (8388 vs. 2602 pg/ml; P < 0.01) but also significantly elevated in the IUGR patients (6952 pg/ml; P < 0.01). Pregnancy with IUGR, but without maternal symptoms, was characterized by elevated sEng concentrations in circulation. Although this finding is less pronounced when compared with preeclampsia, sEng seems to be involved in different clinical manifestations of placental pathology.

Respiratory outcome in preterm small for gestational age fetuses with or without abnormal umbilical artery Doppler and/or maternal hypertension

Objective. To study respiratory outcome in preterm small for gestational age (SGA) fetuses with or without signs of intrauterine growth restriction due to placental insufficiency, and with or without maternal hypertension.Methods. This was a retrospective study of 187 neonates with birth weight <10th percentile and gestational age <34 weeks. Results from umbilical artery Doppler velocimetry were used to identify the abnormal Doppler subgroup.Results. No significant difference in respiratory outcome between SGA fetuses with normal (SGA-N) or abnormal (SGA-A) umbilical artery Doppler examination was found. Within the SGA-A group, the respiratory distress syndrome (RDS) incidence (OR 5.6, 95% CI 1.7–18.3), RDS grade (OR 6.7, 95% CI 1.2–38.5), and need for surfactant (OR 5.3, 95% CI 1.1–24.4) were higher in infants of women with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome as compared to those of normotensive mothers.Conclusions. Lung maturation is not accelerated with placental insufficiency. SGA-A fetuses of mothers with HELLP syndrome have a significantly poorer respiratory outcome than those with healthy mothers. Possibly, fetuses of mothers with HELLP syndrome are subjected to ‘oxidative stress’ causing lung damage rather than lung maturation.

Oral N-acetylcysteine Administration Does Not Stabilize the Process of Established Severe Preeclampsia

Numerous disorders, including adult respiratory distress syndrome and AIDS, are associated with a deficiency of glutathione, an intracellular antioxidant. Because N-acetylcysteine is a precursor of glutathione as well as a direct radical scavenger, and because preeclampsia is associated with decreased levels of several antioxidants, a randomized, double-blind, placebo-controlled trial of orally administered N-acetylcysteine was undertaken in women with severe, early-onset preeclampsia and/or HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome. Severe preeclampsia was defined as a diastolic blood pressure of 110 mm Hg or higher with proteinuria of at least 0.3 g/L. Half of the 38 women admitted to the study received 3 effervescent tablets containing 600 mg N-acetylcysteine every 8 hours, whereas the others received placebo tablets. The median interval from treatment to delivery was 6 days in the women given N-acetylcysteine and 5 days in placebo recipients, not a significant difference. The treatment group had stable maternal plasma N-acetylcysteine levels of 20 μmol/L. Whole blood and plasma levels of glutathione and other thiols were unaffected in actively treated women except for lower plasma homocysteine levels. Gestational age at delivery did not differ significantly between the 2 groups. A majority of women in both groups underwent operative delivery because of the mother's worsening condition or fetal distress. Women in the 2 groups had comparable numbers of complications. Approximately one third of those in each group reported side effects. Rates of neonatal morbidity and mortality did not differ in the 2 groups. The investigators conclude that oral treatment with N-acetylcysteine does not improve either maternal or neonatal outcomes in cases of severe preeclampsia and/or HELLP syndrome. It remains possible, however, that earlier treatment might confer benefit.

Thrombotic Thrombocytopenic Purpura Masquerading as Hemolysis, Elevated Liver Enzymes, Low Platelets (HELLP) Syndrome in Late Pregnancy

Thrombotic thrombocytopenic purpura rarely presents during late pregnancy or immediately postpartum. This report describes the clinical course of a patient considered to have hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome but later determined to have thrombotic thrombocytopenic purpura. At 37 weeks of gestation, a multiparous woman was diagnosed with HELLP syndrome. She received high-dose dexamethasone, magnesium, antihypertensives, and platelets before delivery. Over the next 36 hours, renal function acutely worsened and death ensued. One week after death a plasma ADAMTS13 activity of 4% was reported. Thrombotic thrombocytopenic purpura can mimic HELLP syndrome late in gestation. Lack of response to dexamethasone within 12-24 hours and atypical relationships among laboratory values are two clues that thrombotic thrombocytopenic purpura may be the underlying pathology and that plasma exchange is emergently needed.

Soluble endoglin contributes to the pathogenesis of preeclampsia

Preeclampsia is a pregnancy-specific hypertensive syndrome that causes substantial maternal and fetal morbidity and mortality. Maternal endothelial dysfunction mediated by excess placenta-derived soluble VEGF receptor 1 (sVEGFR1 or sFlt1) is emerging as a prominent component in disease pathogenesis. We report a novel placenta-derived soluble TGF-beta coreceptor, endoglin (sEng), which is elevated in the sera of preeclamptic individuals, correlates with disease severity and falls after delivery. sEng inhibits formation of capillary tubes in vitro and induces vascular permeability and hypertension in vivo. Its effects in pregnant rats are amplified by coadministration of sFlt1, leading to severe preeclampsia including the HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome and restriction of fetal growth. sEng impairs binding of TGF-beta1 to its receptors and downstream signaling including effects on activation of eNOS and vasodilation, suggesting that sEng leads to dysregulated TGF-beta signaling in the vasculature. Our results suggest that sEng may act in concert with sFlt1 to induce severe preeclampsia.

Dexamethasone Treatment Does Not Improve the Outcome of Women With HELLP Syndrome: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial

One of the most serious presentations of preeclampsia is the HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome. Treatment has generally been limited to supportive measures and management of complications, but recent clinical trials—which were not double-blind or placebo-controlled—suggest that dexamethasone may stabilize the disorder and even improve it in the antepartum period, maximizing postpartum recovery. The present randomized, double-blind, placebo-controlled trial enrolled 132 women, 60 of them pregnant and 72 puerperal, who met criteria for complete HELLP syndrome. They were randomly assigned to a treatment or placebo group and in the former case received 10 mg dexamethasone intravenously at 12-hour intervals until delivery and three further doses after delivery. The puerperal women received three doses of dexamethasone. All women received, in addition, magnesium sulfate intravenously and, when needed, an antihypertensive agent, initially nifedipine and subsequently clonidine or amlodipine if necessary to lower the diastolic blood pressure. Hospital time was less for women given dexamethasone, although not to a significant degree. The treatment and placebo groups were similar in the time needed to reach a platelet count exceeding 100,000/mm3. There also was no difference in the proportion of women reaching a lactate dehydrogenase level less than 600 U/L before discharge. Treatment did not hasten recovery in patients with an aspartate aminotransferase level less than 70 U/L before discharge. Urine output was comparable in the treatment and control groups. Three of four maternal deaths were in steroid-treated women. No substantial differences were evident when pregnant and puerperal women were analyzed separately. These findings do not support using dexamethasone to treat HELLP syndrome in preeclamptic women who are in late pregnancy or the early postpartum period.

Fas (TNFRSF6) Gene Polymorphism in Pregnant Women With Hemolysis, Elevated Liver Enzymes, and Low Platelets and in Their Neonates

To estimate whether an A>G polymorphism at position -670 in the gene coding for Fas (gene symbol TNFRSF6) is associated with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. In a retrospective study, buccal swabs from 81 women with the complete form of HELLP syndrome and 83 normotensive control women with uncomplicated full-term pregnancy, and 110 of their neonates, were analyzed for the presence of the TNFRSF6-670 polymorphism. Investigators were blinded to clinical outcomes. Pregnant women heterozygous for the TNFRSF6-670 genotype were more likely than those homozygous for TNFRSF6-670*A allele to have HELLP syndrome (P = .01; odds ratio 2.7, 95% confidence interval 1.2-5.9). Moreover, patients with homozygous carriage of the TNFRSF6-670*G allele were more likely than those homozygous for the wild type of the Fas gene (TNFRSF6-670*A/A) to have HELLP syndrome (P = .006; odds ratio 4.0, 95% confidence interval 1.7-9.8). In contrast, TNFRSF6-670 genotype distribution of neonates born to mothers with HELLP syndrome was not statistically different from that found in neonates born to healthy pregnant women (P = .4). In patients with HELLP syndrome, no association between TNFRSF6 genotype distribution and severity of hemolysis, platelet counts or liver enzymes levels was noted. A single A>G nucleotide substitution at position -670 in the maternal but not neonatal TNFRSF6 gene coding for Fas is associated with a higher risk for HELLP syndrome. II-2.