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

Pathogenesis of the syndrome of hemolysis, elevated liver enzymes, and low platelet count (HELLP): a review

HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome is serious for the mother and the offspring. HELLP occurs in 0.2-0.8% of pregnancies and in 70-80% of cases it coexists with preeclampsia (PE). This review concerns the pathogenetic mechanisms of HELLP syndrome with an emphasis on differences between HELLP and early onset PE. The syndromes show a familial tendency. A previous HELLP pregnancy is associated with an increased risk of HELLP as well as PE in subsequent pregnancies, indicating related etiologies. No single world-wide genetic cause for excessive risk of HELLP or PE has been identified. Combinations of multiple gene variants, each with a moderate risk, with contributing effects of maternal and environmental factors, are probable etiological mechanisms. Immunological maladaptation is the most probable trigger of the insult to the invading trophoblast. This insult occurs early in the first trimester, as indicated by marker molecules in maternal blood. The levels of fetal messenger RNAs in maternal blood at gestational weeks 15-20 are significantly more abnormal in HELLP than in PE, suggesting that the insult is more extensive in HELLP. High levels of HLA-DR in maternal blood in women with HELLP may suggest a similarity to the rejection reaction. In third trimester placentas, gene derangement is more extensive in HELLP. Anti-angiogenic factors released into maternal blood induce the maternal syndromes. Maternal blood levels of anti-angiogenic sFlt1 are similar, but endoglin and Fas Ligand levels are possibly higher in HELLP than in PE. These factors trigger the vascular endothelium, resulting in an enhanced inflammatory response which is stronger in HELLP. Activated coagulation and complement, with high levels of activated leucocytes, inflammatory cytokines, TNF-α, and active von Willebrand factor, induce thrombotic microangiopathy with platelet-fibrin thrombi in microvessels. The angiopathy results in consumption of circulating platelets, causes hemolysis in affected microvessels and reduces portal blood flow in the liver. Placental Fas Ligand damages hepatocytes, resulting in periportal necrosis. In about one half of women with HELLP, activation of coagulation factors and platelets precipitates disseminated intravascular coagulation, which in a minority becomes uncompensated and contributes to life-threatening multiorgan failure.

Utility of Multidetector CT in Severe Postpartum Hemorrhage

Postpartum hemorrhage is one of the leading causes of maternal mortality worldwide. According to the time when postpartum hemorrhage develops, it is classified as (a) primary, or early, postpartum hemorrhage (within the first 24 hours after delivery) or (b) secondary, or late, postpartum hemorrhage (>24 hours to 6 weeks after delivery). Primary postpartum hemorrhage may be caused by uterine atony (75%-90% of cases), trauma of the lower portion of the genital tract, uterine rupture, uterine inversion, bladder flap hematoma, retention of blood clots or placental fragments, and coagulation disorders. Secondary postpartum hemorrhage may be caused by uterine subinvolution, coagulopathies, and abnormalities of the uterine vasculature. Extrauterine sources of bleeding include rectus sheath hematoma, direct arterial injuries, and the HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Severe postpartum hemorrhage is a life-threatening condition that is diagnosed on the basis of the findings from clinical examination, with or without ultrasonography. Computed tomography (CT) and magnetic resonance imaging are useful in the characterization of postpartum hemorrhage when medical treatment fails. Multidetector CT has an important role when intraabdominal bleeding is suspected and can be considered in cases of recurrent bleeding after embolization, as well as for the evaluation of postsurgical complications. A proposed clinical and CT imaging algorithm for postpartum hemorrhage is presented. A multidisciplinary approach to postpartum hemorrhage is essential to optimize the role of diagnostic and interventional radiology in obstetric hemorrhage, to avoid hysterectomy and thus preserve fertility.

Subcapsular liver hematoma causing cardiac tamponade in HELLP syndrome

HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome is an obstetric complication with heterogeneous presentation, multisystem involvement and variable prognosis, but which usually resolves after delivery. We report a case of HELLP syndrome with subcapsular hematoma of the liver causing extrapericardial cardiac tamponade. The subcapsular hematoma and cardiac tamponade were managed conservatively.

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A Case of HELLP Syndrome with Multiple Complications

Hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome is a rare complication of pregnancy. The mortality rate associated with HELLP syndrome increases when life-threatening complications occur. A 37-year-old woman at 37 weeks of gestation developed severe cerebral hemorrhage at the beginning of labor induction and was transferred to our hospital, where HELLP syndrome was diagnosed. She developed disseminated intravascular coagulation (DIC), hepatic hematoma, and cerebral infarction after surgery. On day 68, she was transferred to her local hospital. Careful observation and rapid management can save patients with severe complications of HELLP syndrome.

HELLP Needs Aggressive Help

HELLP (Hemolysis Elevated Liver Enzymes and Low Platelets) syndrome is a multi-system pregnancy associated disorder, commonly seen in patients with pre-eclampsia but can occur alone. It is significantly associated with maternal-fetal morbidity and mortality. A triad of hemolysis elevated liver enzymes and thrombocytopenia after 24 weeks of gestation is diagnostic of this syndrome. HELLP syndrome is classified depending on simple parameters but it dictates severity of the disease. Frequently encountered complications with HELLP syndrome are hemorrhagic stroke, disseminated intravascular coagulation, pulmonary edema, acute renal failure and hepatic rapture. The aggressive supportive care of failing organs with high dose of steroids will decrease the duration of HELLP syndrome, decreases intensive care and hospital stay of these patients as well as reduction in fetal complications. HELLP syndrome is associated with significant increase in morbidity and mortality of pregnant patients; hence it is of vital importance that not only obstetrician, but acute care physicians and intensivist should be aware of this clinical entity. We report a case of Classl, normotensive postpartum HELLP syndrome complicated by pulmonary edema and acute renal failure, successfully managed in our intensive care unit.

Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia between 34 and 37 weeks' gestation (HYPITAT-II): a multicentre, open-label randomised controlled trial.

BackgroundGestational hypertension (GH) and pre-eclampsia (PE) can result in severe complications such as eclampsia, placental abruption, syndrome of Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) and ultimately even neonatal or maternal death. We recently showed that in women with GH or mild PE at term induction of labour reduces both high risk situations for mothers as well as the caesarean section rate. In view of this knowledge, one can raise the question whether women with severe hypertension, pre-eclampsia or deterioration chronic hypertension between 34 and 37 weeks of gestation should be delivered or monitored expectantly. Induction of labour might prevent maternal complications. However, induction of labour in late pre-term pregnancy might increase neonatal morbidity and mortality compared with delivery at term.Methods/DesignPregnant women with severe gestational hypertension, mild pre-eclampsia or deteriorating chronic hypertension at a gestational age between 34+0 and 36+6 weeks will be asked to participate in a multi-centre randomised controlled trial. Women will be randomised to either induction of labour or expectant monitoring. In the expectant monitoring arm, women will be induced only when the maternal or fetal condition detoriates or at 37+0 weeks of gestation. The primary outcome measure is a composite endpoint of maternal mortality, severe maternal complications (eclampsia, HELLP syndrome, pulmonary oedema and thromboembolic disease) and progression to severe pre-eclampsia. Secondary outcomes measures are respiratory distress syndrome (RDS), neonatal morbidity and mortality, caesarean section and vaginal instrumental delivery rates, maternal quality of life and costs. Analysis will be intention to treat. The power calculation is based on an expectant reduction of the maternal composite endpoint from 5% to 1% for an expected increase in neonatal RDS from 1% at 37 weeks to 10% at 34 weeks. This implies that 680 women have to be randomised.DiscussionThis trial will provide insight as to whether in women with hypertensive disorders late pre-term, induction of labour is an effective treatment to prevent severe maternal complications without compromising the neonatal morbidity.Trial RegistrationNTR1792 Clinical trial registration: http://www.trialregister.nl

Standardized Mississippi Protocol Treatment of 190 Patients with HELLP Syndrome: Slowing Disease Progression and Preventing New Major Maternal Morbidity

Objective. To evaluate the effectiveness of the Mississippi Protocol (MP) to treat HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Methods. Uniform early initiation of MP (corticosteroids, magnesium sulfate, systolic blood pressure control) was studied prospectively in patients admitted with severe preeclampsia/class 1 or class 2 HELLP syndrome. Results. One hundred and ninety patients between 2000 and 2007 received MP without suffering maternal death, stroke, or liver rupture. Only 39 of 163 patients (24%) not class 1 when MP began progressed to class 1 disease; only 18.2% of class 1 and 2.4% of class 2 subsequently developed major maternal morbidity. Conclusion. Early initiation of MP inhibits HELLP syndrome disease progression and severity.

Recurrence risks of hypertensive diseases in pregnancy after HELLP syndrome

To determine the recurrence risk for hypertensive diseases in pregnancy after HELLP (Hemolysis Elevated Liver enzymes and Low Platelets) syndrome in a first pregnancy. The study was designed as a cohort study investigating 148 Caucasian primiparae with a diagnosis of HELLP syndrome in a first pregnancy and at least one subsequent pregnancy conducted beyond the 24th gestational week. Diagnoses were verified by reviewing medical records and classified according to ISSHP (International Society for the Study of Hypertension in Pregnancy) criteria. The recurrence risk of HELLP syndrome or other hypertensive disorders in the subsequent pregnancy was calculated with regard to disease severity in the index pregnancy. Among 148 pregnancies subsequent to HELLP syndrome, 56.1% of the women were normotensive. The recurrence rate was 12.8% for HELLP syndrome, 16.2% for pre-eclampsia, and 14.2% for gestational hypertension only. Women with HELLP syndrome ≤32 gestational weeks tended to show a greater risk of complicated subsequent pregnancies compared to women presenting with HELLP after 32 gestational weeks. Women with a diagnosis of HELLP syndrome are at a strongly increased risk of recurrent HELLP syndrome, pre-eclampsia or gestational hypertension, however, currently no clinical or laboratory parameters allow the prediction of recurrence risk in any individual case.

428: Apoptosis pathway is involved in hemolysis, elevated liver enzyme, and low platelet (HELLP) syndrome and intrauterine growth restriction (IUGR)

The neurotrophin family comprises molecules involved in growth, differentiation, survival, regeneration, normal functions of the neuronal system, and in angiogenesis. We investigate the expression pattern of neurotrophic signaling molecules in pregnancies complicated by HELLP (Hemolysis, Elevated Liver enzymes and Low Platelet count) syndrome and IUGR.

Clinical review: Special populations - critical illness and pregnancy

Critical illness is an uncommon but potentially devastating complication of pregnancy. The majority of pregnancy-related critical care admissions occur postpartum. Antenatally, the pregnant patient is more likely to be admitted with diseases non-specific to pregnancy, such as pneumonia. Pregnancy-specific diseases resulting in ICU admission include obstetric hemorrhage, pre-eclampsia/eclampsia, HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, amniotic fluid embolus syndrome, acute fatty liver of pregnancy, and peripartum cardiomyopathy. Alternatively, critical illness may result from pregnancy-induced worsening of pre-existing diseases (for example, valvular heart disease, myasthenia gravis, and kidney disease). Pregnancy can also predispose women to diseases seen in the non-pregnant population, such as acute respiratory distress syndrome (for example, pneumonia and aspiration), sepsis (for example, chorioamnionitis and pyelonephritis) or pulmonary embolism. The pregnant patient may also develop conditions co-incidental to pregnancy such as trauma or appendicitis. Hemorrhage, particularly postpartum, and hypertensive disorders of pregnancy remain the most frequent indications for ICU admission. This review focuses on pregnancy-specific causes of critical illness. Management of the critically ill mother poses special challenges. The physiologic changes in pregnancy and the presence of a second, dependent, patient may necessitate adjustments to therapeutic and supportive strategies. The fetus is generally robust despite maternal illness, and therapeutically what is good for the mother is generally good for the fetus. For pregnancy-induced critical illnesses, delivery of the fetus helps resolve the disease process. Prognosis following pregnancy-related critical illness is generally better than for age-matched non-pregnant critically ill patients.

Platelet monitoring follow-up in a pregnant patient with HELLP syndrome

Monitoring the course of platelet function in HELLP (haemolysis, elevated liver-enzymes and low platelets) syndrome is important for clinical decision-making. We present a primigravid woman developing HELLP syndrome at 29 weeks and 6 days. Platelet function was monitored by multiple electrode aggregometry (MEA), platelet function analyzer (PFA-100®), platelet count and mean platelet volume (MPV) over an 11-day period. MPV and PFA-100® seem better predictors for platelet function than platelet levels.

Left ventricular function many years after recovery from pre-eclampsia

Epidemiological observations have shown that women with pre-eclampsia are at increased risk for subsequent development of cardiovascular disease. We evaluated maternal haemodynamics in asymptomatic women many years after pre-eclampsia and HELLP (haemolysis, elevated liver enzymes and low platelets) syndrome. Case-control study. University-based department of obstetrics. Forty-eight women, 13-18 years after the affected pregnancy: 17 women with a history of HELLP syndrome, 14 women with a history of pre-eclampsia and 17 women following normal pregnancy (control group). Echocardiographic examination was performed in all groups, recording the isovolumetric contraction time and isovolumetric relaxation time (ICT + IVRT), ejection time (ET), myocardial performance index (MPI), transmitral early to atrial filling velocity ratio (MV-E/MV-A), stroke volume (SV) and cardiac output (CO). Cardiac function. Women with previous HELLP syndrome showed a significantly increased MPI (0.34 versus 0.26; P = 0.008) and ICT + IVRT (442.16 versus 415.03; P = 0.01); MV-E/A, SV, ET and CO were not significantly different. Women with a history of pre-eclampsia showed a significantly increased MPI (0.36 versus 0.26; P = 0.006) and decreased ET (317.3 versus 328.93; P = 0.04); ICT + IVRT, MV-E/A, SV and CO were not significantly different. This study confirms epidemiological observations that women with pre-eclampsia are at increased risk for subsequent development of cardiovascular disease. Many years after HELLP syndrome or pre-eclampsia, asymptomatic women have an increased risk for impaired cardiac function as shown by an increased MPI.

Thrombotic Microangiopathy and Occult Neoplasia

Thrombotic thrombocytopenic purpura (TTP), which is typically characterized by fever and central nervous system manifestations and hemolytic uremic syndrome (HUS), in which renal failure is a prominent feature are the most common thrombotic microangiopathies (TMAs). TTP is usually associated with a severe deficiency of ADAMTS13 [a metalloproteinase involved in the degradation of von Willebrand factor (vWF) multimers], causing excessive accumulation of ultra-large vWF multimers and platelet aggregation with organ failure. By contrast, patients with HUS or other TMAs usually display a normal or at least detectable ADAMTS13 activity. A TMA may be occasionally developed in association with HELLP (haemolysis, elevated liver enzymes, and low platelet count) syndrome, infections, cancer and bone marrow transplantation. In cancer patients, TMA may be related to chemotherapeutic regimens or the malignant disease itself. Occasionally, TMA is the first manifestation of an occult cancer, and in large series approximately 3% of patients who were originally diagnosed with TTP, were in fact harboring an occult malignancy. The pathogenesis of cancer-associated TMAs is not completely elucidated, but probably the most important factor is endothelial damage. However, cancer-associated TMAs show some distinct features that should promptly lead to complementary investigations for an underlying malignancy. Weakness, cough and dyspnoea, fever, weight loss, bone and abdominal pain are the most common presenting symptoms. Generally, biochemistry reveals markedly increased LDH levels, increased alkaline phosphatase and the blood smear shows erythromyelemia. Bone marrow biopsy is a valuable tool in order to establishing malignant seeding. Treatment of the underlying neoplasia is the mainstay of therapy and there is no role for plasmapheresis or plasma infusions.

First‐trimester placental growth factor as a marker for hypertensive disorders and SGA

The objective of this study was to examine first-trimester maternal serum placental growth factor (PlGF) levels in pregnancies which later develop hypertensive and growth complications. In this case-control study, PlGF levels were measured by AutoDELFIA immunoassay platform. There were 47 cases of at least one of the following adverse outcomes: pre-eclampsia (PE), small for gestational age (SGA), haemolysis elevated liver enzymes and low platelets (HELLP) and gestational hypertension (GH) and 452 matched controls. PlGF levels were significantly lower in cases of all PE, early PE, HELLP, all SGA, early SGA and SGA without PE, but not in GH, late PE, late SGA, PE with SGA or PE without SGA or HELLP. Low levels of first-trimester PlGF provide a good indicator of SGA complications and some hypertensive disorders, in particular severe cases of PE such as early onset and HELLP syndrome.

The use of angiogenic biomarkers to differentiate non-HELLP related thrombocytopenia from HELLP syndrome

Objective. Preeclampsia (PE) is diagnosed using clinical criteria and in atypical cases the diagnosis may be inaccurate as there are no specific tests to confirm or exclude PE. This study sought to evaluate the utility of angiogenic biomarkers, sFlt1, sEng and PlGF to distinguish patients with gestational thrombocytopenia and immune thrombocytopenic purpura (ITP) from patients with thrombocytopenia resulting from the HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome, a complication of severe PE.Methods. Serum was collected and the angiogenic biomarkers of patients with ITP and gestational thrombocytopenia (N = 9) were compared to patients with HELLP (N = 11) and PE (N = 11). Circulating levels of these angiogenic biomarkers were also compared by gestational age to 1564 randomly selected normotensive women from the Calcium for Preeclampsia Prevention study.Results. Patients with non-HELLP thrombocytopenia had lower sFlt1 (7.3 ± 3.8 ng/ml vs. 15.5 ± 5 ng/ml, P < 0.001), lower sEng (8.7 ± 3.6 vs. 34 ± 17, P < 0.001) and higher PlGF (484 ± 412 vs. 66.3 ± 44, P = 0.003) than patients with HELLP syndrome. Angiogenic factor abnormalities in patients with PE were similar to patients with HELLP syndrome, suggesting a common pathogenesis. Patients with non-HELLP thrombocytopenia had angiogenic profiles similar to normotensive controls, whereas patients with HELLP syndrome had levels higher than the 90th percentile for sFlt1 and sEng and lower than the 10th percentile for PlGF.Conclusions. Angiogenic biomarkers may be useful in excluding conditions that mimic PE.

A case of atypical HELLP (haemolysis, elevated liver enzymes and low platelet count) syndrome presenting as bleeding from the epidural puncture site during labour – Commentary

Roopa et al. have described a case of atypical HELLP syndrome, presenting as bleeding from the epidural puncture site. Their prompt investigation of this bleeding revealedHELLP syndrome, but this diagnosis could have been significantly delayed because of the absence of hypertension and significant proteinuria. Although described as atypical, this case is typical in the subtlety of presenting signs and symptoms followed by rapid development ofmultisystem problems including post partum haemorrhage, disseminated intravascular coagulation (DIC), pulmonary oedema, and renal dysfunction. The supportive management that Roopa et al. subsequently employed successfully prevented permanent morbidity or mortality. Their case report and reviewof HELLP syndrome is amost useful reminder to us all about this challenging condition. To maintain our vigilance for this condition it is worth considering what can happen in a case like this when the diagnosis of HELLP is missed. Had the initial problem been post partum haemorrhage, perhaps with the subsequent anaemia exaggerated by unrecognised haemolysis, a reasonable response might have been initial fluid resuscitation with crystalloids and colloids, followed by

A case of atypical HELLP (haemolysis, elevated liver enzymes and low platelet count) syndrome presenting as bleeding from the epidural puncture site during labour

Summary HELLP (haemolysis, elevated liver enzymes and low platelet count) syndrome has been recognised as a life threatening complication of pregnant women for many years. The majority of women with HELLP syndrome have hypertension and proteinuria which may be absent in 10–20% of cases–referred to as atypical HELLP. A primigravida received epidural labour analgesia and she continued to bleed from the skin puncture site. Evaluation for the cause of bleed established the diagnosis of atypical HELLP syndrome. Although rarely encountered, an atypical HELLP may have dangerous anaesthetic consequences when clinicians are caught unawares. We report one such case with atypical presentation.

Pathogenesis of Preeclampsia

Preeclampsia is a systemic syndrome that occurs in 3 to 5% of pregnant women and classically manifests as new-onset hypertension and proteinuria after 20 weeks of gestation. Preeclampsia is a leading cause of maternal and neonatal morbidity and mortality. The only known cure is delivery of the placenta. Recent discoveries, however, have led to important advances in understanding the pathogenesis of the condition. Placental antiangiogenic factors are upregulated and disrupt the maternal endothelium. This change in the normal angiogenic balance toward an antiangiogenic state can result in hypertension, proteinuria, glomerular endotheliosis, HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, and cerebral edema-the clinical signs of preeclampsia and eclampsia. The regulation of these antiangiogenic factors in the placenta is unknown. The recent discoveries of upregulated antiangiogenic factors provide promise for future testing to predict and diagnose preeclampsia as well as therapeutic targets for amelioration of the clinical disease.

Hemolysis, elevated liver enzymes, and low platelets syndrome: when is surgical help needed?

Background Life-threatening hemorrhage is a rare event in hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. Epidemiologic data are lacking to predict patients at risk for hemorrhage requiring surgical consultation. We sought to identify early clinical predictors of hemorrhagic complications in patients at risk for HELLP syndrome. Methods Patients at risk for HELLP syndrome from 1997 to 2007 were identified retrospectively. Variables evaluated in at-risk women were maternal age, gestational history, hepatic transaminase levels, and platelet count. Multiple logistic regression analysis was used to identify independent predictors of poor maternal outcomes, which were defined as hemorrhage requiring transfusion of blood products, need for surgical intervention, hepatic rupture, and death. Results A total of 109 at-risk women were identified. Adverse outcomes included transfusions (18%), hemorrhage interventions (8%), damage control laparotomy (2.8%), and hepatic rupture (2.8%). Maternal and perinatal mortality were .9% and 3.7%, respectively. Median transfusion requirements for women with hepatic rupture were 56 U of packed red blood cells, 26 U of fresh-frozen plasma, 18 U of platelets, and 6 U of cryoprecipitate. Multiple logistic regression analysis showed previous gestations ( P = .002), platelet count ( P = .01), and aspartate aminotransferase level increase ( P = .04) were independent predictors of life-threatening hemorrhage. Previous gestations increased the risk of adverse outcome 3-fold. Conclusions Identifiable risk factors predictive of major hemorrhage are thrombocytopenia (<100,000 cells/μL), increase of aspartate aminotransferase level greater than 70 IU/L, and previous gestations.