Maternal plasma level of endothelin is increased in preeclampsia

Endothelin is a potent vasoconstrictor that is reportedly increased in conditions characterized by endothelial damage. Maternal plasma endothelin levels were compared between 27 women with preeclampsia (23 without and 4 with the hemolysis, elevated liver enzymes, and low platelet count syndrome) and 14 women with normotensive pregnancies. The mean +/- SEM plasma endothelin values were significantly higher in patients with preeclampsia uncomplicated by the hemolysis, elevated liver enzymes, and low platelet count syndrome (5.48 +/- 0.30 fmol/ml vs 3.86 +/- 0.28, p less than 0.001). In addition, the preeclamptic group with the hemolysis, elevated liver enzymes, and low platelet count syndrome had significantly higher endothelin levels than those without the syndrome (8.30 +/- 1.62 fmol/ml vs 5.48 +/- 0.30, p less than 0.05). There was no correlation between plasma endothelin values and either systolic or diastolic blood pressure. We conclude that plasma endothelin levels are significantly increased in women with preeclampsia and particularly in those with the hemolysis, elevated liver enzymes, and low platelet count syndrome, suggesting an association with widespread endothelial damage.     

HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome versus severe preeclampsia: Onset at ≤28.0 weeks’ gestation

Objective: Our purpose was to determine whether the onset of the HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome in women at ≤28.0 weeks’ gestation is associated with an increased risk of adverse maternal and perinatal outcomes in comparison with the risk for women with severe preeclampsia but without the HELLP syndrome at a similar gestational age. Study Design: Sixty-four patients with either the HELLP syndrome (n = 32) or severe preeclampsia but absent HELLP syndrome laboratory test results (n = 32), admitted at ≤28.0 weeks’ gestation between July 1, 1992, and April 30, 1999, were studied. Maternal and perinatal outcomes were compared between the 2 groups. Statistical analysis was performed by the Student t test and the Fisher exact test. Results: There were no significant differences between the 2 groups regarding African-American race (59% vs 75%), nulliparity (50% vs 56%), or the use of corticosteroids (59% vs 78%). There were no maternal deaths. One woman with the HELLP syndrome had a liver hematoma. The rate at which transfusion of blood products was required was significantly greater in women with the HELLP syndrome than in those with severe preeclampsia only (25% vs 3%; P < .05). There were no significant differences between the 2 groups with respect to eclampsia (16% vs 13%), abruptio placentae (6% vs 9%), disseminated intravascular coagulopathy (13% vs 0%), pulmonary edema (13% vs 6%), acute renal failure (3% vs 0%), pleural effusion (3% vs 3%), or ascites (6% vs 16%). No significant differences were found between the 2 groups with respect to neonatal death (11% vs 17%), respiratory distress syndrome (78% vs 86%), or composite neonatal morbidity. Conclusions: Except for the need for transfusion of blood products in women with the HELLP syndrome, onset at ≤28.0 weeks’ gestation is not associated with an increased risk of adverse maternal or neonatal outcomes in comparison with the risk for women with severe preeclampsia but without the HELLP syndrome at a similar gestational age. (Am J Obstet Gynecol 2000;183:1475-9.)     

Long-Term Follow-up in Patients with a History of (H)Ellp Syndrome

Objective. To provide long-term follow-up data on women with a history of hemolysis, elevated liver enzymes, and low platelets [(H)ELLP] syndrome regarding the risk of recurrence in subsequent pregnancies and disease in later life.

Methods. All women admitted to the Academic Medical Centre between January 1984 and January 1996 with (H)ELLP syndrome and a living singleton fetus in utero were included. Women with known preexisting diseases were excluded. The (H)ELLP syndrome was defined as elevated liver enzymes (serum aspartate aminotransferase or serum alanine aminotransferase ≥ 50 U/L) and low platelet count (<100 × 10⁹/L). Those patients with hemolysis (LDH ≥ 600 U/L) were classified as HELLP, the remaining ones were classified as ELLP. The participants were asked to fill out a questionnaire regarding their general health and their own obstetric and medical history and that of their first- and second-degree relatives.

Results. One hundred sixteen (94%) of 123 women responded; 4 women had died. The median age of the group was 36.0 years at completion of the questionnaire; the median interval after the index pregnancy was 5.7 years (3–12.9). The incidence of hypertension requiring medical treatment was three times higher than in a reference population of Dutch women between 20 and 40 years old. The need for psychological support was frequent. Thirty-nine patients (34%) refrained from further pregnancies. Twenty-nine percent of the first subsequent pregnancies were complicated by gestational hypertension (GH), but only 2% had (H)ELLP syndrome. Birth weight was, on average, 1385 g higher and gestational age at delivery 5 weeks later in the first subsequent pregnancy irrespective of a recurrence of GH. A family history of cardiovascular disease or preeclampsia was common in the total group; however, this did not influence the recurrence rate. Multiparity, gestational age at delivery <30 weeks, and birth weight <1000 g in the index pregnancy increased the risk of recurrence of GH in the first subsequent pregnancy significantly.

Conclusions. (H)ELLP syndrome is a severe complication of pregnancy that has not only short-term but also long-term sequelae.     

The Maternal Benefits of Corticosteroids with HELLP (Hemolysis,Elevated Liver Enzymes,Low Platelet Count) Syndrome

Objectives: To determine the more effective regime in improving hematologic abnormalities associated with HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome, by comparing two different antenatal dosing protocols for dexamethasone (given primarily for fetal lung maturity).Study Design: A retrospective cohort study of 30 women between 24 and 34 weeks’ gestation, diagnosed with HELLP syndrome prior to delivery, who received 2 doses of dexamethasone 12 mg intramuscularly, given either 24 hours apart or 12 hours apart.Results: There was a shorter time from the first corticosteroid dose to the beginning of improvement with the 12-hour regime for platelet count (11 hours [9, 25 hours] versus 69 hours [41, 112 hours], median [quartiles], P = 0.003) and for alkaline phosphatase (25 hours [5, 44 hours] versus 59 hours [31, 69 hours], median [quartiles], P = 0.02). Worsening recurred from 11 hours, for alanine aminotransferase (ALT) and aspartate transaminase (AST), to 32 hours, for uric acid, after initial improvement. Hematologic improvement occurred in 37% (for ALT) to 67% (for alkaline phosphatase) of women overall.Conclusion: A temporary improvement in the hematologic parameters of HELLP syndrome can occur with antenatal dexa-methasone administration, with the 12-hour regime having quicker onset to improvement in platelet count and alkaline phosphatase.     

Factors relevant to mode of preterm delivery with syndrome of HELLP (hemolysis,elevated liver enzymes,and low platelets)

OBJECTIVE: Our purpose was to investigate factors relevant to mode of delivery for patients with preterm (<34 weeks) gestation complicated by the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP). STUDY DESIGN: The pregnancies of 189 patients with HELLP syndrome and delivery <34 weeks' gestation between January 1980 and October 1991 were studied retrospectively. Only patients with class 1 (platelet nadir ≤50,000 per microliter, n = 83) and class 2 (platelet nadir >50,000 to ≤100,000 per microliter, n = 106) HELLP syndrome were included. Maternal and perinatal factors relevant to type of delivery were reviewed. RESULTS: The incidence of cesarean delivery for all patients was 76.2% (primary rate 72.4%). Abdominal delivery occurred equally between class 1 (78.3%) and class 2 (74.5%) patients. Cesarean section was the mode of delivery for 87% of pregnancies at <30 weeks' gestation in contrast to 68% of pregnancies at≥30 weeks but <34 weeks' gestation (odds ratio 3.2, 95% confidence interval 1.4 to 7.5, p < 0.005). Indications for cesarean section included deteriorating maternal condition alone (50%), deteriorating maternal and fetal condition (27%), nonvertex fetal presentation (11.5%), and failure to progress (11%). Induction of labor was significantly more successful during the≥30 but <34 weeks' pregnancy interval (47.5%) than in pregnancies at <30 weeks (15.2%) (odds ratio 0.2, 95% confidence interval 0.1 to 0.55, p < 0.001). A trial of labor was successful in 22% of patients with an initial modified Bishop score ≤2 versus 45% with an initial Bishop >2 (odds ratio 0.5, 95% confidence interval 0.2 to 1.3, p = 0.16). CONCLUSION: Parturients with class 1 and 2 HELLP syndrome at <34 weeks' gestation are at high risk for cesarean delivery. At a gestational age <30 weeks, the likelihood of successful labor induction with vaginal delivery is remote, especially in association with an unfavorable cervix or the absence of labor. (AM J Obstet Gynecol 1994;170:1828-34.)     

Hepatic imaging in HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count)

OBJECTIVES: Our objective was to describe the hepatic imaging findings in selected patients with HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count) and to correlate these findings with the severity of concurrent clinical and laboratory abnormalities. STUDY DESIGN: Patients with laboratory criteria for HELLP syndrome with complaints of severe right upper quadrant abdominal pain in association with either shoulder pain, neck pain, or relapsing hypotension underwent imaging of the liver. Clinical and laboratory parameters were then correlated with the hepatic imaging findings. RESULTS: Thirty-four patients were evaluated in this study. Computed tomographic scanning of the liver was used for 33 patients. Additional imaging evaluations included magnetic resonance imaging for 4 patients and ultrasonographic evaluation of the liver for 5 patients. In 15 cases (45%) the computed tomographic results were abnormal. The most frequent abnormal hepatic imaging findings were subcapsular hematoma (n = 13) and intraparenchymal hemorrhage (n = 6). There was no statistically significant correlation between the presence of an abnormal hepatic imaging finding and the severity of liver function test abnormalities. However, the severity of thrombocytopenia did correlate with hepatic imaging findings (p = 004). In particular, an abnormal hepatic imaging finding was noted for 10 of 13 patients (77%) with a platelet count of ≤20 × 10⁹/L (p = 0012). CONCLUSIONS: Abnormalities in liver function test results do not accurately reflect the presence of abnormal hepatic imaging findings in HELLP syndrome. Patients with HELLP syndrome having complaints of right upper quadrant pain and neck pain, shoulder pain, or relapsing hypotension should undergo imaging of the liver. (Am J Obstet Gynecol 1996;174:1820-7.)     

Hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome with pituitary apoplexy

After hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome was diagnosed in a 35-year-old woman at 39 weeks' gestation, magnetic resonance imaging and hormone examination revealed pituitary apoplexy with panhypopituitarism and diabetes insipidus. Evaluation of pituitary function should be considered in patients with HELLP syndrome.     

Pregnancy outcome in 303 cases with severe preeclampsia

The purpose of the present clinical investigation was to determine the influence of aggressive management, associated medical/obstetric complications, race, and gestational age on fetal, neonatal, and maternal risks associated with severe preeclampsia. Three hundred and three consecutive pregnancies complicated by severe preeclampsia were studied. All patients were delivered within 48 hours after admission to the perinatal center. In 91 patients the disease was superimposed on chronic hypertension. There was a significant difference between patients with and those without prior chronic hypertension regarding perinatal mortality (32 versus 7.7%), incidence of abruptio placentae (10 versus 4%), and frequency of small-for-gestational-age infants (33 versus 14%). Fifty-one patients (17%) had thrombocytopenia, 26 (8.5%) had hemolysis, elevated liver enzymes and low platelet count syndrome, and 22 (7.3%) had disseminated intravascular coagulopathy. There was significant difference between white and black patients regarding the frequency of thrombocytopenia (28 versus 13%), hemolysis, elevated liver enzymes, and low platelet count syndrome (19.7 versus 5.3%), and coagulopathy (13 versus 1.4%). However, most of this apparent racial difference resulted from higher incidence of abnormal hematologic findings among patients who had conservative management by private physicians before transfer. Perinatal survival was zero when severe preeclampsia developed at or before 28 weeks, whereas it was 100% when disease developed after 36 weeks' gestation. The above factors should be considered in counselling patients with severe preeclampsia.     

Acute onset of severe hemolysis, elevated liver enzymes, and low platelet count syndrome in a patient with a partial hydatidiform mole at 17 weeks gestation

Preeclampsia is uncommon prior to 24 weeks gestation and has been associated with partial and complete hydatidiform moles. We present an unusual case in which a patient was diagnosed with preeclampsia at 17 weeks gestation. Ultrasound findings were consistent with a partial hydatidiform mole. Within 24 hours of the onset of symptoms, the patient developed severe hemolysis, elevated liver enzymes, and low platelet count syndrome, with a platelet count of 20 x 10 (9) cells/L. Termination of pregnancy was performed with rapid resolution of signs, symptoms, and laboratory abnormalities. Triploid 69,XXY was confirmed at karyotype analysis. This case demonstrates the acuteness in which life-threatening maternal conditions can arise with this uncommon complication of pregnancy, and the importance of correct identification of the characteristic ultrasonographic findings associated with a partial hydatidiform mole.     

Current management of the HELLP syndrome

The HELLP syndrome as part of the microangiopathic syndromes requires special attention in terms of a rapid and accurate diagnostic and differential diagnostic workup because of its possibly rapid clinical deterioration. It is defined by the classical triad of hemolysis,elevated liver enzymes and low platelet counts which may lead to prognostically relevant problems in differentiating it from thrombotic-thrombocytopenic purpura and hemolytic-uremic syndrome and other pregnancy-related and unrelated liver diseases, i.e. mainly clinical and laboratory similarities to other liver diseases such as acute fatty liver or intrahepatic cholestasis in pregnancy or pregnancy-unrelated settings like viral hepatitides. The management in the different phases of pregnancy is described in detail. Therapeutic options to prolong pregnancy are discussed as are the possibilities of prophylaxis in subsequent pregnancies and aspects of the followup.     

The spectrum of severe preeclampsia: Comparative analysis by HELLP (hemolysis, elevated liver enzyme levels, and low platelet count) syndrome classification

Objective: This study was undertaken to explore the spectrum of maternal disease with a triple classification system of HELLP (hemolysis, elevated liver enzyme levels, and low platelet count) syndrome and compare these classes with severe preeclampsia without HELLP syndrome. Study Design: In this retrospective analytic study the pregnancies of 777 patients with class 1, 2, or 3 HELLP syndrome were compared and contrasted with those of 193 women with severe preeclampsia but without HELLP syndrome. Results: Eclampsia, epigastric pain, nausea and vomiting, significant proteinuria, major maternal morbidity, and stillbirth increased as HELLP syndrome worsened from class 3 to class 1. In contrast, headache and diastolic hypertension were more common among the significantly heavier patients with severe preeclampsia without HELLP syndrome. Approximately half of pregnancies complicated by class 1 HELLP syndrome exhibited significant maternal morbidity, compared with only 11% of those complicated by severe preeclampsia without HELLP syndrome. Although a significant trend was apparent in increasing levels of lactate dehydrogenase, aspartate aminotransferase, and uric acid as HELLP syndrome worsened, there was considerable variation within groups. Conclusion: Laboratory and clinical indices of disease severity in patients with severe preeclampsia or eclampsia generally were highest with class 1 HELLP syndrome and were lowest when HELLP syndrome was absent. Class 3 HELLP syndrome is considered a clinically significant transitional group. (Am J Obstet Gynecol 1999;180:1373-84.)     

Addition of platelet transfusions to corticosteroids does not increase the recovery of severe HELLP syndrome

OBJECTIVE: The objective was to evaluate the effect of dexamethasone and platelet transfusion treatment on recovery in patients with class 1 hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. MATERIAL AND METHODS: All women with class 1 HELLP syndrome (true HELLP syndrome) who were seen at the hospital Complejo Hospitalario de la Caja de Seguro Social de Panama, Panama between July 1996 and June 2004 took part in a retrospective, comparative study. They were divided into two groups. One group received dexamethasone and the other group received dexamethasone plus platelet transfusion. True HELLP syndrome was defined as hemolysis, elevated liver enzymes, and maternal platelet nadir < or =50,000 platelets/microl. MAIN OUTCOME MEASURE: The primary endpoint was resolution of the HELLP syndrome as recognized by normalization of the platelet count (> or =150,000/microl) and the mean length (measured in days) of the postpartum stay in hospital. RESULTS: Forty-six women with true HELLP syndrome were studied. Twenty-six patients received dexamethasone and 20 received dexamethasone plus platelet transfusion. The normalization of the platelet count was significantly more rapid in the dexamethasone group (p<0.004) and the postpartum hospital stay was significantly more prolonged in the dexamethasone plus platelet transfusion group (p<0.02). There was no maternal death. CONCLUSIONS: The findings suggest the initiation of high-dose dexamethasone therapy in women with true HELLP syndrome, with the next step being delivery, and probably platelet count < or =50,000/microl alone is not always an indication for platelet transfusion.     

Correlation of Platelet Count Changes with Liver Cell Destruction in Hellp Syndrome

Objective. HELLP syndrome is defined as a subset of preeclampsia involving a combination of hemolysis, low platelets affecting the circulatory system, and elevated liver enzymes, reflecting liver cell destruction. Our objective was to assess the correlation between the platelet count changes and liver cell destruction as indicated by aspartate aminotransferase (AST) levels. Method. We reviewed the records of 15 preeclamptic patients who developed HELLP syndrome as defined by 1) hemolysis, 2) elevated liver enzymes with an AST greater than 70 U/L (>2 SD above mean), and 3) low platelets (<100×10⁹/L). In these patients, both platelet counts and AST were assessed every 4–6 hr before and after delivery until recovery. At least eight laboratory assessments were done on each patient and were available for review. In each patient, the correlation between platelet count and AST levels was done using the Spearman rank order correlation coefficient. Results. A negative correlation was found between platelet count and AST levels. A correlation coefficient of greater than 0.8 occurred in 53% of cases. The correlation coefficient ranged from 0.1 to 0.93. In all cases, improvement of liver cell dysfunction occurred within 4 hr of recovery of platelet count. At 72 hr postpartum, 73% of the platelet counts had not recovered to >150×10⁹/L, and 66% of patients with abnormally elevated AST levels had not returned to <35 U/L. Conclusions. Liver dysfunction and platelet count are poorly correlated in individual cases. This lack of correlation is evident both during decline and recovery of the platelet counts. Changes in platelet count cannot be used as a proxy for liver dysfunction in severe preeclampsia with HELLP syndrome.     

Preeclampsia/eclampsia with hemolysis, elevated liver enzymes, and thrombocytopenia

Data are presented to define a unique group of preeclamptic/eclamptic women with the findings of hemolysis, elevated liver enzymes, and a low platelet count. This syndrome is a variant of severe preeclampsia and may develop either antepartum or postpartum. A nonobstetric diagnosis such as gastrointestinal or hematologic disease is often made. When the patient presents with the hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome, supportive therapy is used and delivery expedited to improve maternal and fetal outcome.     

Sonographic liver changes prior to clinical signs of preeclampsia

Abnormal liver findings on sonography consistent with subcapsular hematoma were seen in a patient prior to clinical and laboratory evidence of preeclampsia and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome.     

Hemodialysis rescued the mother in a case of severe chronic renal failure accompanied by perirenal hematoma due to HELLP syndrome.

We present a case of severe maternal renal failure, accompanied by HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count). Since her renal function deteriorated in addition to the anemia and thrombocytopenia from 25 weeks' gestation, hemodialysis was performed three times a week. Unfortunately intra-uterine fetal death suddenly occurred at 30 weeks' gestation, and maternal right perirenal hematoma was diagnosed after delivery. The anemia and thrombocytopenia improved dramatically and the perirenal hematoma resolved uneventfully by late puerperium. The management of severe maternal renal failure with HELLP syndrome is described.     

Soluble HLA-DR levels in the maternal circulation of normal and pathologic pregnancy

OBJECTIVE: The purpose of this study was to determine that circulating HLA-DR molecules are important candidates for the monitoring of maternal immunostimulation and immunosuppression. STUDY DESIGN: Concentrations of soluble HLA-DR molecules were estimated in EDTA plasma samples of 61 nonpregnant women, 123 healthy pregnant women in the second trimester, 66 healthy women who were delivered at term, and 136 women who were delivered because of complications such as uncontrollable preterm intrauterine activation, abruptio placentae, intrauterine growth retardation, preeclampsia, and HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome. RESULTS: In comparison to nonpregnant women, the normal course of pregnancy was associated with strongly increasing levels of soluble HLA-DR from second trimester on until term. In comparison to women who were delivered preterm because of uncontrollable intrauterine activation, increased soluble HLA-DR concentrations were detected in case of HELLP syndrome (P <.05), although decreased levels were detected in the case of intrauterine growth retardation, preeclampsia (P <.01), and abruptio placentae (P <.01). CONCLUSION: Dysregulation of the maternal immune response to pregnancy may play an important role in the cause of complicated pregnancies.     

Preeclampsia: a microvesicular fat disease of the liver?

To study the interrelationship between preeclampsia, the syndrome of hemolysis, elevated liver enzymes, and low platelet count, and acute fatty liver of pregnancy, 41 liver specimens from 41 preeclamptic women with and without liver dysfunction were examined for the amount of fat deposited in hepatocytes. All 41 specimens stained with oil red O on frozen sections showed a significant amount of microvesicular fat droplets in varying degrees. In contrast, only 11 of the 41 stained conventionally (with hematoxylin-eosin) showed significant fatty infiltration. The density of hepatocellular fat correlated positively with plasma urate concentration and negatively with the platelet count. These findings suggest that preeclampsia may be one of several microvesicular fatty diseases of the liver and that acute fatty liver of pregnancy may be the most severe form.