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A Review of HELLP Syndrome William M. Curtin, MD Louis Weinstein, MD HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome is a variant of severe preeclampsia which is associated with substantial maternal and perinatal morbidity and mortality. As with preeclampsia, the etiology and pathogenesis of HELLP syndrome is not completely understood. An increase in vascular thrombosis and activation of the coagulation system may be important in the clinical presentation of this disorder. Laboratory criteria for the diagnosis of HELLP syndrome have been classically described but lack uniformity among different institutions. Aggressive management of HELLP syndrome with expeditious delivery appears to yield the lowest perinatal mortality rates. Conservative or expectant management has been associated with higher stillbirth rates with antenatal corticosteroids not causing resolution of the laboratory abnormalities. Resolution of laboratory abnormalities in HELLP syndrome runs a protracted course over several days after delivery. Despite nearly two decades since HELLP syndrome has been defined as a clinical entity, treatment for the disorder still remains delivery of the patient.

Although the laboratory abnormalities in HELLP syndrome were described decades ago,1 it was in 1982 that Weinstein devised the acronym HELLP (H 5 hemolysis, EL 5 elevated liver enzymes, and LP 5 low platelets) to define a subset of severe preeclampsia seen in 29 patients.2 The need to recognize HELLP syndrome as a unique form of severe preeclampsia was emphasized, because often patients were given a nonobstetric diagnosis, such as cholecystitis or hepatitis, and treatment was delayed. Aggressive treatment with maternal stabilization and expeditious delivery was advocated to prevent maternal and perinatal mortality. HELLP syndrome is reported to occur in 20% of women with severe preeclampsia and in 10% of women with eclampsia.3 Magann and associates4 reported the incidence of HELLP syndrome to be 0.11% among all live born deliveries over a 12-year period at the University of Mississippi Medical Center. Maternal mortality ranges from 0% to 4%.2,3,5 Perinatal mortality appears to be primarily related to the gestational age at delivery. The focus of this review on HELLP syndrome will be on pathoDepartment of Obstetrics and Gynecology (W. M. C., L. W.), Division of Maternal Fetal Medicine (L. W.), Medical College of Ohio, Toledo, OH. Address correspondence and reprint requests to William M. Curtin, MD, Department of Obstetrics & Gynecology, Medical College of Ohio, Ruppert Center, Suite 1500, 3120 Glendale Avenue, Toledo, OH 43614-5809.

genesis, characteristics of affected patients, laboratory criteria for diagnosis, sources of maternal and perinatal morbidity, and mortality and management of complications. The possible role for conservative management and antenatal treatment with the intention of prolonging pregnancy will be explored. Pathogenesis The etiology of preeclampsia remains unclear with the pathogenesis being incompletely understood. Theories on the causation center on abnormal placentation resulting in placental ischemia and the production of a circulating toxic factor causing endothelial injury.6 The disturbance in endothelial cells is believed to cause vascular constriction, increased capillary leakage, and platelet aggregation resulting in the clinical picture of hypertension, proteinuria, edema, and thrombocytopenia. It is unclear why certain patients with severe preeclampsia develop HELLP syndrome. It is possible that these patients have more endothelial injury with greater activation of the coagulation system. Paternoster et al.7 showed evidence of a compensated disseminated intravascular coagulation (DIC) in patients with HELLP syndrome when compared with normotensive control patients with preeclampsia without HELLP. They found statistically significant increases in plasma fibronectin and D-dimer levels and decreases in antithrombin-III levels when the patients with HELLP syndrome were compared to the patients with preeclampsia. The HELLP group and the preeclamptic group also showed significant decreases in protein C and S activity as compared to the control normotensive group, but no significant differences in comparison to each other. Routine tests to detect DIC (fibrinogen, prothrombin time, partial thromboplastin time), were not significantly different among the three groups with the exception of the partial thromboplastin time between the control and preeclamptic group. The findings of these investigators suggest more endothelial damage, consumption of coagulation inhibitors, and activation of fibrinolysis in patients with HELLP syndrome than in patients with preeclampsia without HELLP and normotensive controls.7 Further support for the role of an enhanced thrombotic tendency in the pathogenesis of HELLP syndrome was provided by Dekker et al.8 in a study of 101 patients with severe early-onset preeclampsia, 53 of who had HELLP syndrome. They demonstrated by testing, at least 10 weeks postpartum, that greater than 50% of patients had an abnormality associated with an increased tendency toward thrombosis. The most common abnormalities identified were anticardiolipin antibodies, protein S deficiency, hyperhomocysteinemia, and activated proJournal of Perinatology (1999) 19(2) 138 –143 © 1999 Stockton Press. All rights reserved. 0743– 8346/99 $12

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A Review of HELLP Syndrome

tein C resistance. The authors speculated that identification of these abnormalities may provide a basis for pharmacologic management in subsequent pregnancies. Immunologic factors may be the underlying initiator of preeclampsia and HELLP syndrome. It is possible that a maternal cellmediated immune response to pregnancy with cytokine-mediated endothelial damage is important in HELLP syndrome. Haeger et al.9 reported increased plasma levels of tumor necrosis factor-a at the time of delivery in patients with HELLP syndrome as compared to normal pregnant controls. Tumor necrosis factor-a, by its effect on endothelial cells and coagulation, may be important in the pathophysiology of preeclampsia and HELLP syndrome. The histologic pattern of injury in the liver in preeclampsia is one of fibrin deposition in the periportal sinusoids and hemorrhage into the space of Disse with resultant hepatocellular necrosis.10 Blood can dissect through portal connective tissue and collect to form subcapsular liver hematoma. Aarnoudse et al.11 studied needle biopsies of the liver in patients with HELLP syndrome and noted periportal lesions consisting of neutrophilic infiltrates, necrosis of hepatocytes and fibrin microthrombi, and fibrin deposits in the sinusoids. They concluded that the basic histopathologic changes in the liver are identical to those previously described for preeclampsia. Barton and colleagues12 found periportal hemorrhage, fibrin deposition, and fatty infiltration in 11 patients with HELLP syndrome who were delivered by cesarean section and underwent needle biopsy of the liver under direct visualization. They found no correlation between the severity of the histologic findings and the clinical and laboratory findings. HELLP syndrome shares clinical and laboratory features with acute fatty liver of pregnancy. Liver biopsy in acute fatty liver of pregnancy demonstrates microvesicular fatty infiltration of hepatocytes.13 Liver specimens examined for fat deposition from preeclamptic patients with and without liver dysfunction demonstrate significant amounts of microvesicular fat.14 This has led to speculation that preeclampsia, HELLP syndrome, and acute fatty liver of pregnancy are all part of the same pathologic spectrum.14,15 Maternal Characteristics HELLP syndrome occurs in women at all reproductive ages, with a mean age of approximately 24 years.2,3 It has been described in most ethnic groups in the United States and occurs in both primigravida and multiparous patients. Approximately 19% have pre-existing chronic hypertension.2,3 In Sibai and colleagues’ study3 of 442 pregnancies with HELLP syndrome, 70% were diagnosed antepartum and 30% postpartum. Mean gestational age at delivery is approximately 32 weeks and ranges from 24 to 39 weeks.2,5 Clinical Presentation Presenting symptoms include malaise, right upper quadrant tenderness, nausea, and vomiting. Blood pressure elevation in HELLP syndrome is variable in degree, with relative (.30/15 mm Hg over baseJournal of Perinatology (1999) 19(2) 138 –143

Curtin and Weinstein

line) or absolute hypertension ($140/90 mm Hg) present in all patients. Weinstein reported right upper quadrant tenderness to palpation in all patients and edema in 69%.2 Although HELLP syndrome reportedly can occur in the absence of proteinuria, the few studies including data on proteinuria show that it is present in varying degrees in all patients.2,16 Laboratory Diagnosis The laboratory criteria used for diagnosis of HELLP syndrome vary among institutions, and comparisons of patients between institutions are complicated by the lack of uniform definitions of the three components of the disorder. Hemolysis, the most difficult feature to detect and probably the most specific, is frequently not defined. Tests for liver enzymes include several different methods for enzyme analysis with varied reference ranges. Thrombocytopenia has been classically defined as ,100,000/ml. The following reviews diagnostic criteria used in HELLP syndrome. Hemolysis Markers for hemolysis include elevated indirect bilirubin and low haptoglobin levels. Morphologic features on peripheral blood smear that are indicative of hemolysis include schistocytosis, polychromasia (implying reticulocytosis), anisocytosis, and poikilocytosis. Schistocytes (red cell fragments) and burr cells (irregularly contracted red cells with prominent spicules) are associated with small blood vessel disease or fibrin deposition in small blood vessels and thus are features of microangiopathic hemolytic anemia.17 Weinstein defined hemolysis based on the presence of schistocytes and/or Burr cells on peripheral smear and believed that microangiopathic hemolytic anemia was present to some degree in all patients with HELLP syndrome.2 Most patients with HELLP syndrome are not anemic on presentation but may develop a drop in hematocrit out of proportion to the amount of blood loss at delivery.2 In a prospective study measuring laboratory markers of hemolysis in HELLP syndrome, Wilke and colleagues18 found an abnormal peripheral smear in only 11 of 25 patients. In patients with normal splenic function, abnormal red cells may be cleared rapidly from the circulation and may not be readily apparent on peripheral blood smears.19 Sibai recommended that, in addition to an abnormal blood smear, increased bilirubin and lactate dehydrogenase (LDH) be required for the diagnosis of hemolysis.20 Although these additional criteria may be useful in the diagnosis of hemolysis, neither of these tests is specific. Only elevated indirect bilirubin is indicative of hemolysis, and LDH is found not only in red blood cells, but also in liver, skeletal muscle, cardiac muscle, and kidney. Paternoster et al.7 demonstrated LDH elevations in some patients with preeclampsia and found bilirubin elevations in only 25% of their patients with HELLP syndrome. Reductions in serum haptoglobin, however, were found in all patients with HELLP syndrome. In Wilke’s study18 reduced haptoglobin levels were identified in all of their patients with HELLP syndrome. They also performed electrophoretic separation of LDH isoenzymes in five patients with HELLP syndrome and found that the elevated plasma LDH levels in 4 of 5 139


patients were associated with a relative increase in the LDH5 isoenzyme, which is of liver origin.18 In summary, the most sensitive and objective marker of hemolysis in the HELLP syndrome is a reduced serum haptoglobin level. Elevated Liver Enzymes Hepatic injury in HELLP syndrome is manifest by elevation in aspartate aminotransferase (AST), formerly termed serum glutamate oxaloacetate transaminase (SGOT), and alanine aminotransferase (ALT), formerly serum glutamate pyruvate transaminase (SGPT). LDH elevation also occurs in liver injury. Although Weinstein did not define the degree of liver enzyme elevation necessary for HELLP syndrome diagnosis, Sibai made specific recommendations2,3,20; he defined elevated liver enzymes by an AST (SGOT) value of 70 U/l. The latter value correlated to three standard deviations above the mean in their hospital laboratory. Other authors have used elevation of AST and ALT to two standard deviations above the mean to define the elevated liver enzyme component of HELLP syndrome.7,21 Low Platelets In Weinstein’s study, 18 of 29 patients had thrombocytopenia, defined as a platelet count of ,100,000/ml, on admission, and all 29 patients had a nadir platelet count of ,100,000/ml.2 Other authors have also defined thrombocytopenia as a platelet count of ,100,000/ml.3,7,22 Maternal Mortality and Morbidity Maternal mortality in HELLP syndrome ranges from 0% to 4%.2,3,5 In Sibai’s series,3 maternal death in HELLP syndrome was from various complications: one from ruptured liver hematoma, one from pulmonary embolism, and three from diffuse hypoxic encephalopathy. Raval5 reported one maternal death from DIC, and Weinstein2 reported one maternal death in a patient with severe microangiopathic hemolytic anemia, marked hyperbilirubinemia, and massive ascites. As HELLP syndrome frequently occurs before term with an unfavorable cervix, cesarean section is a common mode of delivery, with rates ranging from 42% to 98%.2,3,22 Blood product transfusion, with its associated risks, has been used frequently. One study noted transfusion in 25% of patients.23 DIC has been described in up to 15% of patients, half of whom had placental abruption.23 Wound hematoma or infection is a common complication after cesarean section and presents in 7% to 14% of HELLP syndrome patients.16,23 Acute renal failure has been reported as a complication in 8%, the majority secondary to acute tubular necrosis.3 Ecclampsia is seen in 4% to 9% of HELLP patients.3,23 Other complications reported include severe ascites (8%), pleural effusion (6%), pulmonary edema (6%), and subcapsular liver hematoma requiring laparotomy (1%).3 Perinatal Mortality and Morbidity Perinatal mortality in HELLP syndrome ranges from 5% to nearly 20%.2,16,22,24 Studies that advocate expectant or temporizing management have higher perinatal mortality rates, mainly because of stillbirths.16,24 In a study of 51 patients with HELLP syndrome not in labor 140


and with a live fetus upon admission, van Pampus and colleagues24 reported a perinatal mortality rate of 19.6%. There were 10 fetal deaths and 1 neonatal death. Neonatal survival in infants born to mothers with HELLP syndrome is mainly dependent upon gestational age and birth weight at delivery. It does not appear that HELLP syndrome, independent of gestational age, increases neonatal mortality. Magann and associates4 at the University of Mississippi showed that ultimate neonatal salvage was primarily related to gestational age and birth weight at delivery and not due to the severity of the HELLP syndrome. Weinstein reported hematologic abnormalities (thrombocytopenia, leukopenia, and abnormal peripheral smears) in the neonates born to mothers with HELLP syndrome.2 He speculated that some humoral substance crossing the placenta may result in these findings. Neonatal thrombocytopenia has been reported in up to 50% of pregnancies complicated by HELLP syndrome,5 but it is not unique to this entity. No correlation has been demonstrated between maternal and neonatal platelet counts.22 Leukopenia and/or neutropenia were present in up to 40% of neonates in HELLP syndrome2,22 but have also occurred in infants born to mothers with preeclampsia in the absence of HELLP.25 Weinstein noted that 92% of newborn infants born to mothers with HELLP syndrome had abnormal peripheral blood smears with burr cells and/or schistocytes.2 Although these findings are suggestive of hemolysis in the fetus, anemia at birth is uncommon in infants from mothers with HELLP syndrome. Little data is available on liver enzymes in infants born to mothers with HELLP syndrome. Harms and colleagues22 evaluated liver enzymes in 13 neonates born to mothers with HELLP syndrome and found slight elevations in only two. Timing of Delivery Because of the potential for maternal and perinatal mortality in HELLP syndrome, aggressive management with expeditious delivery has been advocated.2,20,22 This does not preclude vaginal delivery if the cervix is sufficiently ripe for induction of labor. Sibai states that, in the absence of laboratory evidence of DIC and absent fetal lung maturity, antenatal corticosteroids to accelerate fetal lung maturity can be given with delivery 48 hours later.20 He emphasized the need for continuous maternal and fetal monitoring during this period. Studies that advocate aggressive management and delivery regardless of gestational age demonstrate the lowest perinatal mortality rates.2,22 Harms and colleagues22 managed 80 pregnancies with HELLP syndrome with immediate cesarean section, regardless of gestational age, and reported an overall perinatal mortality rate of 5.6%. In some cases, the laboratory abnormalities in HELLP syndrome will resolve with conservative management. Van Pampus et al.24 reported a series of 51 patients with HELLP syndrome who were managed expectantly in order to prolong pregnancy; delivery was performed mainly for fetal indications. In 30% laboratory abnormalities normalized. The median prolongation of pregnancy in their entire group of patients was only 3 days. There were no maternal deaths in Journal of Perinatology (1999) 19(2) 138 –143


this series but forms of maternal morbidity included eclampsia, antihypertensive treatment, temporary hemiplegia, and postpartum deep venous thrombosis. The perinatal mortality rate was 19.6% with all deaths being stillbirths. Visser and Wallenburg16 compared 128 patients with HELLP syndrome to 128 patients with preeclampsia at a gestational age of ,34 weeks. They treated each group with bedrest, pharmacologic vasodilatation, and plasma volume expansion under central hemodynamic monitoring. They noted no difference in pregnancy prolongation or perinatal mortality between the two groups and concluded that their data did not support a general recommendation of prompt termination of pregnancy in HELLP syndrome. There were no maternal deaths in either group. The mothers with HELLP syndrome had significantly more hemorrhagic problems, mainly wound hematomas following cesarean section. The authors noted that 43% of patients with HELLP syndrome had a complete antepartum resolution. In this group of patients median prolongation of pregnancy was 21 days as compared to 10 days in the entire group of HELLP patients. They had 11 stillbirths with a median birth weight of 680 gm among the HELLP patients. Although fetal distress was recognized before stillbirth in 10 of 11 cases, the authors did not intervene because fetal growth restriction at an early gestational age was believed to portend a poor prognosis for meaningful neonatal survival. Unfortunately, one stillbirth, caused by placental abruption, occurred at 34 weeks with a birth weight of 2370 gm. Magann and associates26 evaluated the effect of antepartum corticosteroids in preterm HELLP syndrome in a prospective, randomized study of 25 patients with HELLP syndrome. Twelve pregnancies with HELLP syndrome, a mean gestational age of 30.7 weeks, and a mean admission platelet count of 69,300/ml were given dexamethasone (10 mg) intravenously every 12 hours until delivery. The control group was 13 HELLP patients with a mean gestational age of 32.8 weeks and a mean platelet count of 106,800/ml who received no steroids. There were no patients with platelet counts of ,50,000/ml included in this study. Delivery was performed for a deteriorating maternal or fetal condition, gestational age .34 weeks, or a platelet count of #50,000/ml. The authors found the dexamethasone-treated group had significantly increased urinary output and platelet counts and reduced ALT and LDH levels over time in comparison to the untreated group. The steroid group had a longer interval from initiation to delivery than the control group (41 versus 15 hours). The authors noted that steroids stabilized disease in HELLP syndrome and that the effect was temporary. Expectant management, temporizing or corticosteroid treatment cannot be advocated when there is a reasonable chance of fetal survival and the diagnosis of HELLP syndrome is based on strict criteria.23 The lowest perinatal mortality rates occur with aggressive management.2,22 Post Partum Course Martin and colleagues27 evaluated the time course of disease resolution in 158 postpartum patients with HELLP syndrome. They found Journal of Perinatology (1999) 19(2) 138 –143


that platelet counts continued to decrease until 24 to 48 hours after delivery. A platelet count of .100,000/ml was spontaneously achieved within 72 hours of the platelet nadir in most patients in their study. LDH levels peaked at 24 to 48 hours after delivery with a downward trend in LDH by the fourth postpartum day. Martin et al.28 have also advocated the use of dexamethasone in the postpartum period to accelerate recovery. They performed a retrospective study of 43 women with postpartum HELLP syndrome who were treated with dexamethasone (10 mg IV at 12-hour intervals until disease remission) compared with 237 similar patients who received no steroids. They reported more rapid normalization of platelet counts and LDH values and a reduction in transfusion, respiratory therapy, invasive hemodynamic monitoring, morbidity secondary to infection, and length of postpartum hospital course. One prospective randomized trial evaluated the routine initiation of dexamethasone in patients with postpartum HELLP syndrome.29 The steroid-treated group had a significantly increased platelet count by 30 hours postpartum in comparison to controls. There was no difference in the incidence of abnormal uterine bleeding or wound infection in the treated and untreated groups. The authors found no significant difference in blood pressure, urinary output, LDH, AST, or ALT values between the dexamethasone-treated patients and controls at any time by 72 hours postpartum. Management of Selected Complications Anemia Blood components utilized in patients with HELLP syndrome have included packed red cells, fresh frozen plasma, and platelets. The decision to transfuse red blood cells should be based on clinical assessment of the patient’s status rather than an arbitrary hemoglobin or hematocrit value. There are relatively few specific clinical indications for the use of fresh frozen plasma.30 Coagulopathy without an obvious source of bleeding, such as placental abruption or subcapsular liver hematoma, is uncommon in HELLP syndrome.23 Therefore the need for FFP transfusion in HELLP syndrome would be fairly infrequent. Thrombocytopenia Platelet transfusion therapy is an area of medicine based largely on consensus rather than evidence-based guidelines.31,32 Therapeutic platelet transfusion is believed to be indicated in patients with significant bleeding if the platelet disorder is likely to be causing or contributing to this bleeding and the platelet count is ,50,000/ml.31 Although a platelet count of ,50,000/ml in patients undergoing surgery is frequently cited as a threshold for prophylactic platelet transfusion,33 the risk of bleeding has not been defined. Platelet transfusion is believed to be contraindicated in thrombotic thrombocytopenic purpura and hemolytic uremic syndrome32; these disorders are characterized by platelet consumption, and are in this respect, similar to HELLP syndrome. Roberts and colleagues,34 in a retrospective, descriptive study of intrapartum platelet counts in HELLP syndrome, reported an antepartum platelet count of #40,000/ml to be predictive of postpartum 141


bleeding problems. The types of bleeding problems encountered were from abdominal incision sites after cesarean delivery, and episiotomy sites after vaginal delivery. Mucus membrane bleeding was not a clinically significant problem and no patients had central nervous system bleeding. The effect of prophylactic platelet transfusion was studied in patients with platelet counts of ,40,000/ml. They found no difference in postpartum bleeding problems between the patients who received prophylactic platelet transfusion and those who did not. Furthermore, the postpartum platelet counts in the transfused patients were not significantly different from the patients who were not transfused. The data suggest that prophylactic platelet transfusion in HELLP syndrome is not of value in preventing bleeding complications and that transfused platelets are quickly consumed. Subcapsular Hematoma Subcapsular liver hematoma has been reported in 1% of pregnancies complicated by HELLP syndrome and may result in maternal death.3 Computed tomography, magnetic resonance imaging, or ultrasound can be used to detect and monitor this complication.35 Barton and Sibai35 have recommended close observation in women with unruptured subcapsular hematoma, provided that maternal condition is stable. Hematoma size can be followed by serial computed tomography or ultrasound until the defect resolves. Ruptured liver hematoma is a surgical emergency with evacuation and drainage of the hematoma, packing as needed and suturing of lacerations if possible.35 Recurrence Risk in Subsequent Pregnancies Sullivan et al.21 found, in patients with a prior pregnancy affected by HELLP syndrome and a nadir platelet count of #100,000/ml, a 19% incidence of HELLP syndrome and a 23% incidence of preeclampsiaeclampsia in subsequent pregnancies. Sibai and colleagues36 at the University of Tennessee reported recurrent preeclampsia in 19% but recurrent HELLP syndrome in only 3%. Conclusion Widespread recognition and earlier diagnosis of HELLP syndrome as a variant of severe preeclampsia have lead to an improvement in maternal and perinatal outcome. Unfortunately, the only cure for HELLP syndrome is delivery, even at early gestational ages. Further advancement in prevention and possibly treatment of the disorder will rest upon a more complete understanding of the etiology and pathogenesis of preeclampsia. At this time, the clinician is advised to consider aggressive management with expeditious delivery when treating a patient with HELLP syndrome. References 1. Pritchard JA, Weisman R, Ratnoff OD, Vosburgh GJ. Intravascular hemolysis, thrombocytopenia, and other hematologic abnormalities associated with severe toxemia of pregnancy. N Engl J Med 1954;250:89 –98. 2. Weinstein L. Syndrome of hemolysis, elevated liver enzymes, and low platelet

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count: a severe consequence of hypertension in pregnancy. Am J Obstet Gynecol 1982;142:159 – 67. 3. Sibai BM, Ramadan MK, Usta I, Salama M, Mercer BM, Friedman SA. Maternal morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes, and low platelets. Am J Obstet Gynecol 1993;169:1000 – 6. 4. Magann EF, Perry KG, Chauhan SP, Graves GR, Blake PG, Martin JN. Neonatal salvage by weeks gestation in pregnancies complicated by HELLP syndrome. J Soc Gynecol Invest 1994;1:206 –9. 5. Raval DS, Co S, Reid MA, Pildes R. Maternal and neonatal outcome of pregnancies complicated with maternal HELLP syndrome. J Perinatol 1997;17:266 –9. 6. Van Beek E, Peters LLH. Pathogenesis of preeclampsia: a comprehensive model. Obstet Gynecol Surv 1998;53:233–9. 7. Paternoster DM, Stella A, Simioni P, Mussap M, Plebani M. Coagulation and plasma fibronectin parameters in HELLP syndrome. Int J Gynecol Obstet 1995; 50:263– 8. 8. Dekker GA, de Vries JIP, Doelitsch PM, et al. Underlying disorders associated with severe early-onset preeclampsia. Am J Obstet Gynecol 1995;173:1042– 8. 9. Haeger M, Unander M, Andersson B, Tarkowski A, Arnestad JP, Bengtsson A. Increased release of tumor necrosis factor-alpha and interleukin-6 in women with the syndrome of hemolysis, elevated liver enzymes and low platelet count. Acta Obstet Gynecol Scand 1996;75:695–701. 10. Crawford JM. The liver and the biliary tree. In: Cotrans RS, Kumar V, Robbins SL, editors. Robbins Pathologic Basis of Disease, 5th Edition. Philadelphia: WB Saunders & Co.; 1994. p. 875. 11. Aarnoudse JG, Houthoff HJ, Weits J, Vellenga E, Huisjes HJ. A syndrome of liver damage and intravascular coagulation in the last trimester of normotensive pregnancy: a clinical and histopathological study. Br J Obstet Gynaecol 1986;93: 145–55. 12. Barton JR, Riely CA, Adamec TA, Shanklin DR, Khoury AD, Sibai BM. Hepatic histopathologic condition does not correlate with laboratory abnormalities in HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count). Am J Obstet Gynecol 1992;167:1538 – 43. 13. Schorr-Lesnick B, Lebovic E, Dworkin B, Rosenthal WS. Liver diseases unique to pregnancy. Am J Gastroenterol 1991;86:659 –70. 14. Minakami H, Oka N, Sato T, Tamada T, Yasuda Y, Hirota N. Preeclampsia: a microvesicular fat disease of the liver? Am J Obstet Gynecol 159:1043–7. 15. Dani R, Mendes GS, de Laurentys Medeiros J, Peret FJ, Nunes A. Study of the liver changes occurring in preeclampsia and their possible pathogenetic connection with acute fatty liver of pregnancy. Am J Gastroenterol 1996;91:292– 4. 16. Visser W, Wallenburg HCS. Temporising management of severe pre-eclampsia with and without the HELLP syndrome. Br J Obstet Gynaecol 1995;102:111–7. 17. Morris MW, Davey FR. Basic examination of blood. In: Henry JB, editor. Clinical Diagnosis and Management by Laboratory Methods, 19th Edition. Philadelphia: WB Saunders & Co.; 1996. p. 579. 18. Wilke G, Schutz E, Armstrong VW, Kuhn W. Haptoglobin as a sensitive marker of hemolysis in HELLP-syndrome. Int J Gynecol Obstet 1992;39:29 –34. 19. Pincus MR. Interpreting laboratory results: reference values and decision making. In: Henry JB, editor. Clinical Diagnosis and Management by Laboratory Methods, 19th Edition. Philadelphia: WB Saunders & Co.; 1996. p. 79. Journal of Perinatology (1999) 19(2) 138 –143


20. Sibai BM. The HELLP syndrome (hemolysis, elevated liver enzymes and low platelets): much ado about nothing? Am J Obstet Gynecol 1990;162:311– 6. 21. Sullivan CA, Magann EF, Perry KG, Roberts WE, Blake PG, Martin JN. The recurrence risk of the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP) in subsequent gestations. Am J Obstet Gynecol 1994;171:940 –3. 22. Harms K, Rath W, Herting E, Kuhn W. Maternal hemolysis, elevated liver enzymes, low platelet count, and neonatal outcome. Am J Perinatol 1995;12:1–7. 23. Audibert F, Friedman SA, Frangieh AY, Sibai BM. Clinical utility of strict diagnostic criteria for the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) syndrome. Am J Obstet Gynecol 1996;175:460 – 4.


28. Martin JN, Perry KG, Blake PG, May WA, Moore A, Robinette L. Better outcomes are achieved with dexamethasone therapy for postpartum HELLP (hemolysis, elevated liver enzymes, and thrombocytopenia) syndrome. Am J Obstet Gynecol 1997;177:1011–7. 29. Vigil-De Gracia P, Garcia-Caccrcs E. Dexamethasone in the post-partum treatment of HELLP syndrome. Int J Gynaecol Obstet 1997;59:217–21. 30. NIH Consensus Conference. Fresh frozen plasma: indications and risk. JAMA 1985;253:551–3. 31. NIH Consensus Conference. Platelet transfusion therapy. JAMA 1987;257:1777– 80.

24. van Pampus MG, Wolf H, Westenberg SM, van der Post JAM, Bonsel GJ, Treffers PE. Maternal and perinatal outcome after expectant management of the HELLP syndrome compared with preeclampsia without HELLP syndrome. Eur J Obstet Gynecol Reprod Biol 1998;76:31– 6.

32. Contreras M. Final statement from the consensus conference on platelet transfusion. Transfusion 1998;38:796 –7.

25. Koenig JM, Christensen RD. Incidence, neutrophil kinetics, and natural history of neonatal neutropenia associated with maternal hypertension. N Engl J Med 1989; 321:557– 62.

34. Roberts WE, Perry KG, Woods JB, Files JC, Blake PG, Martin JN. The intrapartum platelet count in patients with HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome: is it predictive of later hemorrhagic complications? Am J Obstet Gynecol 1994;171:799 – 804.

26. Magann EF, Bass D, Chauhan SP, Sullivan DL, Martin RW, Martin JN. Antepartum corticosteroids: disease stabilization in patients with the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP). Am J Obstet Gynecol 1994;171:1148 –53. 27. Martin JN, Blake PG, Perry KG, McCaul JF, Hess LW, Martin RW. The natural history of HELLP syndrome: patterns of disease progression and regression. Am J Obstet Gynecol 1991;164:1500 –13.

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33. American Association of Blood Banks. Guidelines for Blood Utilization Review. Bethesda: AABB; 1994. p. 8 –11.

35. Barton JR, Sibai BM. Hepatic imaging in HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count). Am J Obstet Gynecol 1996;174:1820 –7. 36. Sibai BM, Ramadan MK, Chari RS, Friedman SA. Pregnancies complicated by HELLP syndrome (hemolysis, elevated liver enzymes and low platelets): subsequent pregnancy outcome and long-term prognosis. Am J Obstet Gynecol 1995; 172:125–9.

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