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State of the Art ⅢⅢⅢⅢⅢⅢⅢⅢⅢⅢⅢⅢⅢⅢ A Review of HELLP Syndrome

William M. Curtin, MD genesis, characteristics of affected patients, laboratory criteria for Louis Weinstein, MD 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 prolong- HELLP (, elevated liver enzymes, and low ) syndrome ing will be explored. 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 Pathogenesis understood. An increase in vascular thrombosis and activation of the The etiology of preeclampsia remains unclear with the pathogenesis system may be important in the clinical presentation of this being incompletely understood. Theories on the causation center on disorder. Laboratory criteria for the diagnosis of HELLP syndrome have abnormal placentation resulting in placental ischemia and the pro- been classically described but lack uniformity among different duction of a circulating toxic factor causing endothelial injury.6 The institutions. Aggressive management of HELLP syndrome with disturbance in endothelial cells is believed to cause vascular constric- expeditious delivery appears to yield the lowest perinatal mortality rates. tion, increased capillary leakage, and aggregation resulting in Conservative or expectant management has been associated with higher the clinical picture of , , , and throm- rates with antenatal not causing resolution of bocytopenia. the laboratory abnormalities. Resolution of laboratory abnormalities in It is unclear why certain patients with severe preeclampsia de- HELLP syndrome runs a protracted course over several days after delivery. velop HELLP syndrome. It is possible that these patients have more Despite nearly two decades since HELLP syndrome has been defined as a endothelial injury with greater activation of the coagulation system. clinical entity, treatment for the disorder still remains delivery of the Paternoster et al.7 showed evidence of a compensated disseminated patient. intravascular coagulation (DIC) in patients with HELLP syndrome when compared with normotensive control patients with preeclampsia Although the laboratory abnormalities in HELLP syndrome were without HELLP. They found statistically significant increases in described decades ago,1 it was in 1982 that Weinstein devised the plasma fibronectin and D-dimer levels and decreases in antithrom- acronym HELLP (H ϭ hemolysis, EL ϭ elevated liver enzymes, bin-III levels when the patients with HELLP syndrome were compared and LP ϭ low platelets) to define a subset of severe preeclampsia to the patients with preeclampsia. The HELLP group and the pre- seen in 29 patients.2 The need to recognize HELLP syndrome as a eclamptic group also showed significant decreases in protein C and S unique form of severe preeclampsia was emphasized, because activity as compared to the control normotensive group, but no signif- often patients were given a nonobstetric diagnosis, such as chole- icant differences in comparison to each other. Routine tests to detect cystitis or hepatitis, and treatment was delayed. Aggressive treat- DIC (, prothrombin time, partial thromboplastin time), ment with maternal stabilization and expeditious delivery was were not significantly different among the three groups with the ex- advocated to prevent maternal and perinatal mortality. ception of the partial thromboplastin time between the control and HELLP syndrome is reported to occur in 20% of women with preeclamptic group. The findings of these investigators suggest more severe preeclampsia and in 10% of women with .3 Ma- endothelial damage, consumption of coagulation inhibitors, and gann and associates4 reported the incidence of HELLP syndrome to activation of fibrinolysis in patients with HELLP syndrome than in patients with preeclampsia without HELLP and normotensive be 0.11% among all live born deliveries over a 12-year period at 7 the University of Mississippi Medical Center. Maternal mortality controls. 2,3,5 Further support for the role of an enhanced thrombotic tendency ranges from 0% to 4%. Perinatal mortality appears to be pri- 8 marily related to the at delivery. in the pathogenesis of HELLP syndrome was provided by Dekker et al. The focus of this review on HELLP syndrome will be on patho- in a study of 101 patients with severe early-onset preeclampsia, 53 of who had HELLP syndrome. They demonstrated by testing, at least 10 Department of and Gynecology (W. M. C., L. W.), Division of Maternal Fetal Medi- weeks postpartum, that greater than 50% of patients had an abnor- cine (L. W.), Medical College of Ohio, Toledo, OH. mality associated with an increased tendency toward thrombosis. The Address correspondence and reprint requests to William M. Curtin, MD, Department of Ob- stetrics & Gynecology, Medical College of Ohio, Ruppert Center, Suite 1500, 3120 Glendale most common abnormalities identified were anticardiolipin antibod- Avenue, Toledo, OH 43614-5809. ies, protein S deficiency, hyperhomocysteinemia, and activated pro-

Journal of Perinatology (1999) 19(2) 138–143 © 1999 Stockton Press. All rights reserved. 0743–8346/99 $12 138 http://www.stockton-press.co.uk A Review of HELLP Syndrome Curtin and Weinstein

tein C resistance. The authors speculated that identification of these line) or absolute hypertension (Ն140/90 mm Hg) present in all abnormalities may provide a basis for pharmacologic management in patients. Weinstein reported right upper quadrant tenderness to palpa- subsequent . tion in all patients and edema in 69%.2 Although HELLP syndrome Immunologic factors may be the underlying initiator of pre- reportedly can occur in the absence of proteinuria, the few studies eclampsia and HELLP syndrome. It is possible that a maternal cell- including data on proteinuria show that it is present in varying de- mediated immune response to pregnancy with -mediated grees in all patients.2,16 endothelial damage is important in HELLP syndrome. Haeger et al.9 reported increased plasma levels of tumor factor-␣ at the Laboratory Diagnosis time of delivery in patients with HELLP syndrome as compared to The laboratory criteria used for diagnosis of HELLP syndrome vary ␣ normal pregnant controls. - , by its effect on among institutions, and comparisons of patients between institutions endothelial cells and coagulation, may be important in the patho- are complicated by the lack of uniform definitions of the three com- physiology of preeclampsia and HELLP syndrome. ponents of the disorder. Hemolysis, the most difficult feature to detect The histologic pattern of injury in the liver in preeclampsia is one and probably the most specific, is frequently not defined. Tests for liver of deposition in the periportal sinusoids and hemorrhage into 10 enzymes include several different methods for enzyme analysis with the space of Disse with resultant hepatocellular necrosis. can varied reference ranges. has been classically de- dissect through portal connective tissue and collect to form subcapsu- Ͻ ␮ 11 fined as 100,000/ l. The following reviews diagnostic criteria used lar liver . Aarnoudse et al. studied needle biopsies of the in HELLP syndrome. liver in patients with HELLP syndrome and noted periportal lesions consisting of neutrophilic infiltrates, necrosis of and Hemolysis fibrin microthrombi, and fibrin deposits in the sinusoids. They con- Markers for hemolysis include elevated indirect and low cluded that the basic histopathologic changes in the liver are identical levels. Morphologic features on peripheral blood smear to those previously described for preeclampsia. Barton and col- that are indicative of hemolysis include schistocytosis, polychromasia leagues12 found periportal hemorrhage, fibrin deposition, and fatty (implying reticulocytosis), anisocytosis, and poikilocytosis. Schisto- infiltration in 11 patients with HELLP syndrome who were delivered cytes (red cell fragments) and burr cells (irregularly contracted red by cesarean section and underwent needle biopsy of the liver under cells with prominent spicules) are associated with small blood vessel direct visualization. They found no correlation between the severity of disease or fibrin deposition in small blood vessels and thus are fea- the histologic findings and the clinical and laboratory findings. tures of microangiopathic .17 Weinstein defined HELLP syndrome shares clinical and laboratory features with hemolysis based on the presence of and/or Burr cells on acute fatty liver of pregnancy. Liver biopsy in acute fatty liver of preg- peripheral smear and believed that microangiopathic hemolytic ane- nancy demonstrates microvesicular fatty infiltration of hepatocytes.13 mia was present to some degree in all patients with HELLP syndrome.2 Liver specimens examined for fat deposition from preeclamptic pa- Most patients with HELLP syndrome are not anemic on presentation tients with and without liver dysfunction demonstrate significant but may develop a drop in hematocrit out of proportion to the amounts of microvesicular fat.14 This has led to speculation that amount of blood loss at delivery.2 In a prospective study measuring preeclampsia, HELLP syndrome, and acute fatty liver of pregnancy are laboratory markers of hemolysis in HELLP syndrome, Wilke and col- all part of the same pathologic spectrum.14,15 leagues18 found an abnormal peripheral smear in only 11 of 25 pa- tients. In patients with normal splenic function, abnormal red cells Maternal Characteristics may be cleared rapidly from the circulation and may not be readily apparent on peripheral blood smears.19 Sibai recommended that, in HELLP syndrome occurs in women at all reproductive ages, with a addition to an abnormal blood smear, increased bilirubin and lactate mean age of approximately 24 years.2,3 It has been described in most dehydrogenase (LDH) be required for the diagnosis of hemolysis.20 ethnic groups in the United States and occurs in both primigravida Although these additional criteria may be useful in the diagnosis of and multiparous patients. Approximately 19% have pre-existing hemolysis, neither of these tests is specific. Only elevated indirect chronic hypertension.2,3 bilirubin is indicative of hemolysis, and LDH is found not only in red In Sibai and colleagues’ study3 of 442 pregnancies with HELLP blood cells, but also in liver, skeletal muscle, cardiac muscle, and syndrome, 70% were diagnosed antepartum and 30% postpartum. kidney. Paternoster et al.7 demonstrated LDH elevations in some pa- Mean gestational age at delivery is approximately 32 weeks and tients with preeclampsia and found bilirubin elevations in only 25% ranges from 24 to 39 weeks.2,5 of their patients with HELLP syndrome. Reductions in serum hapto- globin, however, were found in all patients with HELLP syndrome. In Clinical Presentation Wilke’s study18 reduced haptoglobin levels were identified in all of Presenting symptoms include malaise, right upper quadrant tender- their patients with HELLP syndrome. They also performed electro- ness, , and . elevation in HELLP syn- phoretic separation of LDH isoenzymes in five patients with HELLP drome is variable in degree, with relative (Ͼ30/15 mm Hg over base- syndrome and found that the elevated plasma LDH levels in 4 of 5

Journal of Perinatology (1999) 19(2) 138–143 139 Curtin and Weinstein A Review of HELLP Syndrome

patients were associated with a relative increase in the LDH5 isoen- and with a live upon admission, van Pampus and colleagues24 zyme, which is of liver origin.18 In summary, the most sensitive and reported a perinatal mortality rate of 19.6%. There were 10 fetal objective marker of hemolysis in the HELLP syndrome is a reduced deaths and 1 neonatal death. serum haptoglobin level. Neonatal survival in infants born to mothers with HELLP syn- drome is mainly dependent upon gestational age and at Elevated Liver Enzymes delivery. It does not appear that HELLP syndrome, independent of Hepatic injury in HELLP syndrome is manifest by elevation in aspar- gestational age, increases neonatal mortality. Magann and associates4 tate aminotransferase (AST), formerly termed serum glutamate ox- at the University of Mississippi showed that ultimate neonatal salvage aloacetate transaminase (SGOT), and alanine aminotransferase was primarily related to gestational age and birth weight at delivery (ALT), formerly serum glutamate pyruvate transaminase (SGPT). and not due to the severity of the HELLP syndrome. LDH elevation also occurs in liver injury. Although Weinstein did not Weinstein reported hematologic abnormalities (thrombocytope- define the degree of liver enzyme elevation necessary for HELLP syn- nia, leukopenia, and abnormal peripheral smears) in the neonates drome diagnosis, Sibai made specific recommendations2,3,20;hede- born to mothers with HELLP syndrome.2 He speculated that some fined elevated liver enzymes by an AST (SGOT) value of 70 U/l. The humoral substance crossing the may result in these findings. latter value correlated to three standard deviations above the mean in Neonatal thrombocytopenia has been reported in up to 50% of preg- their hospital laboratory. Other authors have used elevation of AST nancies complicated by HELLP syndrome,5 but it is not unique to this and ALT to two standard deviations above the mean to define the entity. No correlation has been demonstrated between maternal and elevated liver enzyme component of HELLP syndrome.7,21 neonatal platelet counts.22 Leukopenia and/or neutropenia were Low Platelets present in up to 40% of neonates in HELLP syndrome2,22 but have also In Weinstein’s study, 18 of 29 patients had thrombocytopenia, defined occurred in infants born to mothers with preeclampsia in the absence as a platelet count of Ͻ100,000/␮l, on admission, and all 29 patients of HELLP.25 Weinstein noted that 92% of newborn infants born to had a nadir platelet count of Ͻ100,000/␮l.2 Other authors have also mothers with HELLP syndrome had abnormal peripheral blood defined thrombocytopenia as a platelet count of Ͻ100,000/␮l.3,7,22 smears with burr cells and/or schistocytes.2 Although these findings are suggestive of hemolysis in the fetus, anemia at birth is uncom- Maternal Mortality and Morbidity mon in infants from mothers with HELLP syndrome. Little data is available on liver enzymes in infants born to mothers with HELLP Maternal mortality in HELLP syndrome ranges from 0% to 4%.2,3,5 In syndrome. Harms and colleagues22 evaluated liver enzymes in 13 Sibai’s series,3 in HELLP syndrome was from various neonates born to mothers with HELLP syndrome and found slight complications: one from ruptured liver hematoma, one from pulmo- elevations in only two. nary , and three from diffuse hypoxic encephalopathy. Ra- val5 reported one maternal death from DIC, and Weinstein2 reported one maternal death in a patient with severe microangiopathic hemo- Timing of Delivery lytic anemia, marked hyperbilirubinemia, and massive ascites. Because of the potential for maternal and perinatal mortality in As HELLP syndrome frequently occurs before term with an unfa- HELLP syndrome, aggressive management with expeditious delivery vorable cervix, cesarean section is a common mode of delivery, with 2,20,22 2,3,22 has been advocated. This does not preclude if the rates ranging from 42% to 98%. Blood product transfusion, with cervix is sufficiently ripe for induction of labor. Sibai states that, in the its associated risks, has been used frequently. One study noted transfu- absence of laboratory evidence of DIC and absent fetal lung maturity, sion in 25% of patients.23 DIC has been described in up to 15% of 23 antenatal corticosteroids to accelerate fetal lung maturity can be patients, half of whom had . Wound hematoma given with delivery 48 hours later.20 He emphasized the need for con- or infection is a common after cesarean section and 16,23 tinuous maternal and fetal monitoring during this period. Studies presents in 7% to 14% of HELLP syndrome patients. Acute renal that advocate aggressive management and delivery regardless of ges- failure has been reported as a complication in 8%, the majority sec- 2,22 3 tational age demonstrate the lowest perinatal mortality rates. ondary to acute tubular necrosis. Ecclampsia is seen in 4% to 9% of 22 3,23 Harms and colleagues managed 80 pregnancies with HELLP syn- HELLP patients. Other complications reported include severe ascites drome with immediate cesarean section, regardless of gestational age, (8%), pleural effusion (6%), (6%), and subcapsu- 3 and reported an overall perinatal mortality rate of 5.6%. lar liver hematoma requiring laparotomy (1%). In some cases, the laboratory abnormalities in HELLP syndrome will resolve with conservative management. Van Pampus et al.24 re- Perinatal Mortality and Morbidity ported a series of 51 patients with HELLP syndrome who were man- Perinatal mortality in HELLP syndrome ranges from 5% to nearly aged expectantly in order to prolong pregnancy; delivery was per- 20%.2,16,22,24 Studies that advocate expectant or temporizing manage- formed mainly for fetal indications. In 30% laboratory abnormalities ment have higher perinatal mortality rates, mainly because of still- normalized. The median prolongation of pregnancy in their entire births.16,24 In a study of 51 patients with HELLP syndrome not in labor group of patients was only 3 days. There were no maternal deaths in

140 Journal of Perinatology (1999) 19(2) 138–143 A Review of HELLP Syndrome Curtin and Weinstein

this series but forms of maternal morbidity included eclampsia, anti- that platelet counts continued to decrease until 24 to 48 hours after hypertensive treatment, temporary hemiplegia, and postpartum deep delivery. A platelet count of Ͼ100,000/␮l was spontaneously venous thrombosis. The perinatal mortality rate was 19.6% with all achieved within 72 hours of the platelet nadir in most patients in their deaths being . study. LDH levels peaked at 24 to 48 hours after delivery with a down- Visser and Wallenburg16 compared 128 patients with HELLP ward trend in LDH by the fourth postpartum day. Martin et al.28 have syndrome to 128 patients with preeclampsia at a gestational age of also advocated the use of dexamethasone in the to Ͻ34 weeks. They treated each group with bedrest, pharmacologic accelerate recovery. They performed a retrospective study of 43 women vasodilatation, and plasma volume expansion under central hemody- with postpartum HELLP syndrome who were treated with dexametha- namic monitoring. They noted no difference in pregnancy prolonga- sone (10 mg IV at 12-hour intervals until disease remission) com- tion or perinatal mortality between the two groups and concluded that pared with 237 similar patients who received no steroids. They re- their data did not support a general recommendation of prompt ter- ported more rapid normalization of platelet counts and LDH values mination of pregnancy in HELLP syndrome. There were no maternal and a reduction in transfusion, respiratory therapy, invasive hemody- deaths in either group. The mothers with HELLP syndrome had signif- namic monitoring, morbidity secondary to infection, and length of icantly more hemorrhagic problems, mainly wound postpartum hospital course. One prospective randomized trial evalu- following cesarean section. The authors noted that 43% of patients ated the routine initiation of dexamethasone in patients with postpar- with HELLP syndrome had a complete antepartum resolution. In this tum HELLP syndrome.29 The steroid-treated group had a significantly group of patients median prolongation of pregnancy was 21 days as increased platelet count by 30 hours postpartum in comparison to compared to 10 days in the entire group of HELLP patients. They had controls. There was no difference in the incidence of abnormal uter- 11 stillbirths with a median birth weight of 680 gm among the HELLP ine bleeding or wound infection in the treated and untreated groups. patients. Although was recognized before stillbirth in 10 The authors found no significant difference in blood pressure, urinary of 11 cases, the authors did not intervene because fetal growth restric- output, LDH, AST, or ALT values between the dexamethasone-treated tion at an early gestational age was believed to portend a poor prog- patients and controls at any time by 72 hours postpartum. nosis for meaningful neonatal survival. Unfortunately, one stillbirth, caused by placental abruption, occurred at 34 weeks with a birth Management of Selected Complications weight of 2370 gm. 26 Anemia Magann and associates evaluated the effect of antepartum Blood components utilized in patients with HELLP syndrome have corticosteroids in preterm HELLP syndrome in a prospective, random- included packed red cells, fresh frozen plasma, and platelets. The ized study of 25 patients with HELLP syndrome. Twelve pregnancies decision to transfuse red blood cells should be based on clinical as- with HELLP syndrome, a mean gestational age of 30.7 weeks, and a sessment of the patient’s status rather than an arbitrary ␮ mean admission platelet count of 69,300/ l were given dexametha- or hematocrit value. There are relatively few specific clinical indica- sone (10 mg) intravenously every 12 hours until delivery. The control tions for the use of fresh frozen plasma.30 without an group was 13 HELLP patients with a mean gestational age of 32.8 obvious source of bleeding, such as placental abruption or subcapsu- ␮ weeks and a mean platelet count of 106,800/ l who received no ste- lar liver hematoma, is uncommon in HELLP syndrome.23 Therefore Ͻ ␮ roids. There were no patients with platelet counts of 50,000/ l the need for FFP transfusion in HELLP syndrome would be fairly included in this study. Delivery was performed for a deteriorating infrequent. maternal or fetal condition, gestational age Ͼ34 weeks, or a platelet count of Յ50,000/␮l. The authors found the dexamethasone-treated Thrombocytopenia group had significantly increased urinary output and platelet counts Platelet transfusion therapy is an area of medicine based largely on and reduced ALT and LDH levels over time in comparison to the un- consensus rather than evidence-based guidelines.31,32 Therapeutic treated group. The steroid group had a longer interval from initiation platelet transfusion is believed to be indicated in patients with signifi- to delivery than the control group (41 versus 15 hours). The authors cant bleeding if the platelet disorder is likely to be causing or contrib- noted that steroids stabilized disease in HELLP syndrome and that the uting to this bleeding and the platelet count is Ͻ50,000/␮l.31 Al- effect was temporary. though a platelet count of Ͻ50,000/␮l in patients undergoing Expectant management, temporizing or treatment surgery is frequently cited as a threshold for prophylactic platelet cannot be advocated when there is a reasonable chance of fetal sur- transfusion,33 the risk of bleeding has not been defined. Platelet trans- vival and the diagnosis of HELLP syndrome is based on strict crite- fusion is believed to be contraindicated in thrombotic thrombocytope- ria.23 The lowest perinatal mortality rates occur with aggressive nic purpura and hemolytic uremic syndrome32; these disorders are management.2,22 characterized by platelet consumption, and are in this respect, similar to HELLP syndrome. Post Partum Course Roberts and colleagues,34 in a retrospective, descriptive study of Martin and colleagues27 evaluated the time course of disease resolu- intrapartum platelet counts in HELLP syndrome, reported an antepar- tion in 158 postpartum patients with HELLP syndrome. They found tum platelet count of Յ40,000/␮l to be predictive of postpartum

Journal of Perinatology (1999) 19(2) 138–143 141 Curtin and Weinstein A Review of HELLP Syndrome

bleeding problems. The types of bleeding problems encountered were count: a severe consequence of hypertension in pregnancy. Am J Obstet Gynecol from abdominal incision sites after cesarean delivery, and episiotomy 1982;142:159–67. sites after vaginal delivery. Mucus membrane bleeding was not a 3. Sibai BM, Ramadan MK, Usta I, Salama M, Mercer BM, Friedman SA. Maternal clinically significant problem and no patients had central nervous morbidity and mortality in 442 pregnancies with hemolysis, elevated liver en- system bleeding. The effect of prophylactic platelet transfusion was zymes, and low platelets. Am J Obstet Gynecol 1993;169:1000–6. Ͻ ␮ studied in patients with platelet counts of 40,000/ l. They found 4. Magann EF, Perry KG, Chauhan SP, Graves GR, Blake PG, Martin JN. Neonatal no difference in problems between the patients salvage by weeks gestation in pregnancies complicated by HELLP syndrome. J who received prophylactic platelet transfusion and those who did not. Soc Gynecol Invest 1994;1:206–9. Furthermore, the postpartum platelet counts in the transfused patients 5. Raval DS, Co S, Reid MA, Pildes R. Maternal and neonatal outcome of pregnan- were not significantly different from the patients who were not trans- cies complicated with maternal HELLP syndrome. J Perinatol 1997;17:266–9. fused. The data suggest that prophylactic platelet transfusion in HELLP syndrome is not of value in preventing bleeding complications 6. Van Beek E, Peters LLH. Pathogenesis of preeclampsia: a comprehensive model. and that transfused platelets are quickly consumed. Obstet Gynecol Surv 1998;53:233–9. 7. Paternoster DM, Stella A, Simioni P, Mussap M, Plebani M. Coagulation and Subcapsular Hematoma plasma fibronectin parameters in HELLP syndrome. Int J Gynecol Obstet 1995; Subcapsular liver hematoma has been reported in 1% of pregnancies 50:263–8. complicated by HELLP syndrome and may result in maternal death.3 8. Dekker GA, de Vries JIP, Doelitsch PM, et al. Underlying disorders associated with Computed tomography, magnetic resonance imaging, or ultrasound severe early-onset preeclampsia. Am J Obstet Gynecol 1995;173:1042–8. can be used to detect and monitor this complication.35 Barton and Sibai35 have recommended close observation in women with unrup- 9. Haeger M, Unander M, Andersson B, Tarkowski A, Arnestad JP, Bengtsson A. tured subcapsular hematoma, provided that maternal condition is Increased release of tumor necrosis factor-alpha and interleukin-6 in women stable. Hematoma size can be followed by serial computed tomogra- with the syndrome of hemolysis, elevated liver enzymes and low platelet count. Acta Obstet Gynecol Scand 1996;75:695–701. phy or ultrasound until the defect resolves. Ruptured liver hematoma is a surgical emergency with evacuation and drainage of the hema- 10. Crawford JM. The liver and the biliary tree. In: Cotrans RS, Kumar V, Robbins SL, toma, packing as needed and suturing of lacerations if possible.35 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 Recurrence Risk in Subsequent Pregnancies damage and intravascular coagulation in the last trimester of normotensive Sullivan et al.21 found, in patients with a prior pregnancy affected by pregnancy: a clinical and histopathological study. Br J Obstet Gynaecol 1986;93: HELLP syndrome and a nadir platelet count of Յ100,000/␮l, a 19% 145–55. incidence of HELLP syndrome and a 23% incidence of preeclampsia- 12. Barton JR, Riely CA, Adamec TA, Shanklin DR, Khoury AD, Sibai BM. Hepatic eclampsia in subsequent pregnancies. Sibai and colleagues36 at the histopathologic condition does not correlate with laboratory abnormalities in University of Tennessee reported recurrent preeclampsia in 19% but HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count). recurrent HELLP syndrome in only 3%. Am J Obstet Gynecol 1992;167:1538–43. 13. Schorr-Lesnick B, Lebovic E, Dworkin B, Rosenthal WS. Liver diseases unique to Conclusion pregnancy. Am J Gastroenterol 1991;86:659–70. 14. Minakami H, Oka N, Sato T, Tamada T, Yasuda Y, Hirota N. Preeclampsia: a Widespread recognition and earlier diagnosis of HELLP syndrome as a microvesicular fat disease of the liver? Am J Obstet Gynecol 159:1043–7. variant of severe preeclampsia have lead to an improvement in mater- nal and perinatal outcome. Unfortunately, the only cure for HELLP 15. Dani R, Mendes GS, de Laurentys Medeiros J, Peret FJ, Nunes A. Study of the liver syndrome is delivery, even at early gestational ages. Further advance- changes occurring in preeclampsia and their possible pathogenetic connection ment in prevention and possibly treatment of the disorder will rest with acute fatty liver of pregnancy. Am J Gastroenterol 1996;91:292–4. upon a more complete understanding of the etiology and pathogene- 16. Visser W, Wallenburg HCS. Temporising management of severe pre-eclampsia sis of preeclampsia. At this time, the clinician is advised to consider with and without the HELLP syndrome. Br J Obstet Gynaecol 1995;102:111–7. aggressive management with expeditious delivery when treating a 17. Morris MW, Davey FR. Basic examination of blood. In: Henry JB, editor. Clinical patient with HELLP syndrome. Diagnosis and Management by Laboratory Methods, 19th Edition. Philadelphia: WB Saunders & Co.; 1996. p. 579. References 18. Wilke G, Schutz E, Armstrong VW, Kuhn W. Haptoglobin as a sensitive marker of 1. Pritchard JA, Weisman R, Ratnoff OD, Vosburgh GJ. Intravascular hemolysis, hemolysis in HELLP-syndrome. Int J Gynecol Obstet 1992;39:29–34. thrombocytopenia, and other hematologic abnormalities associated with severe 19. Pincus MR. Interpreting laboratory results: reference values and decision mak- toxemia of pregnancy. N Engl J Med 1954;250:89–98. ing. In: Henry JB, editor. Clinical Diagnosis and Management by Laboratory 2. Weinstein L. Syndrome of hemolysis, elevated liver enzymes, and low platelet Methods, 19th Edition. Philadelphia: WB Saunders & Co.; 1996. p. 79.

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20. Sibai BM. The HELLP syndrome (hemolysis, elevated liver enzymes and low 28. Martin JN, Perry KG, Blake PG, May WA, Moore A, Robinette L. Better outcomes platelets): much ado about nothing? Am J Obstet Gynecol 1990;162:311–6. are achieved with dexamethasone therapy for postpartum HELLP (hemolysis, 21. Sullivan CA, Magann EF, Perry KG, Roberts WE, Blake PG, Martin JN. The recur- elevated liver enzymes, and thrombocytopenia) syndrome. Am J Obstet Gynecol rence risk of the syndrome of hemolysis, elevated liver enzymes, and low platelets 1997;177:1011–7. (HELLP) in subsequent gestations. Am J Obstet Gynecol 1994;171:940–3. 29. Vigil-De Gracia P, Garcia-Caccrcs E. Dexamethasone in the post-partum treat- ment of HELLP syndrome. Int J Gynaecol Obstet 1997;59:217–21. 22. Harms K, Rath W, Herting E, Kuhn W. Maternal hemolysis, elevated liver en- zymes, low platelet count, and neonatal outcome. Am J Perinatol 1995;12:1–7. 30. NIH Consensus Conference. Fresh frozen plasma: indications and risk. JAMA 1985;253:551–3. 23. Audibert F, Friedman SA, Frangieh AY, Sibai BM. Clinical utility of strict diagnos- tic criteria for the HELLP syndrome (hemolysis, elevated liver enzymes, and low 31. NIH Consensus Conference. Platelet transfusion therapy. JAMA 1987;257:1777– platelets) syndrome. Am J Obstet Gynecol 1996;175:460–4. 80. 24. van Pampus MG, Wolf H, Westenberg SM, van der Post JAM, Bonsel GJ, Treffers 32. Contreras M. Final statement from the consensus conference on platelet transfu- PE. Maternal and perinatal outcome after expectant management of the HELLP sion. Transfusion 1998;38:796–7. syndrome compared with preeclampsia without HELLP syndrome. Eur J Obstet 33. American Association of Blood Banks. Guidelines for Blood Utilization Review. Gynecol Reprod Biol 1998;76:31–6. Bethesda: AABB; 1994. p. 8–11. 25. Koenig JM, Christensen RD. Incidence, neutrophil kinetics, and natural history of 34. Roberts WE, Perry KG, Woods JB, Files JC, Blake PG, Martin JN. The intrapartum neonatal neutropenia associated with maternal hypertension. N Engl J Med 1989; platelet count in patients with HELLP (hemolysis, elevated liver enzymes, and 321:557–62. low platelets) syndrome: is it predictive of later hemorrhagic complications? Am J 26. Magann EF, Bass D, Chauhan SP, Sullivan DL, Martin RW, Martin JN. Antepar- Obstet Gynecol 1994;171:799–804. tum corticosteroids: disease stabilization in patients with the syndrome of hemo- 35. Barton JR, Sibai BM. Hepatic imaging in HELLP syndrome (hemolysis, elevated lysis, elevated liver enzymes, and low platelets (HELLP). Am J Obstet Gynecol liver enzymes, and low platelet count). Am J Obstet Gynecol 1996;174:1820–7. 1994;171:1148–53. 36. Sibai BM, Ramadan MK, Chari RS, Friedman SA. Pregnancies complicated by 27. Martin JN, Blake PG, Perry KG, McCaul JF, Hess LW, Martin RW. The natural HELLP syndrome (hemolysis, elevated liver enzymes and low platelets): subse- history of HELLP syndrome: patterns of disease progression and regression. Am J quent pregnancy outcome and long-term prognosis. Am J Obstet Gynecol 1995; Obstet Gynecol 1991;164:1500–13. 172:125–9.

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