High-Dose Corticosteroids in the Treatment of HELLP Syndrome

Lynda J. Solheim, MD; Peter S. Bernstein, MD, MPH


March 18, 2004

Hemolysis, abnormal liver function tests, and thrombocytopenia have been recognized as complications of pregnancy for many years. Some of these components were first reported in the obstetric literature over 100 years ago. In 1892, Schmorl first described coagulation defects and microthrombi. In 1982, Dr. Louis Weinstein coined the term HELLP syndrome (Hemolysis, Elevated Liver enzymes, and Low Platelets) when he described 29 cases of severe preeclampsia-eclampsia complicated by thrombocytopenia, abnormal peripheral smear, and abnormal liver function tests.[1] The need to recognize HELLP as a unique form of severe preeclampsia was apparent, because patients were often given a nonobstetric diagnosis and treatment was delayed. He proposed that HELLP syndrome was a severe consequence of hypertension in pregnancy -- separate from preeclampsia -- and that women were being misdiagnosed. Debate still exists regarding whether HELLP syndrome is a disease entity, a severe manifestation of preeclampsia, or part of a continuum.

There is also considerable debate regarding the definition, diagnosis, incidence, etiology, and management of HELLP syndrome. It is a multisystem disease that is characterized by microangiopathic hemolytic anemia, hepatic dysfunction, and thrombocytopenia. Sibai estimated it to affect 2% to 20% of patients labeled with severe preeclampsia[2,3] and 10% of women with eclampsia.[3] It is often insidious in onset and not accompanied by the usual signs of preeclampsia, hypertension, and proteinuria, and therefore is easy to miss in its earlier, milder form. Criteria to establish the diagnosis of HELLP syndrome generally accepted are as follows:

  1. Hemolysis: abnormal peripheral smear, increased bilirubin < 1.2 mg/dL, and increased lactic dehydrogenase > 600 IU/L;

  2. Elevated liver enzymes: aspartate aminotransferase (AST) ≥ 72 IU/L, lactate dehydrogenase (LDH) > 600 IU/L; and

  3. Thrombocytopenia: platelet count < 100,000/mm3.

Martin and colleagues[4] developed the Mississippi triple class system to classify patients on the basis of thrombocytopenia severity, which is in common use today. Class 1 is defined by the presence of microangiopathic hemolytic anemia and hepatic dysfunction in addition to a maternal platelet nadir ≤ 50,000/microL, class 2 by a platelet nadir > 50,000 to ≤ 100,000/microL, and class 3 by a platelet nadir > 100,000 to ≤ 150,000/microL.

The etiology and pathogenesis of preeclampsia and HELLP syndrome remain unclear. Some theories center on the explanation that abnormal placentation results in placental ischemia and the production of a circulating toxin that causes endothelial cell injury.[5] The injury is believed to cause vascular constriction within multiple organ systems, activation of the coagulation system, increased capillary permeability, and platelet activation with platelet consumption in the microvasculature, all resulting in hypertension, proteinuria, edema, and thrombocytopenia. Why certain women with severe preeclampsia develop HELLP syndrome is unclear, but it has been postulated that these women may have more endothelial injury with greater activation of the coagulation system. Immunologic factors have also been proposed as the underlying initiator of preeclampsia and HELLP syndrome. Maternal cell-mediated immune response to pregnancy with cytokine-mediated endothelial damage may be an important factor.

HELLP syndrome occurs across all ethnicities, races, socioeconomic classes, and age ranges. It is seen in both primigravidas and multiparous patients. Presenting symptoms include epigastric or right upper quadrant pain (65%), nausea and vomiting (50%), malaise (90%), and nonspecific viral syndrome-like symptoms; some patients may present with hematuria or gastrointestinal bleeding.[3] Hypertension and proteinuria may be absent or only slightly abnormal. The differential diagnosis is vast and includes acute fatty liver of pregnancy, appendicitis, gallbladder disease, gastroenteritis, hemolytic uremic syndrome, hepatic encephalopathy, systemic lupus erythematosus, thrombotic thrombocytopenic purpura, and viral hepatitis.

Maternal complications seen in pregnancies complicated by HELLP syndrome include blood product transfusion, disseminated intravascular coagulation, pleural effusion, acute renal failure, abruptio placentae, ascites, pulmonary edema, cerebral edema, retinal detachment, laryngeal edema, subcapsular liver hematoma, adult respiratory distress syndrome, and maternal and fetal death.[3] The severity of these potential complications emphasizes why rapid resolution of this disease process is an important focus for all obstetricians.

Martin and colleagues[6] retrospectively studied the course of disease progression and regression in 158 patients with HELLP syndrome treated at the University of Mississippi between 1980 and 1989 to better understand the time course and pattern of laboratory abnormalities ( Table 1 ). They observed that in class 1 HELLP, most patients had a platelet nadir on postpartum day (PPD) 1, and all patients achieved a platelet count > 100,000/mm3 by PPD 11. Class 2 patients saw a platelet nadir between PPD 1 and 2, and all patients achieved a platelet count > 100,000/mm3 by PPD 6. Class 1 achieved an LDH peak on PPD 2 and class 2 saw a peak on PPD 1. Hematocrit nadir occurred on PPD 2 in class 1 and PPD 3 in class 2. Serum concentrations of AST and ALT paralleled that of LDH, with AST generally higher than ALT during the acute phase of the disease, around delivery. The disease appeared to achieve peak intensity during the first 24 to 48 hours after delivery.[6] How rapidly a patient recovers from HELLP syndrome depends on many factors, including when in the course of the disease delivery is achieved, with expectant management being associated with more severe disease and longer recovery (ie, some patients never reach a class 1 level because they are delivered before then, so recovery is faster.)

As noted previously, many of the signs, symptoms, and hematologic and biochemical abnormalities found in patients with HELLP syndrome are also associated with a number of medical and surgical disorders. The management of HELLP syndrome is therefore often complicated by treatments that are inappropriate or misguided due to inaccurate diagnosis, which adds to the controversy surrounding the treatment of HELLP syndrome. Sibai summarized some of the modalities described in the literature that were used to treat or reverse this syndrome.[2] (See Table 2 .)

There are few randomized, controlled trials that have looked at treatment of HELLP syndrome. One intervention, which seems promising, is the use of high-dose corticosteroids. Magann and colleagues[7] studied 40 women with HELLP syndrome who were randomized immediately postpartum; 20 were assigned to a high-dose steroid group (dexamethasone q12h [10 mg, 10 mg, 5 mg, 5 mg] over 36 hours), and 20 were assigned to the control group, who received no steroids. The steroid group recovered from the disease process more rapidly, as measured by mean arterial pressure, urinary output, platelet count, LDH, and AST. Vigil-De Gracia and colleagues[8] also compared the puerperal courses of women with HELLP syndrome: 17 received postpartum dexamethasone 10 mg q12h x 3 doses, and 17 received no corticosteroids during the puerperium course. The steroid-treated group had an accelerated recovery of their platelet count, but not their liver enzymes and blood pressure. Similarly, Yalcin and colleagues[9] studied 30 patients with HELLP syndrome, 15 randomly assigned to dexamethasone (10 mg then 10 mg then 5 mg and finally 5 mg given at 12-hour intervals over 36 hours postpartum) and 15 who did not receive any steroids. The study group showed statistically significant improvement in mean arterial blood pressure, AST level, urine output, and platelet count.

It appears that the use of steroids helps to expedite improvement of laboratory parameters and thus may shorten the hospital course and prevent major maternal complications. ACOG practice guidelines on the management of HELLP syndrome do not yet endorse routine use of corticosteroids because of the small amount of evidence proving its benefit. Many centers around the world have begun to use a high-dose corticosteroid regimen in the treatment of HELLP syndrome because of the findings of the studies mentioned above -- the laboratory improvements, a potential effect on length of hospitalization, the potential for increased safety when using regional anesthesia in labor, and potentially reduced maternal and fetal complications. Treatment options otherwise consist of supportive care and hopeful waiting, with management of complications as they arise.

This promising therapy has the potential to revolutionize the management of HELLP syndrome. It seems warranted on the basis of the small amount of data currently available to consider this therapy for the patients with the most severe cases of this serious condition. However, in view of the small number of randomized, controlled trials and case reports in the literature, a larger randomized controlled trial is needed to better elucidate the risks and benefits of this therapy and to determine which patients are the best candidates for it.


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