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Severe hypoglycemia associated with HELLP syndrome
Severe hypoglycemia associated with HELLP syndrome Charles C. Egley, M.D., JoAnne Gutliph, M.D., and Watson A. Bowes, Jr., M.D. Chapel Hill, North Caroli1Ul Presented is a case of the syndrome of hemolysis, elevated liver enzymes, and low platelet counts, in which severe maternal hypoglycemia occurred 8 hours after delivery. It is proposed that the hepatic pathologic features in this case were severe enough to interfere with glycogenolysis and glyconeogenesis. (AM J 0BSTET GYNECOL 1985;152:576-7.)
Key words: HELLP syndrome, preeclampsia, hypoglycemia This article describes a case of severe maternal hypoglycemia associated with the syndrome of hemolysis, elevated liver enzymes, and low platelet counts (HELLP). Case report R. C., an 18-year-old primigravid woman, presented at 30 weeks' gestation with uterine contractions, vaginal bleeding, and a 2-week history of nausea, vomiting, and epigastric pain. Her prenatal course was remarkable only in that a twin gestation had been diagnosed 7 weeks previously. Blood pressure values had been normal at each prenatal visit, and proteinuria had been absent. On admission, she was found to have scleral icterus, jaundice of mucous membranes, mild epigastric tenderness, pretibial edema, hyperreflexia, a blood pressure of 156/108 mm Hg and proteinuria (1 +).Fetal heart tones could not be heard, and real-time sonography confirmed the death of both fetuses. Admission laboratory tests included: hematocrit, 43%; platelet count, 156,000/mm'; fibrinogen, 37 mg/dl; amylase, 69 U/L; and uric acid, 13.7 mg/dl. Liver function tests included: serum glutamic oxaloacetic transaminase, 140 U/ml; serum glutamic pyruvic transaminase, 97 U/ ml; lactate dehydrogenase, 776 U/dl; alkaline phosphatase, 303 U/ml; total bilirubin, 11.3 mg/dl; and serum albumin, 3.1 gm/100 ml. An intravenous infusion of lactated Ringer's solution was started, and intravenous magnesium sulfate therapy was instituted. Three hours after admission, the patient was delivered of a 2,160 gm stillborn male infant and an 1,800 gm stillborn female infant. Blood lost at delivery was estimated at 600 ml. During the remainder of the patient's hospitalization, the diastolic blood pressure values remained between 90 and 100 torr. By 3 hours after delivery, the hemaFrom the Division of Maternal and Fetal Medicine, Department of Obstetrics and Gynecology, University of North Carolina School of Medicine. Received for publication September 25, 1984; revised November 27, 1984; accepted December 11, 1984.
Reprint requests: Dr. Charles C. Egley, 214 MacNider Bldg., 202H, University of North Carolina, Chapel Hill, NC 27514.
576
tocrit had fallen to 31.6%, and schistocytes were found on peripheral smear. Eight hours after delivery, the patient suddenly became unresponsive and developed decerebrate posturing. The blood pressure was 140/90 mm Hg. Arterial blood gases included: pH, 7.43; Pco2 , 40; and Po2 , 87. The serum magnesium level was 5.3 mEq/L; calcium, 9.3 mg/dl; fibrinogen, 23 mg/dl; platelet count, 109,000/mm'; and plasma glucose, 3 mg/dl. She became immediately responsive after the intravenous administration of 100 gm of glucose. All intravenous lines and bags were analyzed for insulin, and no evidence of exogenous insulin was found. Thereafter, all intravenous infusions contained 5% dextrose. There were no subsequent episodes of hypoglycemia. By 18 hours after delivery, the platelet count had fallen to 94,000/mm', and the fibrinogen level to 14 mg/dl. Levels of clotting factors V and VII were 20% and 11%, respectively, thus implying a failure of hepatic synthesis of these factors as a major contributor to the coagulopathy. Although the patient continued to do well clinically, with no excessive vaginal bleeding, by the fourth postpartum day, she continued to have depressed levels of hepatically produced clotting factors, including factors V (53%), VII (12%), IX (25%), and X (37%). The total bilirubin was 9.3 mg/dl, with a direct component of 5.9 mg/dl. The serum albumin was 1.7 gm/100 ml. The platelet count had increased to 166,000/mm'. Hepatitis B screening tests (HBSAg, HBSAb, HBCAb, HACAb) were negative. A sonogram of the gallbladder was normal. The intravenous infusions were discontinued, and subsequent plasma glucose values were in the normal range. By the sixth postpartum day, all coagulation tests produced normal values. Six weeks after delivery, all findings on liver function tests, coagulation studies, and a fasting plasma glucose test were normal. Comment At the time of admission, this patient was thought to have the HELLP syndrome and twin fetal death. HELLP syndrome, as described by Weinstein,' is characterized by thrombocytopenia, hemolysis (microangio-
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pathic anemia), and abnormal liver enzymes in the preeclamptic or eclamptic patient. Killam et al. 2 had earlier described five similar cases of pregnancy-induced hypertension complicated by acute liver disease and disseminated intravascular coagulation. One of Killam et al.'s patients was described as having moderate scleral icterus. Both Weinstein and Killam et al. recommended aggressive management with expedient delivery. Thus, our patient was treated with magnesium sulfate, and delivery was assured. Postpartum, she was found to be in a hypoglycemic coma approximately 7 hours after intravenous fluid had been changed from glucose-containing solution to lactated Ringer's solution. Known causes of hypoglycemia, including exogenous insulin administration, an insulin-secreting tumor, and panhypopituitarism, were excluded. Hypoglycemia has not been described as being part of the HELLP syndrome. Hypoglycemia, however, has been well described as part of the syndrome of acute fatty liver of pregnancy. The exact relationship between preeclampsia and acute fatty liver of pregnancy remains undetermined. Possibly, a spectrum of hepatic damage ranging from preeclampsia to HELLP syndrome to acute fatty liver of pregnancy may occur in pregnancy. Indeed, Pockros
Hypoglycemia and HELLP syndrome
577
et aP report that, in cases of acute fatty liver of pregnancy, "early recognition of hypoglycemia and prevention of coma by dextrose infusions has significantly lowered the number of patients who became encephalopathic." In any case, it appears that early delivery and meticulous supportive care are the mainstays of therapy. The hepatic pathologic features in this case of HELLP syndrome appear to have been severe enough to have interfered not only with the production of hepatically produced coagulation factors, but also with glycogenolysis and glyconeogenesis. Careful attention to hypoglycemia and clotting factors is essential. This case illustrates in particular the need for continuous infusions of dextrose and monitoring of serum glucose. REFERENCES I. Weinstein L. Syndrome of hemolysis, elevated liver enzymes, and low platelet count: a severe consequence of hypertension of pregnancy. AMJ 0BSTET GYNECOL 1982; 142:159. 2. Killam AP, Dillard SH, Patton RC, Pederson PR. Pregnancy-induced hypertension complicated by acute liver disease and disseminated intravascular coagulation. AMJ OBSTETGYNECOL 1975;123:823. 3. Pockros PJ, Peters RL, Reynolds TB. Idiopathic fatty liver of pregnancy: findings in ten cases. Medicine 1984;63: I.
Key words: HELLP syndrome, preeclampsia, hypoglycemia This article describes a case of severe maternal hypoglycemia associated with the syndrome of hemolysis, elevated liver enzymes, and low platelet counts (HELLP). Case report R. C., an 18-year-old primigravid woman, presented at 30 weeks' gestation with uterine contractions, vaginal bleeding, and a 2-week history of nausea, vomiting, and epigastric pain. Her prenatal course was remarkable only in that a twin gestation had been diagnosed 7 weeks previously. Blood pressure values had been normal at each prenatal visit, and proteinuria had been absent. On admission, she was found to have scleral icterus, jaundice of mucous membranes, mild epigastric tenderness, pretibial edema, hyperreflexia, a blood pressure of 156/108 mm Hg and proteinuria (1 +).Fetal heart tones could not be heard, and real-time sonography confirmed the death of both fetuses. Admission laboratory tests included: hematocrit, 43%; platelet count, 156,000/mm'; fibrinogen, 37 mg/dl; amylase, 69 U/L; and uric acid, 13.7 mg/dl. Liver function tests included: serum glutamic oxaloacetic transaminase, 140 U/ml; serum glutamic pyruvic transaminase, 97 U/ ml; lactate dehydrogenase, 776 U/dl; alkaline phosphatase, 303 U/ml; total bilirubin, 11.3 mg/dl; and serum albumin, 3.1 gm/100 ml. An intravenous infusion of lactated Ringer's solution was started, and intravenous magnesium sulfate therapy was instituted. Three hours after admission, the patient was delivered of a 2,160 gm stillborn male infant and an 1,800 gm stillborn female infant. Blood lost at delivery was estimated at 600 ml. During the remainder of the patient's hospitalization, the diastolic blood pressure values remained between 90 and 100 torr. By 3 hours after delivery, the hemaFrom the Division of Maternal and Fetal Medicine, Department of Obstetrics and Gynecology, University of North Carolina School of Medicine. Received for publication September 25, 1984; revised November 27, 1984; accepted December 11, 1984.
Reprint requests: Dr. Charles C. Egley, 214 MacNider Bldg., 202H, University of North Carolina, Chapel Hill, NC 27514.
576
tocrit had fallen to 31.6%, and schistocytes were found on peripheral smear. Eight hours after delivery, the patient suddenly became unresponsive and developed decerebrate posturing. The blood pressure was 140/90 mm Hg. Arterial blood gases included: pH, 7.43; Pco2 , 40; and Po2 , 87. The serum magnesium level was 5.3 mEq/L; calcium, 9.3 mg/dl; fibrinogen, 23 mg/dl; platelet count, 109,000/mm'; and plasma glucose, 3 mg/dl. She became immediately responsive after the intravenous administration of 100 gm of glucose. All intravenous lines and bags were analyzed for insulin, and no evidence of exogenous insulin was found. Thereafter, all intravenous infusions contained 5% dextrose. There were no subsequent episodes of hypoglycemia. By 18 hours after delivery, the platelet count had fallen to 94,000/mm', and the fibrinogen level to 14 mg/dl. Levels of clotting factors V and VII were 20% and 11%, respectively, thus implying a failure of hepatic synthesis of these factors as a major contributor to the coagulopathy. Although the patient continued to do well clinically, with no excessive vaginal bleeding, by the fourth postpartum day, she continued to have depressed levels of hepatically produced clotting factors, including factors V (53%), VII (12%), IX (25%), and X (37%). The total bilirubin was 9.3 mg/dl, with a direct component of 5.9 mg/dl. The serum albumin was 1.7 gm/100 ml. The platelet count had increased to 166,000/mm'. Hepatitis B screening tests (HBSAg, HBSAb, HBCAb, HACAb) were negative. A sonogram of the gallbladder was normal. The intravenous infusions were discontinued, and subsequent plasma glucose values were in the normal range. By the sixth postpartum day, all coagulation tests produced normal values. Six weeks after delivery, all findings on liver function tests, coagulation studies, and a fasting plasma glucose test were normal. Comment At the time of admission, this patient was thought to have the HELLP syndrome and twin fetal death. HELLP syndrome, as described by Weinstein,' is characterized by thrombocytopenia, hemolysis (microangio-
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pathic anemia), and abnormal liver enzymes in the preeclamptic or eclamptic patient. Killam et al. 2 had earlier described five similar cases of pregnancy-induced hypertension complicated by acute liver disease and disseminated intravascular coagulation. One of Killam et al.'s patients was described as having moderate scleral icterus. Both Weinstein and Killam et al. recommended aggressive management with expedient delivery. Thus, our patient was treated with magnesium sulfate, and delivery was assured. Postpartum, she was found to be in a hypoglycemic coma approximately 7 hours after intravenous fluid had been changed from glucose-containing solution to lactated Ringer's solution. Known causes of hypoglycemia, including exogenous insulin administration, an insulin-secreting tumor, and panhypopituitarism, were excluded. Hypoglycemia has not been described as being part of the HELLP syndrome. Hypoglycemia, however, has been well described as part of the syndrome of acute fatty liver of pregnancy. The exact relationship between preeclampsia and acute fatty liver of pregnancy remains undetermined. Possibly, a spectrum of hepatic damage ranging from preeclampsia to HELLP syndrome to acute fatty liver of pregnancy may occur in pregnancy. Indeed, Pockros
Hypoglycemia and HELLP syndrome
577
et aP report that, in cases of acute fatty liver of pregnancy, "early recognition of hypoglycemia and prevention of coma by dextrose infusions has significantly lowered the number of patients who became encephalopathic." In any case, it appears that early delivery and meticulous supportive care are the mainstays of therapy. The hepatic pathologic features in this case of HELLP syndrome appear to have been severe enough to have interfered not only with the production of hepatically produced coagulation factors, but also with glycogenolysis and glyconeogenesis. Careful attention to hypoglycemia and clotting factors is essential. This case illustrates in particular the need for continuous infusions of dextrose and monitoring of serum glucose. REFERENCES I. Weinstein L. Syndrome of hemolysis, elevated liver enzymes, and low platelet count: a severe consequence of hypertension of pregnancy. AMJ 0BSTET GYNECOL 1982; 142:159. 2. Killam AP, Dillard SH, Patton RC, Pederson PR. Pregnancy-induced hypertension complicated by acute liver disease and disseminated intravascular coagulation. AMJ OBSTETGYNECOL 1975;123:823. 3. Pockros PJ, Peters RL, Reynolds TB. Idiopathic fatty liver of pregnancy: findings in ten cases. Medicine 1984;63: I.