Imitators of severe pre-eclampsia 197ascites and bleeding from severe coagulopathy. Because of Table 1 Imitators of Severe Pre-eclampsia/HELLP Syndromethese ﬁndings, the diagnosis may be initially confused with ● AFLPpre-eclampsia.1,2,6 Neurologic ﬁndings may range from nor- ● TTPmal to lethargy, agitation, confusion, and even coma.8,9,13,14 ● HUS ● Exacerbation of lupus erythematosusLaboratory Findings ● Catastrophic antiphospholipid syndromeThe complete blood count usually reveals hemoconcentra- ● Systemic viral sepsis (disseminated herpes) ● Systemic inﬂammatory response syndrome/septic shocktion, elevated white blood count, and platelet count that is ● Other conditions (cholestasis of pregnancy, necrotizinginitially normal but may be low.1-6 Coagulation ﬁndings re- pancreatitis, etc.)veal low ﬁbrinogen, prolonged prothrombin time (PT), andlow levels of antithrombin.1-10 These abnormalities are re-lated to reduced production of these factors by the liver andare consistent with disseminated intravascular coagulopathy is not possible to be performed once the tissue has been(DIC). In contrast, the DIC seen in severe pre-eclampsia and submitted to routine parafﬁn blocks. Liver biopsy should beabruptio placentae is due to abnormal consumption.15 Serum performed only after correction of coagulopathy. However,electrolytes will reveal evidence of metabolic acidosis with this is rarely used in clinical practice, and the diagnosis iselevated creatinine and uric acid values. Blood sugar may be usually made based on clinical and laboratory ﬁndings.1-9normal but is usually low in the postpartum period.1-6,8,9,13 In addition to the other conditions listed in Box I, theBlood sugars may also be elevated in association with second- differential diagnosis of AFLP should include idiopathic cho-ary pancreatitis.1,8 Liver enzymes, such as AST, ALT, alkaline lestasis of pregnancy, Budd-Chiari syndrome, adult-onsetphosphatase, and bilirubin, will be elevated. The increase in Reye’s syndrome, and drug-induced hepatic toxicity (acet-bilirubin is mainly of the conjugated form, with levels usually aminophen overdose, tetracycline-induced toxicity, anticon-exceeding 5 mg/dL. Ammonia levels are also increased, par- vulsant drugs hypersensitivity, and methyldopa hepati-ticularly in late stage of the disease. Amylase and lipase values tis).1,4,21may be elevated in the presence of concomitant pancreati-tis.1,8 Hepatitis proﬁle for A, B, and C will be negative. Ultrasonography of the liver may reveal the presence of Maternal and Perinatal Complicationsincreased echogenicity in severe cases; however, it is less AFLP is associated with an increased risk of maternal mortal-sensitive than computed tomography (CT) and magnetic res- ity and morbidities. In the past, the rate of maternal death wasonance imaging (MRI).16-20 In addition, quantitation of liver close to 70%; however, recent data indicate a mortality rate ofdensity by ultrasound is subjective and operator-dependent. Ͻ10%, but maternal complications remain high. Table 1 descri-CT scan of the liver may show decrease or diffuse attenuation bes maternal complications in recent series of AFLP.1-11,14,22,23in the liver. However, none of these techniques are sufﬁ- Recently, Davidson and coworkers reported on three womenciently sensitive to exclude a diagnosis of AFLP.2,20 with triplet gestation who had AFLP proven by liver biopsy Liver biopsy is the gold standard for conﬁrming the diag- who survived. They suggested that women with triplets are atnosis of AFLP. Histopathologic ﬁndings in AFLP reveal swol- increased risk for AFLP because of potential for increasedlen, pale hepatocytes with central nuclei.21 The diagnosis can production of fatty acid metabolites by three fetuses. It hasbe made only on a frozen section liver biopsy with special been suggested that the improved maternal survival in recentstains for fat, such as oiled red (O).1,4 Plans to perform this years was related to the supportive care and aggressive man-stain should be made before the biopsy procedure because it agement of serious maternal complications by a multidisci- plinary group of physicians from various specialties.2-9 Recently, Knight, and coworkers11 reported a prospective national study of AFLP in the UK. The participants included 57 women with AFLP diagnosed mostly by clinical criteria; 55 had abdominal ultrasound scan, but only 12 (27%) had either ascites and/or abnormal liver ﬁndings. Forty-two (74%) were diagnosed antepartum and 15 (26%) postpartum (within 4 days of delivery). In general, most of these patients had a biochemical diagnosis of AFLP (mild prolongation of PT, PTT, normal platelets), only 8 (16%) had acute renal failure, and 4 (7%) required ventilatory support. There was only 1 maternal death (1.8%) in a patient who received a liver transplant.14 Both perinatal mortality and morbidities are increased in patients of AFLP.2-9,20 The perinatal mortality among 160 births (142 pregnancies) in recent case series was 13.1%.9,22Figure 1 Liver biopsy ﬁndings in herpes hepatitis. (Color version of In addition, neonatal morbidity remains high because of theﬁgure is available online.) high rate of preterm delivery (74%) among reported cases.
198 B.M. SibaiThe average gestational age at delivery was 34 weeks (range, can be used to maintain blood sugars above 60 mg/dL. Ane-25-42 weeks).2-9,22 mia and DIC should be treated as needed by a packed red In the study by Knight and coworkers,11 the perinatal mor- blood cells, platelets, and fresh frozen plasma. It is importanttality was 10.4% among 67 infants (6 stillbirths and 1 neo- to aggressively treat maternal hypotension to avoid furthernatal death). injury to the liver, kidneys, and other organs. Invasive hemo- dynamic monitoring may be necessary in some patients to assess fully the intravascular volumes and maintain cardiacManagement of AFLP output, and in patients who develop acute respiratory dis-The clinical course of women with AFLP is usually character- tress syndrome (ARDS).ized by progressive and sometimes sudden deterioration in Pancreatitis is a potentially lethal complication of AFLP,maternal and fetal conditions.9 Therefore, patients in whom and thus all patients with AFLP should undergo serial screen-AFLP is considered require hospitalization in a labor and ing of serum lipase and amylase for several days after thedelivery unit. Fetal heart rate monitoring and/or performing onset of hepatic dysfunction.1,8 Abnormalities in these en-of a biophysical proﬁle should be performed concurrently zymes typically appear after hepatic and renal dysfunction.with maternal evaluation. Evidence of fetal compromise may The development of pseudocysts with secondary infectionsbe present even in those with stable maternal conditions. or hemorrhagic pancreatitis with resultant retroperitonealNonreassuring fetal testing may be secondary to maternal bleeding increases the risk for maternal death.8acidosis and/or reduced uteroplacental blood ﬂow.1-6 The In general, most patients with AFLP will start to improvepresence of maternal acidosis may be reﬂected in reduced- 2-3 days after delivery. In some cases, however, deteriorationto-absent fetal movement, absent fetal breathing, or tone dur- in liver function tests, renal function, mental status, and co-ing biophysical proﬁle testing.1 agulopathy may continue for about 1 week. In such cases, The next step in management is to conﬁrm or exclude the some authors suggest using plasmapheresis to improve ma-diagnosis of AFLP according to the clinical ﬁndings and re- ternal outcome. This method of treatment was recently re-sults of blood tests.1,23 The presence of bleeding and/or severe ported in six such cases with no maternal death. However,coagulopathy requires transfusion with fresh frozen plasma the value of such therapy remains unclear. In rare cases, aand other blood products as needed. The ultimate treatment patient will progress into fulminant hepatic failure, requiringfor this condition is maternal stabilization and delivery be- liver transplantation.21cause there are no reports of women recovering from AFLPspontaneously. The presence of AFLP is not an indication fordelivery by cesarean section because of the risks of bleeding Counseling of Women with AFLPcomplications in the presence of coagulopathy.2-6,10 The de- Several case reports and case series22-26 have noted an asso-cision to perform cesarean delivery should be based on fetal ciation between the development of AFLP and/or HELLPgestational age, fetal condition, and presence of labor. Induc- syndrome and a deﬁciency of long-chain 3-hydroxyacyl-co-tion of labor with an attempt for vaginal delivery within 24 enzyme A dehydrogenase (LCHAD) in infants born tohours is a reasonable approach. Because of the associated women with the above complications. This disorder of mito-coagulopathy, most anesthesiologists will avoid epidural an- chondrial fatty acid oxidation might lead to signiﬁcant in-algesia. Maternal analgesia during labor can be provided by crease in maternal fatty acid levels that are highly toxic to theintermittent use of small doses of systemic opioids. The use of liver. Based on these ﬁndings, some authors suggest thatpudendal block should be avoided because of the risk of women with AFLP as well as their partners and childrenbleeding and hematoma formation into this area. Caution should undergo molecular testing for Glu 474 Gln mutationshould be exercised to avoid vaginal trauma and lacerations in the LCHAD.22,24 Screening for this mutation would allowduring vaginal delivery.1 early diagnosis and treatment in newborns of affected moth- In case of cesarean delivery, the patient should receive ers and would allow counseling about subsequent pregnan-general anesthesia. It is advisable to avoid incisions that re- cies.22,25 The risk of recurrence is increased in women whoquire extensive dissection, such as the Pfannenstiel incision, are carriers for this mutation, particularly if the fetus is alsoand meticulous attention should be given to secure hemosta- affected during a subsequent pregnancy. There are few casesis. It is advisable to perform a midline incision, to use a reports describing recurrent AFLP in women without thesubfascial drain, and to keep the skin incision open for at above mutation2,4; however, the risk of this recurrence re-least 48 hours to avoid hematoma formation.1,23 mains unknown because of the limited number of pregnan- In the postpartum period, the patient should be monitored cies reported following AFLP in these women.very closely with careful evaluation of vital signs, intake–output, and bleeding. Some of these patients may developacute refractory hypotensive shock in the immediate postpar- Thrombotic Microangiopathiestum period. Serial measurements of hematologic, hepatic, Thrombotic thrombocytopenic purpura (TTP) and hemo-and renal function should be performed and recorded in an lytic uremic syndrome (HUS) are two microangiopathic dis-organized fashion. Blood sugars should be monitored every orders that are extremely rare during pregnancy/postpartum.few hours with a bedside glucometer because of the risk of They are usually reported as case reports or small case se-hypoglycemia in the postpartum period. Glucose infusions ries.1,26-35 Thus, their expected development during preg-