Muna Tahlak, MD, FACOG Latifa Hospital

Objectives Update on the disease focus on diagnosis Complications timing and mode of delivery mortality and morbidity controversial aspects of corticosteroid use

Latifa Hospital is a tertiary center on average 6000 deliveries per year >80% high risk obstetric care 465 pregnant women had hypertensive disorder (8%)

Causes of maternal death in developed countries Other direct causes of deaths21.3 Hypertensive disorders16.1 Embolism 14.9 Haemorrhage13.4 Abortion8.2 Ectopic pregnancy4.9 Unclassified deaths 4.8 Sepsis/infection2.1 WHO data on maternal mortality

Team Work

HELLP Syndrome Weinstein regarded signs and symptoms to constitute an entity separate from severe preeclampsia and in 1982 named the condition HELLP H = Haemolysis EL = Elevated Liver enzymes LP = Low Platelets currently regarded as a variant of severe preeclampsia or a complication.

The HELLP syndrome occurs in about 0.5 to 0.9% of all pregnancies and in 10 to 20% of cases with severe preeclampsia

70% of the cases develops before delivery with a peak frequency between the 27th and 37th gestational weeks 10% occur before the 27th week 20% beyond the 37th gestational week

HELLP syndrome usually develops within the first 48 hours in women who have had proteinuria and hypertension prior to delivery

hypertension and proteinuria absent in 10–20% of the cases

Symptoms right upper abdominal quadrant epigastric pain nausea and vomiting 30–60% of women have headache 20% visual symptoms partial HELLP syndrome fewer symptoms less complications

Reported frequency of signs and symptoms of HELLP syndrome Sign/symptomFrequency, percent Proteinuria86 to 100 Hypertension82 to 88 Right upper quadrant/epigastrict pain40 to 90 Nausea, vomiting29 to 84 Headache33 to 61 Visual changes10 to 20 Jaundice5

Haemolysis, one of the major characteristics of the disorder, is due to a microangiopathic haemolytic anaemia

Normal peripheral blood smear

Microangiopathic smear

H(hemolysis) high LDH concentration unconjugated bilirubin low or undetectable haptoglobin concentration is a more specific indicator. Low haptoglobin concentration (< 1 g/L – < 0.4 g/L)

Elevated Liver enzymes(EL) Elevation of liver enzymes may reflect the haemolytic process as well as liver involvement. Haemolysis contributes to the elevated levels of LDH enhanced asparate aminotransferase (AST) and alanine aminotransferase (ALAT) levels are mostly due to liver injury

Low platelet(LP) Thrombocytopenia < 150·10 9 /L) caused by gestational thrombocytopenia (GT) (59%) immune thrombocytopenic purpura (ITP) (11%) preeclampsia (10%) HELLP syndrome (12%). PLTs < 100·10 9 /L are relatively rare in preeclampsia and gestational thrombocytopenia, frequent in ITP and obligatory in the HELLP syndrome (according to the Sibai definition)

Diagnosis Many different criteria Biochemical markers Clinical Preeclampsia ELLP

Diagnostic criteria two major definitions for diagnosing the HELLP syndrome

Professor Baha Sibai Professor and Chairman of the Department of Obstetrics and Gynecology at the University of Cincinnati College of Medicine leading authority in the care and treatment of women with preeclampsia and eclampsia, has published more than 500 peer-reviewed articles

Tennessee Classification System Platelets ≤ 100·10 9 /L AST ≥ 70 IU/L LDH ≥ 600 IU/L Sibai has proposed strict criteria for "true" or "complete" HELLP syndrome Intravascular haemolysis is diagnosed by abnormal peripheral blood smear, increased serum bilirubin (≥ 20.5 μmol/L or ≥ 1.2 mg/100 mL) and elevated LDH levels (> 600 units/L (U/L)

Mississippi classification Class 1 Platelets ≤ 50·10 9 /L AST ≥ 70 IU/LAST LDH ≥ 600 IU/L

Mississippi classification Class 2 Platelets ≤ 100·10 9 /L ≥ 50·10 9 /L AST or ALT ≥ 70 IU/L LDH ≥ 600 IU/L

Mississippi classification Class 3 Platelets ≤ 150·10 9 /L ≥ 100·10 9 /L AST or ALT ≥ 40 IU/L LDH ≥ 600 IU/L

Differential diagnosis viral hepatitis cholangitis and other acute disease ITP acute fatty liver of pregnancy (AFLP) haemolytic uremic syndrome (HUS) thrombotic thrombocytopenic purpura (TTP) systemic lupus erythematosus (SLE)

Complications reported in the HELLP syndrome Maternal complicationsOccurrence (%) Eclampsia4–9 Abruptio placentae9–20 DIC5–56 Acute renal failure7–36 Severe ascites4–11 Cerebral oedema1–8 Pulmonary oedema3–10

Complications reported in the HELLP syndrome Maternal complicationsOccurrence (%) Subcapsular liver hematomaBetween 0.9% and <2% Liver rupture>200 cases or about 1.8% Cerebral infarctionFew case reports Cerebral Haemorrhage1.5–40 Maternal death1–25 Wound hematoma/infection 2 7–14 Retinal detachment1

Maternal Mortality Stroke45% Cardiac Arrest40% DIC39% ARDS27% Renal failure27% Sepsis24% Hepatic Rupture20% Hypoxic encephalopathy15% Contributing factors to deaths in 54 women with HELLP syndrome From Isler and co-authors,1999

Complications reported in the HELLP syndrome Foetal/neonatal complications Perinatal death7.4–34 IUGR38–61 Preterm delivery70 (15% < 28 gestational weeks) Neonatal thrombocytopenia15–50 RDS5.7–40

Management of pregnant women with HELLP syndrome Immediate delivery > 34 weeks' gestation or later Nonreassuring tests of fetal status Presence of severe maternal disease: multiorgan dysfunction, DIC, liver infarction or hemorrhage, renal failure, or abruptio placenta

27 to 34 weeks of gestation Delivery within 48 hours evaluation stabilization steroid treatment for fetal lung maturity

Steroid use no clear evidence of any effect of corticosteroids on substantive clinical outcomes. insufficient evidence for the routine use The use of corticosteroids only to increase rate of recovery in platelet count if considered clinically worthwhile. Cochrane Review of 11 trials comparing corticosteroids with placebo/no treatment

before 24 weeks' gestation, termination of pregnancy should be strongly considered

Method of Delivery Vaginal Cesarean section

Anesthesia Choice According to ACOG Regional anesthesia is preferred for women with preeclapmsia and eclampsia General anesthesia carries more risk than regional

Anesthesia Choice What platelet count is adequate for regional anesthesia? No absolute answer Platelet counts >100,000/ul are acceptable to most anesthesiologists Platelet counts in 50, ,000 range are potential candidates according to ACOG

Risk of spinal or epidural hematoma Paralysis

Frederick P. Zuspan, M.D An internationally recognized authority in the field of maternal-fetal medicine An expert on preeclampsia In the 1960s, Zuspan pioneered the use intravenous magnesium sulfate to prevent convulsions in women with preeclampsia. His treatment protocol was adopted internationally and is still used to treat preeclampsia nearly 50 years later

there's an empty plaque at Chicago's famous Lying-in Hospital waiting for the engraved name of the person who discoveres the cause.

Summary HELLP syndrome is unique to pregnancy HELLP syndrome develops in approximately 1 of 1000 pregnancies overall and 10 to 20 percent of pregnancies with severe preeclampsia/eclampsia Delivery and supportive management is cure Multidisciplinary approach Tertiary center

Summary outcome for mothers with HELLP syndrome is generally good, but serious complications can occur Recommendations are against giving dexamethasone for treatment