HELLP Syndrome

Diagnosis

Indications for Testing

• Pregnant patient presenting with clinical picture of preeclampsia, thrombocytopenia, or acute liver failure

Criteria for Diagnosis

• Patients lacking all 3 of the criteria for HELLP (hemolysis, elevated liver enzymes, and low platelets) can be deemed partial HELLP

Laboratory Testing

• CBC – anemia, thrombocytopenia (<100,000/mm³ to meet criteria)
  • Peripheral smear – helmet cells, burr cells, schistocytes (all signs of microangiopathic hemolysis)
• Liver function tests – elevated
  • Aspartate aminotransferase (AST) – 2 times the upper reference limit (to meet criteria)
  • Lactate dehydrogenase (LD) – markedly elevated (≥600 U/L to meet criteria)
    • LD criteria should be based on the upper limits of normal values in the lab where specimen is processed

Differential Diagnosis

• Thrombocytopenia
  • Thrombotic microangiopathies
    • Thrombotic thrombocytopenic purpura (TTP)
    • Hemolytic uremic syndrome (HUS)
  • Disseminated intravascular coagulation
  • Idiopathic thrombocytopenic purpura
  • Systemic lupus erythematosus
  • Antiphospholipid syndrome
  • Sepsis
• Hemolysis
  • TTP
  • HUS
  • DIC
• Elevated liver enzymes
  • TTP
  • HUS
  • DIC
  • Acute fatty liver of pregnancy
  • Acute hepatitis
  • Cholangitis
  • Cholecystitis
  • Acute pancreatitis

Clinical Background

HELLP syndrome refers to the constellation of Hemolysis, Elevated Liver function tests, and Low Platelet count seen in pregnant women and sometimes considered to be a severe form of eclampsia.

Epidemiology

• Incidence – 4-5/1,000 pregnancies
  • 5-10% of pregnancies with preeclampsia
  • 30-50% of pregnancies with eclampsia
• Age – childbearing years
• Sex – exclusively in pregnant or postpartum females

Risk Factors

• Caucasian race
• Multiparity
• Age – >34 years
• Presence of preeclampsia or eclampsia
• Fetus affected with fatty acid oxidation defect – ie, defects such as long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency

Pathophysiology

• Placenta in preeclampsia is poorly perfused, which releases factors that create endothelial dysfunction
• Endothelial dysfunction causes platelet aggregation and altered ratio of thromboxane to prostacyclin
• Thrombin-induced activation of the coagulation cascades leads to hemolytic anemia and multiorgan microvascular injury

Clinical Presentation

• Usually occurs during pregnancy
  • 2/3 of patients are diagnosed antepartum
  • Typically does not present prior to 3rd trimester
  • Postpartum presentation usually within first week
• Symptoms
  • Nonspecific – malaise, fatigue
  • Gastrointestinal – right upper quadrant pain, nausea, emesis
  • Central nervous system – headache, confusion
  • Cardiovascular – hypertension
• Complications
  • Maternal
    • Subcapsular hematomas and liver rupture
    • Abruptio placentae
    • Disseminated intravascular coagulation (DIC)
    • Severe postpartum bleeding
    • Stroke, cerebral hemorrhage
    • Renal failure
    • Increased risk of HELLP in subsequent pregnancies
  • Fetal/perinatal
    • Prematurity
    • Placental insufficiency
    • Intrauterine growth restriction
    • Neonatal intraventricular hemorrhage

Treatment

• Consider fetus delivery  
  • Medical emergency with maternal mortality of 1-2% and fetal mortality of 10-30%
  • ≥34 weeks – immediate delivery if maternal status not rapidly improving
  • <34 weeks but ≥27 weeks – delivery within 48 hours after medical stabilization
  • <27 weeks – conservative management based on maternal health
    • Conservative treatment is contraindicated in women with DIC
• Glucocorticosteroid therapy
  • Nonrandomized studies suggest therapy may improve outcomes
    • Maternal dosing – high dose versus repeated dose
    • Fetal dosing – based on standard treatment to promote fetal lung maturity

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory