HELLP Syndrome

HELLP syndrome, the constellation of Hemolysis, Elevated Liver function tests, and Low Platelet count, is a complication of preeclampsia and eclampsia that occurs in pregnant women. It is rare but can have devastating consequences. Laboratory monitoring in pregnant women with gestational hypertension or preeclampsia includes platelet counts and liver enzymes. The treatment for HELLP syndrome is delivery after 34 weeks.

Diagnosis

Indications for Testing

  • During pregnancy
    • New-onset high blood pressure or blood pressure increase in patients with established high blood pressure
    • Proteinuria

Criteria for Diagnosis

Diagnostic Criteria for HELLP Syndrome
  Hemolysis Elevated Liver Enzymes Low Platelets

Martin Criteria (1991)

LDH >600 U/L

AST >40 U/L

Platelet count <150 x 109/L

Sibai Criteria (1993)

Abnormal peripheral smear (schistocytes)

LDH >600 U/L

Bilirubin >1.2 mg/dL

AST >70 U/L

Platelet count <100 x 109/L 

AST, aspartate aminotransferase; LDH, lactate dehydrogenase

Source: Rajasekhar, American Society of Hematology (ASH), 2013

  • Patients with preeclampsia or eclampsia with one to two HELLP criteria (hemolysis, elevated liver enzymes, and low platelets) can be deemed as having partial HELLP

Laboratory Testing

  • CBC
    • Hemoglobin and hematocrit – evaluate for hemolysis
    • Platelets – low platelet counts increase risk in preeclampsia
      • Counts of <100,000/mm3 meet HELLP criterion
  • Blood smear – evaluate for evidence of microangiopathic hemolysis
    • Helmet cells
    • Burr cells
    • Schistocytes
  • Reticulocyte count – consider to evaluate for presence of hemolysis
  • Liver enzymes
    •  AST – 2 times the upper reference limit meets criteria
  • LDH – markedly elevated (>600 U/L meets criteria)
  • Urine protein
    • Evaluate kidney protein losses
    • Extent of proteinuria does not correlate with disease severity
    • 24-hour collection is preferred, but spot urine for protein/creatinine ratio can be used for screening
  • Renal function markers – evaluate for kidney damage
  • Testing to rule out other conditions, if clinically indicated
    • Prothrombin time (PT), partial thromboplastin time (PTT), D-dimer, fibrinogen for disseminated intravascular coagulation (DIC) evaluation
    • Lupus anticoagulant, anticardiolipin, anti-beta-2 glycoprotein 1 for antiphospholipid syndrome (APS) evaluation
    • Fibrinogen, white blood cells, PT/PTT, uric acid, ammonia, glucose for acute fatty liver of pregnancy (AFLP) evaluation
       

Differential Diagnosis

Monitoring

Monitoring for gestational hypertension and preeclampsia – weekly testing for platelet counts, liver enzymes, urine protein

Background

Epidemiology

  • Incidence – 0.6% of pregnant women (ASH, 2013)
    • 5-10% of pregnancies with preeclampsia
    • 30-50% of pregnancies with eclampsia

Classification

  • The American College of Obstetricians and Gynecologists (ACOG) classifies various gestational hypertensive disorders as follows
    • Chronic hypertension – high blood pressure that predates conception or is detected before 20 weeks of gestation
    • Gestational hypertension – new-onset high blood pressure detected after 20 weeks of gestation without proteinuria
    • Preeclampsia/eclampsia
      • Preeclampsia – new-onset high blood pressure detected after week 20 of gestation with proteinuria; can be with or without severe features
        • Preeclampsia with severe features
          • Thrombocytopenia, impaired liver function, renal insufficiency, pulmonary edema, cerebral or visual changes
          • HELLP is a complication of preeclampsia with severe features
      • Eclampsia – convulsive phase of disorder, often preceded by headaches, vision changes, and altered mental status
    • Chronic hypertension with superimposed preeclampsia – preeclampsia/eclampsia in patients with previous chronic hypertension

Risk Factors

  • White race
  • Multiparity
  • Age >34 years
  • Presence of preeclampsia or eclampsia
  • Fetus affected with fatty acid oxidation defect (eg, long-chain 3-hydroxyacyl-CoA dehydrogenase [LCHAD] deficiency)
  • Previous pregnancy with HELLP

Pathophysiology

  • Placenta in preeclampsia is poorly perfused, which causes release of 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
    • Two thirds of patients are diagnosed antepartum
    • Typically does not present before third trimester
    • Postpartum presentation usually occurs within first week after delivery
  • Signs/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
      • 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

ARUP Lab Tests

Use with hepatic function panel and LDH in the diagnosis of HELLP

Use with LDH and CBC in the diagnosis of HELLP

Panel includes albumin; alkaline phosphatase; AST; alanine aminotransferase; bilirubin, direct; protein; bilirubin, total

Use with hepatic function panel and CBC in diagnosis of HELLP

Screening test to evaluate kidney function

Related Tests

Initial test for suspected bleeding disorder

Aid in diagnosing and following DIC

Preferred initial panel for strong suspicion of APS

Determine if fibrinogen deficiency is a potential cause of bleeding

Medical Experts

Contributor

Genzen

Jonathan R. Genzen, MD, PhD
Associate Professor of Clinical Pathology, University of Utah
Chief Operations Officer, Medical Director of Automated Core Laboratory, ARUP Laboratories
Contributor

Lehman

Christopher M. Lehman, MD
Associate Professor of Clinical Pathology, University of Utah
Medical Director, University of Utah Health Hospital Clinical Laboratory, ARUP Laboratories

References

Additional Resources