HELLP Syndrome

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

• 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

• Thrombocytopenia
  • Gestational thrombocytopenia
  • Thrombotic microangiopathies
    • Thrombotic thrombocytopenic purpura (TTP)
    • Hemolytic uremic syndrome (HUS)
  • Idiopathic thrombocytopenic purpura (primary or secondary)
  • Systemic lupus erythematosus
  • APS
  • Sepsis/DIC
  • AFLP
• Hemolysis
  • Thrombotic microangiopathies (TTP, HUS)
  • DIC
  • Infections
• Elevated liver enzymes
  • Thrombotic microangiopathies (TTP, HUS)
  • DIC
  • AFLP
  • Acute hepatitis
  • Cholangitis​/cholecystitis
  • Acute pancreatitis

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

• Caucasian 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