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

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