Reproductive · PANCE / PANRE

HELLP Syndrome

Hemolysis, Elevated Liver enzymes, Low Platelets — severe variant of preeclampsia.

Also known as: HELLP, HELLP syndrome, severe preeclampsia variant

Overview

A severe form of preeclampsia characterized by microangiopathic hemolytic anemia, hepatocellular dysfunction, and thrombocytopenia. Diagnosis does not require hypertension or proteinuria, although most patients have one or both.

Epidemiology

Occurs in 0.5-0.9% of all pregnancies and in 10-20% of women with severe preeclampsia. Most cases present between 28 and 36 weeks; up to 30% develop postpartum (usually within 48 hours).

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Risk factors

  • Prior preeclampsia or HELLP, multiparity (in contrast to preeclampsia in primigravidas)
  • Maternal age >35, white race, BMI extremes
  • Chronic hypertension, antiphospholipid syndrome, thrombophilia
  • Multiple gestation

Pathophysiology

Abnormal placentation with defective spiral artery remodeling leads to placental ischemia and release of antiangiogenic factors (sFlt-1, soluble endoglin) and inflammatory mediators. Widespread endothelial dysfunction causes microvascular thrombosis, hepatic sinusoidal fibrin deposition (hepatocyte necrosis, elevated transaminases), and consumption of platelets. RBCs are sheared in microthrombi, producing schistocytes and intravascular hemolysis.

Clinical presentation

Symptoms

  • Right upper quadrant or epigastric pain (90%) — from hepatic capsular distension
  • Nausea, vomiting (50%)
  • Headache, visual disturbances, malaise
  • Up to 15% have neither hypertension nor proteinuria

Signs / physical exam

  • Hypertension (variable severity), RUQ tenderness, jaundice (uncommon)
  • Edema, brisk reflexes/clonus
  • Petechiae or bleeding with severe thrombocytopenia

Classic findings

Pregnant patient at 28-36 wk with epigastric/RUQ pain, schistocytes on smear, elevated AST/ALT, and platelets <100k.

Differential diagnosis

  • Acute fatty liver of pregnancy (AFLP) — Hypoglycemia, marked hyperammonemia, hyperbilirubinemia, coagulopathy out of proportion to platelet drop — Swansea criteria
  • Thrombotic thrombocytopenic purpura (TTP) — Severe thrombocytopenia, MAHA, neurologic symptoms, fever, renal involvement; ADAMTS13 <10%
  • Hemolytic uremic syndrome (HUS) / aHUS — AKI predominates; often postpartum; complement dysregulation
  • Viral hepatitis — Marked transaminase elevation, hepatitis serologies positive; no MAHA
  • SLE flare / catastrophic APS — Multiorgan involvement, low complement, anti-dsDNA, antiphospholipid antibodies
  • Severe preeclampsia without HELLP — Hypertension and proteinuria predominate; no hemolysis, normal LFTs and platelets

Diagnostic workup

Diagnostic criteria

Tennessee classification: hemolysis (LDH >=600, abnormal smear, or low haptoglobin), AST >=70, platelets <100,000. Mississippi classification grades severity by platelet nadir.

Labs

  • CBC with smear: schistocytes, helmet cells, anemia, platelets <100,000/microL
  • AST and ALT >=2x upper limit of normal (typically 70 IU/L or greater)
  • LDH >=600 IU/L (reflects hemolysis and hepatic injury); indirect bilirubin elevated; low haptoglobin
  • Coagulation studies (PT, PTT, fibrinogen) to evaluate for DIC
  • Comprehensive metabolic panel, uric acid, urinalysis with protein quantification, creatinine

Imaging

  • Abdominal ultrasound or CT if subcapsular hematoma or hepatic rupture suspected
  • Fetal: ultrasound for growth, AFI, BPP; continuous monitoring

Diagnostic algorithm

ComponentThreshold (Tennessee)
HemolysisLDH >=600 IU/L, schistocytes on smear, low haptoglobin, or indirect bilirubin >=1.2
Elevated Liver enzymesAST >=70 IU/L (>=2x ULN)
Low PlateletsPlatelet count <100,000/microL
Partial HELLPAny 1-2 criteria — still warrants close monitoring
Tennessee diagnostic criteria for HELLP syndrome.

Treatment

First-line

  • Definitive treatment is delivery — timing depends on gestational age and maternal/fetal status
  • Maternal stabilization: magnesium sulfate for seizure prophylaxis (4-6 g IV load, then 1-2 g/h)
  • Blood pressure control if severe range (SBP >=160 or DBP >=110): IV labetalol, hydralazine, or oral nifedipine
  • Antenatal corticosteroids (betamethasone or dexamethasone) if 24 0/7 to 33 6/7 wk to accelerate lung maturity; dexamethasone has been studied for HELLP itself but does NOT improve maternal outcomes
  • Platelet transfusion only if active bleeding or platelets <20,000 (or <50,000 prior to cesarean)
  • Fresh frozen plasma / cryoprecipitate if DIC develops
  • Immediate delivery (>=34 wk, or any GA with maternal/fetal compromise, DIC, abruption, hepatic infarction or rupture)
  • Expectant management for 24-48 h ONLY between 24 0/7 and 33 6/7 wk in selected stable patients to complete steroids

Second-line / adjunct

  • Mode of delivery: cervical favorability and fetal condition guide induction vs cesarean — HELLP itself is not an indication for cesarean
  • Postpartum continued magnesium 24 h; close monitoring for 48-72 h since hemolysis and platelet nadir typically occur after delivery before improving

Complications

  • DIC, placental abruption, acute kidney injury
  • Subcapsular hepatic hematoma and hepatic rupture (rare, catastrophic)
  • Pulmonary edema, ARDS, cerebral hemorrhage
  • Eclampsia, maternal death (estimated 1-3%)
  • Fetal/neonatal: IUGR, preterm birth, perinatal death (7-20%)

PANCE pearls

  • RUQ or epigastric pain in late pregnancy is HELLP until proven otherwise — do not dismiss as reflux.
  • Thrombocytopenia in HELLP is usually <100,000; if platelets are <20,000 or hemolysis is profoundly out of proportion, consider TTP and check ADAMTS13.
  • Hepatic subcapsular hematoma can rupture catastrophically — avoid abdominal palpation under anesthesia and counsel against vigorous activity.
  • Recurrence risk in subsequent pregnancy is 3-25% for HELLP and up to 50% for any hypertensive disease of pregnancy.
  • HELLP can present or worsen postpartum; consider it in any postpartum woman with new RUQ pain, malaise, or thrombocytopenia.

References

  • ACOG PB 222 — ACOG Practice Bulletin 222: Gestational Hypertension and Preeclampsia (Obstet Gynecol 2020)
  • Sibai BM — Sibai BM. Diagnosis, controversies, and management of HELLP syndrome (Obstet Gynecol 2004)
  • HYPITAT — Koopmans et al., Lancet 2009 — induction vs expectant in late preterm hypertensive disease

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