HELLP Syndrome

HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) is one of the most severe manifestations of the preeclampsia spectrum, occurring in 0.2–0.6% of pregnancies and complicating up to 20% of cases with preeclampsia with severe features. [1-2] It carries a maternal mortality rate of 1–3% and demands rapid recognition and expeditious delivery. [3-4]

• Gestational age: Most cases occur between 27–37 weeks; however, 20–30% present or progress postpartum (within 48 hours to 1 week after delivery) [1-2]
• RUQ/epigastric pain: Present in ~65–90% of symptomatic patients — the most common presenting complaint [1-2]
• Nausea/vomiting: Reported in 35–50% of cases; often mistaken for gastritis, GERD, or viral illness [2][4]
• Malaise and generalized weakness: Present in up to 90% [2]
• Headache: ~30% of patients; may herald eclampsia [1]
• Rapid weight gain and edema: 65% report recent weight gain [1]
• Visual disturbances: Scotomata, blurred vision — suggest cerebral involvement
• Key pitfall: Up to 15% of patients lack hypertension or proteinuria, making the presentation insidious and atypical [2-3]

• AST >2,000 IU/L or LDH >3,000 IU/L → increased mortality risk [2]
• Shoulder pain or referred right shoulder pain → suspect hepatic subcapsular hematoma or rupture [1][4]
• Hypotension, abdominal distension, or shock → hepatic rupture until proven otherwise [1][4]
• Severe abdominal pain with fever and leukocytosis → hepatic infarction [4-5]
• Seizures → eclampsia (can occur even without severe hypertension)
• Rapidly declining platelet count (average ~40% drop per day during disease aggravation) [2]
• DIC (8–21% of cases), acute renal failure (8–15%), placental abruption (10–16%) [3]

• Magnesium sulfate: Loading dose 4–6 g IV over 15–20 min, then 1–2 g/hr maintenance for seizure prophylaxis [6]
• Antihypertensives (for BP ≥160/110 mmHg): IV labetalol, IV hydralazine, or oral immediate-release nifedipine — initiate within 30–60 minutes [6]
• Antenatal corticosteroids: Betamethasone or dexamethasone for fetal lung maturity if <34 weeks; Cochrane review found no maternal mortality benefit from corticosteroids for disease attenuation, only improved platelet count [2][4]
• Platelet transfusion: No contraindication; transfuse for platelets <50,000 if cesarean delivery anticipated, <30,000 for vaginal delivery, or >40,000 for invasive procedures [4-5]
• Avoid: Thrombopoietin receptor agonists (eltrombopag, lusutrombopag) — extreme caution given hypercoagulable state of pregnancy [5]
• Avoid: NSAIDs in the setting of thrombocytopenia and renal dysfunction

• NPO status should be maintained once delivery is planned, particularly if cesarean section is anticipated
• No specific dietary triggers or management; hydration and electrolyte monitoring are supportive measures
• Postpartum: Resume regular diet as tolerated once clinically stable

• Neurologic: Headache, visual changes (scotomata, blurred vision), altered mental status, seizure activity
• GI: RUQ/epigastric pain, nausea, vomiting, abdominal distension
• Hematologic: Easy bruising, petechiae, mucosal bleeding (signs of thrombocytopenia/DIC)
• Renal: Decreased urine output, dark urine (hemoglobinuria)
• Pulmonary: Dyspnea (pulmonary edema)
• Obstetric: Vaginal bleeding (placental abruption), decreased fetal movement

• Prior history of preeclampsia or HELLP in previous pregnancies (recurrence risk ~5–19%)
• Family history of preeclampsia or hypertensive disorders of pregnancy
• History of autoimmune disease (SLE, antiphospholipid syndrome) — these can mimic or coexist with HELLP
• Social context: Access to tertiary care, support system for potential NICU stay

• Advanced maternal age [4-5]
• Nulliparity or multiparity [4-5]
• Prior preeclampsia or HELLP syndrome
• Multiple gestation
• Chronic hypertension, diabetes mellitus, chronic kidney disease [7]
• Autoimmune disease (SLE, antiphospholipid syndrome)
• Obesity
• Genetic and environmental factors triggering systemic angiopathic inflammatory response [5]

This is a critical section — misdiagnosis can be fatal, particularly if TTP is mistaken for HELLP. [8-9]

• Acute fatty liver of pregnancy (AFLP): More prominent hypoglycemia, hypofibrinogenemia, elevated bilirubin, renal failure, and coagulopathy; Swansea criteria may help differentiate; fibrinogen, creatinine, cholesterol, and total bilirubin levels assist in distinguishing from HELLP [7][10]
• Thrombotic thrombocytopenic purpura (TTP): Severe thrombocytopenia (<20,000), neurologic features, minimal liver enzyme elevation, LDH:AST ratio >22:1 (vs ~2:1 in HELLP); ADAMTS13 activity <10–20% is definitive [9][11]
• Atypical hemolytic uremic syndrome (aHUS): Progressive renal failure predominates; complement-mediated; may require anti-complement therapy (eculizumab) [12]
• Antiphospholipid syndrome: Check anticardiolipin, anti-β2-glycoprotein, lupus anticoagulant
• Severe sepsis/DIC: Fever, source of infection, positive cultures
• Viral hepatitis: Check hepatitis serologies
• Exacerbation of SLE: Check complement levels, anti-dsDNA

Pearl: If MAHA and thrombocytopenia do not improve within 48–72 hours postpartum, strongly consider TTP or aHUS and obtain ADAMTS13 activity. [12]

• Prior preeclampsia, HELLP, or eclampsia
• Chronic hypertension or renal disease
• Autoimmune conditions (SLE, APS)
• Thrombophilia
• Prior liver disease
• Diabetes mellitus
• History of thrombotic microangiopathy

• Vital signs: Hypertension (≥140/90 in ~85%; ≥160/110 in severe cases); tachycardia if hemorrhaging; hypotension if hepatic rupture [1][3]
• General: Edema, weight gain, ill-appearing
• Abdomen: RUQ tenderness (most common finding), epigastric tenderness, hepatomegaly, peritoneal signs (if hepatic rupture)
• Skin: Jaundice (uncommon, ~5–40% depending on series), petechiae, ecchymoses [3-4]
• Neurologic: Hyperreflexia, clonus (pre-eclamptic features), altered mental status
• Fundoscopic: Papilledema, retinal hemorrhages (rare but concerning)
• Obstetric: Fetal heart rate monitoring — assess for non-reassuring patterns

Diagnostic triad (all three required per ACOG): [2][6]

• LDH ≥600 IU/L (marker of hemolysis)
• AST/ALT ≥2× upper limit of normal
• Platelets <100,000/μL

Additional labs

• CBC with peripheral smear (schistocytes, helmet cells — microangiopathic hemolytic anemia)
• Haptoglobin (decreased), indirect bilirubin (elevated), reticulocyte count
• Coagulation panel: PT/INR, PTT, fibrinogen (to assess for DIC)
• BMP: Creatinine (renal function), glucose (hypoglycemia suggests AFLP)
• Urine protein/creatinine ratio or 24-hour urine protein
• Type and screen
• ADAMTS13 activity if TTP is suspected (LDH:AST >22:1, platelets <20,000, neurologic symptoms) [9][11]
• Uric acid (often elevated in preeclampsia spectrum)

Monitoring: Labs should be repeated at least every 12 hours until delivery and through the postpartum period. [2]

Mortality markers: AST >2,000 IU/L or LDH >3,000 IU/L. [2]

• Hepatic ultrasound: Obtain at baseline in all HELLP patients to evaluate for subcapsular hematoma, intraparenchymal hemorrhage, or infarction [1][5]
• CT or MRI abdomen: Indicated when AST/ALT >1,000 IU/L, severe abdominal pain, or shoulder pain — more accurate than ultrasound for hepatic complications [4]
• Obstetric ultrasound: Fetal growth assessment, amniotic fluid volume, biophysical profile
• Imaging is unnecessary for routine HELLP without severe abdominal pain or markedly elevated transaminases

• Peripheral blood smear: Schistocytes confirm microangiopathic hemolytic anemia — the hallmark of the disorder [1]
• Direct Coombs test: Should be negative (Coombs-negative hemolytic anemia) [3]
• ADAMTS13 activity: <10–20% confirms TTP; critical to obtain if clinical picture is atypical [8][11]
• LDH:AST ratio: >22:1 suggests TTP/aHUS rather than HELLP (mean ~32:1 in TTP vs ~2:1 in HELLP) [9]
• Swansea criteria: May help differentiate AFLP from HELLP [7]
• Fetal non-stress test / biophysical profile: Continuous fetal monitoring

• ECG is not a primary diagnostic tool for HELLP but should be obtained if:
  • Severe hypertension (to assess for LVH, ischemia)
  • Magnesium sulfate administration (monitor for cardiac effects — prolonged PR, widened QRS at toxic levels)
  • Hemodynamic instability or chest pain
  • Hyperkalemia from renal failure
• Watch for signs of magnesium toxicity: Prolonged PR interval, heart block, cardiac arrest at levels >12 mEq/L

HELLP syndrome is a life-threatening obstetric emergency representing the severe end of the preeclampsia spectrum. Key clinical pearls:

• Onset is often insidious — symptoms mimic common third-trimester complaints (nausea, epigastric discomfort, fatigue) [2]
• 15% of patients are normotensive and aproteinuric — do not rely on hypertension or proteinuria to make the diagnosis [2-3]
• Disease progression is rapid: platelet count can drop ~40% per day [2]
• Postpartum HELLP accounts for 20–30% of cases and can present up to 1 week after delivery [1-2]
• Complications: DIC (8–21%), renal failure (8–15%), placental abruption (10–16%), subcapsular hematoma (0.9%), hepatic rupture, eclampsia [3]
• Fetal prognosis is most strongly linked to gestational age at delivery [4]

Initial stabilization

• IV access, continuous maternal and fetal monitoring
• Magnesium sulfate: 4–6 g IV loading dose → 1–2 g/hr maintenance for seizure prophylaxis [6]
• Antihypertensive therapy for BP ≥160/110 mmHg: IV labetalol (20 mg initial, escalate to 40–80 mg q10 min), IV hydralazine (5–10 mg q20 min), or PO nifedipine IR (10–20 mg q20 min) [6]

Definitive treatment

• Delivery is the only cure — should occur as soon as maternal stabilization is achieved, regardless of gestational age per ACOG [2][6]
• Route of delivery: Induction of labor or cesarean delivery based on obstetric indications
• Antenatal corticosteroids (betamethasone 12 mg IM × 2 doses, 24 hours apart) for fetal lung maturity if <34 weeks — but should not delay delivery if maternal condition is deteriorating [4][6]

Platelet management

• [4-5]

Hepatic complications

• Contained hematomas: Supportive/expectant management [4-5]
• Enlarging hematoma or rupture with hemodynamic instability: Hepatic artery embolization or surgery [4-5]
• Worsening liver failure despite delivery: Transfer to transplant center; liver transplantation is a salvage option [1][4]

• All patients with HELLP require inpatient management from diagnosis through delivery and into the postpartum period [6]
• Tertiary care center with NICU and obstetric ICU capabilities is required, especially if remote from term [2]
• ICU admission criteria: Hemodynamic instability, DIC, hepatic rupture, renal failure, eclampsia, need for massive transfusion
• Postpartum monitoring: Labs (CBC, LFTs, LDH, creatinine) every 12 hours; values typically begin to normalize within 48 hours postpartum [4]
• If labs do not improve within 48–72 hours postpartum, reconsider the diagnosis — evaluate for TTP (ADAMTS13) or aHUS (complement studies) [12]
• Transfer to transplant center if progressive hepatic failure or hepatic rupture [1][13]

• Postpartum BP monitoring: Peak hypertension occurs days 3–6 after delivery; initiate oral antihypertensives if BP ≥150/100 mmHg [14]
• Labs: Repeat CBC, LFTs, LDH, creatinine until trending toward normal
• Return precautions (counsel patient on):
  • Severe headache, visual changes, or seizure activity
  • Worsening RUQ/epigastric pain
  • Shortness of breath (pulmonary edema)
  • Decreased urine output
  • Excessive bleeding or bruising
• Long-term counseling: History of HELLP/preeclampsia confers increased lifetime risk of cardiovascular disease — discuss lifestyle modifications, BP monitoring, and metabolic screening [14]
• Future pregnancy counseling: Recurrence risk of preeclampsia/HELLP; low-dose aspirin (81 mg/day) starting at 12–16 weeks in subsequent pregnancies for those with risk factors [7]
• Expected recovery: Most patients recover fully with labs normalizing within days to weeks postpartum; fetal outcomes are primarily determined by gestational age at delivery [4]

1. Reproductive Health and Liver Disease: Practice Guidance by the American Association for the Study of Liver Diseases. — Sarkar M, Brady CW, Fleckenstein J, et al. Hepatology. 2021.

2. Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin, Number 222. — Committee on Practice Bulletins—Obstetrics Obstetrics and Gynecology. 2020.

3. Pregnancy and the Liver. — Rahim MN, Williamson C, Kametas NA, Heneghan MA. Lancet. 2025.

4. ACG Clinical Guideline: Liver Disease and Pregnancy. — Tran TT, Ahn J, Reau NS. The American Journal of Gastroenterology. 2016.

5. Liver Disease During Pregnancy. — Reau N, Munoz SJ, Schiano T. The American Journal of Gastroenterology. 2022.

6. Hypertensive Disorders of Pregnancy. — Farahi N, Oluyadi F, Dotson AB. American Family Physician. 2024.

7. AGA Clinical Practice Update on Pregnancy-Related Gastrointestinal and Liver Disease: Expert Review. — Kothari S, Afshar Y, Friedman LS, Ahn J. Gastroenterology. 2024.

8. Differentiation Between Severe HELLP Syndrome and Thrombotic Microangiopathy, Thrombotic Thrombocytopenic Purpura and Other Imitators. — Pourrat O, Coudroy R, Pierre F. European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2015.

9. Maternal Morbidity and Mortality in Pregnant/­Postpartum Women With Suspected HELLP Syndrome Identifiable as Probable Thrombotic Thrombocytopenic Purpura or Atypical Hemolytic Uremic Syndrome by High LDH to AST Ratio. — Martin JN, Tucker JM. International Journal of Gynaecology and Obstetrics: The Official Organ of the International Federation of Gynaecology and Obstetrics. 2022.

10. Comparing Acute Fatty Liver of Pregnancy From Hemolysis, Elevated Liver Enzymes, and Low Platelets Syndrome. — Byrne JJ, Seasely A, Nelson DB, Mcintire DD, Cunningham FG. The Journal of Maternal-Fetal & Neonatal Medicine : The Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2022.

11. Immune Thrombotic Thrombocytopenic Purpura. — Pishko AM, Li A, Cuker A. The Journal of the American Medical Association. 2025.

12. Syndromes of Thrombotic Microangiopathy Associated With Pregnancy. — George JN, Nester CM, McIntosh JJ. Hematology. American Society of Hematology. Education Program. 2015.

13. Acute Liver Failure Guidelines. — Shingina A, Mukhtar N, Wakim-Fleming J, et al. The American Journal of Gastroenterology. 2023.

14. Preeclampsia. — Magee LA, Nicolaides KH, von Dadelszen P. The New England Journal of Medicine. 2022.