HELLP Syndrome
HELLP syndrome (Haemolysis, Elevated Liver enzymes, Low Platelets) is a severe variant of pre-eclampsia with significant maternal and fetal morbidity, requiring urgent delivery.
Key Facts
HELLP stands for Haemolysis, Elevated Liver enzymes, Low Platelets Complicates 0.5-0.9% of all pregnancies and 10-20% of severe pre-eclampsia cases 70% of cases occur antepartum (majority between 27-37 weeks), 30% postpartum Mississippi classification grades severity: Class 1 (platelets ≤50), Class 2 (50-100), Class 3 (100-150 × 10⁹/L) Delivery is the definitive treatment; timing guided by gestational age and maternal/fetal condition Maternal mortality 1-3%; complications include DIC (20%), placental abruption (16%), acute renal failure (7%) Dexamethasone may be used to improve platelet count pre-delivery (controversial, limited evidence) Can present without hypertension or proteinuria in up to 15-20% of cases
Overview
Key Facts
HELLP syndrome is a serious complication of pregnancy characterised by haemolysis, elevated liver enzymes, and low platelet count. It is considered a severe variant of pre-eclampsia, though it may present independently.
Epidemiology
- Incidence: 0.5-0.9% of all pregnancies
- Complicates 10-20% of pregnancies with severe pre-eclampsia
- Peak incidence between 27-37 weeks gestation
- 30% of cases present postpartum (usually within 48 hours)
- More common in multiparous women and those >25 years of age
Aetiology
- Shares common pathophysiology with pre-eclampsia: abnormal placentation and endothelial dysfunction
- Risk factors overlap with pre-eclampsia: previous HELLP/pre-eclampsia, nulliparity, age >40, multiple pregnancy, BMI >35, chronic hypertension, autoimmune conditions
- Recurrence rate: 2-19% in subsequent pregnancies
Pathophysiology
- Abnormal trophoblastic invasion leads to placental ischaemia
- Release of inflammatory mediators causes widespread endothelial activation
- Haemolysis: microangiopathic haemolytic anaemia (MAHA) due to endothelial damage and fibrin deposition in microvasculature
- Elevated liver enzymes: periportal and focal hepatic necrosis with hepatic sinusoidal obstruction
- Low platelets: increased consumption due to endothelial damage and DIC
- Hepatic complications can progress to subcapsular haematoma or hepatic rupture
Clinical Presentation
Typical Presentation
- Right upper quadrant or epigastric pain (65-86% of cases)
- Nausea and vomiting (36-50%)
- Malaise and fatigue
- May present with pre-eclamptic features: hypertension, proteinuria, oedema
Atypical Presentations
- Up to 15-20% present without hypertension or proteinuria
- Can mimic acute fatty liver of pregnancy, cholecystitis, hepatitis, or gastroenteritis
- Shoulder tip pain may indicate hepatic capsule distension or diaphragmatic irritation
Red Flags
- Rapidly falling platelet count (<50 × 10⁹/L)
- Rising LDH and falling haptoglobin (progressive haemolysis)
- Epigastric/RUQ pain with shoulder tip pain (hepatic subcapsular haematoma)
- Signs of DIC: widespread bleeding, petechiae, ecchymoses
- Severe hypertension (>160/110 mmHg)
- Visual disturbance, headache, seizures (eclampsia)
- Oliguria or anuria
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| Acute fatty liver of pregnancy | Jaundice, hypoglycaemia, encephalopathy, often late 3rd trimester | Swansea criteria, blood glucose, ammonia |
| Thrombotic thrombocytopenic purpura (TTP) | Fever, MAHA, neurological features, renal impairment | ADAMTS13 activity (<10%) |
| Haemolytic uraemic syndrome (HUS) | Predominantly renal failure with MAHA | Complement studies, stool culture |
| Antiphospholipid syndrome catastrophic | Multi-organ thrombosis, history of APS | Antiphospholipid antibodies |
| Viral hepatitis | Fever, jaundice, hepatitis risk factors | Hepatitis serology |
| Cholecystitis | RUQ pain, Murphy's sign, fever | USS abdomen |
| Systemic lupus erythematosus flare | Multi-system features, rash, arthritis | ANA, anti-dsDNA, complement |
Diagnosis / Investigation
Bedside
- Blood pressure monitoring
- Urinalysis (proteinuria)
- CTG for continuous fetal monitoring
- Fluid balance chart
Bloods
- FBC: platelet count (<150 × 10⁹/L confirms low platelets)
- Blood film: schistocytes, fragmented red cells (evidence of MAHA)
- LFTs: AST/ALT elevated (≥70 IU/L), raised bilirubin
- LDH: elevated (>600 IU/L indicates haemolysis)
- Haptoglobin: low or absent (consumed in haemolysis)
- Coagulation screen: PT, APTT, fibrinogen (DIC screen)
- D-dimer: elevated in DIC
- U&Es: creatinine, uric acid (renal involvement)
- Group and save / crossmatch: prepare for transfusion
Imaging
- Liver ultrasound: assess for subcapsular haematoma, hepatic infarction
- CT abdomen if suspecting hepatic rupture
- Obstetric ultrasound: fetal growth, liquor volume, umbilical artery Dopplers
Special Tests
- ADAMTS13 if TTP suspected
- Antiphospholipid antibodies if indicated
Management
Non-pharmacological
- Multidisciplinary management: obstetrics, haematology, anaesthetics, hepatology
- High-dependency or intensive care monitoring
- Strict fluid balance
- Crossmatch and prepare blood products
Pharmacological
- Antihypertensives: labetalol (first-line), nifedipine, or hydralazine as per NICE NG133
- Magnesium sulphate: seizure prophylaxis (4g IV loading, 1g/hr maintenance)
- Corticosteroids for fetal lung maturity: betamethasone 12mg IM × 2 doses (24h apart) if <34 weeks
- Dexamethasone for maternal benefit (to improve platelet count): evidence is limited; some centres use 10mg IV 12-hourly
- Blood product replacement: platelets if <50 × 10⁹/L or actively bleeding; FFP/cryoprecipitate if DIC
- Tranexamic acid 1g IV if significant haemorrhage
Surgical/Interventional
- Delivery is the definitive treatment
- ≥34 weeks: deliver within 24-48 hours
- <34 weeks: stabilise, administer steroids, deliver if maternal condition deteriorates
- Mode of delivery: vaginal delivery may be attempted if cervix favourable; caesarean section if urgent
- If hepatic rupture: emergency laparotomy with hepatic packing
Referral Criteria
- Consultant obstetrician and anaesthetist involvement mandatory
- Haematology input for DIC management
- Hepatology/surgical input if hepatic complications
- Follow-up at 6-8 weeks postpartum with blood tests
Prognosis
- Maternal mortality: 1-3% (higher in developing countries)
- Perinatal mortality: 7-20% (largely dependent on gestational age at delivery)
- Complications: DIC (20%), placental abruption (16%), acute renal failure (7%), pulmonary oedema (6%), hepatic rupture (1-2%)
- Most haematological and hepatic abnormalities resolve within 48-72 hours postpartum
- Platelet nadir typically at 24-48 hours postpartum
- Recurrence risk in subsequent pregnancies: 2-19%
- Long-term: increased risk of chronic hypertension and cardiovascular disease
Other Relevant Information
Mississippi Classification
| Class | Platelet Count | LDH | AST/ALT |
|---|---|---|---|
| Class 1 (Severe) | ≤50 × 10⁹/L | ≥600 IU/L | ≥70 IU/L |
| Class 2 (Moderate) | 50-100 × 10⁹/L | ≥600 IU/L | ≥70 IU/L |
| Class 3 (Mild) | 100-150 × 10⁹/L | ≥600 IU/L | ≥40 IU/L |
Tennessee Diagnostic Criteria
| Parameter | Threshold |
|---|---|
| Haemolysis | Abnormal blood film, LDH ≥600 IU/L, bilirubin ≥20.5 μmol/L |
| Elevated liver enzymes | AST ≥70 IU/L |
| Low platelets | <100 × 10⁹/L |
Differential: HELLP vs AFLP
| Feature | HELLP | AFLP |
|---|---|---|
| Platelets | Very low | Mildly low |
| Liver enzymes | Very high | Moderately high |
| Hypoglycaemia | Rare | Common |
| Coagulopathy | DIC pattern | Low fibrinogen |
| Jaundice | Mild | Prominent |