HELLP Syndrome

Quick Answer

HELLP Syndrome is a severe variant of pre-eclampsia characterised by Haemolysis, Elevated Liver enzymes, and Low Platelets. It represents a life-threatening obstetric emergency requiring ICU admission for multi-organ support and urgent delivery planning.

Key Clinical Features:

• Microangiopathic haemolysis (schistocytes, elevated LDH, low haptoglobin)
• Elevated liver transaminases (AST ≥70 U/L)
• Thrombocytopenia (<100 × 10⁹/L)
• RUQ/epigastric pain (present in 65-90%), nausea/vomiting, malaise
• Hypertension may be ABSENT in 15-20% of cases

Emergency Management:

1. Maternal stabilisation: Airway, breathing, circulation with blood product support
2. Blood pressure control: Labetalol/hydralazine IV (target <160/110 mmHg)
3. Magnesium sulfate: 4g IV loading, then 1g/hour for seizure prophylaxis
4. Platelet transfusion if <20 × 10⁹/L (or <50 if bleeding/surgery planned)
5. Urgent delivery: Definitive treatment regardless of gestation in severe cases
6. Corticosteroids: Betamethasone for fetal lung maturity (<34 weeks)

Mortality:

• Maternal: 1-3% overall; up to 25% with hepatic rupture
• Perinatal: 7-35% (prematurity, abruption, IUGR)

Must-Know Facts:

• DELIVERY is the only definitive treatment - timing depends on severity and gestation
• Resolution expected 24-72 hours postpartum; if persistent, consider TTP/aHUS
• Hepatic rupture is catastrophic (50-80% mortality) - requires surgical/IR intervention
• 15-20% present WITHOUT hypertension - diagnosis requires high index of suspicion
• Recurrence risk: 3-5% in subsequent pregnancies; 20-25% risk of pre-eclampsia

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CICM Exam Focus

What Examiners Expect

Second Part Written (SAQ):

Common SAQ stems:

• "A 32-year-old primigravida at 34 weeks presents to ICU with epigastric pain, thrombocytopenia (platelets 45 × 10⁹/L), elevated LFTs, and microangiopathic haemolysis. Describe your approach to diagnosis and management."
• "Compare and contrast HELLP syndrome with TTP and AFLP. Discuss the key differentiating features and implications for management."
• "A patient with HELLP syndrome develops severe RUQ pain and hypotension 6 hours postpartum. Outline your approach to diagnosis and management."
• "Discuss the pathophysiology of HELLP syndrome and the rationale for corticosteroid therapy."

Expected depth:

• Tennessee/Mississippi classification of HELLP
• Systematic approach to thrombocytopenia differential in pregnancy
• Understanding that delivery is definitive treatment
• Evidence for corticosteroids (maternal platelet recovery vs fetal lung maturity)
• Management of complications: DIC, AKI, hepatic haematoma, abruption
• Postpartum monitoring and recovery timeline

Second Part Hot Case:

Typical presentations:

• Day 1 postpartum with worsening thrombocytopenia and liver function despite delivery
• Oliguric patient with HELLP on MgSO4 infusion, coagulopathic, requiring transfusion
• Post-caesarean patient with persistent hypotension and rising lactate

Examiners assess:

• Recognition of HELLP severity and complications
• Systematic A-E assessment in critically ill obstetric patient
• Understanding of post-delivery recovery timeline
• Blood product transfusion thresholds in obstetric coagulopathy
• When to suspect alternative diagnosis (TTP if no recovery by 72h postpartum)
• Communication with obstetric team and family

Second Part Viva:

Expected discussion areas:

• Pathophysiology: Endothelial dysfunction, complement activation, placental ischaemia
• Microangiopathic haemolysis mechanism and laboratory features
• Hepatic subcapsular haematoma: Presentation, diagnosis, management
• Delivery timing: Balancing maternal stabilisation with fetal well-being
• Corticosteroids: Dexamethasone for maternal platelets vs betamethasone for fetal lungs
• Post-delivery management: MgSO4 duration, platelet nadir timing, recovery monitoring
• Differential diagnosis: ADAMTS13 for TTP, Swansea criteria for AFLP
• Indigenous health considerations: Higher pre-eclampsia rates, access to tertiary care

Examiner expectations:

• Safe, consultant-level decision-making
• Evidence-based practice with guideline citations (SOMANZ, ISSHP)
• Understanding of multidisciplinary team coordination
• Recognition of maternal/fetal conflict and ethical considerations in periviable deliveries
• Cultural sensitivity in family communication

Common Mistakes

• Missing HELLP in patients without hypertension (15-20% have normal BP)
• Confusing HELLP with TTP and delaying plasma exchange when appropriate
• Using platelet transfusion inappropriately (will be consumed if underlying process ongoing)
• Delaying delivery in severe HELLP while attempting to "stabilise"
• Not continuing magnesium for 24-48 hours postpartum
• Expecting immediate recovery - platelet nadir typically occurs 24-48h post-delivery
• Forgetting to rule out hepatic haematoma in patients with severe RUQ pain

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Key Points

Must-Know Facts

1. Definition: HELLP syndrome is a severe variant of pre-eclampsia defined by: Haemolysis (schistocytes, LDH >600 U/L, haptoglobin undetectable), Elevated Liver enzymes (AST ≥70 U/L), Low Platelets (<100 × 10⁹/L).

2. Tennessee Classification: Full HELLP = all three criteria; Partial HELLP = one or two criteria (still significant risk). All abnormalities must be confirmed.

3. Mississippi Classification (Severity):

   • Class 1: Platelets <50 × 10⁹/L (most severe)
   • Class 2: Platelets 50-100 × 10⁹/L
   • Class 3: Platelets 100-150 × 10⁹/L with haemolysis and elevated LFTs

4. Atypical Presentations: 15-20% present WITHOUT hypertension; 15% present postpartum (up to 7 days); right upper quadrant pain present in only 65-90%.

5. Delivery is Definitive: Regardless of gestation in severe cases (Class 1, DIC, hepatic haematoma, renal failure, abruption). Expectant management ONLY in stable Class 2-3 at <34 weeks in tertiary centre.

6. Platelet Recovery: Nadir typically 24-48h post-delivery; recovery expected by 72-96h. If no recovery by 72h, suspect TTP/aHUS - check ADAMTS13.

7. Corticosteroids: Betamethasone for fetal lung maturity (<34 weeks). Dexamethasone for maternal platelet recovery is CONTROVERSIAL - may accelerate recovery but no mortality benefit.

8. Hepatic Haematoma/Rupture: Subcapsular haematoma in 1-2%; rupture in <1% but 50-80% mortality. Suspect with severe RUQ pain, hypotension, shoulder tip pain. CT/US diagnosis. Management: IR embolisation, surgery, massive transfusion.

9. Transfusion Thresholds: Platelets <20 × 10⁹/L (or <50 if bleeding/surgery); FFP for INR >1.5 with bleeding; fibrinogen <2 g/L requires cryoprecipitate.

10. Recurrence Risk: 3-5% HELLP recurrence; 20-25% develop pre-eclampsia in subsequent pregnancies. Counsel and offer aspirin prophylaxis from 12 weeks in future pregnancies.

Memory Aids

Mnemonic "HELLP" Diagnostic Criteria:

• H: Haemolysis (schistocytes, LDH >600, haptoglobin <25 mg/dL)
• E: Elevated liver enzymes (AST ≥70 U/L or >2× ULN)
• LL: Low Platelets (<100 × 10⁹/L)
• P: Pre-eclampsia spectrum (though BP may be normal)

"ABRUPT" Complications of HELLP:

• A: Abruption (placental)
• B: Bleeding (DIC, hepatic rupture)
• R: Renal failure (AKI)
• U: Uterine complications (postpartum haemorrhage)
• P: Pulmonary oedema
• T: Transfusion requirements (massive haemorrhage)

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Definition & Epidemiology

Definition

HELLP Syndrome is a severe variant of pre-eclampsia characterised by the triad of microangiopathic Haemolysis, Elevated Liver enzymes, and Low Platelets. First described by Weinstein in 1982, it represents a form of thrombotic microangiopathy (TMA) with multiorgan involvement and high maternal-fetal morbidity and mortality (PMID: 7183553).

Tennessee Classification (Sibai) - Most Widely Used (PMID: 2342739):

Mississippi Classification (Martin) - Severity Grading (PMID: 2363680):

Epidemiology

International Data (PMID: 19896722, 30135024):

• Incidence: 0.5-0.9% of all pregnancies
• 10-20% of women with severe pre-eclampsia develop HELLP
• 70% occur antepartum (most between 27-37 weeks)
• 30% occur postpartum (typically within 48 hours, can be up to 7 days)
• Median gestational age at diagnosis: 34 weeks

Australian/NZ Data (SOMANZ Guidelines 2023, AIHW Maternal Deaths Report):

• Pre-eclampsia/eclampsia affects 5-10% of Australian pregnancies
• HELLP complicates approximately 0.5% of pregnancies
• Maternal mortality ratio from hypertensive disorders: 0.67 per 100,000 births (2012-2021)
• ICU admission rate for severe pre-eclampsia/HELLP: 5-10%
• Aboriginal and Torres Strait Islander maternal mortality ratio: 17.5 per 100,000 vs 5.5 per 100,000 for non-Indigenous

Risk Factors:

Non-modifiable:

• Nulliparity (2-3× increased risk)
• Age >40 years or <20 years
• Previous pre-eclampsia or HELLP (20-25% recurrence of hypertensive disorder)
• Multiple gestation (2× increased risk)
• Family history of pre-eclampsia
• Chronic hypertension
• Pre-existing renal disease
• Autoimmune disease (SLE, antiphospholipid syndrome)
• Thrombophilia

Modifiable:

• Obesity (BMI >30)
• Inter-pregnancy interval >10 years
• Assisted reproductive technology
• New paternity

Indigenous Health Considerations (PMID: 24995628, AIHW 2023):

• Aboriginal and Torres Strait Islander women: 2-3× higher rates of pre-eclampsia
• Higher rates of chronic hypertension, diabetes, renal disease
• Younger age at first pregnancy
• Later presentation to antenatal care
• Geographic barriers to tertiary obstetric services
• Higher ICU admission rates for severe pre-eclampsia (OR 1.8)
• Māori women (NZ): 2× higher maternal mortality than NZ Europeans

Outcomes:

• Maternal mortality: 1-3% overall; up to 25% with hepatic rupture
• Perinatal mortality: 7-35% (primarily from prematurity, abruption, IUGR)
• Complications: DIC 20-40%, AKI 3-8%, abruption 7-20%, pulmonary oedema 5-10%
• Recurrence in subsequent pregnancy: 3-5% for HELLP; 20-25% for pre-eclampsia

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Applied Basic Sciences

This section bridges First Part basic sciences with Second Part clinical practice

Anatomy

Hepatic Anatomy Relevant to HELLP:

Liver Blood Supply:

• Portal vein: 75% of hepatic blood flow (nutrient-rich, partially deoxygenated)
• Hepatic artery: 25% of blood flow (oxygenated)
• Dual blood supply makes liver relatively resistant to ischaemia
• However, in HELLP, microvascular thrombosis affects sinusoidal circulation

Liver Capsule (Glisson's Capsule):

• Fibrous capsule surrounding liver
• Rich in sensory innervation (pain receptors)
• Capsular distension causes RUQ/epigastric pain characteristic of HELLP
• Subcapsular haematoma develops between parenchyma and capsule
• Rupture through capsule causes life-threatening haemoperitoneum

Hepatic Haematoma Locations:

• Subcapsular: Most common, often right lobe (60-80%)
• Intraparenchymal: Less common but may rupture into subcapsular space
• Anterior surface: Higher rupture risk

Placental Anatomy:

Spiral Arteries:

• Maternal vessels that supply intervillous space
• Normally remodelled by trophoblast invasion (first/second trimester)
• Loss of muscular wall allows low-resistance, high-flow placental circulation
• In pre-eclampsia/HELLP: Failed remodelling leads to placental ischaemia

Uteroplacental Circulation:

• Normal: High-flow, low-resistance circulation
• Pre-eclampsia: High-resistance circulation, reduced placental perfusion
• Leads to fetal growth restriction and placental dysfunction

Physiology

Normal Pregnancy Haemostatic Changes (PMID: 22226120):

Pregnancy is a procoagulant state:

• Increased factors: VII, VIII, X, XII, vWF, fibrinogen (up to 50% increase)
• Decreased: Protein S (40% decrease), antithrombin (10-20% decrease)
• Platelet count: May decrease by 10% (gestational thrombocytopenia)
• D-dimer: Elevated throughout pregnancy (normal pregnancy levels differ from non-pregnant)

Normal Pregnancy Cardiovascular Changes:

• Blood volume: 40-50% increase
• Cardiac output: 30-50% increase
• Systemic vascular resistance: Decreased by 25-30%
• Blood pressure: Nadir in second trimester, rises in third

Pathophysiology

Pathophysiology of HELLP Syndrome (PMID: 30135024, 24583062):

HELLP syndrome is a form of thrombotic microangiopathy (TMA) resulting from placenta-derived factors causing systemic endothelial dysfunction.

Stage 1: Abnormal Placentation

In the first trimester:

• Failed trophoblast invasion of spiral arteries
• Spiral arteries retain muscular wall (high resistance)
• Placental hypoperfusion and ischaemia develop

Stage 2: Placental Ischaemia and Factor Release

The hypoxic placenta releases:

• sFlt-1 (soluble fms-like tyrosine kinase-1): Anti-angiogenic, binds VEGF and PlGF
• Soluble Endoglin (sEng): Inhibits TGF-β signalling
• Syncytiotrophoblast debris: Microparticles trigger inflammation
• Inflammatory cytokines: TNF-α, IL-6, IL-8

These factors cause:

• VEGF and PlGF sequestration → endothelial dysfunction
• Reduced nitric oxide production
• Increased endothelin-1 and thromboxane A2

Stage 3: Endothelial Dysfunction and Microangiopathy

Endothelial injury leads to:

Microangiopathic Haemolysis:

• Fibrin deposition in microvasculature
• Mechanical destruction of RBCs passing through fibrin strands
• Schistocytes (fragmented RBCs) on blood film
• Elevated LDH (released from damaged RBCs)
• Depleted haptoglobin (binds free haemoglobin)
• Elevated indirect bilirubin

Liver Injury:

• Hepatic sinusoidal endothelial damage
• Fibrin deposition and microthrombi in sinusoids
• Periportal hepatocyte necrosis
• Elevated AST/ALT (hepatocyte leakage)
• Capsular distension → RUQ pain
• Subcapsular haematoma in severe cases

Thrombocytopenia:

• Platelet consumption at sites of endothelial injury
• Increased platelet aggregation and activation
• Platelet destruction in microvasculature
• Bone marrow production cannot compensate

Complement Activation (PMID: 28155309):

Recent evidence suggests complement dysregulation:

• Elevated C5a, C5b-9, and Bb levels in HELLP
• Some patients have complement gene mutations (CFH, CFI, CFB, C3)
• May explain overlap with atypical HUS
• Rationale for eculizumab in refractory cases (case reports)

Hepatic Subcapsular Haematoma and Rupture (PMID: 24503516):

Mechanism:

1. Severe periportal necrosis from microvascular thrombosis
2. Haemorrhage into liver parenchyma
3. Blood accumulates under Glisson's capsule
4. Capsular distension causes severe RUQ pain
5. Continued haemorrhage may lead to rupture → haemoperitoneum

Risk factors for rupture:

• Severe thrombocytopenia (<50 × 10⁹/L)
• Coagulopathy (DIC)
• Trauma (abdominal palpation, convulsions, CPR)
• Delay in diagnosis

Pharmacology

Key ICU Drugs for HELLP Syndrome:

1. Magnesium Sulfate

• Class: Anticonvulsant, vasodilator
• Mechanism:
  • NMDA receptor antagonist (reduces neuronal excitability)
  • Calcium channel blocker (vasodilation)
  • Reduces cerebral vasospasm
  • Neuroprotective effects
• ICU Indication: Seizure prophylaxis in severe pre-eclampsia/HELLP, treatment of eclamptic seizures
• Dosing:
  • "Loading: 4g IV over 20 minutes"
  • "Maintenance: 1g/hour IV continuous"
  • "Eclamptic seizure: Additional 2g IV bolus"
  • Continue for 24-48 hours postpartum
• Monitoring:
  • Patellar reflexes (absent = toxicity)
  • Respiratory rate (depression if >4-5 mmol/L)
  • Urine output (reduce dose if oliguria)
  • Serum magnesium if renal impairment
• Therapeutic level: 2.0-3.5 mmol/L
• Toxicity: >3.5 mmol/L loss of reflexes; >5 mmol/L respiratory depression; >6.5 mmol/L cardiac arrest
• Antidote: Calcium gluconate 1g (10 mL of 10%) IV over 10 minutes
• Evidence: MAGPIE trial (PMID: 12049882) - 58% reduction in eclampsia risk

2. Labetalol

• Class: Combined alpha- and beta-adrenergic blocker (α:β ratio 1:7 IV)
• Mechanism: Reduces SVR (alpha-blockade) without reflex tachycardia (beta-blockade)
• ICU Indication: First-line antihypertensive in pre-eclampsia/HELLP
• Dosing:
  • "Bolus: 20 mg IV, then 20-80 mg q10-15min (max 300 mg)"
  • "Infusion: 1-2 mg/min, titrate to BP"
• Target BP: <160/110 mmHg initially, then 130-150/80-100 mmHg
• Contraindications: Asthma, severe bradycardia, heart block, heart failure
• PBS/TGA: Available, commonly used

3. Hydralazine

• Class: Direct arteriolar vasodilator
• Mechanism: Relaxes vascular smooth muscle, reduces SVR
• ICU Indication: Second-line antihypertensive
• Dosing: 5-10 mg IV q20min (max 20 mg)
• Adverse Effects: Reflex tachycardia, headache (may mimic worsening pre-eclampsia)
• Caution: Headache side effect may confuse clinical assessment

4. Nifedipine

• Class: Dihydropyridine calcium channel blocker
• Mechanism: Arterial vasodilation
• ICU Indication: Oral option for BP control
• Dosing: 10-20 mg PO q20-30min (max 50 mg)
• Route: Oral immediate-release; AVOID sublingual (unpredictable, precipitous hypotension)
• Interaction: May potentiate magnesium-induced neuromuscular blockade

5. Corticosteroids

Betamethasone (Fetal Lung Maturity):

• Indication: <34 weeks gestation, delivery anticipated within 7 days
• Dosing: 11.4 mg (12 mg) IM, two doses 24 hours apart
• Evidence: Reduces RDS, IVH, necrotising enterocolitis in preterm infants (PMID: 28555588)

Dexamethasone (Maternal Platelet Recovery) - CONTROVERSIAL:

• Proposed mechanism: Reduces endothelial damage, accelerates platelet recovery
• Dosing studied: 10 mg IV q12h until platelets >100 × 10⁹/L
• Evidence: Systematic reviews show faster platelet recovery but NO mortality benefit (PMID: 22592693)
• SOMANZ 2023: Does NOT recommend routine dexamethasone for maternal platelet recovery
• Consider: In severe thrombocytopenia (<50 × 10⁹/L) when delivery cannot be delayed

Pathology

Histopathology (PMID: 2342739):

Liver:

• Periportal hepatocyte necrosis (characteristic)
• Fibrin deposition in sinusoids
• Microthrombi in hepatic microvasculature
• Haemorrhage into Disse space
• Subcapsular haematoma in severe cases
• May progress to intraparenchymal haemorrhage

Kidney:

• Glomerular endotheliosis (endothelial cell swelling)
• Fibrin deposition in glomerular capillaries
• Similar to pre-eclampsia
• Usually reversible with delivery

Placenta:

• Infarcts
• Accelerated villous maturation
• Decidual vasculopathy
• Retroplacental haemorrhage (abruption)

Blood Film (CRITICAL for diagnosis):

• Schistocytes (fragmented RBCs) - hallmark
• Helmet cells, burr cells
• Polychromasia (reticulocyte response)
• Nucleated RBCs in severe cases
• Thrombocytopenia evident

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Clinical Presentation

ICU Admission Scenarios

Typical Presentations:

Scenario 1: Classic Antepartum HELLP

• History: 34-year-old primigravida at 32 weeks, 2-day history of epigastric pain, nausea, malaise
• Examination: BP 168/105 mmHg, RUQ tenderness, mild oedema, fundal height small for dates
• Investigations: Platelets 52 × 10⁹/L, AST 285 U/L, LDH 890 U/L, schistocytes on film
• Severity: Class 1 HELLP - high risk, requires urgent delivery after stabilisation

Scenario 2: HELLP Without Hypertension

• History: 28-year-old at 36 weeks presents with nausea, vomiting, and "flu-like" symptoms
• Examination: BP 128/82 mmHg (normal), mild RUQ tenderness, no oedema
• Investigations: Platelets 68 × 10⁹/L, AST 195 U/L, elevated LDH, low haptoglobin
• Severity: Class 2 HELLP - easily missed without high index of suspicion

Scenario 3: Postpartum HELLP

• History: 30-year-old, 36 hours post-emergency caesarean for fetal distress, now confused and oliguric
• Examination: BP 175/115 mmHg, jaundiced, bruising at IV sites, decreased urine output
• Investigations: Platelets 28 × 10⁹/L (falling from 95 pre-op), AST 450 U/L, creatinine rising, DIC evident
• Severity: Class 1 with DIC - critical, requires aggressive ICU management

Scenario 4: HELLP with Hepatic Haematoma

• History: 32-year-old at 30 weeks, sudden severe RUQ pain radiating to shoulder, syncopal episode
• Examination: Hypotensive (BP 85/50), tachycardic, rigid abdomen, fetal bradycardia on CTG
• Investigations: Platelets 42 × 10⁹/L, Hb falling, free fluid on FAST scan
• Severity: Catastrophic - ruptured subcapsular haematoma, requires emergency surgery and massive transfusion

Symptoms & Signs

History:

• Chief complaint: RUQ or epigastric pain (65-90%), nausea/vomiting (35-50%), malaise
• Associated symptoms:
  • Headache (30-60%)
  • Visual disturbances (17-20%)
  • Shoulder tip pain (referred from diaphragm - RED FLAG for hepatic haematoma)
  • Reduced fetal movements
  • Bleeding/bruising
• Time course: Typically develops over days, but can progress rapidly
• May be confused with: Gastroenteritis, gallbladder disease, hepatitis, peptic ulcer

Examination:

General:

• Appearance: May appear unwell, jaundiced in severe cases
• Vital signs: Hypertension (85% of cases), but 15% have NORMAL BP
• Oedema: Variable, may have facial/peripheral oedema

A - Airway:

• Usually patent
• May be compromised if eclamptic seizure or altered consciousness

B - Breathing:

• Respiratory rate: May be elevated (compensation for metabolic acidosis)
• Pulmonary oedema: 5-10% (crackles, hypoxia)
• Pleural effusions: May be present

C - Circulation:

• Heart rate: Tachycardia (compensation for blood loss, hypovolaemia)
• Blood pressure: Elevated in 85%; NORMAL in 15%
• Perfusion: May be impaired if haemorrhaging or DIC

D - Disability/Neurology:

• GCS: Usually normal; decreased if eclampsia, PRES, or hepatic encephalopathy
• Hyperreflexia: Present in most
• Clonus: >3 beats is pathological
• Visual: Photophobia, scotomata, cortical blindness (PRES)

E - Exposure/Everything Else:

• Abdomen:
  • RUQ/epigastric tenderness (hepatic capsule distension) - 65-90%
  • May be rigid if haemoperitoneum
  • Fundal height may be small (IUGR)
  • Uterine tenderness (abruption)
• Skin:
  • Petechiae, purpura (thrombocytopenia)
  • Bruising (coagulopathy)
  • Jaundice (haemolysis, liver dysfunction)
• Oedema: Peripheral, facial, pulmonary

Severity Scoring

Mississippi Classification for Severity:

Indicators of Severe Disease Requiring Immediate Delivery:

• Platelets <50 × 10⁹/L (Class 1)
• DIC present
• Hepatic haematoma or rupture
• Renal failure (creatinine >106 μmol/L or oliguria)
• Placental abruption
• Pulmonary oedema
• Eclampsia or PRES
• Persistent severe hypertension (≥160/110 despite treatment)
• Fetal compromise

Differential Diagnosis

Key Differentials (PMID: 30135024, 21091117):

1. Thrombotic Thrombocytopenic Purpura (TTP):

   • Distinguishing features: ADAMTS13 activity <10%, fever, neurological symptoms predominant, minimal liver involvement, may occur any trimester
   • Key difference: Does NOT resolve with delivery; requires plasma exchange
   • Investigation: URGENT ADAMTS13 level
   • Clinical clue: Severe neurological symptoms, less liver involvement, no recovery post-delivery

2. Atypical Haemolytic Uraemic Syndrome (aHUS):

   • Distinguishing features: ADAMTS13 >10%, severe renal failure predominant, complement activation, may have genetic component
   • Key difference: Renal failure more severe than expected for HELLP; may respond to eculizumab
   • Investigation: Complement studies (C3, C4, factor H/I), ADAMTS13

3. Acute Fatty Liver of Pregnancy (AFLP):

   • Distinguishing features: Swansea criteria (>6 criteria), hypoglycaemia, hyperammonaemia, encephalopathy, coagulopathy (low fibrinogen), minimal haemolysis initially
   • Key difference: Hypoglycaemia is hallmark; liver synthetic failure more prominent
   • Investigation: Blood glucose, ammonia, fibrinogen (very low)
   • Overlap: 50% have concurrent HELLP features

4. Systemic Lupus Erythematosus (SLE) Flare:

   • Distinguishing features: Known SLE, active serology (anti-dsDNA positive, low C3/C4), other organ involvement (nephritis, serositis)
   • Key difference: Active lupus serology; complement consumed
   • Investigation: ANA, anti-dsDNA, C3, C4

5. Catastrophic Antiphospholipid Syndrome (CAPS):

   • Distinguishing features: Antiphospholipid antibodies positive, multiple organ thromboses, prior thrombosis/pregnancy loss
   • Key difference: Thrombosis in multiple organs simultaneously
   • Investigation: aPL (lupus anticoagulant, anticardiolipin, anti-β2GP1)

Diagnostic Algorithm: Differentiating HELLP from TTP and AFLP:

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Investigations

Laboratory Investigations

Bedside Tests:

Arterial Blood Gas:

• pH: May be low (metabolic acidosis)
• PaCO2: May be low (respiratory compensation)
• PaO2: May be low if pulmonary oedema
• Lactate: Elevated if tissue hypoperfusion, hepatic dysfunction
• Base excess: Negative (metabolic acidosis)
• Glucose: Usually normal (low in AFLP)

Typical ABG in HELLP: pH 7.32, PaCO2 30, PaO2 85 (FiO2 0.4), HCO3 17, BE -8, Lactate 3.2

Blood Tests:

Haematology:

• Haemoglobin: May be low (haemolysis, blood loss)
• Platelet count: <100 × 10⁹/L (diagnostic); <50 = Class 1
• Blood film: ESSENTIAL - schistocytes, helmet cells, fragmented RBCs

Haemolysis Markers (PMID: 2342739):

• LDH: >600 U/L (most sensitive for haemolysis and tissue damage)
• Haptoglobin: <25 mg/dL or undetectable (binds free Hb - depleted in haemolysis)
• Bilirubin (indirect/unconjugated): Elevated
• Reticulocyte count: Elevated (response to haemolysis)

Liver Function:

• AST: ≥70 U/L (or ≥2× ULN) - diagnostic criterion
• ALT: Usually elevated (but AST more sensitive for HELLP)
• ALP: Mildly elevated (placental origin)
• GGT: Mildly elevated
• Albumin: Low

Renal Function:

• Creatinine: May be elevated (AKI in 3-8%)
• Urea: Elevated if renal impairment
• Uric acid: Often elevated (poor prognostic marker)

Coagulation (PMID: 30135024):

• PT/INR: May be prolonged (liver dysfunction, DIC)
• APTT: May be prolonged
• Fibrinogen: Normal or low; <2 g/L suggests DIC
• D-dimer: Elevated (normal in pregnancy - interpret with caution)
• DIC screening: Score ≥5 = overt DIC

Specific Tests:

Imaging

Abdominal Ultrasound (PMID: 24503516):

• Indications: Severe RUQ pain, suspected hepatic haematoma, hypotension, falling Hb
• Findings in HELLP:
  • "Subcapsular haematoma: Hyperechoic/hypoechoic fluid collection under capsule"
  • "Intraparenchymal haemorrhage: Heterogeneous hepatic lesion"
  • "Free fluid: Haemoperitoneum if ruptured"
• Sensitivity: 60-80% for subcapsular haematoma

CT Abdomen (PMID: 24503516):

• More sensitive than ultrasound for hepatic haematoma
• Findings:
  • "Subcapsular haematoma: Crescentic hyperdense collection"
  • "Active bleeding: Contrast extravasation"
  • "Haemoperitoneum: Free fluid"
• Indication: Haemodynamically stable with suspected haematoma, planning intervention

MRI:

• Excellent for hepatic haematoma characterisation
• Rarely used acutely due to time constraints

Fetal Ultrasound:

• Growth assessment (IUGR common)
• Amniotic fluid index
• Doppler studies (umbilical artery, middle cerebral artery)
• Biophysical profile

Physiological Monitoring

Non-Invasive Monitoring:

• Continuous ECG: Arrhythmias (electrolyte disturbances, magnesium toxicity)
• SpO2: Pulmonary oedema, respiratory failure
• NIBP: Every 15 min initially (target <160/110 then 130-150/80-100)
• Temperature: Fever suggests infection
• Respiratory rate: Compensation for acidosis, pulmonary oedema

Invasive Monitoring:

• Arterial line: Essential if on antihypertensive infusion or unstable
• CVP: May be misleading in pre-eclampsia (intravascular depletion)
• Urinary catheter: Hourly urine output (target ≥0.5 mL/kg/hr)

Fetal Monitoring:

• Continuous CTG: Fetal heart rate, decelerations
• Abnormalities: Late decelerations, reduced variability, bradycardia

Organ-Specific Monitoring:

• Platelet count: Every 6-12h (watch for nadir at 24-48h post-delivery)
• LFTs: Daily until normalising
• Creatinine: Daily
• Coagulation: If DIC, every 6-12h
• Magnesium level: If renal impairment or suspected toxicity

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ICU Management

This is the core clinical section

Initial Resuscitation (First Hour)

A - Airway:

• Assessment: Level of consciousness, ability to protect airway
• Intervention: Intubation indicated for:
  • GCS <8 (eclampsia, PRES)
  • Respiratory failure (pulmonary oedema)
  • Massive haemorrhage with shock
  • Eclamptic seizure with airway compromise
• RSI considerations:
  • "Pregnancy: Difficult airway anticipated, rapid desaturation, aspiration risk"
  • "Drug choice: Propofol (reduced dose), rocuronium"
  • Left lateral tilt (if antepartum) to prevent aortocaval compression

B - Breathing:

• Oxygen therapy: Target SpO2 92-96%
• Assess for pulmonary oedema (crackles, hypoxia, CXR infiltrates)
• Non-invasive ventilation: Consider for pulmonary oedema
• Intubation: If NIV fails, respiratory failure, or need for surgery

C - Circulation:

Blood Pressure Control (PMID: 25629740):

• Target: <160/110 mmHg within 30-60 minutes; then 130-150/80-100 mmHg
• Avoid precipitous drops (risk of placental hypoperfusion if antepartum)

First-Line Antihypertensive:

• Labetalol: 20 mg IV bolus, repeat 20-80 mg q10-15min (max 300 mg)
• Hydralazine: 5-10 mg IV q20min (max 20 mg)
• Nifedipine: 10-20 mg PO q20-30min (if IV access unavailable)

Fluid Management:

• RESTRICT total IV fluids to 80-100 mL/hour (pulmonary oedema risk)
• Use crystalloid (Hartmann's or normal saline)
• Blood products as indicated (see below)

Blood Product Transfusion (PMID: 30135024):

Note on Platelet Transfusion:

• Platelets will be rapidly consumed if underlying process ongoing
• Transfuse immediately before procedures (caesarean, regional anaesthesia)
• Aim for >50 × 10⁹/L for caesarean section
• Aim for >75-80 × 10⁹/L for epidural/spinal (relative contraindication if <75)

D - Disability:

• GCS monitoring
• Magnesium sulfate for seizure prophylaxis (see below)
• Glucose: Monitor (low in AFLP)

E - Everything Else:

• Fetal monitoring: Continuous CTG if antepartum
• Source control: Identify complications (abruption, DIC, haematoma)
• Team activation: Obstetrics, anaesthetics, neonatology, haematology

Magnesium Sulfate Protocol

MAGPIE Trial Evidence (PMID: 12049882):

• 58% reduction in eclampsia (RR 0.42, 95% CI 0.29-0.60)
• NNT = 63 for moderate pre-eclampsia to prevent one seizure
• Trend towards reduced maternal mortality

Dosing Regimen (SOMANZ 2023):

Renal Impairment Adjustments:

Monitoring for Toxicity:

• Patellar reflexes: Absent = STOP infusion
• Respiratory rate: <12/min = STOP infusion
• Urine output: <25 mL/hr = reduce dose

Magnesium Toxicity Treatment:

1. STOP infusion immediately
2. Calcium gluconate 1g (10 mL of 10%) IV over 10 minutes
3. Airway support and ventilation if needed
4. Check magnesium level

Corticosteroids

For Fetal Lung Maturity (<34 weeks, delivery anticipated):

• Betamethasone: 11.4 mg (12 mg) IM × 2 doses, 24 hours apart
• OR Dexamethasone: 6 mg IM × 4 doses, 12 hours apart
• Evidence: Reduces RDS, IVH, NEC (Cochrane PMID: 28555588)
• Do NOT delay delivery for steroid completion in unstable patients

For Maternal Platelet Recovery - CONTROVERSIAL:

• Dexamethasone 10 mg IV q12h has been used
• Evidence: Cochrane review (PMID: 22592693) - faster platelet recovery, NO mortality benefit
• SOMANZ 2023: Does NOT recommend routine use
• Consider only if: Severe thrombocytopenia (<50 × 10⁹/L), delivery cannot be delayed, high bleeding risk

Delivery - The Definitive Treatment

Delivery is the ONLY definitive treatment for HELLP (PMID: 19896722).

Indications for Immediate Delivery (regardless of gestation):

• Mississippi Class 1 (<50 × 10⁹/L platelets)
• DIC with active bleeding
• Hepatic haematoma or rupture
• Renal failure (creatinine rising, oliguria)
• Pulmonary oedema refractory to treatment
• Eclampsia or PRES
• Persistent severe hypertension (≥160/110 despite maximal therapy)
• Placental abruption
• Fetal distress or non-reassuring CTG
• Gestation ≥34 weeks (lower threshold for delivery)

Expectant Management (only in selected cases):

• Conditions: Class 2-3 HELLP, <34 weeks, tertiary centre with NICU, stable maternal condition
• Monitoring: ICU or high-dependency unit, continuous fetal monitoring
• Duration: Maximum 24-48 hours to allow corticosteroid effect
• Immediate delivery if: Deterioration, Class 1 develops, complications

Mode of Delivery:

• Caesarean section: Most common in severe/unstable cases
• Vaginal delivery: Consider if favourable cervix, stable condition, adequate platelets
• Regional anaesthesia: Relative contraindication if platelets <75-80 × 10⁹/L
• General anaesthesia: May be required for coagulopathy, urgency

Perioperative Considerations:

• Platelet transfusion immediately before procedure (target >50 × 10⁹/L)
• FFP for coagulopathy
• Massive transfusion protocol available
• Avoid excessive fluid (pulmonary oedema risk)
• Continue magnesium through surgery and postpartum

Post-Delivery Management

Expected Timeline of Recovery (PMID: 30135024):

RED FLAG: If no improvement by 72h post-delivery:

• Suspect TTP (check ADAMTS13), aHUS (complement studies)
• Consider plasma exchange (discuss with haematology)

Post-Delivery Management:

1. Continue magnesium for 24-48 hours
2. Continue antihypertensive therapy (may need to wean gradually)
3. Monitor platelet count q12-24h until rising
4. Monitor LFTs daily until improving
5. Restrict fluids (third-space fluid mobilises day 2-4)
6. Watch for pulmonary oedema (highest risk 24-48h postpartum)
7. VTE prophylaxis when coagulation normalises (typically day 3-5)
8. Avoid NSAIDs (worsen hypertension, renal function, platelet dysfunction)
9. Avoid ergometrine (causes vasoconstriction)

Postpartum Discharge Criteria:

• Platelets >100 × 10⁹/L and rising
• LFTs improving
• BP controlled on oral medication
• Urine output adequate
• No signs of complications

Management of Complications

Hepatic Subcapsular Haematoma/Rupture (PMID: 24503516):

Subcapsular Haematoma (Unruptured):

• Diagnosis: CT or US showing subcapsular collection
• Management:
  • Immediate delivery if not already delivered
  • Avoid abdominal palpation, straining, seizures
  • Correct coagulopathy aggressively
  • Serial imaging q12-24h
  • Blood product support
  • Conservative management successful in 60-70%
• Intervention indications: Expansion, haemodynamic instability, pain progression

Ruptured Haematoma (Haemoperitoneum):

• Mortality: 50-80%
• Presentation: Sudden severe pain, shock, rigid abdomen, shoulder tip pain
• Management:
  • Activate massive transfusion protocol
  • Immediate surgical consultation
  • IR embolisation if available and patient stable
  • "Surgery: Packing, resection, ligation of bleeding vessels"
  • Liver transplant may be required in extreme cases

DIC Management (PMID: 24583062):

• Replace blood products:
  • "Platelets: Target >50 × 10⁹/L if bleeding"
  • "FFP: Target INR <1.5"
  • "Cryoprecipitate: Target fibrinogen >2 g/L"
  • "PRBCs: Maintain Hb >70 g/L"
• Treat underlying cause (delivery)
• Tranexamic acid: 1g IV (consider if ongoing haemorrhage)
• Recombinant factor VIIa: Reserved for life-threatening bleeding refractory to above

Acute Kidney Injury:

• Indications for RRT:
  • Refractory hyperkalaemia (K+ >6.5 despite medical therapy)
  • Severe metabolic acidosis (pH <7.15)
  • Refractory pulmonary oedema
  • Uraemic complications
• Modality: CRRT preferred (haemodynamic instability common)
• Anticoagulation: Regional citrate or no anticoagulation if coagulopathic
• Prognosis: Most recover renal function post-delivery

Pulmonary Oedema:

• Management:
  • Restrict fluids
  • Upright positioning (if possible)
  • Oxygen/NIV (CPAP 5-10 cmH2O)
  • Diuretics (furosemide 20-40 mg IV) if volume overloaded
  • Intubation if severe respiratory failure
• Note: May occur despite low CVP (capillary leak)

Australian-Specific Considerations

SOMANZ Guidelines 2023:

• Magnesium sulfate for seizure prophylaxis in severe pre-eclampsia/HELLP
• BP target <160/110 initially, then 130-150/80-100
• Delivery is definitive treatment
• Corticosteroids for fetal lung maturity <34 weeks
• Do NOT routinely use dexamethasone for maternal platelet recovery

Indigenous Health:

Aboriginal and Torres Strait Islander Considerations:

• 2-3× higher rates of pre-eclampsia and hypertensive disorders
• Barriers to care: Geographic isolation, late antenatal care presentation
• Cultural safety:
  • Involve Aboriginal Health Workers (AHW) and Aboriginal Liaison Officers (ALO)
  • Family-centred care (extended family involvement in decisions)
  • "Birthing on Country" may be important - discuss early
  • Clear communication, interpreter services if needed
  • Acknowledge connection to Country
• Lower threshold for tertiary transfer
• Early retrieval service activation (RFDS)
• Telehealth for remote consultations
• Longer observation period before discharge

Māori Health (New Zealand):

• 2× higher maternal mortality
• Whānau (family) involvement essential
• Māori Health Workers/Kaiāwhina for cultural support
• Respect tikanga (customs) in care delivery

Retrieval Medicine:

• Early activation of state retrieval services
• RFDS for remote/rural transfers
• Transfer criteria: Severe HELLP, <32 weeks, need for surgical/ICU capability not locally available
• In-flight considerations: Continue magnesium, BP monitoring, fetal monitoring

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Monitoring & Complications

ICU-Specific Monitoring

Daily Parameters:

• Vital signs: Hourly initially, then q4h when stable
• Fluid balance: Strict intake/output, aim for even or slightly negative balance
• Urine output: Hourly (target ≥0.5 mL/kg/hr)
• Platelet count: q12h until nadir, then daily until recovering
• LFTs: Daily until improving
• Coagulation: q12-24h if DIC or coagulopathic
• Creatinine: Daily

Trend Monitoring:

• Platelet trajectory: Nadir at 24-48h, expect rise by 72h
• LFT trajectory: Peak at 24-48h, expect improvement by 72h
• If NO improvement by 72 h: Suspect TTP/aHUS

Safety Monitoring:

• Magnesium toxicity: Reflexes, respiratory rate, level if renal impairment
• Signs of hepatic haematoma: Severe RUQ pain, hypotension, falling Hb
• Signs of abruption: Vaginal bleeding, uterine tenderness, fetal distress
• Signs of PRES: Headache, visual disturbance, seizures, altered consciousness

Complications

Early Complications (First 24-48 hours):

1. DIC (Disseminated Intravascular Coagulation)

• Incidence: 20-40% of Class 1 HELLP
• Presentation: Bleeding from multiple sites, oozing, petechiae
• Diagnosis: Prolonged PT/APTT, fibrinogen <2 g/L, elevated D-dimer, falling platelets
• Management: Blood products (FFP, cryo, platelets), delivery, treat underlying cause
• Prognosis: Usually resolves with delivery

2. Placental Abruption

• Incidence: 7-20%
• Presentation: Vaginal bleeding, abdominal pain, uterine tenderness, fetal distress
• Diagnosis: Clinical (US may be normal in 50%)
• Management: Emergency delivery (usually caesarean), massive transfusion
• Prognosis: Maternal/fetal mortality depends on severity

3. Acute Kidney Injury

• Incidence: 3-8%
• Risk factors: DIC, haemorrhage, NSAID use, volume depletion
• Management: Fluid restriction (paradoxically), RRT if indicated
• Prognosis: Usually recovers post-delivery

4. Pulmonary Oedema

• Incidence: 5-10%
• Peak risk: 24-48h postpartum (third-space fluid mobilisation)
• Prevention: Fluid restriction (80-100 mL/hr total)
• Management: Diuretics, NIV/CPAP, intubation if severe

5. Hepatic Haematoma

• Incidence: 1-2% subcapsular; <1% rupture
• Presentation: Severe RUQ pain, shoulder tip pain, hypotension
• Diagnosis: US/CT
• Management: Conservative if stable; IR embolisation or surgery if expanding/ruptured

Late Complications (Beyond 48 hours):

6. Persistent Disease (No Recovery by 72h)

• Suspect: TTP (ADAMTS13 <10%), aHUS (complement dysregulation)
• Investigation: ADAMTS13, complement studies, genetic testing
• Management: Plasma exchange for TTP; eculizumab for aHUS
• Haematology/nephrology consultation essential

7. PRES (Posterior Reversible Encephalopathy Syndrome)

• Incidence: Up to 80% of eclampsia on MRI
• Presentation: Headache, visual disturbances, seizures, altered consciousness
• Diagnosis: MRI (posterior white matter oedema)
• Management: BP control, magnesium, seizure management
• Prognosis: Usually reversible with treatment

8. Stroke (Haemorrhagic or Ischaemic)

• Incidence: 0.5-1%
• Risk: Severe hypertension, coagulopathy
• Presentation: Focal neurology, decreased consciousness
• Diagnosis: CT head
• Management: BP control, neurosurgical consultation, supportive care

ICU-Acquired Complications:

• Ventilator-associated pneumonia (if intubated)
• Central line-associated bloodstream infection
• VTE (delayed prophylaxis due to coagulopathy)
• Pressure injuries

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Prognosis & Outcome Measures

Mortality

Maternal Mortality (PMID: 19896722, 30135024):

• Overall: 1-3%
• Class 1 HELLP: 2-5%
• With DIC: 5-10%
• With hepatic rupture: 50-80%
• With stroke: 20-30%

Perinatal Mortality:

• Overall: 7-35%
• Primary causes: Prematurity, abruption, IUGR
• Improved with antenatal corticosteroids and modern NICU care

Morbidity

Short-Term Maternal Morbidity:

• Blood transfusion required: 30-60%
• ICU admission: 20-40% of HELLP cases
• DIC: 20-40%
• AKI requiring RRT: 3-8%
• Pulmonary oedema: 5-10%
• Hepatic haematoma: 1-2%

Long-Term Outcomes:

• Most recover fully
• Chronic hypertension: 20-50% within 10 years
• Cardiovascular disease: 2-4× increased lifetime risk
• Recurrence risk:
  • "HELLP in subsequent pregnancy: 3-5%"
  • "Pre-eclampsia in subsequent pregnancy: 20-25%"
  • Earlier onset if recurs

Fetal/Neonatal Morbidity:

• Prematurity complications: RDS, IVH, NEC, sepsis
• IUGR: 30-40%
• Long-term neurodevelopmental outcomes: Generally good if survive neonatal period

Prognostic Factors

Good Prognostic Factors:

• Later gestational age at diagnosis (>34 weeks)
• Class 2-3 HELLP (platelets >50 × 10⁹/L)
• Rapid recovery post-delivery (platelet rise by 72h)
• No hepatic haematoma
• No DIC
• Single gestation
• Tertiary centre care

Poor Prognostic Factors:

• Class 1 HELLP (<50 × 10⁹/L platelets)
• DIC present
• Hepatic haematoma or rupture
• AKI or multi-organ failure
• Eclampsia or PRES
• Early gestational age (<28 weeks)
• Delayed diagnosis or treatment
• Remote location (delayed access to tertiary care)
• Placental abruption

Scoring Systems

Mississippi Classification:

• Class 1: Highest complication rate (DIC 40%, maternal mortality 2-5%)
• Class 2: Moderate risk
• Class 3: Lowest complication rate

SOFA Score:

• May be used to track multi-organ dysfunction
• Rising SOFA indicates deterioration

MODS Score:

• Alternative to SOFA for multi-organ assessment

Australian/NZ Outcome Data

ANZICS CORE Data:

• Obstetric ICU admissions: ~1% of total ICU admissions
• Hypertensive disorders: Leading medical cause of obstetric ICU admission
• ICU mortality for hypertensive disorders: 1-3%

Indigenous Health Outcomes:

• Higher maternal mortality ratio (17.5 vs 5.5 per 100,000)
• Later presentation, higher severity at diagnosis
• Lower rates of early antenatal care
• Geographic barriers to tertiary care
• Ongoing efforts to improve equity in obstetric outcomes

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SAQ Practice (Full Exam-Level)

SAQ 1: HELLP with Hepatic Complication

Time Allocation: 10 minutes
Total Marks: 20

Stem:

A 29-year-old nulliparous woman at 31 weeks gestation is admitted to ICU following emergency caesarean section for HELLP syndrome and fetal distress. She was initially stable postoperatively but 6 hours later develops sudden severe RUQ pain radiating to her right shoulder, and becomes hypotensive.

Current observations:

• HR: 125 bpm
• BP: 78/48 mmHg
• RR: 28/min
• SpO2: 92% on 6L O2
• Temperature: 37.1°C
• Urine output: 15 mL in last hour

Investigations:

Pre-operative (6 hours ago):

• Platelets: 48 × 10⁹/L
• Hb: 102 g/L
• AST: 385 U/L
• LDH: 920 U/L
• INR: 1.3

Current:

• Platelets: 32 × 10⁹/L
• Hb: 68 g/L
• AST: 520 U/L
• LDH: 1250 U/L
• INR: 1.8
• Fibrinogen: 1.4 g/L
• Lactate: 5.8 mmol/L

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Question 1.1 (8 marks)

What is the most likely diagnosis? List the key clinical and laboratory features that support this diagnosis.

Question 1.2 (6 marks)

Outline your immediate management priorities in the first 30 minutes.

Question 1.3 (6 marks)

The patient is stabilised and imaging confirms a large subcapsular haematoma with active bleeding. Discuss the options for definitive management.

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Model Answer

Question 1.1 (8 marks total)

Diagnosis: Ruptured hepatic subcapsular haematoma with haemorrhagic shock, in the context of Class 1 HELLP syndrome complicated by DIC. (2 marks)

Clinical Features Supporting Diagnosis (3 marks):

• Sudden severe RUQ pain radiating to shoulder (referred diaphragmatic irritation - pathognomonic)
• Haemorrhagic shock: Hypotension (BP 78/48), tachycardia (HR 125), oliguria, elevated lactate
• Context of severe HELLP (Class 1 - platelets <50 × 10⁹/L pre-operatively)
• Onset 6 hours post-caesarean section (typical timing for this complication)

Laboratory Features Supporting Diagnosis (3 marks):

• Falling haemoglobin: 102 → 68 g/L (acute blood loss)
• Falling platelets: 48 → 32 × 10⁹/L (consumption + haemorrhage)
• Worsening coagulopathy: INR 1.3 → 1.8, fibrinogen 1.4 g/L (<2 g/L = DIC)
• Rising LDH: 920 → 1250 U/L (ongoing haemolysis and tissue damage)
• Elevated lactate: 5.8 mmol/L (tissue hypoperfusion)
• Rising AST: 385 → 520 U/L (ongoing hepatic injury)

Key Point: This presentation is classic for hepatic haematoma rupture - the combination of sudden severe RUQ/shoulder pain, shock, and falling Hb in postpartum HELLP patient should prompt immediate imaging and activation of massive transfusion protocol.

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Question 1.2 (6 marks total)

Immediate Management Priorities (First 30 Minutes):

1. Resuscitation (Massive Haemorrhage Protocol) (2 marks):

• Activate massive transfusion protocol (MTP)
• Large-bore IV access × 2 (if not already)
• Blood products:
  • "PRBCs: Target Hb >70 g/L (transfuse empirically - cross-matched or O-negative)"
  • "FFP: Target INR <1.5 (ratio 1:1 with PRBCs)"
  • "Cryoprecipitate: Target fibrinogen >2 g/L (give 10 units)"
  • "Platelets: Target >50 × 10⁹/L (1 adult therapeutic dose)"
• Tranexamic acid: 1g IV
• Fluid resuscitation: Crystalloid until blood available

2. Haemodynamic Support (1 mark):

• Vasopressors if persistent hypotension despite transfusion (noradrenaline)
• Arterial line for continuous BP monitoring
• Target MAP ≥65 mmHg

3. Airway/Breathing (1 mark):

• High-flow oxygen or NIV
• Intubation if deteriorating conscious level, respiratory failure, or surgery planned
• ABG for acid-base status

4. Investigations and Team Activation (1 mark):

• Urgent imaging: CT abdomen with contrast (if stable enough) OR bedside ultrasound/FAST if unstable
• Activate: Surgical team (hepatobiliary if available), interventional radiology, anaesthetics, blood bank

5. Other Priorities (1 mark):

• Continue magnesium sulfate (seizure prophylaxis)
• Urinary catheter if not in situ
• Prepare for theatre or IR suite
• Keep patient warm (prevent hypothermia)
• Consider calcium gluconate 1g IV for hypocalcaemia from massive transfusion

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Question 1.3 (6 marks total)

Definitive Management Options for Hepatic Haematoma with Active Bleeding:

1. Interventional Radiology (IR) Embolisation (2 marks):

• Indications: Haemodynamically stabilisable, active arterial bleeding identified, IR capability available
• Procedure: Selective hepatic artery embolisation (coils, Gelfoam)
• Advantages: Minimally invasive, can be definitive, preserves liver parenchyma
• Limitations: Requires stable patient for transfer to IR, may not control venous bleeding, may need repeat procedures
• Success rate: 60-80% for bleeding control

2. Surgical Intervention (2 marks):

• Indications: Haemodynamically unstable, peritonitis, failed IR, lack of IR availability
• Options:
  • "Damage control surgery: Packing with planned relook at 24-48h"
  • Direct suture repair of capsular tears
  • Argon beam coagulation for surface bleeding
  • Hepatic artery ligation (rarely needed)
  • Partial hepatectomy (extreme cases)
• Advantages: Can control diffuse bleeding, addresses peritoneal contamination
• Risks: High morbidity, liver failure if extensive resection

3. Conservative Management (0.5 marks):

• NOT appropriate in this case (active bleeding, shock)
• Only for stable contained haematomas

4. Liver Transplantation (0.5 marks):

• Last resort for massive hepatic necrosis
• Very rarely required
• Discuss with transplant centre if liver failure develops

Decision-Making Factors (1 mark):

• Patient stability: IR preferred if can be stabilised; surgery if unstable
• Local resources: Availability of IR vs surgical expertise
• Nature of bleeding: Arterial (IR-amenable) vs venous (may need surgery)
• Response to resuscitation: If not responding despite MTP, proceed directly to OR

Multidisciplinary Approach:

• Surgical team (hepatobiliary surgeon if available)
• Interventional radiology
• ICU for post-procedure care
• Blood bank for ongoing transfusion support

---

Common Mistakes:

• Not recognising the classic presentation of hepatic rupture (shoulder tip pain + shock)
• Delaying massive transfusion activation
• Attempting conservative management in unstable patient
• Forgetting tranexamic acid

Examiner Comments:

• Candidates should recognise this as a surgical emergency
• Systematic approach to haemorrhagic shock expected
• Knowledge of both IR and surgical options expected
• Must mention massive transfusion protocol by name

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SAQ 2: HELLP vs TTP Differentiation

Time Allocation: 10 minutes
Total Marks: 20

Stem:

A 26-year-old woman at 28 weeks gestation presents with confusion, headache, and petechiae. She is normotensive with BP 118/74 mmHg.

Investigations:

• Platelets: 18 × 10⁹/L
• Hb: 78 g/L
• AST: 85 U/L
• LDH: 1850 U/L
• Creatinine: 145 μmol/L
• Blood film: Schistocytes +++
• Haptoglobin: Undetectable
• Fibrinogen: 3.2 g/L

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Question 2.1 (8 marks)

Construct a differential diagnosis for this presentation. Discuss the key features that would differentiate between the two most likely diagnoses.

Question 2.2 (6 marks)

What additional investigations would you order, and what results would confirm your suspected diagnosis?

Question 2.3 (6 marks)

The ADAMTS13 activity returns at 3%. Outline your management plan.

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Model Answer

Question 2.1 (8 marks total)

Differential Diagnosis (2 marks):

1. Thrombotic Thrombocytopenic Purpura (TTP) - Most likely
2. HELLP Syndrome - Must be excluded
3. Atypical Haemolytic Uraemic Syndrome (aHUS)
4. Haemolytic Uraemic Syndrome (typical)
5. Catastrophic Antiphospholipid Syndrome (CAPS)

Key Differentiating Features: TTP vs HELLP (6 marks):

Analysis of This Case: This presentation favours TTP over HELLP because:

• Normal blood pressure (HELLP has hypertension in 85%)
• Prominent neurological symptoms (confusion - hallmark of TTP)
• Very low platelets (18 × 10⁹/L - typically lower in TTP)
• Mild liver enzyme elevation (HELLP would have AST ≥70 with more significant elevation expected)
• Very high LDH (more consistent with severe haemolysis of TTP)
• Normal fibrinogen (DIC not present)
• Can occur earlier in pregnancy (TTP can occur at any gestation)

CRITICAL DISTINCTION: TTP will NOT improve with delivery and requires plasma exchange. HELLP resolves with delivery. Incorrect diagnosis has life-threatening consequences.

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Question 2.2 (6 marks total)

Additional Investigations (3 marks):

Results Confirming TTP (3 marks):

• ADAMTS13 activity <10%: DIAGNOSTIC of TTP
• ADAMTS13 inhibitor positive: Confirms acquired (autoimmune) TTP
• ADAMTS13 inhibitor negative with <10% activity: Consider congenital TTP (Upshaw-Schulman syndrome)

Other Expected Findings in TTP:

• Severely low haptoglobin or undetectable (✓ present)
• Very elevated LDH (often >1000) (✓ present at 1850)
• Schistocytes on blood film (✓ present)
• Normal or mildly elevated liver enzymes (✓ AST 85)
• Normal fibrinogen (✓ 3.2 g/L - distinguishes from DIC)

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Question 2.3 (6 marks total)

Management of TTP in Pregnancy (ADAMTS13 3%) (6 marks):

1. Plasma Exchange (PEX) - URGENT first-line therapy (2 marks):

• Initiate within 4-8 hours of diagnosis
• Dose: 1-1.5 plasma volumes daily
• Fresh frozen plasma as replacement fluid
• Continue daily until: Platelets >150 × 10⁹/L for 2 consecutive days + normalising LDH
• Mechanism: Removes autoantibody, replaces ADAMTS13

2. Immunosuppression (1 mark):

• Corticosteroids: Methylprednisolone 1g IV daily × 3 days OR prednisolone 1 mg/kg
• Rituximab: Consider if refractory or relapsing (375 mg/m² weekly × 4)
• Caution: Rituximab in pregnancy - discuss risks/benefits

3. Caplacizumab (0.5 marks):

• Anti-vWF nanobody - prevents platelet-vWF interaction
• Accelerates response to PEX
• Limited pregnancy data but used in severe cases
• Dose: 10 mg IV on day 1, then 10 mg SC daily

4. Supportive Care (1 mark):

• ICU admission
• Platelet transfusion: AVOID unless life-threatening bleeding (can exacerbate microthrombi)
• RBC transfusion for symptomatic anaemia
• Folic acid supplementation
• VTE prophylaxis when platelets recover
• Avoid aspirin until platelets >50 × 10⁹/L

5. Fetal Considerations (1 mark):

• Continuous fetal monitoring
• Delivery does NOT treat TTP - continue PEX through delivery if needed
• Timing of delivery: Based on fetal status and maternal stability
• Mode: Vaginal preferred if stable; caesarean if fetal distress
• Coordinate with MFM, neonatology, haematology

6. Multidisciplinary Team (0.5 marks):

• Haematology (lead for TTP management)
• MFM/Obstetrics
• ICU
• Blood bank (PEX resources)
• Neonatology

Key Points:

• Do NOT delay PEX for delivery
• Delivery will NOT improve TTP
• PEX can be continued peripartum
• Monitor for relapse post-delivery

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Common Mistakes:

• Diagnosing HELLP and expecting delivery to resolve the problem
• Delaying plasma exchange while awaiting ADAMTS13 results
• Transfusing platelets (can worsen TTP)
• Not involving haematology early

Examiner Comments:

• Must differentiate TTP from HELLP - different treatments with different outcomes
• ADAMTS13 <10% is diagnostic threshold
• Plasma exchange is life-saving and must be initiated urgently

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Viva Scenarios

Viva Scenario 1: Delivery Timing in HELLP

Stem: "A 32-year-old woman at 29 weeks gestation is admitted to ICU with HELLP syndrome. Platelets 62 × 10⁹/L, AST 245 U/L, LDH 780 U/L. Blood pressure is controlled at 145/92 mmHg on labetalol. The fetus appears well on CTG."

Duration: 12 minutes (2 min reading + 10 min discussion)

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Opening Question:

"What are the key considerations in deciding on the timing of delivery for this patient?"

Expected Answer (2-3 minutes):

This patient has Class 2 HELLP syndrome at an early gestation (29 weeks). The decision regarding delivery timing involves balancing maternal risks against fetal prematurity.

Maternal Considerations:

• Current stability: BP controlled, Class 2 (not most severe)
• Risk of deterioration: HELLP can progress rapidly to Class 1, DIC, abruption, hepatic complications
• Response to expectant management: Only appropriate in selected stable cases
• Location: Must be in tertiary centre with NICU and ICU capability

Fetal Considerations:

• 29 weeks: Significant prematurity risks (RDS, IVH, NEC, sepsis)
• Neonatal survival: ~90% at 29 weeks with modern NICU care
• Long-term outcomes: Higher morbidity at earlier gestations
• Benefit of antenatal corticosteroids: Reduces RDS, IVH, mortality
• Each day gained <32 weeks improves outcomes

Balancing Factors:

• ACOG/SOMANZ recommend delivery at ≥34 weeks regardless of severity
• At <34 weeks with stable Class 2-3 HELLP, can consider brief expectant management
• Class 1 or any deterioration mandates immediate delivery regardless of gestation

My Approach: In this case, the patient is relatively stable (Class 2, BP controlled). I would consider a brief period of expectant management (24-48 hours) to administer corticosteroids for fetal lung maturity, with very close monitoring and a low threshold for delivery.

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Follow-up Question 1 (2-3 minutes):

"The obstetric team wants to delay delivery for 48 hours to complete corticosteroids. What are your monitoring requirements and criteria for immediate delivery?"

Expected Answer:

Monitoring Requirements:

• ICU or high-dependency unit admission
• Continuous fetal CTG monitoring
• Platelet count every 6-12 hours
• LFTs, LDH every 12 hours
• Creatinine daily
• Coagulation studies every 12-24 hours
• Hourly urine output
• BP every 15-30 minutes initially
• Continuous magnesium infusion with toxicity monitoring

Criteria for Immediate Delivery (Regardless of Steroid Completion):

• Platelets falling to <50 × 10⁹/L (progression to Class 1)
• Development of DIC (fibrinogen <2 g/L, rising INR)
• Severe persistent hypertension (≥160/110) despite maximal therapy
• Pulmonary oedema
• Eclamptic seizure
• Signs of hepatic haematoma (severe RUQ pain)
• Non-reassuring fetal status (persistent bradycardia, late decelerations)
• Placental abruption (bleeding, uterine tenderness)
• Renal failure (rising creatinine, oliguria)
• Any maternal clinical deterioration
• Patient request for delivery

Key Point: Expectant management is only for stable patients in tertiary centres. The decision must be re-evaluated continuously, and delivery should not be delayed if any deterioration occurs.

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Follow-up Question 2 (2-3 minutes):

"The patient receives betamethasone. At 24 hours, platelets have fallen to 45 × 10⁹/L. What is your recommendation?"

Expected Answer:

Immediate Delivery is Now Indicated:

• Platelets have crossed the Class 1 threshold (<50 × 10⁹/L)
• This represents deterioration despite expectant management
• Class 1 HELLP has highest complication rates (DIC, abruption, hepatic complications)
• Further waiting increases maternal risk without proportional fetal benefit

Preparation for Delivery:

Timing: Urgent (within 2-6 hours, not emergent unless other complications)

Mode of Delivery:

• Caesarean section likely given gestation and urgency
• Vaginal delivery possible if cervix favourable and rapid delivery expected
• Decision in conjunction with obstetric team

Anaesthetic Considerations:

• Regional anaesthesia: Relative contraindication at platelets <50 × 10⁹/L
• If caesarean required: General anaesthesia most likely
• If vaginal delivery and epidural desired: Consider platelet transfusion first (target >50 × 10⁹/L)

Pre-operative Preparation:

• Platelet transfusion immediately before procedure (1 adult therapeutic dose)
• Target: Platelets >50 × 10⁹/L for surgery
• FFP available if INR prolonged
• Cross-match blood (4-6 units PRBCs)
• Continue magnesium sulfate through delivery
• Neonatology team present

Post-Delivery:

• Expect platelet nadir at 24-48h post-delivery
• Continue magnesium for 24-48h
• Monitor for complications (DIC, hepatic haematoma, pulmonary oedema)
• Recovery expected by 72-96h

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Follow-up Question 3 (2-3 minutes):

"The obstetrician asks about using dexamethasone to improve the platelet count and delay delivery further. What is the evidence?"

Expected Answer:

Evidence for Dexamethasone in HELLP:

Proposed Mechanism:

• Anti-inflammatory effects
• Reduces endothelial activation
• May accelerate hepatic synthesis of clotting factors

What Studies Show:

• Cochrane Review (PMID: 22592693): 11 trials, 550 patients
  • Dexamethasone may accelerate platelet recovery (by ~24h)
  • NO difference in maternal mortality
  • NO difference in serious maternal morbidity
  • NO difference in perinatal outcomes

Guideline Recommendations:

• SOMANZ 2023: Does NOT recommend routine dexamethasone for maternal HELLP
• ACOG: Does NOT recommend corticosteroids for maternal HELLP treatment
• Rationale: No proven mortality or major morbidity benefit; may delay definitive treatment (delivery)

My Recommendation: I would NOT recommend using dexamethasone to delay delivery in this patient. She has already progressed to Class 1 HELLP, indicating active disease. Delaying delivery further increases maternal risk without proven benefit. The patient has already received betamethasone for fetal lung maturity (the evidence-based use of corticosteroids in this setting).

When Dexamethasone Might Be Considered:

• Severe thrombocytopenia (<20 × 10⁹/L) when delivery absolutely cannot be delayed
• To buy time for transfer to tertiary centre
• But NOT as a substitute for delivery in Class 1 HELLP

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Examiner's Expected Level:

Pass:

• Understands that delivery is definitive treatment
• Can articulate criteria for immediate delivery
• Knows that expectant management is only for stable patients in tertiary centres
• Aware that corticosteroids (dexamethasone) for maternal platelet recovery lack mortality benefit
• Systematically covers monitoring requirements

Fail:

• Advocates delaying delivery without recognising deterioration
• Cannot articulate clear criteria for delivery
• Does not recognise Class 1 as indication for delivery
• Confuses fetal steroids with maternal HELLP treatment
• Unsafe approach to coagulopathy or anaesthesia

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Viva Scenario 2: Postpartum HELLP with Diagnostic Uncertainty

Stem: "A 35-year-old woman is 48 hours post-caesarean section for severe pre-eclampsia. She was improving but now has platelets falling from 95 to 42 × 10⁹/L, rising LDH (1200 U/L), and confusion. Her blood pressure is 124/78 mmHg."

Duration: 12 minutes (2 min reading + 10 min discussion)

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Opening Question:

"This patient is deteriorating despite delivery. What diagnoses are you considering?"

Expected Answer (2-3 minutes):

This is concerning for a thrombotic microangiopathy (TMA) that is not resolving as expected post-delivery.

Differential Diagnosis:

1. Worsening/Persistent HELLP Syndrome:

   • Can continue to deteriorate for 24-48h post-delivery before improving
   • Platelet nadir typically at 24-48h
   • However, IMPROVEMENT should be evident by 72h

2. Thrombotic Thrombocytopenic Purpura (TTP):

   • May coexist with pregnancy or be triggered by it
   • Confusion is hallmark neurological feature
   • Normal blood pressure typical
   • Will NOT improve with delivery - requires plasma exchange
   • ADAMTS13 <10% is diagnostic

3. Atypical Haemolytic Uraemic Syndrome (aHUS):

   • Complement-mediated TMA
   • May be triggered by pregnancy
   • Renal failure usually more prominent
   • ADAMTS13 >10%
   • May require eculizumab

4. Postpartum Sepsis:

   • Could cause thrombocytopenia, confusion
   • Look for fever, elevated WCC, source
   • Would expect different clinical picture

5. Other Causes of Postpartum Confusion:

   • PRES (check MRI)
   • Postpartum psychosis
   • Septic encephalopathy
   • Metabolic (hypoglycaemia, hyponatraemia)

Key Concern: At 48 hours post-delivery, HELLP should be improving, not deteriorating. The falling platelets and rising LDH suggest an ongoing active process. TTP must be urgently excluded.

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Follow-up Question 1 (2-3 minutes):

"What investigations would you order, and what would you do while awaiting results?"

Expected Answer:

Urgent Investigations:

Actions While Awaiting ADAMTS13 Result:

1. Do NOT wait for ADAMTS13 before acting - results may take 24-48h in some centres

2. Presumptive Treatment for TTP if High Suspicion:

   • Contact haematology URGENTLY
   • Arrange plasma exchange (PEX)
   • If ADAMTS13 likely to be delayed >24h, consider empiric PEX
   • Rationale: TTP mortality is very high without treatment; PEX is low risk

3. Supportive Care:

   • ICU monitoring
   • Avoid platelet transfusion unless life-threatening bleeding (may worsen TTP)
   • RBC transfusion for symptomatic anaemia
   • Magnesium sulfate continuation (seizure prophylaxis)
   • BP monitoring (less relevant as BP is normal)

4. Do NOT assume this is "just delayed HELLP recovery" - this pattern is atypical

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Follow-up Question 2 (2-3 minutes):

"The ADAMTS13 comes back at 45%. The patient's platelets are now 28 × 10⁹/L and creatinine is 280 μmol/L. What now?"

Expected Answer:

Revised Diagnosis: With ADAMTS13 at 45% (>10%), this is NOT TTP.

Most Likely Diagnosis Now: Atypical Haemolytic Uraemic Syndrome (aHUS) or possibly severe prolonged HELLP.

Features Suggesting aHUS:

• ADAMTS13 >10% (excludes TTP)
• Prominent renal failure (creatinine 280 μmol/L)
• Ongoing TMA post-delivery (not improving as HELLP should)
• May have complement dysregulation

Additional Investigations for aHUS:

• Complement C3, C4, CH50
• Factor H, Factor I antibodies
• CFH, CFI, MCP genetic testing (can take weeks but important for prognosis)
• Shiga toxin (unlikely without diarrhoeal prodrome)

Management of aHUS:

1. Eculizumab (anti-C5 antibody):

   • First-line treatment for aHUS
   • Dose: 900 mg IV weekly × 4, then 1200 mg q2 weekly
   • Must have meningococcal vaccination (or antibiotic prophylaxis if urgent)
   • Discuss with nephrology and haematology
   • Can be life-saving

2. Supportive Care:

   • Renal replacement therapy if indicated
   • Blood product support (platelets can be given if aHUS, unlike TTP)
   • BP control if hypertensive

3. Plasma Exchange:

   • Less effective in aHUS than TTP
   • May provide some benefit before eculizumab available
   • Should not delay eculizumab

4. Consider Severe Prolonged HELLP:

   • Some HELLP cases take longer to resolve
   • If improving (even slowly), may be late-resolving HELLP
   • But renal failure this severe is unusual

Multidisciplinary Team:

• Nephrology (aHUS expertise, RRT)
• Haematology
• Genetics (for testing)
• Pharmacy (eculizumab access)

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Follow-up Question 3 (2-3 minutes):

"How would you approach the family discussion about this unexpected deterioration?"

Expected Answer:

Preparation:

• Gather all clinical information
• Speak with haematology and nephrology about prognosis
• Identify family members/support persons
• Arrange quiet private space
• Allow adequate time

Communication Approach (SPIKES Framework):

S - Setting:

• Private room, adequate seating
• Minimise interruptions
• Have nursing support present

P - Perception:

• "What do you understand about what has been happening with [patient]?"
• Correct misunderstandings gently

I - Invitation:

• "I need to share some concerning news about [patient's] condition."

K - Knowledge: Clear, honest information:

• "After her caesarean section, we expected her blood condition to improve. Unfortunately, it has got worse instead of better."
• "This tells us there may be something else happening beyond the original condition."
• "We are doing tests to find out exactly what is causing this, and we have started treatment."
• Avoid jargon: "Her kidneys are not working as well as they should, and she is confused because of the condition affecting her blood."

E - Emotions:

• Acknowledge their distress
• "This must be very frightening and unexpected."
• Allow silence for processing

S - Strategy and Summary:

• "We are treating her in the ICU with very close monitoring."
• "We have specialists from blood disorders and kidney teams involved."
• "We will keep you updated as we learn more."
• "Do you have questions?"

Key Messages:

• Unexpected deterioration is concerning
• We are acting quickly with appropriate specialists
• We will keep them informed
• Support is available

If Indigenous Patient:

• Involve Aboriginal Health Worker/ALO
• Include extended family in discussions
• Allow time for family consultation
• Cultural considerations (may need to contact family on Country)

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Examiner's Expected Level:

Pass:

• Recognises atypical post-delivery course
• Differentiates between HELLP, TTP, and aHUS based on ADAMTS13
• Knows that TTP requires plasma exchange, aHUS may require eculizumab
• Demonstrates compassionate communication approach
• Involves appropriate specialists

Fail:

• Cannot differentiate TMA subtypes
• Does not recognise need for ADAMTS13 testing
• Inappropriate management (e.g., waiting for HELLP to resolve)
• Poor communication skills
• Does not involve multidisciplinary team