How do you differentiate and manage Thrombotic Thrombocytopenic Purpura (TTP) versus Hemolysis, Elevated Liver enzymes, and Low Platelet count (HELLP) syndrome in a pregnant woman presenting with abdominal pain, vomiting, and petechiae?

Differentiating and Managing TTP vs HELLP Syndrome in Pregnancy

Immediate Diagnostic Approach

In a pregnant woman presenting with abdominal pain, vomiting, and petechiae with thrombocytopenia and microangiopathic hemolytic anemia, you must immediately distinguish between HELLP syndrome and TTP because the management differs critically: HELLP requires urgent delivery while TTP requires plasma exchange, and delays in either can be fatal. 1

Key Clinical Discriminators

Timing and pregnancy status:

• HELLP syndrome occurs predominantly in the third trimester (typically ≥34 weeks) and is associated with preeclampsia in 80% of cases 2, 3
• TTP can occur at any gestational age and both antepartum and postpartum 1
• Approximately 15% of HELLP cases have no hypertension, making diagnosis more challenging 2

Laboratory differentiation using LDH/AST ratio:

• An LDH to AST ratio ≥22.12 strongly suggests TTP rather than HELLP syndrome (AUC = 0.99) 4
• TTP patients have LDH/AST ratios of 77 ± 42, while HELLP patients have ratios of 20 ± 2 4
• This ratio provides rapid discrimination when ADAMTS-13 results are not immediately available 4

Severity of thrombocytopenia:

• TTP typically presents with more severe thrombocytopenia (<30,000/mm³) 1, 4
• HELLP syndrome usually has platelets between 20,000-100,000/mm³, though can overlap 5, 6

Renal involvement pattern:

• Progressive kidney injury with less severe thrombocytopenia suggests complement-mediated TMA 1
• Minimal kidney involvement with severe thrombocytopenia suggests TTP 1

Neurological symptoms:

• Neurological impairment (confusion, altered mental status, focal deficits) strongly suggests TTP 7, 1
• HELLP syndrome rarely presents with neurological symptoms unless eclampsia develops 5

Critical Laboratory Workup

Essential immediate tests:

• Complete blood count with peripheral smear showing schistocytes (microangiopathic hemolytic anemia) 5, 1
• LDH, AST, ALT to calculate the LDH/AST ratio 4
• Bilirubin, haptoglobin (decreased in hemolysis) 5
• Coagulation profile (PT, aPTT, fibrinogen, fibrin degradation products) - typically normal in TTP, may be abnormal in HELLP 5, 1
• Creatinine and urea for renal function 5, 1
• ADAMTS-13 activity level (send immediately but do not wait for results to treat) 7, 1

ADAMTS-13 interpretation:

• ADAMTS-13 activity <5-10% confirms TTP 7, 1
• However, HELLP-induced acute liver failure can cause secondary ADAMTS-13 deficiency, creating diagnostic confusion 7

Management Algorithm

If HELLP Syndrome is Diagnosed

Immediate management priorities:

• Urgent delivery is the definitive treatment regardless of gestational age 5, 8
• Stabilize before delivery with blood pressure control and correction of coagulopathy 5, 8

Pre-delivery stabilization:

• Insert central venous catheter via internal jugular approach to assess intravascular volume (these patients are typically hypovolemic despite appearing edematous) 5, 8
• Insert urinary catheter for hourly output monitoring 5, 8
• Administer fresh frozen plasma 400 mL to increase plasma volume if CVP is low (target CVP 3-8 mmHg) 5, 8
• Transfuse platelets (6 units) immediately before surgery to achieve count >50,000/mm³ 5, 8
• Commence hydralazine infusion to maintain mean arterial pressure 100-105 mmHg 5, 8

Post-delivery intensive management:

• Transfer to ICU or high-dependency unit for continuous monitoring 5, 8
• Continue magnesium sulfate for 24 hours post-delivery to prevent eclamptic seizures 8
• Maintain strict fluid balance for 24 hours after delivery to avoid pulmonary edema 8
• Monitor for disease peak at 24 hours postpartum with serial laboratory tests 8
• Watch for hepatic hemorrhage/hematoma (abdominal pain, right shoulder pain) - perform ultrasound if suspected 8
• Do NOT give corticosteroids to improve maternal outcomes in HELLP syndrome 8

If TTP is Diagnosed or Suspected

When to suspect TTP over HELLP:

• LDH/AST ratio ≥22.12 4
• Severe thrombocytopenia (<30,000/mm³) with minimal liver enzyme elevation 1, 4
• Neurological symptoms present 7, 1
• No improvement or worsening after delivery 9, 1

Immediate TTP management:

• Initiate plasma exchange (plasmapheresis) immediately - do not wait for ADAMTS-13 results 9, 7, 1
• Daily plasma exchange until platelet count normalizes and hemolysis resolves 7, 1
• Hematology consultation urgently 9

When Diagnosis is Uncertain

Trial plasmapheresis approach:

• If ADAMTS-13 results are not immediately available and clinical judgment cannot distinguish with certainty, initiate a short trial of plasmapheresis with close observation of immediate response 9
• This is particularly important if the patient deteriorates postpartum despite delivery 9, 1
• Absence of improvement or progression of MAHA, thrombocytopenia, and renal dysfunction after delivery mandates consideration of TTP or complement-mediated TMA 1

Critical Pitfalls to Avoid

Diagnostic pitfalls:

• HELLP and TTP can coexist or complicate one another 9, 7
• HELLP-induced acute liver failure can cause secondary TTP through ADAMTS-13 deficiency 7
• 20% of HELLP cases lack classic preeclampsia signs (hypertension, proteinuria) 2, 3
• Upper abdominal pain can mimic gastroenterologic diseases (cholecystitis, appendicitis), causing dangerous delays 3

Management pitfalls:

• Avoid aggressive fluid resuscitation in HELLP syndrome - this significantly increases pulmonary edema risk 8
• Do not delay delivery in HELLP syndrome waiting for laboratory improvement 5, 8
• Do not withhold plasma exchange in suspected TTP while waiting for ADAMTS-13 results 9, 1
• Platelet transfusion threshold <50,000/mm³ for HELLP patients undergoing surgery 5, 8

Post-Recovery Counseling

For HELLP syndrome survivors:

• 20% recurrence risk in future pregnancies 8
• Recommend aspirin prophylaxis 150 mg nightly starting before 16 weeks gestation until 36 weeks or delivery in subsequent pregnancies 8
• First-trimester screening for early-onset preeclampsia 8