TTP

Question 1

Epidemiology of Acquired TTP

Answer 1

• Most common in adults aged 20–50 years.
  
  • Female predominance (2:1).
  • 8x higher incidence in African Americans.
    >Secondary causes include:
  • Pregnancy
  • SLE (rheumatologic)
  • Malignancy
  • HIV
  • Ticlopidine (rare)

Question 2

What are the clinical manifestations of TTP

Answer 2

Classic Pentad (seen in only ~5%)

*	Thrombocytopenia (100%)
*	MAHA – microangiopathic hemolytic anemia (100%)
*	Neurological symptoms (~70%)
*	Renal injury (~50%)
*	Fever (~20%)

Neurological (~70%)
* Waxing/waning symptoms: HA, seizures, stroke, delirium, coma
* PRES or infarction on imaging
* Often fully reversible with treatment

Renal (~50%)
* Milder than other TMAs; dialysis in ~15%
* Hematuria/hemoglobinuria; possible HTN

GI (~50%)
* Pain, N/V, diarrhea, possible pancreatitis
* Bloody diarrhea from mesenteric thrombosis (mimics ST-HUS)

Cardiac
* Microinfarction to transmural MI
* Arrhythmias, heart failure, pericardial effusion

Question 3

What is the PLASMIC score?

Answer 3

Entry Criteria for PLASMIC Score
* TMA features: schistocytes, thrombocytopenia, LDH >420, clinical concern for TTP

Scoring (1 point each):
1. Platelets <30,000
2. Hemolysis: Retic >2.5%, ↓Haptoglobin, or indirect bili >2 mg/dL
3. No malignancy
4. No transplant
5. MCV <90 fL
6. INR <1.5
7. Creatinine <2.0 mg/dL

Interpretation:
* 0–4 = Low risk
* 5 = Intermediate risk (6% ADAMTS13 deficiency)
* 6–7 = High risk (90% sensitivity, 92% specificity for TTP)
→ Start plasma exchange empirically

Question 4

Treatment

Answer 4

💉 Treatment of Acquired TTP

[1] FFP while waiting for plasma exchange
* 2 units initially, then 1 unit q4h if delay >6–8h
* Consider diuretics to prevent fluid overload

[2] Plasma Exchange (PEX)
* Removes vWF multimers and anti-ADAMTS13 Abs
* Start within 6 hours ideally
* Dose: 60 mL/kg daily; twice daily if life-threatening
* Continue until:
* Platelets >150K
* LDH <1.5× ULN
* No new ischemia
* Stable for 2 consecutive days before stopping

Cautions:
* No platelets before catheter placement
* Monitor for hypocalcemia
* Time meds post-PEX to avoid removal
* Draw labs before exchange

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[3] Caplacizumab
* Anti-vWF antibody fragment → blocks platelet-vWF interaction
* Dosing: 10 mg IV → then 10 mg SC daily × 30 days after PEX
* ↓ ICU time (HERCULES RCT); risk of mild bleeding

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[4] Immunosuppression
* Steroids:
* High-dose methylprednisolone (10 mg/kg/day) or prednisone 1 mg/kg/day
* Rituximab:
- For ADAMTS13 <10%
- Administer immediately after PEX to avoid clearance

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[5] BP Control
* Target SBP <140 mmHg
* HTN worsens erythrocyte fragmentation

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[6] Avoid Blood Products
- Platelets: Avoid unless life-threatening bleed
- RBCs: Only if Hb <7 g/dL and symptomatic

*	Folate: Supplement to support erythropoiesis

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[7] DVT Prophylaxis
* High VTE risk (~30%)
* Start when platelets >30K

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[8] Antiplatelet Therapy
* Aspirin may be given if platelets >50K
* ⚠️ Use caution with caplacizumab due to bleeding risk

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[9] Myocardial Infarction in TTP
* Microvascular, not due to plaque rupture
* Treat TTP aggressively, avoid cath/stents
* Use aspirin if platelets >50K
* Avoid vasopressin (↑vWF release)

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[10] Stress Ulcer Prophylaxis
* Indicated due to GI involvement and anticoagulation use

Question 5

Pathophysiology of TTP

Answer 5

🧬 Pathophysiology of TTP
* ADAMTS13 deficiency:
- Most often acquired (autoantibody)
- Rarely congenital (Upshaw-Schulman syndrome)
* ↓ADAMTS13 → vWF multimers accumulate → platelet aggregation → microthrombi → MAHA & organ ischemia

Question 6

Congenital TTP

Answer 6

👶 Congenital TTP (Upshaw-Schulman)
* Autosomal recessive ADAMTS13 deficiency
* May present during pregnancy
* Treated with plasma infusions (not immunosuppression)