✅ Model Answer:
• Diagnosis: Thrombotic thrombocytopenic purpura (TTP) – ADAMTS13 deficiency <10%. Classic pentad: thrombocytopenia, microangiopathic hemolytic anemia (MAHA), fever, neurologic symptoms (confusion), and renal impairment (not always present).
• Any other test: ADAMTS13 Activity, ADAMTS13 inhibitor (autoantibody) to differentiate acquired vs congenital; complement studies (if atypical HUS considered).
• What to do next: Emergency: Start daily plasma exchange (PLEX) and corticosteroids (methylprednisolone 1g/day). Avoid platelet transfusion (unless life-threatening bleeding).
• Follow-up plan: Continue PLEX daily until platelet count normalizes and LDH improves. If refractory, add rituximab (anti-CD20) or caplacizumab. Monitor for relapse. If congenital TTP (Upshaw-Schülman), prophylactic plasma infusions.

✅ Model Answer:
• ADAMTS13: A disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13. It is a von Willebrand factor (VWF)-cleaving protease.
• Pathophysiology:
- Acquired TTP (most common): Autoantibodies (IgG) inhibit ADAMTS13, leading to accumulation of ultra-large VWF multimers.
- Congenital TTP (Upshaw-Schülman): ADAMTS13 gene mutations causing deficient ADAMTS13 activity.
- Result: Ultra-large VWF multimers cause excessive platelet aggregation and microthrombi formation in small vessels → platelet consumption (thrombocytopenia) and red blood cell shearing (MAHA – schistocytes).
- Organ damage: Microthrombi lead to ischemia in brain (confusion, seizures), kidneys, heart, and other organs.

✅ Model Answer:
• Classic pentad (not always all present):
- Thrombocytopenia: Low platelets (<50,000/µL).
- Microangiopathic hemolytic anemia (MAHA): Hemoglobin ↓, LDH ↑, haptoglobin ↓, schistocytes on smear.
- Neurologic symptoms: Confusion, headache, seizures, stroke, fluctuating consciousness.
- Fever: Often low-grade, due to cytokine release.
- Renal impairment: Elevated creatinine, hematuria (less common than in HUS).
• Other features:
- Bleeding: Petechiae, purpura, mucosal bleeding (due to thrombocytopenia).
- Abdominal pain: From microvascular ischemia.
- Fatigue, weakness.
• Onset: Acute, often rapid progression.

✅ Model Answer:
• Complete blood count (CBC):
- Platelets: Low (<50,000/µL).
- Hemoglobin: Low (anemia).
- Reticulocyte count: Elevated (hemolysis).
• Peripheral smear:
- Schistocytes: Fragmented red blood cells (helmet cells, triangular cells) – hallmark of MAHA.
• Hemolysis markers:
- LDH: Elevated.
- Haptoglobin: Low/undetectable.
- Indirect bilirubin: Elevated.
- Direct Coombs test: Negative (to rule out autoimmune hemolytic anemia).
• ADAMTS13 activity:
- Severe deficiency: <10% (diagnostic for TTP).
- ADAMTS13 inhibitor: Positive in acquired TTP (autoantibody).
• Renal function: Creatinine, BUN, urinalysis.
• Coagulation studies: PT, PTT, fibrinogen (usually normal – differentiates from DIC).

✅ Model Answer:
• Plasma exchange (PLEX):
- Treatment of choice: Daily PLEX (1-1.5 plasma volumes) until platelet count normalizes (>150,000) for ≥2 days and LDH improves.
- Mechanism: Removes autoantibodies and replenishes ADAMTS13.
- Duration: Usually 5-10 days (can be longer).
• Corticosteroids:
- Methylprednisolone: 1g/day IV for 3 days, then prednisone 1 mg/kg/day (to suppress autoantibody production).
• Caplacizumab:
- Anti-VWF nanobody that inhibits platelet aggregation.
- Dose: 10 mg IV loading, then 10 mg SC daily (for acquired TTP).
- Advantage: Faster platelet recovery, reduces relapse.
• Rituximab:
- Anti-CD20 monoclonal antibody for refractory or relapsed TTP.
- Dose: 375 mg/m² weekly for 4 weeks.
• Avoid: Platelet transfusions (unless life-threatening bleeding) – can worsen thrombosis.

✅ Model Answer:
• Neurologic complications:
- Stroke: Ischemic or hemorrhagic.
- Seizures: Due to cerebral microthrombi.
- Confusion, altered mental status.
- Permanent neurologic deficits: In severe cases.
• Renal complications:
- Acute kidney injury (AKI): Less common than in HUS, but can occur.
- Hypertension.
• Cardiac complications:
- Myocardial ischemia, arrhythmias.
• Bleeding: Due to severe thrombocytopenia (petechiae, purpura, mucosal bleeding).
• Relapse: In ~30-40% of acquired TTP (especially within the first year).
• Death: If untreated, mortality is >90%; with PLEX, mortality is 10-20%.

✅ Model Answer:
• Prognosis:
- Excellent with prompt PLEX and immunotherapy.
- Without treatment: Mortality >90%.
- With PLEX: Survival >80-90%.
- Relapse: Common (30-40%) in acquired TTP (monitor ADAMTS13).
- Congenital TTP: Recurrent episodes; requires prophylactic plasma infusions.
• Long-term follow-up:
- Monitor ADAMTS13 activity: Regular surveillance (every 3-6 months) to detect relapse.
- Neurologic monitoring: For residual deficits.
- Renal function monitoring: Blood pressure, creatinine.
- Education: Recognize early signs of relapse (bruising, fatigue, confusion).
- Avoid: Estrogen-containing medications (can trigger relapse).
- Genetic counseling: For congenital TTP (ADAMTS13 gene mutations).

✅ Model Answer:
• ADAMTS13: A von Willebrand factor (VWF)-cleaving protease that regulates platelet adhesion by cleaving ultra-large VWF multimers.
• Role:
- Normal function: Cleaves ultra-large VWF multimers into smaller, less thrombogenic fragments.
- In TTP: ADAMTS13 activity is <10% (either due to autoantibodies in acquired TTP or genetic mutations in congenital TTP).
- Result: Ultra-large VWF multimers accumulate, causing excessive platelet aggregation → microthrombi → thrombocytopenia and MAHA.
• Diagnostic value:
- ADAMTS13 activity <10%: Diagnostic of TTP (differentiates from HUS, DIC, other MAHA syndromes).
- ADAMTS13 inhibitor: Detects autoantibodies (acquired TTP).
• Monitoring: ADAMTS13 activity is used to monitor response to treatment and detect relapse (especially in acquired TTP).