What is the most appropriate treatment for a patient with fever, headache, petechiae, anemia, thrombocytopenia, elevated lactate dehydrogenase (LDH), and indirect hyperbilirubinemia?

Thrombotic Thrombocytopenic Purpura (TTP) Requiring Immediate Plasma Exchange

This patient has thrombotic thrombocytopenic purpura (TTP) and requires urgent plasma exchange as the definitive treatment (Option C).

Clinical Diagnosis

This patient presents with the classic pentad features of TTP:

• Microangiopathic hemolytic anemia: Hemoglobin 112 g/L with elevated reticulocytes (5.6%), elevated LDH (690 IU/L), elevated indirect bilirubin (48 µmol/L), and schistocytes on peripheral smear 1
• Thrombocytopenia: Platelet count of 32 × 10^9/L 1
• Fever: Temperature 38.6°C 1
• Neurological symptoms: Headache 1
• Normal coagulation parameters: APTT 33 sec, INR 1.0, PT 10 sec—distinguishing TTP from DIC 1

The combination of thrombocytopenia with microangiopathic hemolytic anemia is mandatory for TTP diagnosis, and when these two criteria are met, plasma exchange should be performed immediately 1.

Why Plasma Exchange (Option C) is Correct

Daily therapeutic plasma exchange (TPE) remains the basis of management for TTP and should be initiated emergently 1. The evidence strongly supports this approach:

• TPE has resulted in excellent remission and survival rates, with complete response achieved in 85.3% of patients 1
• A 2013 multicenter retrospective study of 163 TTP patients demonstrated that TPE should be performed immediately when diagnostic criteria are met 1
• TTP is fatal if not treated with plasma exchange—mortality approaches 90% without treatment 1
• TPE should be performed at 1-1.5 times plasma volume daily using fresh frozen plasma as replacement fluid until LDH normalizes and platelet count recovers to >150 × 10^9/L, then slowly tapered 1

Why Other Options Are Incorrect

Option A (IVIg and Prednisone): This is the treatment for immune thrombocytopenic purpura (ITP), not TTP 2. ITP presents with isolated thrombocytopenia without hemolysis, normal LDH, and normal bilirubin 2. This patient has clear evidence of microangiopathic hemolytic anemia with elevated LDH (690 IU/L) and indirect bilirubin (48 µmol/L), excluding ITP as the diagnosis.

Option B (Platelet Transfusion): Platelet transfusion is contraindicated in TTP as it can worsen microvascular thrombosis and precipitate further organ damage. The thrombocytopenia in TTP results from platelet consumption in microthrombi, not decreased production 1.

Option D (Argatroban): This anticoagulant is used for heparin-induced thrombocytopenia (HIT), not TTP. The patient's normal coagulation parameters (APTT, INR, PT) and absence of heparin exposure make HIT unlikely 1.

Treatment Protocol

The immediate management should include:

• Start daily plasma exchange immediately at 1-1.5 times plasma volume using fresh frozen plasma 1
• Continue TPE daily until LDH normalizes and platelet count exceeds 150 × 10^9/L 1
• Monitor platelet count and LDH levels to guide treatment duration—the median number of TPE sessions is 13 (range 1-80) 1
• Consider adding corticosteroids (methylprednisolone 1 mg/kg), though evidence shows no significant advantage over TPE alone for complete response rates (82.1% vs 76.7%, p=0.746) 1

Critical Pitfalls to Avoid

• Do not delay plasma exchange while awaiting ADAMTS13 levels—clinical diagnosis is sufficient to initiate treatment, as TTP is rapidly fatal without intervention 1
• Avoid platelet transfusion unless life-threatening bleeding occurs, as platelets can exacerbate microvascular thrombosis 1
• Do not confuse with ITP—the presence of hemolysis (elevated LDH, indirect bilirubin, schistocytes) distinguishes TTP from ITP 2, 1
• Monitor for treatment response: failure to improve within days should prompt consideration of refractory TTP requiring additional immunosuppression (rituximab, vincristine) 1, 3