What is the recommended management for an adult with suspected acquired thrombotic thrombocytopenic purpura?

Management of Acquired Thrombotic Thrombocytopenic Purpura (TTP)

Immediately initiate daily therapeutic plasma exchange (TPE) combined with immunosuppressive therapy as soon as acquired TTP is suspected—this is the cornerstone of treatment that transformed survival from <10% to 80-90%. 1, 2

Immediate First-Line Treatment

Plasma Exchange Protocol

• Begin daily TPE at 1-1.5 plasma volumes using fresh frozen plasma (FFP) as replacement fluid 3, 2
• Continue daily TPE until platelet count normalizes (>150 × 10⁹/L) and serum LDH normalizes, then slowly taper 3
• TPE supplies the deficient ADAMTS13 enzyme and removes autoantibodies 2

Caplacizumab Administration (FDA-Approved)

• Administer 11 mg intravenous bolus at least 15 minutes prior to the first plasma exchange 1
• Follow with 11 mg subcutaneous injection after completion of plasma exchange on day 1 1
• Continue 11 mg subcutaneous daily following each plasma exchange session 1
• After completing plasma exchange period, continue 11 mg subcutaneous daily for 30 days 1
• If signs of persistent disease (suppressed ADAMTS13 activity) remain, extend treatment for maximum 28 additional days 1
• Discontinue caplacizumab if patient experiences more than 2 recurrences while on therapy 1

Immunosuppressive Therapy

• Add rituximab as first-line immunosuppressive agent targeting ADAMTS13 autoantibodies 2
• Corticosteroids (prednisone or methylprednisolone) can be used with or without plasma exchange 3, 2
• Studies show no statistical advantage of adding steroids to TPE alone (OR 79% vs 75.8%, CR 57.9% vs 60.6%), but combination remains standard practice 3

Refractory or Severe Disease Management

Intensification Strategies

• For patients unresponsive to daily TPE and rituximab, escalate to twice-daily TPE 4
• Twice-daily TPE should be combined with rituximab in most cases (84% of severe cases) 4
• Median duration of twice-daily TPE is 3 days (range 2-22 days) 4
• This approach achieves durable complete remission in 94.7% of severe cases within median 25.5 days 4

Additional Salvage Therapies

• Pulses of cyclophosphamide for persistently refractory disease despite twice-daily TPE (used in 31.6% of severe cases) 4, 2
• Vincristine or cyclosporine A as alternative immunosuppressive options 2
• Salvage splenectomy in truly refractory cases 2
• Daratumumab shows promise for eradicating persistent ADAMTS13-inhibiting autoantibodies and restoring ADAMTS13 activity, achieving clinical remission in initial diagnosed cases 5

Critical Management Considerations

Anticoagulation and Antiplatelet Agents

• Avoid concomitant use of antiplatelet agents or anticoagulants during caplacizumab therapy 1
• Withhold caplacizumab 7 days prior to elective surgery, dental procedures, or other invasive interventions 1

Prognostic Factors

• Presence of fever is a bad prognostic indicator requiring prolonged TPE treatment 3
• Primary TTP has significantly better response rates than secondary TTP (CR 74.2% vs 29.4%, p=0.005) 3
• Number of TPE sessions is a statistically important factor influencing probability of response 3

Replacement Fluid Selection

• FFP is standard replacement fluid; cryosupernatant plasma (CSP) shows no superiority over FFP 3

Monitoring Requirements

• Daily platelet counts and LDH levels during acute treatment 3
• ADAMTS13 activity levels to guide treatment duration and detect persistent disease 1, 5
• Long-term follow-up crucial to identify autoimmune diseases, control relapses, and evaluate psychophysical sequelae 2

Common Pitfalls to Avoid

• Do not delay TPE while awaiting ADAMTS13 results—initiate immediately upon clinical suspicion 2
• Do not use plasma infusion alone without plasma exchange, as this is inadequate for removing autoantibodies 2
• Do not miss the 12-hour window for caplacizumab dosing—beyond this, skip the dose and resume regular schedule 1
• Do not continue caplacizumab beyond 2 recurrences, as this indicates treatment failure 1