What are the interventions for thrombotic thrombocytopenic purpura (TTP)?

Interventions for Thrombotic Thrombocytopenic Purpura (TTP)

The first-line treatment for thrombotic thrombocytopenic purpura is therapeutic plasma exchange (TPE) combined with immunosuppressive therapy, typically corticosteroids, with the addition of caplacizumab for acquired TTP. 1, 2

Diagnosis and Initial Assessment

• TTP is characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and organ ischemia linked to disseminated microvascular platelet-rich thrombi 2
• Rapid diagnosis is crucial for initiating appropriate treatment, as delay in identification is associated with increased mortality 1
• Initial workup should include:
  • Peripheral blood smear to check for schistocytes 1
  • ADAMTS13 activity level and inhibitor titer 1
  • LDH, haptoglobin, reticulocyte count, bilirubin, and urinalysis 1
  • Prothrombin time, activated partial thromboplastin time, and fibrinogen 1
  • Blood group and antibody screen, and direct antiglobulin test 1

First-Line Treatment

Therapeutic Plasma Exchange (TPE)

• TPE should be initiated immediately upon diagnosis of TTP 1, 2
• Standard regimen: Daily TPE with 1-1.5 times plasma volume replacement using fresh frozen plasma until normalization of serum LDH and platelet count recovery to >150×10^9/L 3
• TPE supplies deficient ADAMTS13 and removes autoantibodies against ADAMTS13 2, 4
• Continue daily TPE until clinical response, then taper gradually 3, 4

Immunosuppressive Therapy

• Corticosteroids should be administered concurrently with TPE 1, 2
  • Methylprednisolone 1 g IV daily for 3 days, with the first dose typically administered immediately after the first TPE for severe cases 1
  • Prednisone 1-2 mg/kg/day for less severe cases 1

Caplacizumab

• Caplacizumab is indicated for treatment of adult patients with acquired TTP, in combination with plasma exchange and immunosuppressive therapy 5
• Administration: Single 11 mg bolus intravenous injection prior to the first plasma exchange, followed by daily subcutaneous injection of 11 mg after completion of plasma exchange 5
• Continue for the duration of daily plasma exchange and for 30 days thereafter 5
• Clinical trials showed caplacizumab resulted in faster platelet count recovery and lower rates of TTP-related death and recurrence compared to placebo 5

Management of Refractory TTP

For patients who fail to respond to standard therapy:

• Intensify plasma exchange to twice-daily sessions 6
• Add rituximab (anti-CD20 monoclonal antibody) 1, 2, 6
• Consider additional immunosuppressive agents:
  • Cyclophosphamide 1, 6
  • Vincristine 1, 6
  • Cyclosporine A 1, 6
  • Bortezomib for severe refractory cases 6
• Salvage splenectomy may be considered in cases unresponsive to medical therapy 2, 6

Severity-Based Treatment Approach

Grade 1 (Evidence of RBC destruction without clinical consequences)

• Hold immune checkpoint inhibitors if TTP is related to immunotherapy 1
• Monitor closely with regular laboratory tests 1

Grade 2 (Evidence of RBC destruction with mild anemia and thrombocytopenia)

• Administer 0.5-1 mg/kg/day prednisone 1
• Consider TPE if there is evidence of organ involvement 1

Grade 3-4 (Severe thrombocytopenia, anemia, and organ involvement)

• Immediate TPE with FFP replacement 1, 3
• High-dose corticosteroids (1-2 mg/kg/day prednisone or methylprednisolone) 1
• Add caplacizumab for acquired TTP 5
• Consider rituximab early in the course for severe presentations 1, 6
• For life-threatening cases (Grade 4), admit to intensive care and consider more aggressive immunosuppression 1

Special Considerations

• Different plasma preparations (solvent/detergent plasma vs. quarantine fresh-frozen plasma) appear to have similar outcomes in adults with acquired TTP 7
• Long-term follow-up is crucial to identify the occurrence of other autoimmune diseases, control relapses, and evaluate psychophysical sequelae 2
• Platelet transfusions should generally be avoided unless there is life-threatening bleeding, as they may exacerbate microvascular thrombosis 4
• Congenital TTP (Upshaw-Schulman syndrome) requires different management approaches, primarily focused on plasma infusion rather than exchange 2

Common Pitfalls

• Delayed recognition and treatment of TTP significantly increases mortality 1, 2
• Failure to obtain ADAMTS13 activity level before initiating treatment may complicate diagnosis 1
• Premature discontinuation of TPE can lead to exacerbations 3, 4
• Not distinguishing between immune-mediated TTP and other thrombotic microangiopathies (such as atypical HUS or drug-induced TMA) can lead to inappropriate treatment 2
• Overlooking the need for long-term follow-up and monitoring for relapses 2