What is the treatment for Thrombotic Thrombocytopenic Purpura (TTP)?

Treatment of Thrombotic Thrombocytopenic Purpura (TTP)

Immediately initiate therapeutic plasma exchange (TPE) combined with corticosteroids and rituximab as soon as TTP is suspected—delay in treatment directly increases mortality. 1

Immediate Recognition and Emergency Management

Do not wait for ADAMTS13 results to begin treatment. The diagnosis of TTP is clinical, based on thrombocytopenia and microangiopathic hemolytic anemia (schistocytes on peripheral smear, elevated LDH, decreased hemoglobin and haptoglobin). 1, 2

Critical First Steps:

• Obtain immediate hematology consultation upon suspicion of TTP 1
• Confirm schistocytes on peripheral blood smear to support the diagnosis 1
• Send ADAMTS13 activity level and inhibitor titer before starting treatment, but proceed with therapy without waiting for results 1, 2
• Use the PLASMIC score (≥5 points indicates intermediate-to-high risk) to risk-stratify patients and support the decision to treat 1

Laboratory Workup to Obtain:

• Complete blood count with peripheral smear 1
• LDH, haptoglobin, reticulocyte count, indirect bilirubin 1
• Coagulation studies (PT, aPTT, fibrinogen) 1
• Blood type and antibody screen, direct antiglobulin test 1
• Creatinine and urinalysis 1

First-Line Treatment Protocol

Therapeutic Plasma Exchange (TPE):

Begin daily TPE immediately as the cornerstone of TTP treatment. 1, 3, 4 TPE supplies deficient ADAMTS13 and removes autoantibodies and ultra-large von Willebrand factor multimers. 2, 4

• Continue daily TPE until platelet count normalizes and LDH decreases, typically for at least 2 days after platelet count >150,000/μL 3, 4
• Monitor daily: platelet count, hemoglobin, LDH, and clinical status during active TPE 1

Corticosteroid Therapy:

Administer methylprednisolone 1 g IV daily for 3 days, with the first dose given immediately after the first TPE session. 1

• Following initial high-dose therapy, transition to prednisone 1-2 mg/kg/day 1
• Continue corticosteroids until complete remission, then taper gradually 4, 5

Rituximab:

Rituximab should be offered as part of initial therapy for acquired TTP. 1, 3, 5

• Complete the full course of rituximab if initiated (typically 375 mg/m² weekly for 4 weeks) 1, 5
• Rituximab targets CD20-positive B cells that produce anti-ADAMTS13 autoantibodies 3, 4

Adjunctive Therapy: Caplacizumab

Consider caplacizumab for patients with severe ADAMTS13 deficiency, particularly if ADAMTS13 activity is severely reduced with elevated inhibitor or anti-ADAMTS13 IgG. 1

• Caplacizumab is an anti-von Willebrand factor nanobody that inhibits platelet-VWF binding and prevents microthrombi formation 3, 5
• Discontinue caplacizumab if no exacerbation occurs within 3-5 days after stopping TPE 1
• Caplacizumab rapidly normalizes platelet counts and reduces TTP-related mortality 6

Critical Management Pitfalls to Avoid

Platelet Transfusions:

Avoid platelet transfusions unless life-threatening hemorrhage occurs, as they may worsen thrombosis. 1 This is a common and dangerous error—platelet transfusions can fuel microvascular thrombosis in TTP.

Red Blood Cell Transfusions:

Transfuse RBCs only the minimum necessary to relieve symptoms or achieve hemoglobin 7-8 g/dL in stable patients. 1

• Coordinate with blood bank before any transfusions 1

Refractory or Severe TTP

For patients not responding to standard therapy or presenting with life-threatening complications, consider additional immunosuppression: 1, 4, 5

• Cyclosporine A 4, 5, 7
• Cyclophosphamide 4, 5, 7
• Vincristine 4, 5, 7
• Mycophenolate mofetil 1
• Anti-thymocyte globulin 1
• Bortezomib 4, 5
• N-acetylcysteine 4, 5
• Salvage splenectomy 4, 5

For early relapsing patients (within days to weeks), increase steroid dosages and add cyclophosphamide plus vincristine. 7 For late relapsing patients, FFP infusion with increased steroids and immunosuppressive agents is effective. 7

Ongoing Monitoring

• Weekly monitoring of hemoglobin levels until steroid taper is complete 1
• Long-term follow-up is crucial to identify relapses, monitor for other autoimmune diseases, and evaluate psychophysical sequelae 4, 5
• TTP has a relapsing tendency, occurring approximately 2-fold more frequently in women 4

Special Considerations

In patients with systemic lupus erythematosus presenting with thrombotic microangiopathy, TTP should be considered and ADAMTS13 testing performed, with comanagement with an experienced hematologist. 1

For congenital TTP (hereditary ADAMTS13 deficiency), plasma infusion is often sufficient for prophylaxis or treatment, though recombinant ADAMTS13 is under investigation. 2, 4, 5