What are the management options for Thrombotic Thrombocytopenic Purpura (TTP) after failure of Rituximab (rituximab)

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Last updated: May 8, 2025View editorial policy

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From the Guidelines

For patients with immune thrombocytopenia (ITP) who have failed rituximab, I recommend proceeding with thrombopoietin receptor agonists (TPO-RAs) as the next line of treatment, considering the greater durability of response seen with ongoing use of these agents 1. When managing ITP after rituximab failure, it's crucial to individualize treatment based on duration of ITP, frequency of bleeding episodes, comorbidities, age, medication adherence, and patient values and preferences.

  • For patients with ITP of < 12 months’ duration, TPO-RAs may be preferable due to their durability of response, although rituximab could be an option for those who value avoiding long-term treatment or cannot afford TPO-RAs.
  • For adults who have had ITP for > 12 months, TPO-RAs, splenectomy, and rituximab are viable options, with the choice depending on patient preferences regarding surgery and long-term therapy. Key considerations in selecting second-line therapy include:
  • Duration of ITP
  • Patient values and preferences
  • Cost and accessibility of treatment options
  • Desire to avoid surgery or long-term medication The American Society of Hematology 2019 guidelines suggest that TPO-RAs are a preferred option for many patients due to their efficacy and durability of response, as seen in clinical trials 1. However, splenectomy and rituximab remain important considerations, particularly for patients who place a high value on avoiding long-term therapy or have specific preferences regarding treatment approach. Ultimately, the choice of second-line treatment should be made on a case-by-case basis, taking into account the individual patient's needs and circumstances, as outlined in the guidelines 1.

From the Research

TTP Management After Failure of Rituximab

  • The management of thrombotic thrombocytopenic purpura (TTP) after failure of rituximab is a complex issue, with various treatment options available 2, 3, 4, 5, 6.
  • Plasma exchange is the standard treatment for TTP, and it has been shown to be effective in achieving complete remission in 77-83% of cases 4, 6.
  • Rituximab, a chimeric monoclonal antibody against CD20, has been recognized as a useful therapy for antibody-mediated autoimmune disease, including TTP 2, 3, 5.
  • In cases where rituximab is not effective, maintenance rituximab may be considered to prevent relapses, as shown in a case report where a patient with acquired TTP achieved remission with maintenance rituximab 3.
  • Other treatment options, such as corticosteroids, vincristine, and cyclophosphamide, may also be considered in combination with plasma exchange and rituximab 2, 4, 5, 6.
  • The choice of treatment depends on various factors, including the patient's response to previous treatments, the presence of autoantibodies, and the severity of the disease 2, 3, 4, 5, 6.

Treatment Options

  • Plasma exchange: daily sessions until complete remission is achieved 4, 6.
  • Rituximab: 375 mg/m2/week for 4 weeks, or maintenance rituximab 375 mg/m2/3 months for 2 years 2, 3.
  • Corticosteroids: prednisone 1 mg/kg/day 4, 6.
  • Vincristine: may be considered in combination with plasma exchange and rituximab 2, 5.
  • Cyclophosphamide: may be considered in combination with plasma exchange and rituximab 3, 6.

Patient Monitoring

  • Regular monitoring of platelet count, lactate dehydrogenase, and hemoglobin levels is essential to assess the patient's response to treatment 4, 6.
  • ADAMTS-13 activity and autoantibody titers should also be monitored to assess the patient's response to treatment and to predict the risk of relapse 2, 3, 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Therapeutic plasma exchange in patients with thrombotic thrombocytopenic purpura: a retrospective multicenter study.

Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis, 2013

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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