Remission of Chronic Thrombotic Thrombocytopenic Purpura after Treatment with Cyclophosphamide and Rituximab

21 January 2003 | Volume 138 Issue 2 | Pages 105-108

Background: Thrombotic thrombocytopenic purpura (TTP) in adults is usually caused by autoantibody inhibitors of ADAMTS13. Treatment with plasma exchange is often effective but does not address the underlying autoimmune process.

Objective: To report the efficacy of intensive immunosuppressive therapy in refractory TTP.

Design: Case report.

Setting: University medical center.

Patient: 42-year-old woman with chronic relapsing TTP.

Intervention: Immunosuppression therapy with rituximab and cyclophosphamide.

Measurements: ADAMTS13 activity and inhibitors and hematologic variables for TTP.

Results: For 19 months, the patient had relapsing thrombotic microangiopathy despite plasma exchange; splenectomy; and therapy with vincristine, prednisone, and cyclosporine. ADAMTS13 activity was low, and tests detected an IgG inhibitor that recognized the metalloprotease domain of recombinant ADAMTS13. After treatment with rituximab and cyclophosphamide, the disease remitted, ADAMTS13 levels normalized, and the inhibitor was undetectable. The patient has required no treatment for 13 months.

Conclusion: Intensive immunosuppressive therapy can lead to sustained clinical remission in patients with refractory autoimmune TTP.

Editors' Notes Context Many adults with thrombotic thrombocytopenic purpura (TTP) have autoantibodies that promote clotting by inhibiting a von Willebrand factor–cleaving protease (ADAMTS13) in plasma. Contribution This 42-year-old woman had chronic relapsing TTP despite plasma exchange; splenectomy; and treatment with vincristine, prednisone, and cyclosporine. She had low to absent ADAMTS13 activity and an IgG inhibitor. After immunosuppressive therapy with rituximab and cyclophosphamide, the TTP remitted, ADAMTS13 levels normalized, and the inhibitor was undetectable. Cautions Intensive immunosuppressive therapy aimed at the autoimmune aspect of TTP should be tested in prospective trials before being used widely. –The Editors

 

Author and Article Information

From Washington University School of Medicine, St. Louis, Missouri.

Acknowledgment: The authors thank Vanessa Thomas, RN, for assistance in caring for the patient.

Grant Support: By Howard Hughes Medical Institute and the National Institutes of Health (NHLBI T32 HL07088).

Potential Financial Conflicts of Interest:Expert testimony: L.T. Goodnough.

Requests for Single Reprints: Morey A. Blinder, MD, Washington University School of Medicine, 660 South Euclid Avenue, Box 8125, St. Louis, MO 63110; e-mail, blinder{at}labmed.wustl.edu.

Current Author Addresses: Drs. Zheng and Sadler: Washington University School of Medicine, 660 South Euclid Avenue, Box 8022, St. Louis, MO 63110.

Drs. Pallera and Blinder: Washington University School of Medicine, 660 South Euclid Avenue, Box 8125, St. Louis, MO 63110.

Dr. Goodnough: Washington University School of Medicine, 660 South Euclid Avenue, Box 8118, St. Louis, MO 63110.

Author Contributions: Conception and design: X. Zheng, A.M. Pallera, M.A. Blinder.

Analysis and interpretation of the data: X. Zheng, A.M. Pallera, L.T. Goodnough, J.E. Sadler, M.A. Blinder.

Drafting of the article: X. Zheng, A.M. Pallera, J.E. Sadler, M.A. Blinder.

Critical revision of the article for important intellectual content: X. Zheng, A.M. Pallera, L.T. Goodnough, J.E. Sadler, M.A. Blinder.

Final approval of the article: A.M. Pallera, L.T. Goodnough, J.E. Sadler, M.A. Blinder.

Provision of study materials or patients: X. Zheng, M.A. Blinder.

Obtaining of funding: J.E. Sadler.

Administrative, technical, or logistic support: A.M. Pallera, L.T. Goodnough.

Collection and assembly of data: X. Zheng, A.M. Pallera, M.A. Blinder.