Abstract
We define chronic refractory immune thrombocytopenic purpura (ITP) as ITP with persistent thrombocytopenia following treatment with glucocorticoids and splenectomy. Chronic refractory ITP is uncommon, occurring in fewer than 10% of all adult patients with ITP diagnoses.The goal of treatment is only to achieve a safe platelet count with minimal treatment-related risk. A safe platelet count may be considered to be as low as 10,000/μL, because the risk for major bleeding in otherwise healthy subjects is great only when the platelet count is less than 10,000/μL. Observation without specific treatment is appropriate for patients with moderate thrombocytopenia and no clinically important bleeding symptoms. For patients with chronic refractory ITP who require treatment, there is no consensus for what therapies to use or the sequence in which to use them. For patients with severe and symptomatic thrombocytopenia, the use of anti-CD20 (rituximab) and immunosuppressive agents, alone or in combination, may be most effective.The mechanism of all current therapies is to decrease the accelerated platelet destruction brought about by immunosuppression. An alternative approach, the stimulation of platelet production with thrombopoietic agents, has been successful in investigational studies and may provide a new management option.
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References
Rosthoj S, Hedlund-Treutiger I, Rajantie J, et al. Duration and morbidity of newly diagnosed idiopathic thrombocytopenic purpura in children: a prospective Nordic study of an unselected cohort. J Pediatr. 2003;143:302–307.
Vesely SK, Perdue JJ, Rizvi MA, Terrell DR, George JN. Management of adult patients with idiopathic thrombocytopenic purpura after failure of splenectomy: a systematic review. Ann Intern Med. 2004;140:112–120.
Frederiksen H, Schmidt K. The incidence of ITP in adults increases with age. Blood. 1999;94:909–913.
Cohen YC, Djulbegovic B, Shamai-Lubovitz O, Mozes B. The bleeding risk and natural history of idiopathic thrombocytopenic purpura in patients with persistent low platelet counts. Arch Intern Med. 2000;160:1630–1638.
Portielje JEA, Westendorp RGJ, Kluin-Nelemans HC, Brand A. Morbidity and mortality in adults with idiopathic thrombocytopenic purpura. Blood. 2001;97:2549–2554.
Neylon AJ, Saunders PWG, Howard MR, Proctor SJ, Taylor PRA. Clinically significant newly presenting autoimmune thrombocytopenic purpura in adults: a prospective study of a populationbased cohort of 245 patients. Br J Haematol. 2003;122:966–974.
Bourgeois E, Caulier MT, Delarozee C, Brouillard M, Bauters F, Fenaux P. Long-term follow-up of chronic autoimmune thrombocytopenic purpura refractory to splenectomy: a prospective analysis. Br J Haematol. 2003;120:1079–1088.
McMillan R, Durette C. Long-term outcomes in adults with chronic ITP after splenectomy failure. Blood. 2004;104:956–960.
Kojouri K, Vesely SK, Terrell DR, George JN. Splenectomy for adult patients with idiopathic thrombocytopenic purpura: a systematic literature review to assess long-term platelet count responses, prediction of response, and surgical complications. Blood. 2004;104:2623–2634.
Andersen JC. Response of resistant idiopathic thrombocytopenic purpura to pulsed high-dose dexamethasone therapy. N Engl J Med. 1994;330:1560–1564.
Pizzuto J, Ambriz R. Therapeutic experience on 934 adults with idiopathic thrombocytopenic purpura: Multicentric Trial of the Cooperative Latin American Group on Hemostasis and Thrombosis. Blood. 1984;64:1179–1183.
Quiquandon I, Fenaux P, Caulier MT, Pagniez D, Huart JJ, Bauters F. Re-evaluation of the role of azathioprine in the treatment of adult chronic idiopathic thrombocytopenic purpura: a report on 53 cases. Br J Haematol. 1990;74:223–228.
Provan D, Newland A. Fifty years of idiopathic thrombocytopenic purpura (ITP): management of refractory ITP in adults. Br J Haematol. 2002;118:933–944.
Lacey JV, Penner JA. Management of idiopathic thrombocytopenic purpura in the adult. Semin Thromb Hemost. 1977;3:160–174.
Schiffer CA, Anderson KC, Bennett CL, et al. Platelet transfusion for patients with cancer: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol. 2001;19:1519–1538.
Callow CR, Swindell R, Randall W, Chopra R. The frequency of bleeding complications in patients with haematological malignancy following the introduction of a stringent prophylactic platelet transfusion policy. Br J Haematol. 2002;118:677–682.
van Staa TP, Leufkens HGM, Cooper C. The epidemiology of corticosteroid- induced osteoporosis: a meta-analysis. Osteoporos Int. 2002;13:777–787.
Reiner A, Gernsheimer T, Slichter SJ. Pulse cyclophosphamide therapy for refractory autoimmune thrombocytopenic purpura. Blood. 1995;85:351–358.
George JN, Kojouri K, Perdue JJ, Vesely SK. Management of patients with chronic, refractory idiopathic thrombocytopenic purpura. Semin Hematol. 2000;37:1–10.
Westhoff TH, Jochimsen F, Schmittel A, et al. Fatal hepatitis B virus reactivation by an escape mutant following rituximab therapy [letter]. Blood. 2003;102:1930.
Burton C, Kaczmarski R, Jan-Mohamed R. Interstitial pneumonitis related to rituximab therapy. N Engl J Med. 2003;348:2690–2691.
Voog E, Morschhauser F, Solal-Celigny P. Neutropenia in patients treated with rituximab. N Engl J Med. 2003;348:2691–2694.
Shah C, Grethlein SJ. Case report of rituximab-induced thrombocytopenia [letter]. Am J Hematol. 2004;75:263.
Perotta A, Sunneberg TA, Scott J, et al. Rituxan in the treatment of chronic idiopathic thrombocytopenic purpura (ITP) [abstract]. Blood. 1999;94:14a.
Grossi A, Santini V, Longo G, Balestri F, Ferrini P. Treatment with anti-CD20 antibodies of patients with autoimmune thrombocytopenia with or without haemolytic anemia: worsening in hemoglobin level [abstract]. Blood. 2000;96:253a.
Saleh MN, Gutheil J, Moore M, et al. A pilot study of the anti-CD20 monoclonal antibody rituximab in patients with refractory immune thrombocytopenia. Semin Oncol. 2000;27(suppl 12):99–103.
Stasi R, Pagano A, Stipa E, Amadori S. Rituximab chimeric anti- CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura. Blood. 2001;98:952–957.
Giagounidis AA, Anhuf J, Schneider P, et al.Treatment of relapsed idiopathic thrombocytopenic purpura with the anti-CD20 monoclonal antibody rituximab: a pilot study. Eur J Haematol. 2002;69:95–100.
Stasi R, Stipa E, Forte V, Meo P, Amadori S. Variable patterns of response to rituximab treatment in adults with chronic idiopathic thrombocytopenic purpura [letter]. Blood. 2002;99:3872–3873.
Zaja F, Vianelli N, Sperotto A, et al.The B-cell compartment as the selective target for the treatment of immune thrombocytopenias. Haematologica. 2003;88:538–546.
Shanafelt TD, Madueme HL, Wolf RC, Tefferi A. Rituximab for immune cytopenia in adults: idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, and Evans syndrome. Mayo Clin Proc. 2003;78:1340–1346.
Cooper N, Stasi R, Cunningham-Rundles S, et al. The efficacy and safety of B-cell depletion with anti-CD20 monoclonal antibody in adults with chronic immune thrombocytopenic purpura. Br J Haematol. 2004;125:232–239.
Kuwana M, Nomura S, Fujimura K, et al. Effect of a single injection of humanized anti-CD154 monoclonal antibody on the plateletspecific autoimmune response in patients with autoimmune thrombocytopenic purpura. Blood. 2004;103:1229–1236.
Huhn RD, Fogarty PF, Nakamura R, et al. High-dose cyclophosphamide with autologous lymphocyte-depleted peripheral blood stem cell (PBSC) support for treatment of refractory chronic autoimmune thrombocytopenia. Blood. 2003;101:71–77.
Kappers-Klunne MC, De Haan M, Struijk PC, van Vliet HHDM. Serum thrombopoietin levels in relation to disease status in patients with immune thrombocytopenic purpura. Br J Haematol. 2001;115:1004–1006.
Aledort L, Hayward CPM, Chen M-G, Nichol J, Bussel J. Prospective screening of 205 patients with ITP, including diagnosis, serological markers, and the relationship between platelet counts, endogenous thrombopoietin, and circulating antithrombopoietin antibodies. Am J Hematol. 2004;76:205–213.
Houweerzijl EJ, Blom NR, van der Want JJL, et al. Ultrastructural study shows morphologic features of apoptosis and para-apoptosis in megakaryocytes from patients with idiopathic thrombocytopenic purpura. Blood. 2004;103:500–506.
Chang M, Nakagawa PA, Williams SA, et al. Immune thrombocytopenic purpura (ITP) plasma and purified ITP monoclonal autoantibodies inhibit megakaryocytopoiesis in vitro. Blood. 2003;102:887–895.
Nomura S, Dan K, Hotta T, Fujimura K, Ikeda Y. Effects of pegylated recombinant human megakaryocyte growth and development factor in patients with idiopathic thrombocytopenic purpura. Blood. 2002;100:728–730.
Basser RL, O’Flaherty E, Green M, et al. Development of pancytopenia with neutralizing antibodies to thrombopoietin after multicycle chemotherapy supported by megakaryocyte growth and development factor. Blood. 2002;99:2599–2602.
Broudy VC, Lin NL. AMG531 stimulates megakaryocytopoiesis in vitro by binding to Mpl. Cytokine. 2004;25:52–60.
Kuter DJ, Bussel JB, Aledort L, et al. A phase 2 placebo controlled study evaluating the platelet count and safety of weekly dosing with a novel thrombopoietic protein (AMG531) in thrombocytopenic adult patients with immune thrombocytopenic purpura. Blood. 2004;104:148a-149a.
George JN, Woolf SH, Raskob GE, et al. Idiopathic thromboctyopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood. 1996;88:3–40.
British Committee for Standards in Haematology General Haematology Task Force. Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy. Br J Haematol. 2003;120:574–596.
Cheng Y, Wong RSM, Soo YOY, et al. Initial treatment of immune thrombocytopenic purpura with high-dose dexamethasone. N Engl J Med. 2003;349:831–836.
Guthrie TH, Brannan DP, Prisant LM. Idiopathic thrombocytopenic purpura in the older adult patient. Am J Med Sci. 1988;296:17–21.
Cortelazzo S, Finazzi G, Buelli M, Molteni A, Viero P, Barbui T. High risk of severe bleeding in aged patients with chronic idiopathic thrombocytopenic purpura. Blood. 1991;77:31–33.
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Kojouri, K., George, J.N. Recent Advances in the Treatment of Chronic Refractory Immune Thrombocytopenic Purpura. Int J Hematol 81, 119–125 (2005). https://doi.org/10.1532/IJH97.04173
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DOI: https://doi.org/10.1532/IJH97.04173