2012, Number 4
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Rev Cubana Hematol Inmunol Hemoter 2012; 28 (4)
Refractory primary immune thrombocytopenia: treatment options
Roque-García W
Language: Spanish
References: 99
Page: 327-346
PDF size: 101.87 Kb.
ABSTRACT
The primary immune thrombocytopenia (PIT) is an acquired autoimmune disorder
characterized by transient or persistent decreased platelet count with increased risk
of bleeding. The chronic form of this disease primarily affects adults. Since
spontaneous remissions are rare, patients usually are treated with steroids from the start. Approximately one third of the cases does not respond to steroid regimens;
the second-line treatment is splenectomy, achieving the highest cure rates.
However, between 10 to 30% of patients do not respond to spleen surgical
removal, which is the group of patients with refractory chronic PIT. There is no
evidence on whether this therapeutic regimen is most effective in these cases, so
the treatment remains empirical. In this paper, various treatment options that can
be used in refractory chronic PIT, the action mechanism of drugs, doses and more
frequent adverse effects were reviewed.
REFERENCES
Cooper N, Bussel J. The pathogenesis of immune thrombocytopenic purpura. Br J Haematol. 2006 May;133(4):364-74.
Yu W Ch, Korb J, Sakamoto MK. Idiopathic thrombocytopenic purpura. Pediatr Rev. 2000;21:95-102.
George JN, Woolf SH, Raskob GE, Wasser JS, Aledort LM, Ballem PJ, et al. Idiopathic Thrombocitopenic purpura: a practice guideline developed by explicit methods for The American Society of Hematology. Blood. 1996 Jul 1;88(1):3-40.
Picozzi VJ, Roeske WR, Creger WP. Fate of therapy failures in adult idiopathic thrombocytopenic purpura. Am J Med. 1980 Nov;69(5):690-4.
Neylon AJ, Saunders PWG, Howard MR, Proctor SJ, Taylor PRA. Clinically significant newly presenting autoimmune thrombocytopenic purpura in adults: a prospective study of a population-based cohort of 245 patients. Br J Haematol. 2003 Sept;122(6):966-74.
Vianelli N, Valdre L, Fiacchini M, de Vivo A, Lemoli RM, Poli M, et al. Long-term follow-up of idiopathic thrombocytopenic purpura in 310 patients. Haematologia. 2001 May;86(5):504-9.
Stasi R, Stipa E, Masi M, Cecconi M, Scimo MT, Oliva F, et al. Long-term observation of 208 adults with chronic idiopathic thrombocytopenic purpura. Am J Med 1995 May;98(5):436-42.
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 Jan 1;77(1):31-3.
Fabris F, Zanatta N, Casonata A, Randy ML, Luzzato G, Girolami A. Response to splenectomy in idiopathic thrombocytopenic purpura: Prognostic value of the clinical and laboratory evaluation. Acta Haematol. 1989;81(1):28-33.
Gibson J, May J, Rickard KA, Bautovich G, May J, Kronenberg H. Management of splenectomy failures in chronic immune thrombocytopenic purpura: Role of accessory splenectomy. Aust N Z J Med. 1986 Oct;16(5):695-8.
Akwari OE, Itani KM, Coleman RE, Rosse WF. Splenectomy for primary and recurrent immune thrombocytopenic purpura (ITP). Current criteria for patient selection and results. Ann Surg. 1987 Oct; 206(4):529-41.
Gita T, Rakhee V, Andrew E, Wolanskyj AP. Accessory splenectomy for refractory immune thrombocytopenic purpura. Am J Haematol. June 2011;86:520-3.
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 Int Med. 2004;140:112-20.
George JN. Management of patients with refractory immune thrombocytopenic purpura J Thromb Haemost. 2006 Aug;4(8):1664-72.
Van Staa TP, Leufkens HGM, Cooper C. The epidemiology of corticosteroidinduced osteoporosis: a meta-analysis. Osteoporos Int. 2002 Oct;13(10):777-87.
Andersen JC. Response to resistant idiopathic thrombocytopenic purpura to pulsed high dose Dexamethasone treatment. N Eng J Med. 1994;331:1560-4.
Wali YA, Ailanki Z, Shah W, Zacharia M, Hassan A. Pulse high dose Dexamethasone therapy in children with chronic idiopathic thrombocytopenic purpura. Pediatr Hematol Oncol. 2002;19:329-35.
Arruda VR, Annichino-Bizzacchi JM. High-dose Dexamethasone therapy in chronic idiopathic thrombocytopenic purpura. Ann Hematol. 1996 Oct;73(4):175-7.
Ning-ning Shan, Xiao-juan Zhu, Qian Wang, Chun-yan Wang, Ping Qin, Jun Peng, et al. High-dose dexamethasone protein regulates interleukin-18 and interleukin-18 binding in idiopathic thrombocytopenic purpura. Haematologica. 2009;94(11):1603-7.
Panitsas FP, Theodoropoulou M, Kouraklis A, Karakantza M, Theodorou GL, Zoumbos NC, et al. Adult chronic idiopathic thrombocy topenic purpura (ITP) is the manifestation of a type-1 polarized immune response. Blood. 2004 Apr 1;103(7):2645-7.
Borst F, Keuning JJ, van Hulsteijn H, Sinnige H, Vreugdenhil G. High-dose dexamethasone as a first- and second-line treatment of idiopathic thrombocytopenic purpura in adults. Ann Hematol. 2004 Dec;83(12):764-8.
Mazzuconi MG, Fazi P, Bernasconi S, De Rossi G, Leone Gi, Gugliotta L, et al. Therapy with high dose Dexametasone in previously untrated patients affected by idiopathic thrompocytopenic purpura: a GIMEMA experience. Blood. 2007;4:1401-7.
Imbach P, Barandun S, d'Apuzzo V. High-dose intravenous gammaglobulin for idiopathic thrombocytopenic purpura in childhood. Lancet. 1981 Jun 6;1(8232):1228-31.
Lazarus AH, Crow AR. Mechanism of action of IVIG and anti-D in ITP. Transfus Apher Sci. 2003 Jun;28(3):249-55.
Stasi R, Provan D. Management of immune thrombocytopenic purpura in adults. Mayo Clin Proc. 2004 Apr;79(4):504-22.
Lederman HM, Roifman CM, Lavi S, Gelfand EW. Corticosteroids for prevention of adverse reaction to intravenous immune serum globulin infusions in hipogammaglobunilemic patients. Am J Med. 1986 Sep;81(3):443-6.
Kim HC, Park CL, Cowan III JH, Fattori FD, August CS. Massive intravascular hemolysis associated with intravenous immunoglobulin in bone marrow transplant recipients. Am J Pediatr Hematol/Oncol.1988 Spring;10(1):69-74.
Woodruff RK, Grigg AP, Firkin FC, Smith IL. Fatal thrombotic events during treatment of autoimmune thrombocytopenia with intravenous immunoglobulin in elderly patients. Correspondence. Lancet. 1988;2:217-8.
Ahn YS, Rocha R, Mylvaganam R, García R, Duncan R, Harrington WJ. Longterm danazol therapy in autoimmune thrombocytopenia: unmaintained remission and age-dependent response in women. Ann Intern Med.1989 Nov 1;(9):111:723-9.
Ahn YS, Harrington WJ, Simon SR, Mylvaganam R, Pall LM, So AG. Danazol for the treatment of idiopathic thrombocytopenic purpura. N Engl J Med. 1983 Jun 9(23);308:1396-9.
Mylvaganam R, Ahs YS, García RO, Kim CI, Harrington WJ. Very low dose danazol in idiopathic thrombocytopenic purpura and its role as a immune modulator. Am J Med Sci. 1989 Oct;298(4):215-20.
Nozaki H, Tanaka K, Yonekura S, Shimizu M, Komatsuda M, Nagao T, et al. Low dose danazol in idiopathic thrombocytopenic purpura. Rinsho Ketsueki. 1990 Oct;31(10):1750-1.
Almagro D, Crespo O, González X, Espinosa E. Dosis intermedias de Danazol en la púrpura trombocitopénica idiomática crónica. Rev Iberoamer Tromb Hemostasia. 1996;9:19-21.
Almagro D. Danazol in idiopathic thrombocytopenic purpura. Acta Haematol 1985;74(2):120.
Maloisel F, Andrès E, Zimmer J, Noel E, Zamfir A, Koumarianou A, et al. Danazol therapy in patients with chronic idiopathic thrombocytopenic purpura: long-term results. Am J Med. 2004 May 1;116(9):590-4.
Nesher G, Dollberg L, Zimran A, Hershko C. Hepatosplenic peliosis after danazol and glucocorticoids for ITP. N Engl J Med. 1985 Jan 24;312:242-3.
Arrowsmith JB, Dreis M. Thrombocytopenia alter treatment with Danazol. N Engl J Med. 1986 Aug 28;315(9):585.
Rabinowe SN, Miller KB. Danazol-induced thrombocytopenia. Br J Haematol. 1987 Mar;65(3):383-4.
Manoharan A. Targeted -immunosuppression with Vincristine infusion in the treatment of immune thrombocytopenia. Aust NZ J Med. 1991;21:405-7.
Ahn YS, Hanington WJ, Seelman RC, Eytel CS. Vincristine therapy of idiopathic and secondary thrombocytopenias. N Engl J Med. 1974 Aug 22;291(8):376.
Burton IE, Roberts BE, Child JA, Montgomery DA, Raper CGL. Responses to vincristine in refractory idiopathic thrombocytopenic purpura. Br Med J. 1976 Oct 16;2(6041):918.
Blanchette V, Freedman J, Garvey B. Management of chronic immune thrombocytopenic purpura in children and adults. Sem Hematol. 1998 Jan;35(1):36-51.
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 Dec;64(6):1179-83.
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 Feb;74(2):223-8.
Laros RK, Penner JA: "Refractory'' thrombocytopenic purpura treated successfully with cyclophosphamide. JAMA. 1971 Jan 18;215(3):445-9.
Reiner A, Gemsheimer T, Slichter SJ. Pulse cyclophosphamide therapy for refractory autoimmune thrombocytopenic purpura. Blood. 1995 Jan 15;85(2):351-8.
Smith AG, Prentice AG, Lucie NP, Browning JD, Dagg JH, Rowan RM. Acute myelogenous leukaemia following cytotoxic therapy: five cases and a review. Quart J Med. 1982 Spring;51(202):227-40.
Kappers-Klunne MC, van't Veer MB. Cyclosporin A for the treatment of patients with chronic idiopathic thrombocytopenic purpura refractory to corticosteroids or splenectomy. Br J Haematol. 2001 Jul;114(1):121-5.
Perrotta S, Amendola G, Locatelli F, Conte ML, Rossi F, d'Urzo G, et al. Treatment with short-term, high-dose cyclosporin A in children with refractory chronic idiopathic thrombocytopenic purpura. Br J Haematol. 2003 Apr;121(1):143-7.
Emilia G, Morselli M, Luppi M, Longo G, Marasca R, Gandin G, et al. Long-term salvage therapy with cyclosporin A in refractory idiopathic thrombocytopenic purpura. Blood. 2002 Feb 15;99(4):1482-5.
Choudhary DR, Naithani R, Mahapatra M, Kumar R, Mishra P, Saxena R. Efficacy of Ciclosporine as a single agent therapy in chronic idiopathic thrombocytopenic purpura. Haematologica. 2008 Oct;93(10):61-2.
Zver S, Zupan IP, Cernelc P. Cyclosporin A as an immunosuppressive treatment modality for patients with refractory autoimmune thrombocytopenic purpura after splenectomy failure. Int J Hematol. 2006 Apr;83(3):238-42.
Howard J, Hoffbrand AV, Prentice HG, Mehta A. Mycophenolate mofetil for the treatment of refractory auto-immune haemolytic anaemia and auto-immune thrombocytopenia purpura. Br J Haematol. 2002 Jun;117(3):712-5.
Provan D, Moss AJ, Newland AC, Bussel JB. Efficacy of mycophenolate mofetil as single-agent therapy for refractory immune thrombocytopenic purpura. Am J Hematol. 2006 Jan;81(1):19-25.
Hou M, Peng J, Shi Y, Zhang C, Qin P, Zhao C, et al. Mycophenolate mofetil (MMF) for the treatment of steroid-resistant idiopathic thrombocytopenic purpura. Eur J Haematol. 2003 Jun;70(6):353-57.
Reff ME, Carner K, Chambers KS, Chinn PC, Leonard JE, Raab R, et al. Depletion of B cells in vivo by chimeric mouse human monoclonal antibody to CD 20. Blood. 1994 Jan 15;83(2):435-45.
Godeau B, Porcher R, Fain O, Lefrére F, Fenaux P, Cheze S, et al. Rituximab efficacy and safety in adult splenectomy candidates with chronic immune thrombocytopenic purpura: results of a prospective multicenter phase 2 study. Blood. 2008;112(4):999-1004.
Cartron G, Watier H, Golay J, Solal-Celigny P. From the bench to the bedside: ways to improve rituximab efficacy. Blood. 2004;104:2635-42.
Hofmeister JK, Cooney D, Coggeshall KM. Clustered CD20 induced apoptosis: src-family kinase, the proximal regulator of tyrosine phosphorylation, calcium influx, and caspase 3-dependent apoptosis. Blood Cells Mol Dis. 2000 Apr;26(2):133-43.
Arnold DM, Dentali F, Crowther MA, Meyer RM, Cook RJ, Siqouin C, et al. Systematic review: efficacy and safety of rituximab for adults with idiopathic thrombocytopenic purpura. Ann Intern Med. 2007 Jan 2;146(1):25-33.
Giagounidis AN, Anhuf J, Schneider P, Germing U, Söhngen D, Quabeck K, et al. Treatment of relapsed idiopathic thrombocytopenic purpura with anti CD 20 monoclonal antibody Rituximab: a pilot study. Eur J Haematol. 2002;69:95-100.
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 Nov;78(11):1340-6.
Stasi R, Pagano A, Stipa E, Amadori S. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura. Blood. 2001 Aug 15;98(4):952-7.
Zaja F, Vianelli N, Battista M. Earlier administration of rituximab allows higher rate of longlasting response in adult patients with autoimmune thrombocytopenia. Exp Hematol. 2006;34(5):571-2.
Peñalver FJ, Jiménez-Yuste V, Almargo M. Rituximab in the management of chronic immune thrombocytopenic purpura: an effective and safe therapeutic alternative in refractory patients. Ann Hematol. 2006 Jun;85(6):400-6.
Willis F, Marsh JC, Bevan DH, Killick SB, Lucas G, Griffiths R, et al. The effect of treatment of Campath -1H in patients with autoimmune cytopenias. Br J Haematol. 2001 Sep;114(4):891-8.
Brett S, Baxter G, Cooper H, Jhonston JM, Tite J, Rapson N. Repopulation of blood lymphocyte sub-populations in rheumatoid arthritis patients treated with the depleting humanized monoclonal antibody, Campath-1H. Immunology. 1996 May;88(1):13-9.
Erduran E, Aslan Y, Aliyazicioglu Y, Mocan H, Gedik Y. Plasma soluble interleukin-2 receptor levels in patients with idiopathic thrombocytopenic purpura. Am J Hematol. 1998 Feb;57(2):119-23.
Semple JW, Milev Y, Cosgrave D, Mody M, Hornstein A, Blanchette V, et al. Differences in serum cytokine levels in acute and chronic autoimmune thrombocytopenia purpura: relationship to platelet phenotype and antiplatlelet T-cell reactivity. Blood. 1996 May 15;87(10):4245-54.
Fogarty PF, Seggewis R, Mc Closkey DJ, Boss CA, Dunbar CE, Rick Me. Anti- Interleukin-2 receptor antibody (Daclizumab) treatment of corticosteroid-refractory autoimmune thrombocytopenic purpura. Letters to the editor. Haematologica. 2006 Feb;91(2):277-8.
Kosugi S, Kurata Y, Tomiyama Y, Tahara T, Kato T, Tadokoro S, et al. Circulating thrombopoietin level in chronic immune thrombocytopenic purpura. Br J Haematol. 1996 Jun;93(3):704-6.
Broudy VC, Lin NL. AMG531 estimulates megacaryopoyesis. in vitro by binding to Mpl. Cytoquine. 2004;25:52-60.
Li J, Yang C, Xia Y, Bertino A, Glaspy J, Roberts M, et al. Thrombocytopenia caused by the development of antibodies to thrombopoietin. Blood. 2001 Dec 1;98(12):3241-8.
Andermariam B, Psaila B, Bussel JB. Novel thrombopoietic agents. American Society of Hematology. Educational program book. Hematology. 2007:106-13.
Bussel JB, Kuter DJ, George JN, McMillan R, Aldeport LM, Conklin GT, et al. AMG 531, a thrombopoiesis - stimulating protein, for chronic ITP. N Engl J Med. 2006 Oct 19;355:1672-81.
Bussel JB, Kuter DJ, George JN, Aledort L, Lichtin AE, Lyons RM, et al. Long term dosing of AMG531 is effective and well tolerated in thrombocytopenic patients with immune thrombocytopenic purpura. Blood. 2005;106:68a.
Kuter DJ, Bussel JB, Lyons RM, Pullarkat V, Gernsheimer TB, Senecal FM, et al. Efficacy of Romiplostim in patients with chronic immune thrombocytopenic purpura: a doubled blind randomized controlled trial. Lancet. 2008 Feb 2;371(9610):395-403.
Perreault S, Burzynski J. Romiplostim: A novel thrombopoiesis-stimulating agent Am J Health Syst Pharm. 2009 May 1;66(9):817-24.
Georges JN, Terrell DR. Novel thrombopoietic agents: a new era for management of patients with thrombocytopenia. Haematologica. 2008 Oct;93(10):1445-8.
Jenkins J, Nicholl R, Williams D, Baidoo C, Phillips K, Deng Y, et al. An oral, non-peptide, small molecule thrombopoietin receptor agonist increases platelet counts in healthy subjects. Blood. 2004;104:797a.
Erickson Miller CL, DeLorne E, Tian SS, et al. Discovery and characterization of a selective, non peptidyl thrombopoietin receptor agonist. Exp Hematol. 2005;33:85-93.
Cook L, Cooper N. Eltrombopag a novel approach for the treatment of chronic immune thrombocytopenic purpura: Review and safety considerations. Drug design, development and therapy. 2010 Jul 21;4:138-45.
Bussel JB, Cheng G, Saleh MN, Psaila B, Kovaleva L, Meddeb B, et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med. 2007 Nov 29;357:2237-47.
Cheng G, Saleh MN, Marcher C, Vasey S, Mayer B, Aivado M, et al. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet. 2011 Jan 29;377(9763):393-402.
Passweg JR, Rabusin M, Musso M, Beguin Y, Cesaro S, Ehninger J, et al. Haematopoietic stem vell transplantation for refractory autoimmune cytopenia. Br J Haematol. Jun 2004;125:749-55.
Huhn RD, Fogarty PF, Nakamura R, Read EJ, Leitman SF, Rick ME, et al. Highdose cyclophosphamide with autologous lymphocyte-depleted peripheral blood stem cell (PBSC) support for treatment of refractory chronic autoimmune thrombocytopenia. Blood. 2003 Jan 1;101:71-7.
Butler JP, Durrant ST, Frost T. Succesful remision of chronic refractory autoimmune thrombocytopenic purpura following non-myeloablative allogeneic stem cell transplantation. Bone Marrow Transplantation. 2003 Apr;31(7):621-2.
Suerbaum S, Michetti P. Helicobacter pylori infection. N Engl J Med. 2002 Oct 10;347(15):1175-86.
Logan RP, Walker MM. Infection. ABC of the upper gastrointestinal tract: Epidemiology and diagnosis of Helicobacter pylori. BMJ. 2001 Oct 20;323(7318):920-2.
Gasbarrini A, Franceschi F, Tartaglione R, Landolfi R, Pola P, Gasbarrini G. Regression of autoimmune thrombocytopenia after eradication of Helicobacter pylori. Lancet. 1998 Sept 12;352(9131):878.
Takahashi T, Yujiri T, Shinohara K, Inoue Y, Sato Y, Fujii Y, et al. Molecular mimicry by Helicobacter pylori CagA protein may be involved in the pathogenesis of H. pylori-associated chronic idiopathic thrombocytopenic purpura. Br J Haematol. 2004 Jan;124(1):91-6. 2009;113:1231-40.
Stasi R, Sarpatwari A, Segal JB, Osborn J, Evangelista ML, Cooper N, et al. Effects of eradication of Helicobacter pylori infection in patients with immune thrombocytopenic purpura: a systematic review. Blood. 2009 Feb 5;113(6):1231-40.
Arnold DM, Bernotas A, Nazi I, Stasi R, Kuwana M, Liu Y, et al. Platelet count response to H. pilory treatment in patients with immune thrombocytopenic purpura with and without H. Pilory infection: a systematic review. Haematologica. 2009 Jun;94(6):850-6.
Gottlieb AB. Etanercept for the treatment of psoriasis and psoriatic arthritis. Dermatologic Therapy. 2004 Oct;17(5):401-8.
McMinn JR Jr, Cohen S, Moore J, Lilly S, Parkhurst J, Terrell DR, et al. Complete recovery from refractory immune thrombocytopenic purpura in three patients treated with etanercept. Am J Hematol. 2003 Jun;73(2):135-40.
Litton G. Refractory idiopathic thrombocytopenic purpura treated with the soluble tumor necrosis factor receptor etanercept. Am J Hematol. 2008 Apr;83(4):344.
Jiang H, Chess L. An integrated view of supressor T cell subsets in immunoregulation. J Clin Invest. 2004 Nov;114(9):1198-208.
Kuwana M, Nomura S, Fujimura K, Nagasawa T, Muto Y, Murata Y, et al. Effect of a single injection of humanized anti-CD154 monoclonal antibody on the plateletspecific autoimmune response in patients with immune thrombocytopenic purpura. Blood. 2004 Feb 15;103(4):1229-36.
Patel VL, Schwartz J, Bussel JB. The effect of anti-CD40 ligand in immune thrombocytopenic purpura. Br J Hematol. 2008 May;141(4):545-8.