Annals of Hematology

, Volume 89, Issue 12, pp 1185–1195 | Cite as

Should medical treatment options be exhausted before splenectomy is performed in adult ITP patients? A debate

  • Roberto Stasi
  • Adrian Newland
  • Patrick Thornton
  • Ingrid Pabinger
Review Article


Patients with primary immune thrombocytopenia (ITP) may require treatment to reduce the risk of serious bleeding if platelets remain consistently below 30 × 109/L. While approximately 70–80% of patients respond to an initial course of corticosteroids, relapse is common. For steroid-refractory patients, there is a choice between surgical splenectomy and further medical treatments, based on many factors including the patient’s bleeding history, fitness for surgery, comorbidities, tolerance of adverse events, lifestyle and preferences. Treatments that have traditionally been used (corticosteroids, azathioprine, danazol) suppress the immune system, potentially predisposing patients to infection. Recent insights into the underlying pathophysiology of the disease have allowed the development of targeted therapies, including the thrombopoietin (TPO) receptor agonists, which enhance platelet production. Phase III trials have found romiplostim and eltrombopag to be well tolerated and effective in elevating platelet counts and reducing bleeding in both splenectomised and nonsplenectomised patients with chronic ITP. The B-cell targeted monoclonal antibody rituximab has also shown some potential in this setting, although data are currently limited and there are toxicity concerns. The decision whether to proceed to splenectomy or try other medical therapies in corticosteroid-refractory patients remains patient-specific. Splenectomy has its risks (including perioperative and long-term risks), and relapse/nonresponse are relatively common, but it offers the possibility of cure in the majority of patients. However, newer treatments may potentially allow splenectomy to be deferred for prolonged periods, as well as providing alternative treatment options for patients who fail splenectomy.


Immune thrombocytopenia Splenectomy Thrombopoietin agonists Corticosteroids 



This article is based on a debate between the authors, which took place in Berlin, Germany on June 4th 2009 during the 14th European Haematology Association Congress and was supported by Amgen Europe GmbH, Zug, Switzerland. The authors thank Julia Balfour, Medical Writer, Kilconquhar, Scotland for assistance with the preparation of the manuscript, with financial support from Amgen.

Conflicts of interest disclosures

Authors conflict of interest declarations are as follows: Prof. Newland—Research funding from Amgen, Baxter, GSK and Genentech; consultant and speaker for Amgen and GSK; advisory board for GSK and Pangenetics; Dr. Stasi—advisory boards and/or speaker for GSK and Amgen. Dr. Pabinger—speaker and advisory boards for Amgen and GSK. Dr. Thornton has no conflicts of interest to declare.


  1. 1.
    British Committee for Standards in Haematology General Haematology Task Force (2003) Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy. Br J Haematol 120(4):574–596CrossRefGoogle Scholar
  2. 2.
    George JN, Woolf SH, Raskob GE, Wasser JS, Aledort LM, Ballem PJ et al (1996) Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood 88(1):3–40PubMedGoogle Scholar
  3. 3.
    Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB et al (2010) International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 115(2):168–186CrossRefPubMedGoogle Scholar
  4. 4.
    Bussel J (2006) Treatment of immune thrombocytopenic purpura in adults. Semin Hematol 43(3 Suppl 5):S3–S10, discussion S8–9CrossRefPubMedGoogle Scholar
  5. 5.
    Cines DB, McMillan R (2005) Management of adult idiopathic thrombocytopenic purpura. Annu Rev Med 56:425–442CrossRefPubMedGoogle Scholar
  6. 6.
    Stasi R, Stipa E, Masi M, Cecconi M, Scimo MT, Oliva F et al (1995) Long-term observation of 208 adults with chronic idiopathic thrombocytopenic purpura. Am J Med 98(5):436–442CrossRefPubMedGoogle Scholar
  7. 7.
    Sailer T, Lechner K, Panzer S, Kyrle PA, Pabinger I (2006) The course of severe autoimmune thrombocytopenia in patients not undergoing splenectomy. Haematologica 91(8):1041–1045PubMedGoogle Scholar
  8. 8.
    Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM et al (2009) Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura (ITP) of adults and children: report from an international working group. Blood 113:2386–2393CrossRefPubMedGoogle Scholar
  9. 9.
    Hitzrot JM (1923) Splenectomy in hemorrhagic purpura: idiopathic purpura, essential thrombopenie (Frank). Purpura hemorrhagic protopathique (Hayem). Ann Surg 78(2):185–190CrossRefPubMedGoogle Scholar
  10. 10.
    Kojouri K, Vesely SK, Terrell DR, George JN (2004) Splenectomy for adult patients with idiopathic thrombocytopenic purpura: a systematic review to assess long-term platelet count responses, prediction of response, and surgical complications. Blood 104(9):2623–2634CrossRefPubMedGoogle Scholar
  11. 11.
    Portielje JE, Westendorp RG, Kluin-Nelemans HC, Brand A (2001) Morbidity and mortality in adults with idiopathic thrombocytopenic purpura. Blood 97(9):2549–2554CrossRefPubMedGoogle Scholar
  12. 12.
    Schwartz J, Leber MD, Gillis S, Giunta A, Eldor A, Bussel JB (2003) Long term follow-up after splenectomy performed for immune thrombocytopenic purpura (ITP). Am J Hematol 72(2):94–98CrossRefPubMedGoogle Scholar
  13. 13.
    Naouri A, Feghali B, Chabal J, Boulez J, Dechavanne M, Viala JJ et al (1993) Results of splenectomy for idiopathic thrombocytopenic purpura. Review of 72 cases. Acta Haematol 89(4):200–203CrossRefPubMedGoogle Scholar
  14. 14.
    Cortelazzo S, Finazzi G, Buelli M, Molteni A, Viero P, Barbui T (1991) High risk of severe bleeding in aged patients with chronic idiopathic thrombocytopenic purpura. Blood 77(1):31–33PubMedGoogle Scholar
  15. 15.
    Winslow ER, Brunt LM (2003) Perioperative outcomes of laparoscopic versus open splenectomy: a meta-analysis with an emphasis on complications. Surgery 134(4):647–653, discussion 54–5CrossRefPubMedGoogle Scholar
  16. 16.
    Crary SE, Buchanan GR (2009) Vascular complications after splenectomy for hematologic disorders. Blood 114(14):2861–2868CrossRefPubMedGoogle Scholar
  17. 17.
    Vianelli N, Galli M, de Vivo A, Intermesoli T, Giannini B, Mazzucconi MG et al (2005) Efficacy and safety of splenectomy in immune thrombocytopenic purpura: long-term results of 402 cases. Haematologica 90(1):72–77PubMedGoogle Scholar
  18. 18.
    Bell WR Jr (2000) Long-term outcome of splenectomy for idiopathic thrombocytopenic purpura. Semin Hematol 37(1 Suppl 1):22–25PubMedGoogle Scholar
  19. 19.
    Najean Y, Rain JD, Billotey C (1997) The site of destruction of autologous 111In-labelled platelets and the efficiency of splenectomy in children and adults with idiopathic thrombocytopenic purpura: a study of 578 patients with 268 splenectomies. Br J Haematol 97(3):547–550CrossRefPubMedGoogle Scholar
  20. 20.
    Law C, Marcaccio M, Tam P, Heddle N, Kelton JG (1997) High-dose intravenous immune globulin and the response to splenectomy in patients with idiopathic thrombocytopenic purpura. N Engl J Med 336(21):1494–1498CrossRefPubMedGoogle Scholar
  21. 21.
    Bussel JB, Kaufmann CP, Ware RE, Woloski BM (2001) Do the acute platelet responses of patients with immune thrombocytopenic purpura (ITP) to IV anti-D and to IV gammaglobulin predict response to subsequent splenectomy? Am J Hematol 67(1):27–33CrossRefPubMedGoogle Scholar
  22. 22.
    Bell WR Jr (2002) Role of splenectomy in immune (idiopathic) thrombocytopenic purpura. Blood Rev 16(1):39–41CrossRefPubMedGoogle Scholar
  23. 23.
    George JN (2006) Management of patients with refractory immune thrombocytopenic purpura. J Thromb Haemost 4(8):1664–1672CrossRefPubMedGoogle Scholar
  24. 24.
    McMillan R, Durette C (2004) Long-term outcomes in adults with chronic ITP after splenectomy failure. Blood 104(4):956–960CrossRefPubMedGoogle Scholar
  25. 25.
    George JN, Mathias SD, Go RS, Guo M, Henry DH, Lyons R et al (2009) Improved quality of life for romiplostim-treated patients with chronic immune thrombocytopenic purpura: results from two randomized, placebo-controlled trials. Br J Haematol 144(3):409–415CrossRefPubMedGoogle Scholar
  26. 26.
    Davies JM, Barnes R, Milligan D (2002) Update of guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen. Clinical Medicine 2(5):440–443, London, EnglandPubMedGoogle Scholar
  27. 27.
    Makris M, Greaves M, Winfield DA, Preston FE, Lilleyman JS (1994) Long-term management after splenectomy. Lifelong penicillin unproved in trials. BMJ 308(6921):131–132, Clinical research edPubMedGoogle Scholar
  28. 28.
    El-Alfy MS, El-Sayed MH (2004) Overwhelming postsplenectomy infection: is quality of patient knowledge enough for prevention? Hematol J 5(1):77–80CrossRefPubMedGoogle Scholar
  29. 29.
    Rodeghiero F, Ruggeri M (2008) Is splenectomy still the gold standard for the treatment of chronic ITP? Am J Hematol 83(2):91CrossRefPubMedGoogle Scholar
  30. 30.
    Dorner T, Burmester GR (2008) New approaches of B-cell-directed therapy: beyond rituximab. Curr Opin Rheumatol 20(3):263–268CrossRefPubMedGoogle Scholar
  31. 31.
    George JN, Kojouri K, Perdue JJ, Vesely SK (2000) Management of patients with chronic, refractory idiopathic thrombocytopenic purpura. Semin Hematol 37(3):290–298CrossRefPubMedGoogle Scholar
  32. 32.
    Branehog I, Kutti J, Weinfeld A (1974) Platelet survival and platelet production in idiopathic thrombocytopenic purpura (ITP). Br J Haematol 27(1):127–143CrossRefPubMedGoogle Scholar
  33. 33.
    Branehog I, Weinfeld A (1974) Platelet survival and platelet production in idiopathic thrombocytopenic purpura (ITP) before and during treatment with corticosteroids. Scand J Haematol 12(1):69–79CrossRefPubMedGoogle Scholar
  34. 34.
    Kuter DJ, Bussel JB, Lyons RM, Pullarkat V, Gernsheimer TB, Senecal FM et al (2008) Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet 371(9610):395–403CrossRefPubMedGoogle Scholar
  35. 35.
    Arkfeld DG (2008) The potential utility of B cell-directed biologic therapy in autoimmune diseases. Rheumatol Int 28(3):205–215CrossRefPubMedGoogle Scholar
  36. 36.
    Kaushansky K (1995) Thrombopoietin: the primary regulator of platelet production. Blood 86(2):419–431PubMedGoogle Scholar
  37. 37.
    Wang B, Nichol JL, Sullivan JT (2004) Pharmacodynamics and pharmacokinetics of AMG 531, a novel thrombopoietin receptor ligand. Clin Pharmacol Ther 76(6):628–638CrossRefPubMedGoogle Scholar
  38. 38.
    Newland A, Caulier MT, Kappers-Klunne M, Schipperus MR, Lefrere F, Zwaginga JJ et al (2006) An open-label, unit dose-finding study of AMG 531, a novel thrombopoiesis-stimulating peptibody, in patients with immune thrombocytopenic purpura. Br J Haematol 135(4):547–553CrossRefPubMedGoogle Scholar
  39. 39.
    Bussel JB, Kuter DJ, George JN, McMillan R, Aledort LM, Conklin GT et al (2006) AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP. N Engl J Med 355(16):1672–1681CrossRefPubMedGoogle Scholar
  40. 40.
    Basser RL, O'Flaherty E, Green M, Edmonds M, Nichol J, Menchaca DM et al (2002) Development of pancytopenia with neutralizing antibodies to thrombopoietin after multicycle chemotherapy supported by megakaryocyte growth and development factor. Blood 99(7):2599–2602CrossRefPubMedGoogle Scholar
  41. 41.
    Li J, Yang C, Xia Y, Bertino A, Glaspy J, Roberts M et al (2001) Thrombocytopenia caused by the development of antibodies to thrombopoietin. Blood 98(12):3241–3248CrossRefPubMedGoogle Scholar
  42. 42.
    Nplate® Summary of Product Characteristics. Available at: Last accessed 21 Apr 2010
  43. 43.
    Bussel JB, Kuter DJ, Pullarkat V, Lyons RM, Guo M, Nichol JL (2009) Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP. Blood 113(10):2161–2171, Erratum in: Blood. 2009;113:4822CrossRefPubMedGoogle Scholar
  44. 44.
    Bussel JB, Kuter DJ, Newland A, de Wolf JTM, Wasser J, Chang P et al (2009) Long-term efficacy and safety of romiplostim for the treatment of patients with chronic immune thrombocytopenia (ITP): 5-year update from an open-label extension study. ASH 114(22):681, Annual Meeting AbstractsGoogle Scholar
  45. 45.
    Gernsheimer TB, George JN, Aledort LM, Tarantino MD, Sunkara U, Matthew Guo D, Nichol JL (2010) Evaluation of bleeding and thrombotic events during long-term use of romiplostim in patients with Chronic Immune Thrombocytopenia (ITP). J Thromb Haemost. 8(6):1372–1382CrossRefPubMedGoogle Scholar
  46. 46.
    Kuter DJ, Bain B, Mufti G, Bagg A, Hasserjian RP (2007) Bone marrow fibrosis: pathophysiology and clinical significance of increased bone marrow stromal fibres. Br J Haematol 139(3):351–362CrossRefPubMedGoogle Scholar
  47. 47.
    Bussel JB, Cheng G, Saleh MN, Psaila B, Kovaleva L, Meddeb B et al (2007) Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med 357(22):2237–2247CrossRefPubMedGoogle Scholar
  48. 48.
    Jenkins JM, Williams D, Deng Y, Uhl J, Kitchen V, Collins D et al (2007) Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist. Blood 109(11):4739–4741CrossRefPubMedGoogle Scholar
  49. 49.
    Revolade Summary of Product Characteristics Available at: Last accessed 26 May 2010
  50. 50.
    Bussel JB, Provan D, Shamsi T, Cheng G, Psaila B, Kovaleva L et al (2009) Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet 373(9664):641–648CrossRefPubMedGoogle Scholar
  51. 51.
    Bussel J, Cheng G, Saleh M, Meddeb B, Stone A, Mayer B et al (2008) Long-term safety and efficacy of oral eltrombopag for the treatment of idiopathic thrombocytopenic purpura (ITP). Haematologia 93(S1):949Google Scholar
  52. 52.
    Cheng G, Saleh MN, Bussel JB, Marcher C, Vasey S, Mayer B et al (2008) Oral eltrombopag for the long-term treatment of patients with chronic idiopathic thrombocytopenic purpura: Results of a Phase III, Double- Blind, Placebo-Controlled Study (RAISE). ASH Annual Meeting Abstracts. 112(11):400Google Scholar
  53. 53.
    Mabthera Summary of Product Characteristics 2008. Available at: last accessed: 1 Mar 2010
  54. 54.
    Arnold DM, Dentali F, Crowther MA, Meyer RM, Cook RJ, Sigouin C et al (2007) Systematic review: efficacy and safety of rituximab for adults with idiopathic thrombocytopenic purpura. Ann Intern Med 146(1):25–33PubMedGoogle Scholar
  55. 55.
    Hasan A, Michel M, Patel V, Stasi R, Cunningham-Rundles S, Leonard JP et al (2009) Repeated courses of rituximab in chronic ITP: three different regimens. Am J Hematol 84(10):661–665CrossRefPubMedGoogle Scholar
  56. 56.
    Zaja F, Baccarani M, Mazza P, Bocchia M, Gugliotta L, Zaccaria A et al (2010) Dexamethasone plus rituximab yields higher sustained response rates than dexamethasone monotherapy in adults with primary immune thrombocytopenia. Blood 115(14):2755–2762CrossRefPubMedGoogle Scholar
  57. 57.
    Carson KR, Evens AM, Richey EA, Habermann TM, Focosi D, Seymour JF et al (2009) Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the research on adverse drug events and reports project. Blood 113(20):4834–4840CrossRefPubMedGoogle Scholar
  58. 58.
    US Food and Drug Administration. Information for Healthcare Professionals: Rituximab (marketed as Rituxan). Available at: 2006
  59. 59.
    Provan D, Butler T, Evangelista ML, Amadori S, Newland AC, Stasi R (2007) Activity and safety profile of low-dose rituximab for the treatment of autoimmune cytopenias in adults. Haematologica 92(12):1695–1698CrossRefPubMedGoogle Scholar
  60. 60.
    Zaja F, Battista ML, Pirrotta MT, Palmieri S, Montagna M, Vianelli N et al (2008) Lower dose rituximab is active in adults patients with idiopathic thrombocytopenic purpura. Haematologica 93(6):930–933CrossRefPubMedGoogle Scholar
  61. 61.
    Podolanczuk A, Lazarus AH, Crow AR, Grossbard E, Bussel JB (2009) Of mice and men: an open-label pilot study for treatment of immune thrombocytopenic purpura by an inhibitor of Syk. Blood 113(14):3154–3160CrossRefPubMedGoogle Scholar
  62. 62.
    Li X, Hou M (2008) Emerging drugs for idiopathic thrombocytopenic purpura in adults. Expert Opin Emerg Drugs 13(2):237–254CrossRefPubMedGoogle Scholar
  63. 63.
    Watson-Williams EJ, Macpherson AI, Davidson S (1958) The treatment of idiopathic thrombocytopenic purpura; a review of 93 cases. Lancet 2(7040):221–226CrossRefPubMedGoogle Scholar
  64. 64.
    Todorovic-Tirnanic M, Obradovic V, Rolovic Z, Suvajdzic N, Elezovic I, Colovic M et al (2005) Prediction of the splenectomy efficacy in chronic immune thrombocytopenic purpura. Glas Srpska akademija nauka i umetnosti 48:119–135Google Scholar
  65. 65.
    von dem Borne AE, Vos JJ, Pegels JG, Thomas LL, van der Lilie H (1988) High dose intravenous methylprednisolone or high dose intravenous gammaglobulin for autoimmune thrombocytopenia. Br Med J 296(6617):249–250, Clinical research edCrossRefGoogle Scholar
  66. 66.
    Kuku I, Aydogdu I, Kaya E, Ali Erkurt M, Dikilitas M, Baydar M et al (2005) The early and long-term results of oral high-dose methylprednisolone treatment in adult patients with idiopathic thrombocytopenic purpura. Eur J Haematol 74(3):271–272CrossRefPubMedGoogle Scholar
  67. 67.
    Cheng Y, Wong RS, Soo YO, Chui CH, Lau FY, Chan NP et al (2003) Initial treatment of immune thrombocytopenic purpura with high-dose dexamethasone. N Engl J Med 349(9):831–836CrossRefPubMedGoogle Scholar
  68. 68.
    Stasi R, Brunetti M, Pagano A, Stipa E, Masi M, Amadori S (2000) Pulsed intravenous high-dose dexamethasone in adults with chronic idiopathic thrombocytopenic purpura. Blood Cells Mol Dis 26(6):582–586CrossRefPubMedGoogle Scholar
  69. 69.
    Talar-Williams C, Sneller MC (1994) Complications of corticosteroid therapy. Eur Arch Otorhinolaryngol 251(3):131–136CrossRefPubMedGoogle Scholar
  70. 70.
    Saag KG, Koehnke R, Caldwell JR, Brasington R, Burmeister LF, Zimmerman B et al (1994) Low dose long-term corticosteroid therapy in rheumatoid arthritis: an analysis of serious adverse events. Am J Med 96(2):115–123CrossRefPubMedGoogle Scholar
  71. 71.
    Aledort LM, Hayward CP, Chen MG, Nichol JL, Bussel J (2004) 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 76(3):205–213CrossRefPubMedGoogle Scholar
  72. 72.
    Amgen Inc. Nplate Prescribing information. Available at: Last accessed 3 May 2010. 2008
  73. 73.
    GlaxoSmithKline. Promacta Prescribing Information. Last accessed 3 May 2010. 2009
  74. 74.
    Patel V, Mihatov N, Cooper N, Stasi R, Cunningham-Rundles S, Bussel JB (2006) Long Term Follow-Up of Patients with Immune Thrombocytopenic Purpura (ITP) Whose Initial Response to Rituximab Lasted a Minimum of 1 Year. ASH Annual Meeting Abstracts. 2006 November 16, 108(11):479Google Scholar
  75. 75.
    Adams JR, Nathan DP, Bennett CL (2002) Pharmacoeconomics of therapy for ITP: steroids, i.v.Ig, anti-D, and splenectomy. Blood Rev 16(1):65–67CrossRefPubMedGoogle Scholar
  76. 76.
    Stasi R, Evangelista ML, Stipa E, Buccisano F, Venditti A, Amadori S (2008) Idiopathic thrombocytopenic purpura: current concepts in pathophysiology and management. Thromb Haemost 99(1):4–13PubMedGoogle Scholar
  77. 77.
    Sandoglobulin Summary of Product Characteristics 2008. Available at: Last accessed 08 Apr 09
  78. 78.
    D-Gam Summary of Product Characteristics 2008. Available at: Last accessed: 21 Apr 2010
  79. 79.
    WinRHO Summary of Product Characteristics. 2008. Available at: last accessed: 8 Apr 2009
  80. 80.
    George JN, Buchanan G. ITP Support association platelet reprint series. Available at:
  81. 81.
    Risks and complications of surgery 2007. Available at: accessed at:; last accessed: 13 May 2009
  82. 82.
    Schilling RF (1997) Spherocytosis, splenectomy, strokes, and heat attacks. Lancet 350(9092):1677–1678CrossRefPubMedGoogle Scholar
  83. 83.
    Jais X, Ioos V, Jardim C, Sitbon O, Parent F, Hamid A et al (2005) Splenectomy and chronic thromboembolic pulmonary hypertension. Thorax 60(12):1031–1034CrossRefPubMedGoogle Scholar
  84. 84.
    Robinette CD, Fraumeni JF Jr (1977) Splenectomy and subsequent mortality in veterans of the 1939–45 war. Lancet 2(8029):127–129PubMedGoogle Scholar
  85. 85.
    Kumagai Y, Fujita T, Ozaki M, Sahashi K, Ohkura M, Ohtsu T et al (2007) Pharmacodynamics and pharmacokinetics of AMG 531, a thrombopoiesis-stimulating peptibody, in healthy Japanese subjects: a randomized, placebo-controlled study. J Clin Pharmacol 47(12):1489–1497CrossRefPubMedGoogle Scholar
  86. 86.
    Glaxosmithkline Ltd. Promacta FDA ODAC briefing document 2008Google Scholar
  87. 87.
    Bouroncle BA, Doan CA (1966) Refractory idiopathic thrombocytopenic purpura treated with azathioprine. N Engl J Med 275(12):630–635CrossRefPubMedGoogle Scholar
  88. 88.
    Quiquandon I, Fenaux P, Caulier MT, Pagniez D, Huart JJ, Bauters F (1990) Re-evaluation of the role of azathioprine in the treatment of adult chronic idiopathic thrombocytopenic purpura: a report on 53 cases. Br J Haematol 74(2):223–228CrossRefPubMedGoogle Scholar
  89. 89.
    Sussman LN (1967) Azathioprine in refractory idiopathic thrombocytopenic purpura. Jama 202(4):259–263CrossRefPubMedGoogle Scholar
  90. 90.
    Finch SC, Castro O, Cooper M, Covey W, Erichson R, McPhedran P (1974) Immunosuppressive therapy of chronic idiopathic thrombocytopenic purpura. Am J Med 56(1):4–12CrossRefPubMedGoogle Scholar
  91. 91.
    Reiner A, Gernsheimer T, Slichter SJ (1995) Pulse cyclophosphamide therapy for refractory autoimmune thrombocytopenic purpura. Blood 85(2):351–358PubMedGoogle Scholar
  92. 92.
    Srichaijul T, Boonpucknavig S, Archararit N, Chaisiri-pumkeeree W (1980) Chronic immunologic thrombocytopenic purpura: results of cyclophosphamide therapy before splenectomy. Arch Intern Med 140(5):636–638CrossRefPubMedGoogle Scholar
  93. 93.
    Verlin M, Laros RK Jr, Penner JA (1976) Treatment of refractory thrombocytopenic purpura with cyclophosphamine. Am J Hematol 1(1):97–104CrossRefPubMedGoogle Scholar
  94. 94.
    Krause JR (1982) Chronic idiopathic thrombocytopenic purpura (ITP:) development of acute non-lymphocytic leukemia subsequent to treatment with cyclophosphamide. Med Pediatr Oncol 10(1):61–65CrossRefPubMedGoogle Scholar
  95. 95.
    Emilia G, Messora C, Longo G, Bertesi M (1996) Long-term salvage treatment by cyclosporin in refractory autoimmune haematological disorders. Br J Haematol 93(2):341–344CrossRefPubMedGoogle Scholar
  96. 96.
    Kappers-Klunne MC, van’t Veer MB (2001) Cyclosporin A for the treatment of patients with chronic idiopathic thrombocytopenic purpura refractory to corticosteroids or splenectomy. Br J Haematol 114(1):121–125CrossRefPubMedGoogle Scholar
  97. 97.
    Maloisel F, Andres E, Zimmer J, Noel E, Zamfir A, Koumarianou A et al (2004) Danazol therapy in patients with chronic idiopathic thrombocytopenic purpura: long-term results. Am J Med 116(9):590–594CrossRefPubMedGoogle Scholar
  98. 98.
    Vancine-Califani SM, De Paula EV, Ozelo MC, Orsi FL, Fabri DR, Annichino-Bizzacchi JM (2008) Efficacy and safety of dapsone as a second-line treatment in non-splenectomized adults with immune thrombocytopenic purpura. Platelets 19(7):489–495CrossRefPubMedGoogle Scholar
  99. 99.
    Fanello CI, Karema C, Avellino P, Bancone G, Uwimana A, Lee SJ et al (2008) High risk of severe anaemia after chlorproguanil-dapsone+artesunate antimalarial treatment in patients with G6PD (A-) deficiency. PLoS ONE 3(12):e4031CrossRefPubMedGoogle Scholar
  100. 100.
    Provan D, Moss AJ, Newland AC, Bussel JB (2006) Efficacy of mycophenolate mofetil as single-agent therapy for refractory immune thrombocytopenic purpura. Am J Hematol 81(1):19–25CrossRefPubMedGoogle Scholar
  101. 101.
    Szczepanik AB, Sikorska A, Slomkowski M, Konopka L (2007) The use of vinca alkaloids in preparation for splenectomy of corticosteroid refractory chronic immune thrombocytopenic purpura patients. Int J Lab Hematol 29(5):347–351CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Roberto Stasi
    • 1
    • 5
  • Adrian Newland
    • 2
  • Patrick Thornton
    • 3
  • Ingrid Pabinger
    • 4
  1. 1.Department of HaematologySt. George’s HospitalLondonUK
  2. 2.Department of HaematologyRoyal London HospitalLondonUK
  3. 3.Department of HaematologyMater Misericordiae University HospitalDublinIreland
  4. 4.Clinical Division of Hematology and Hemostaseology, Department of Medicine IMedical University of ViennaViennaAustria
  5. 5.Department of HaematologySt George’s Healthcare NHS TrustLondonUK

Personalised recommendations