Indian Pediatrics

, Volume 49, Issue 10, pp 811–818

Immune thrombocytopenic purpura: Historical perspective, current status, recent advances and future directions

Review Article


Immune thrombocytopenic purpura (ITP) has witnessed many changes and updates over the past decade. The definitions of disease subtypes, course and response to treatment have all been standardized recently. Consequent to the lack of an international consensus management guideline, wide variations exist in treatment practice. This is now being addressed to an extent by the much awaited ITP International Working Group 2010 recommendations. The pathophysiologic mechanisms have been unfolded at cellular, molecular and humoral levels. As a result, many recent advances have taken place in the management of this disorder. This review revisits the history of evolution of ITP, summarizes the current recommendations for management and lists the recent advances and future prospects in this field.

Key words

Childhood Immune thrombocytopenic purpura 


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  1. 1.
    Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an International Working Group. Blood. 2009;113:2386–2393.PubMedCrossRefGoogle Scholar
  2. 2.
    Terrell DR, Beebe LA, Vesely SK, Neas BR, Segal JB, George JN. The incidence of immune thrombocytopenic purpura in children and adults: a critical review of published reports. Am J Hematol. 2010;85:174–180.PubMedCrossRefGoogle Scholar
  3. 3.
    Werlhof PG. Opera Omnia. Hanover: Helwing, 1775: 748. In: Major RH, editor. Classic Descriptions of Disease. 3rd ed. Springfield, IL: CC Thomas, 1965.Google Scholar
  4. 4.
    Osler W. An account of certain organisms occurring in the liquor sanguinis. Proc R Soc Med London. 1874;22: 391–399.CrossRefGoogle Scholar
  5. 5.
    Stasi R, Newland AC. ITP: a historical perspective. Br J Haematol. 2011;153:437–450.PubMedCrossRefGoogle Scholar
  6. 6.
    Harrington WJ, Minnich V, Hollingsworth JW, Moore CV. Demonstration of a thrombocytopenic factor in the blood of patients with thrombocytopenic purpura. J Lab Clin Med. 1951;38:1–10.PubMedGoogle Scholar
  7. 7.
    Wintrobe MM, Cartwright GE, Palmer JG, Kuhns WJ, Samuels LT. Effect of corticotrophin and cortisone on the blood in various disorders in man. Arch Int Med. 1951;88:310–336.CrossRefGoogle Scholar
  8. 8.
    Imbach P, d’Apuzzo V, Hirt A, Rossi E, Vest M, Barandun S, et al. High-dose intravenous gamma globulin for idiopathic thromboctyopenic purpura in childhood. Lancet. 1981;1:1228–1231.PubMedCrossRefGoogle Scholar
  9. 9.
    Bussel, JB, Graziano JN, Kimberly RP, Pahwa S, Aledort LM. Intravenous anti-D treatment of immune thrombocytopenic purpura: analysis of efficacy, toxicity, and mechanism of effect. Blood. 1991;77:1884–1893.PubMedGoogle Scholar
  10. 10.
    Saleh MN, Gutheil J, Moore M, Bunch PW, Butler J, Kunkel L, et al. A pilot study of the anti-CD20 monoclonal antibody rituximab in patients with refractory immune thrombocytopenia. Semin Oncol. 2000;27:99–103.PubMedGoogle Scholar
  11. 11.
    Willis F, Marsh JC, Bevan DH, Killick SB, Lucas G, Griffiths R, et al. The effect of treatment with Campath-1H in patients with autoimmune cytopenias. Br J Haematol. 2001;114:891–898.PubMedCrossRefGoogle Scholar
  12. 12.
    Imbach P, Crowther M. Thrombopoietin receptor agonists for primary immune thrombocytopenia. N Engl J Med. 2011;365:734–741.PubMedCrossRefGoogle Scholar
  13. 13.
    Anoop P. Decision to perform bone marrow aspiration in immune thrombocytopenic purpura must be based on evidence. Pediatr Hematol Oncol. 2008;25:91–92.PubMedCrossRefGoogle Scholar
  14. 14.
    Nugent D, McMillan R, Nichol JL, Slichter SJ. Pathogenesis of chronic immune thrombocytopenia: increased platelet destruction and/or decreased platelet production. Br J Haematol. 2009;146:585–596.PubMedCrossRefGoogle Scholar
  15. 15.
    De Mattia D, Del Vecchio GC, Russo G, De Santis A, Ramenghi U, Notarangelo L, et al; AIEOP-ITP Study Group. Management of chronic childhood immune thrombocytopenic purpura: AIEOP Consensus Guidelines. Acta Haematol. 2010;123:96–109.PubMedCrossRefGoogle Scholar
  16. 16.
    Blanchette V. Childhood chronic immune thrombocytopenic purpura (ITP). Blood Rev. 2002;16:23–26.PubMedCrossRefGoogle Scholar
  17. 17.
    Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010;115:168–186.PubMedCrossRefGoogle Scholar
  18. 18.
    Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117:4190–4207.PubMedCrossRefGoogle Scholar
  19. 19.
    Imbach P, Kuhne T, Muller D, Berchtold W, Zimmerman S, Elalfy M, et al. Childhood ITP: 12 months follow-up data from the prospective registry I of the Intercontinental Childhood ITP Study Group (ICIS). Pediatr Blood Cancer. 2006;46:351–356.PubMedCrossRefGoogle Scholar
  20. 20.
    Hilgartner MW, Lanzkowsky P, Smith CH. The use of azathioprine in refractory idiopathic thrombocytopenic purpura in children. Acta Paediatr Scand. 1970;59:409–415.PubMedCrossRefGoogle Scholar
  21. 21.
    Choudhary DR, Naithani R, Mahapatra M, Kumar R, Mishra P, Saxena R. Efficacy of cyclosporine as a single agent therapy in chronic idiopathic thrombocytopenic purpura. Haematologica. 2008;93:e61–e63.PubMedCrossRefGoogle Scholar
  22. 22.
    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;70:353–357.PubMedCrossRefGoogle Scholar
  23. 23.
    Damodar S, Viswabandya A, George B, Mathews V, Chandy M, Srivastava A. Dapsone for chronic idiopathic thrombocytopenic purpura in children and adults: a report on 90 patients. Eur J Haematol. 2005;75:328–331.PubMedCrossRefGoogle Scholar
  24. 24.
    Marwaha RK, Singh RP, Garewal G, Marwaha N, Prakash D, Sarode R. Danazol therapy in immune thrombocytopenic purpura. Pediatr Hematol Oncol. 1990;7:193–198.PubMedCrossRefGoogle Scholar
  25. 25.
    Minkov M. Critical issues concerning splenectomy for chronic idiopathic thrombocytopenic purpura in childhood. Pediatr Blood Cancer. 2006;47:734–736.PubMedCrossRefGoogle Scholar
  26. 26.
    George JN, Woolf SH, Raskob GE, Wasser JS, Aledort LM, Ballem PJ, et al. Idiopathic thrombocytopenic purpura: A practice guideline developed by explicit methods for the American Society of Hematology. Blood. 1996;88:3–40.PubMedGoogle Scholar
  27. 27.
    Infectious Diseases and Immunization Committee, Canadian Paediatric Society. Prevention and therapy of bacterial infections for children with asplenia or hyposplenia. Paediatr Child Health. 1999;4:417–431.Google Scholar
  28. 28.
    Kiefel V, Santoso S, Weisheit M, Mueller-Eckhardt C. Monoclonal antibody-specific immobilization of platelet antigens (MAIPA): a new tool for the identification of platelet-reactive antibodies. Blood. 1987;70:1722–1726.PubMedGoogle Scholar
  29. 29.
    Woods Jr VL, Oh EH, Mason D, McMillan R. Autoantibodies against the platelet glycoprotein IIb/IIIa complex in patients with chronic ITP. Blood. 1984;63:368–375.PubMedGoogle Scholar
  30. 30.
    Houwerzijl EJ, Blom NR, van der Want JJ, Esselink MT, Koornstra JJ, Smit JW, 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.PubMedCrossRefGoogle Scholar
  31. 31.
    Olsson B, Andersson PO, Jernas M, Jacobsson S, Carlsson B, Carlsson LM, et al. T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nature Med. 2003;9:1123–1124.PubMedCrossRefGoogle Scholar
  32. 32.
    Yu J, Heck S, Patel V, Levan J, Yu Y, Bussel JB, et al. Defective circulating CD25 regulatory T cells in patients with chronic immune thrombocytopenic purpura. Blood. 2008;112:1325–1328.PubMedCrossRefGoogle Scholar
  33. 33.
    Kuter DJ, Gernsheimer TB. Thrombopoietin and platelet production in chronic immune thrombocytopenia. Hematol Oncol Clin North Am. 2009;23:1193–1211.PubMedCrossRefGoogle Scholar
  34. 34.
    Patel VL, Schwartz J, Bussel JB. The effect of anti-CD40 ligand in immune thrombocytopenic purpura. Br J Haematol. 2008;141:545–548.PubMedCrossRefGoogle Scholar
  35. 35.
    Bussel JB, Buchanan GR, Nugent DJ, Gnarra DJ, Bomgaars LR, Blanchette VS, et al. A randomized, double-blind study of romiplostim to determine its safety and efficacy in children with immune thrombocytopenia. Blood. 2011;118:28–36.PubMedCrossRefGoogle Scholar
  36. 36.
    Bussel JB, Provan D, Shamsi T, Cheng G, Psaila B, Kovaleva L, et al. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet. 2009;373:641–648.PubMedCrossRefGoogle Scholar
  37. 37.
    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;357:2237–2247.PubMedCrossRefGoogle Scholar
  38. 38.
    Salama A, Rieke M, Kiesewetter H, von Depka M. Experiences with recombinant FVIIa in the emergency treatment of patients with autoimmune thrombocytopenia: a review of the literature. Ann Hematol. 2009;88:11–15.PubMedCrossRefGoogle Scholar
  39. 39.
    Emmerich F, Bal G, Barakat A, Milz J, Muhle C, Martinez-Gamboa L, et al. High-level serum B-cell activating factor and promoter polymorphisms in patients with idiopathic thrombocytopenic purpura. Br J Haematol. 2007;136: 309–314.PubMedCrossRefGoogle Scholar
  40. 40.
    Li X, Hou M. Emerging drugs for idiopathic thrombocytopenic purpura in adults. Expert Opin Emerg Drugs. 2008;13:237–254.PubMedCrossRefGoogle Scholar
  41. 41.
    Stasi R. Rozrolimupab, symphobodies against rhesus D, for the potential prevention of hemolytic disease of the newborn and the treatment of idiopathic thrombocytopenic purpura. Curr Opin Mol Ther. 2010;12:734–740.PubMedGoogle Scholar
  42. 42.
    Podolanczuk A, Lazarus AH, Crow AR, Grossbard E, Bussel JB. Of mice and men: an open-label pilot study for treatment of immune thrombocytopenic purpura by an inhibitor of Syk. Blood. 2009;113:3154–3160.PubMedCrossRefGoogle Scholar
  43. 43.
    Sandoval C, Visintainer P, Ozkaynak MF, Tugal O, Jayabose S. Clinical features and treatment outcomes of 79 infants with immune thrombocytopenic purpura. Pediatr Blood Cancer. 2004;42:109–112.PubMedCrossRefGoogle Scholar
  44. 44.
    Naithani R, Kumar R, Mahapatra M, Agrawal N, Pati HP, Choudhry VP. Is it safe to avoid bone marrow examination in suspected ITP? Pediatr Hematol Oncol. 2007;24:205–207.PubMedCrossRefGoogle Scholar
  45. 45.
    Anoop P. Variations in the treatment threshold for immune thrombocytopenic purpura. Pediatr Blood Cancer. 2009;52:429–431.PubMedCrossRefGoogle Scholar
  46. 46.
    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.CrossRefGoogle Scholar

Copyright information

© Indian Academy of Pediatrics 2012

Authors and Affiliations

  1. 1.Department of Pediatric Hemato-OncologyGreat Ormond Street Hospital for ChildrenLondonUK
  2. 2.Department of Pediatric Hemato-OncologyApollo HospitalBangaloreIndia

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