Skip to main content
SpringerLink
Log in

Management of Immune Thrombocytopenic Purpura in Children

Potential Role of Novel Agents

  • Leading Article
  • Published:
Pediatric Drugs Aims and scope Submit manuscript

Abstract

The treatment of immune thrombocytopenic purpura (ITP) in children is controversial, requiring individualized assessment of the patient and consideration of treatment options. If the platelet count is >10 000/μL and the patient is asymptomatic, a ‘watch and wait’ strategy is appropriate since most children with ITP will recover completely without pharmacotherapy. If therapy is indicated because of bleeding or a platelet count <10 000/μL, then treatment with glucocorticoids, intravenous immunoglobulin (IVIg), or anti-D are possible initial choices. Glucocorticoid treatment is the least expensive and is our usual first choice of therapy. Its use assumes that the blood counts and blood film have been evaluated to ensure the absence of evidence of alternative diagnoses, such as thrombotic thrombocytopenic purpura or incipient acute leukemia. IVIg is expensive and often causes severe headache, nausea and vomiting, and requires hospitalization at our institution. Anti-D therapy is also expensive and can only be used in patients who are Rhesus D positive. These therapies, even if only transiently effective, can be repeated if necessary. Children usually recover from newly diagnosed ITP, with or without multiple courses of medical therapy.

If the disease becomes ‘persistent’ with severe thrombocytopenia and/or bleeding, and is no longer responsive to the three first-line therapies, the next approach includes the use of thrombopoietin receptor agonists or rituximab. When the disease persists for more than 1 year, it is considered chronic, and, if symptomatic, it may become necessary to consider third-line therapies, including splenectomy, alternative immunosuppressive agents, or combination or investigative chemoimmunotherapy. This review considers the indications, mechanism of action, and effectiveness of the traditional and novel treatment options for patients with ITP.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Table I
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Terrell DR, Beebe LA, Vesely SK, et al. The incidence of immune thrombocytopenic purpura in children and adults: a critical review of published reports. Am J Hematol 2010 Mar; 85(3): 174–80

    PubMed  Google Scholar 

  2. Rodeghiero F, Stasi R, Gernsheimer T, 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 Mar 12; 113(11): 2386–93

    Article  PubMed  CAS  Google Scholar 

  3. Zeller B, Rajantie J, Hedlund-Treutiger I, et al. Childhood idiopathic thrombocytopenic purpura in the Nordic countries: epidemiology and predictors of chronic disease. Acta Paediatr 2005 Feb; 94(2): 178–84

    Article  PubMed  Google Scholar 

  4. Imbach P, Kuhne T, Muller D, et al. Childhood ITP: 12months follow-up data from the prospective registry I of the Intercontinental Childhood ITP Study Group (ICIS). Pediatr Blood Cancer 2006 Mar; 46(3): 351–6

    Article  PubMed  CAS  Google Scholar 

  5. Sprague CC, Harrington WJ, Lange RD, et al. Platelet transfusions and the pathogenesis of idiopathic thrombocytopenic purpura. J Am Med Assoc 1952 Nov 22; 150(12): 1193–8

    Article  PubMed  CAS  Google Scholar 

  6. Shulman NR, Marder VJ, Weinrach RS. Similarities between known antiplatelet antibodies and the factor responsible for thrombocytopenia in idiopathic purpura: physiologic, serologic and isotopic studies. Ann N Y Acad Sci 1965 Jun 30; 124(2): 499–542

    Article  PubMed  CAS  Google Scholar 

  7. Luiken GA, McMillan R, Lightsey AL, et al. Platelet-associated IgG in immune thrombocytopenic purpura. Blood 1977 Aug; 50(2): 317–25

    PubMed  CAS  Google Scholar 

  8. Psaila B, Bussel JB. Refractory immune thrombocytopenic purpura: current strategies for investigation and management. Br J Haematol 2008 Oct; 143(1): 16–26

    Article  PubMed  CAS  Google Scholar 

  9. Deane S, Teuber SS, Gershwin ME. The geoepidemiology of immune thrombocytopenic purpura. Autoimmun Rev 2010 Mar; 9(5): A342–9

    Article  PubMed  Google Scholar 

  10. Peerschke EI, Andemariam B, Yin W, et al. Complement activation on platelets correlates with a decrease in circulating immature platelets in patients with immune thrombocytopenic purpura. Br J Haematol 2010 Feb; 148(4): 638–45

    Article  PubMed  Google Scholar 

  11. Buchanan GR, Adix L. Current challenges in the management of children with idiopathic thrombocytopenic purpura. Pediatr Blood Cancer 2006 Oct 15; 47(5 Suppl.): 681–4

    Article  PubMed  Google Scholar 

  12. Segel GB, Feig SA. Controversies in the diagnosis and management of childhood acute immune thrombocytopenic purpura. Pediatr Blood Cancer 2009 Sep; 53(3): 318–24

    Article  PubMed  Google Scholar 

  13. Semple JW. Infections, antigen-presenting cells, T cells, and immune tolerance: their role in the pathogenesis of immune thrombocytopenia. Hematol Oncol Clin North Am 2009 Dec; 23(6): 1177–92

    Article  PubMed  Google Scholar 

  14. Semple JW, Provan D, Garvey MB, et al. Recent progress in understanding the pathogenesis of immune thrombocytopenia. Curr Opin Hematol 2010 Nov; 17(6): 590–5

    Article  PubMed  CAS  Google Scholar 

  15. Yu J, Heck S, Patel V, et al. Defective circulating CD25 regulatory T cells in patients with chronic immune thrombocytopenic purpura. Blood 2008 Aug 15; 112(4): 1325–8

    Article  PubMed  CAS  Google Scholar 

  16. Cines DB, Bussel JB, Liebman HA, et al. The ITP syndrome: pathogenic and clinical diversity. Blood 2009 Jun 25; 113(26): 6511–21

    Article  PubMed  CAS  Google Scholar 

  17. Olsson B, Andersson PO, Jernas M, et al. T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nat Med 2003 Sep; 9(9): 1123–4

    Article  PubMed  CAS  Google Scholar 

  18. Zhang X, Wang W, Cheng S, et al. 2,3-Diamino acid modifying 3S-tetrahydroisoquinoline-3-carboxylic acids: leading to a class of novel agents with highly unfolded conformation, selective in vitro anti-platelet aggregation and potent in vivo anti-thrombotic activity. Bioorg Med Chem 2010 Feb 15; 18(4): 1536–54

    Article  PubMed  CAS  Google Scholar 

  19. Nugent D, McMillan R, Nichol JL, et al. Pathogenesis of chronic immune thrombocytopenia: increased platelet destruction and/or decreased platelet production. Br J Haematol 2009 Sep; 146(6): 585–96

    Article  PubMed  CAS  Google Scholar 

  20. Chow L, Aslam R, Speck ER, et al. A murine model of severe immune thrombocytopenia is induced by antibody- and CD8+ T cell-mediated responses that are differentially sensitive to therapy. Blood 2010 Feb 11; 115(6): 1247–53

    Article  PubMed  CAS  Google Scholar 

  21. Bolton-Maggs PH, Moon I. Assessment of UK practice for management of acute childhood idiopathic thrombocytopenic purpura against published guidelines. Lancet 1997 Aug 30; 350(9078): 620–3

    Article  PubMed  CAS  Google Scholar 

  22. Bussel JB, Zhang J, Tang S, et al. A randomized, double-blind, placebocontrolled phase II trial on the efficacy, safety and tolerability of E5501 (AKR501) in subjects with chronic immune thrombocytopenia (ITP). ASH Annual Meeting Abstracts. Blood 2010; 116(21): 71

    Google Scholar 

  23. Beck JC, Burke MJ, Tolar J. Response of refractory immune thrombocytopenia after bone marrow transplantation to romiplostim. Pediatr Blood Cancer 2010 Mar; 54(3): 490–1

    Article  PubMed  Google Scholar 

  24. Bussel JB. Update on eltrombopag for ITP. Oncology (Williston Park) 2009 Nov 30; 23(13): 1177–8

    Google Scholar 

  25. Bussel JB, Provan D, Shamsi T, 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 Feb 21; 373(9664): 641–8

    Article  PubMed  CAS  Google Scholar 

  26. Podolanczuk A, Lazarus AH, Crow AR, et al. Of mice and men: an open-label pilot study for treatment of immune thrombocytopenic purpura by an inhibitor of Syk. Blood 2009 Apr 2; 113(14): 3154–60

    Article  PubMed  CAS  Google Scholar 

  27. Tarantino MD, Bolton-Maggs PH. Update on the management of immune thrombocytopenic purpura in children. Curr Opin Hematol 2007 Sep; 14(5): 526–34

    Article  PubMed  CAS  Google Scholar 

  28. Mazzucconi MG, Fazi P, Bernasconi S, et al. Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience. Blood 2007 Feb 15; 109(4): 1401–7

    Article  PubMed  CAS  Google Scholar 

  29. Kuhne T, Blanchette V, Buchanan GR, et al. Splenectomy in children with idiopathic thrombocytopenic purpura: a prospective study of 134 children from the Intercontinental Childhood ITP Study Group. Pediatr Blood Cancer 2007 Nov; 49(6): 829–34

    Article  PubMed  Google Scholar 

  30. Tarantino MD, Young G, Bertolone SJ, et al. Single dose of anti-D immune globulin at 75 microg/kg is as effective as intravenous immune globulin at rapidly raising the platelet count in newly diagnosed immune thrombocytopenic purpura in children. J Pediatr 2006 Apr; 148(4): 489–94

    Article  PubMed  CAS  Google Scholar 

  31. Bennett CM, Rogers ZR, Kinnamon DD, et al. Prospective phase 1/2 study of rituximab in childhood and adolescent chronic immune thrombocytopenic purpura. Blood 2006 Apr 1; 107(7): 2639–42

    Article  PubMed  CAS  Google Scholar 

  32. Rao VK, Dugan F, Dale JK, et al. Use of mycophenolate mofetil for chronic, refractory immune cytopenias in children with autoimmune lymphoproliferative syndrome. Br J Haematol 2005 May; 129(4): 534–8

    Article  PubMed  CAS  Google Scholar 

  33. Calderwood S, Blanchette V, Doyle J, et al. Idiopathic thrombocytopenia and neutropenia in childhood. Am J Pediatr Hematol Oncol 1994 May; 16(2): 95–101

    PubMed  CAS  Google Scholar 

  34. Ahn YS, Harrington WJ, Seelman RC, et al. Vincristine therapy of idiopathic and secondary thrombocytopenias. N Engl J Med 1974 Aug 22; 291(8): 376–80

    Article  PubMed  CAS  Google Scholar 

  35. Carcao MD, Zipursky A, Butchart S, et al. Short-course oral prednisone therapy in children presenting with acute immune thrombocytopenic purpura (ITP). Acta Paediatr Suppl 1998 Jun; 424: 71–4

    PubMed  CAS  Google Scholar 

  36. Rossman MD, Chen E, Chien P, et al. Modulation of Fc gamma receptors on the human macrophage cell line U-937. Cell Immunol 1989 Apr 15; 120(1): 174–87

    Article  PubMed  CAS  Google Scholar 

  37. Kitchens CS, Pendergast JF. Human thrombocytopenia is associated with structural abnormalities of the endothelium that are ameliorated by glucocorticosteroid administration. Blood 1986 Jan; 67(1): 203–6

    PubMed  CAS  Google Scholar 

  38. Mizutani H, Furubayashi T, Imai Y, et al. Mechanisms of corticosteroid action in immune thrombocytopenic purpura (ITP): experimental studies using ITP-prone mice, (NZW x BXSB) F1. Blood 1992 Feb 15; 79(4): 942–7

    PubMed  CAS  Google Scholar 

  39. Huang HS, Sun DS, Lien TS, et al. Dendritic cells modulate platelet activity in IVIg-mediated amelioration of ITP in mice. Blood 2010 Dec 2; 116(23): 5002–9

    Article  PubMed  CAS  Google Scholar 

  40. Provan D, Stasi R, Newland AC, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 2010 Jan 14; 115(2): 168–86

    Article  PubMed  CAS  Google Scholar 

  41. Kane I, Ragucci D, Shatat IF, et al. Comparison of intravenous immune globulin and high dose anti-D immune globulin as initial therapy for childhood immune thrombocytopenic purpura. Br J Haematol 2010 Apr; 149(1): 79–83

    Article  PubMed  CAS  Google Scholar 

  42. De Mattia D, Del Vecchio GC, Russo G, et al. Management of chronic childhood immune thrombocytopenic purpura: AIEOP consensus guidelines. Acta Haematol 2010; 123(2): 96–109

    Article  PubMed  Google Scholar 

  43. Wang J, Wiley JM, Luddy R, et al. Chronic immune thrombocytopenic purpura in children: assessment of rituximab treatment. J Pediatr 2005 Feb; 146(2): 217–21

    Article  PubMed  CAS  Google Scholar 

  44. Tamminga RY, Bruin MC. Rituximab treatment for symptomatic chronic ITP. Pediatr Blood Cancer 2006 Oct 15; 47(5 Suppl.): 714–6

    Article  PubMed  Google Scholar 

  45. Cooper N, Evangelista ML, Amadori S, et al. Should rituximab be used before or after splenectomy in patients with immune thrombocytopenic purpura? Curr Opin Hematol 2007 Nov; 14(6): 642–6

    Article  PubMed  CAS  Google Scholar 

  46. Blanchette V, Bolton-Maggs P. Childhood immune thrombocytopenic purpura: diagnosis and management. Pediatr Clin North Am 2008 Apr; 55(2): 393–420, ix

    Article  PubMed  Google Scholar 

  47. Mueller BU, Bennett CM, Feldman HA, et al. One year follow-up of children and adolescents with chronic immune thrombocytopenic purpura (ITP) treated with rituximab. Pediatr Blood Cancer 2009 Feb; 52(2): 259–62

    Article  PubMed  Google Scholar 

  48. Wiberg FC, Rasmussen SK, Frandsen TP, et al. Production of target-specific recombinant human polyclonal antibodies in mammalian cells. Biotechnol Bioeng 2006 Jun 5; 94(2): 396–405

    Article  PubMed  CAS  Google Scholar 

  49. Bajpai M. Fostamatinib, a Syk inhibitor prodrug for the treatment of inflammatory diseases. IDrugs 2009 Mar; 12(3): 174–85

    PubMed  CAS  Google Scholar 

  50. Dameshek W, Miller EB. The megakaryocytes in idiopathic thrombocytopenic purpura, a form of hypersplenism. Blood 1946 Jan; 1: 27–50

    PubMed  CAS  Google Scholar 

  51. McMillan R, Wang L, Tomer A, et al. Suppression of in vitro megakaryocyte production by antiplatelet autoantibodies from adult patients with chronic ITP. Blood 2004 Feb 15; 103(4): 1364–9

    Article  PubMed  CAS  Google Scholar 

  52. Cheng G, Saleh MN, Marcher C, 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

    Article  PubMed  CAS  Google Scholar 

  53. Gernsheimer TB, George JN, Aledort LM, et al. Evaluation of bleeding and thrombotic events during long-term use of romiplostim in patients with chronic immune thrombocytopenia (ITP). J Thromb Haemost 2010 Jun; 8(6): 1372–82

    Article  PubMed  CAS  Google Scholar 

  54. Kuter DJ, Bussel JB, Lyons RM, et al. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet 2008 Feb 2; 371(9610): 395–403

    Article  PubMed  CAS  Google Scholar 

  55. Gernsheimer T. Chronic idiopathic thrombocytopenic purpura: mechanisms of pathogenesis. Oncologist 2009; 14: 12–21

    Article  PubMed  CAS  Google Scholar 

  56. Gernsheimer TB. The pathophysiology of ITP revisited: ineffective thrombopoiesis and the emerging role of thrombopoietin receptor agonists in the management of chronic immune thrombocytopenic purpura. Hematology Am Soc Hematol Educ Program 2008; 219–26

    Google Scholar 

  57. Bussel JB, Kuter DJ, Pullarkat V, et al. Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP. Blood 2009 Mar 5; 113(10): 2161–71

    Article  PubMed  CAS  Google Scholar 

  58. Erhardt JA, Erickson-Miller CL, Aivado M, et al. Comparative analyses of the small molecule thrombopoietin receptor agonist eltrombopag and thrombopoietin on in vitro platelet function. Exp Hematol 2009 Sep; 37(9): 1030–7

    Article  PubMed  CAS  Google Scholar 

  59. Saleh MN, Bussel JB, Cheng G, et al. Long-term treatment of chronic immune thrombocytopenic purpura with oral eltrombopag: results from the EXTEND study [abstract]. ASH Annual Meeting Abstracts. ASH Annual Meeting Abstracts. Blood 2009; 114(22): 682

    Google Scholar 

  60. Erickson-Miller CL, Delorme E, Tian SS, et al. Preclinical activity of eltrombopag (SB-497115), an oral, nonpeptide thrombopoietin receptor agonist. Stem Cells 2009 Feb; 27(2): 424–30

    Article  PubMed  CAS  Google Scholar 

  61. Desjardins RE, Tempel DL, Lucek R, et al. Single and multiple oral doses of AKR-501 (YM477) increase the platelet count in healthy volunteers [abstract]. ASH Annual Meeting Abstracts. ASH Annual Meeting Abstracts. Blood 2006; 108(11): 477

    Google Scholar 

  62. Bussel JB, Zhang J, Tang S, et al. Efficacy, safety and tolerability of E5501 (AKR501) in a 6-month extension study in subjects with chronic immune thrombocytopenia (ITP) [abstract]. ASH Annual Meeting Abstracts. Blood 2010; 116(21): 3695

    Google Scholar 

  63. Boruchov DM, Gururangan S, Driscoll MC, et al. Multiagent induction and maintenance therapy for patients with refractory immune thrombocytopenic purpura (ITP). Blood 2007 Nov 15; 110(10): 3526–31

    Article  PubMed  CAS  Google Scholar 

  64. Williams JA, Boxer LA. Combination therapy for refractory idiopathic thrombocytopenic purpura in adolescents. J Pediatr Hematol Oncol 2003 Mar; 25(3): 232–5

    Article  PubMed  Google Scholar 

  65. Zhang WG, Ji L, Cao XM, et al. Mycophenolate mofetil as a treatment for refractory idiopathic thrombocytopenic purpura. Acta Pharmacol Sin 2005 May; 26(5): 598–602

    Article  PubMed  CAS  Google Scholar 

  66. Provan D, Moss AJ, Newland AC, et al. Efficacy of mycophenolate mofetil as single-agent therapy for refractory immune thrombocytopenic purpura. Am J Hematol 2006 Jan; 81(1): 19–25

    Article  PubMed  CAS  Google Scholar 

  67. Russo G, Miraglia V, Branciforte F, etal. Effect of eradication of Helicobacter pylori in children with chronic immune thrombocytopenia: a prospective, controlled, multicenter study. Pediatr Blood Cancer 2011 Feb; 56(2): 273–8

    Article  PubMed  Google Scholar 

  68. Treepongkaruna S, Sirachainan N, Kanjanapongkul S, et al. Absence of platelet recovery following Helicobacter pylori eradication in childhood chronic idiopathic thrombocytopenic purpura: a multi-center randomized controlled trial. Pediatr Blood Cancer 2009 Jul; 53(1): 72–7

    Article  PubMed  Google Scholar 

  69. Zaja F, Baccarani M, Mazza P, et al. Dexamethasone plus rituximab yields higher sustained response rates than dexamethasone monotherapy in adults with primary immune thrombocytopenia. Blood 2010 Apr 8; 115(14): 2755–62

    Article  PubMed  CAS  Google Scholar 

  70. Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 2011 Mar; 117(16): 4190–207

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

A.L. Bredlau and G.B. Segel conceived and wrote the manuscript. J.W. Semple was instrumental in describing the pathophysiology of ITP and in designing the relevant figure. No authors received funding for this review. No conflicts of interest were present for any of the authors. We thank Marshall A. Lichtman, MD, for his helpful review.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Division of Hematology/Oncology, University of Rochester, Rochester, NY, USA

    Amy Lee Bredlau MD

  2. Keenan Research Centre, Li Ka Shing Knowledge Institute of St Michael’s Hospital, Department of Pharmacology and Toxicology, Toronto, ON, Canada

    John W. Semple

  3. Departments of Pediatrics and Medicine, Division of Hematology/Oncology, University of Rochester, Rochester, NY, USA

    George B. Segel

Authors
  1. Amy Lee Bredlau MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John W. Semple
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. George B. Segel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amy Lee Bredlau MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bredlau, A.L., Semple, J.W. & Segel, G.B. Management of Immune Thrombocytopenic Purpura in Children. Pediatr-Drugs 13, 213–223 (2011). https://doi.org/10.2165/11591640-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11591640-000000000-00000

Keywords

Search

Navigation