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Semin Thromb Hemost 2011; 37(7): 745-755
DOI: 10.1055/s-0031-1297165
© Thieme Medical Publishers

Childhood Immune Thrombocytopenia: A Changing Therapeutic Landscape

Vicky R. Breakey1 , Victor S. Blanchette1 , 2
  • 1Divison of Hematology/Oncology, Department of Pediatrics, Hospital for Sick Children, Toronto, Canada
  • 2Department of Pediatrics, University of Toronto, Toronto, Canada
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Publikationsverlauf

Publikationsdatum:
20. Dezember 2011 (online)

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ABSTRACT

Childhood immune thrombocytopenia (ITP) is generally a benign self-limiting disorder of young children with <10% of cases requiring regular platelet enhancing therapy at 1 year following diagnosis. Increasingly, children with newly diagnosed ITP, who have isolated thrombocytopenia and no atypical features in the history or physical examination, are managed with minimal investigation and observation alone. The role of up-front, short-course corticosteroid therapy without bone marrow aspiration in this subgroup of cases merits further investigation. For children with clinically significant chronic ITP, the timing of elective splenectomy and the role of splenectomy-sparing strategies such as rituximab continues to be debated. Management of children with combined autoimmune cytopenias secondary to systemic lupus erythematosus, common variable immunodeficiency, and the autoimmune lymphoproliferative syndrome is often a challenge. Splenectomy should be avoided in cases with documented immunodeficiencies because of the increased risk of overwhelming sepsis postsplenectomy. For these cases, as well as for children with resistant primary chronic ITP who have failed splenectomy, the role of therapies such as mycophenolate mofetil, sirolimus, and the thrombopoietins remains to be determined.

KEYWORDS

Immune thrombocytopenic purpura - immune thrombocytopenia - children

REFERENCES

  • 1 Cines D B, Blanchette V S. Immune thrombocytopenic purpura.  N Engl J Med. 2002;  346 (13) 995-1008
    Google Scholar
  • 2 Nugent D, McMillan R, Nichol J L, Slichter S J. Pathogenesis of chronic immune thrombocytopenia: increased platelet destruction and/or decreased platelet production.  Br J Haematol. 2009;  146 (6) 585-596
    Google Scholar
  • 3 George J N, Woolf S H, Raskob G E et al.. Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology.  Blood. 1996;  88 (1) 3-40
    Google Scholar
  • 4 Provan D, Newland A, Norfolk D British Committee for Standards in Haematology General Haematology Task Force et al. Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy.  Br J Haematol. 2003;  120 (4) 574-596
    Google Scholar
  • 5 Provan D, Stasi R, Newland A C et al.. International consensus report on the investigation and management of primary immune thrombocytopenia.  Blood. 2010;  115 (2) 168-186
    Google Scholar
  • 6 Neunert C, Lim W, Crowther M, Cohen A, Solberg Jr L, Crowther M. American Society of Hematology. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia.  Blood. 2011;  117 (16) 4190-4207
    Google Scholar
  • 7 Blanchette V S, Carcao M. Childhood acute immune thrombocytopenic purpura: 20 years later.  Semin Thromb Hemost. 2003;  29 (6) 605-617
    Google Scholar
  • 8 Blanchette V S, Price V. Childhood chronic immune thrombocytopenic purpura: unresolved issues.  J Pediatr Hematol Oncol. 2003;  25 (Suppl 1) S28-S33
    Google Scholar
  • 9 Blanchette V, Bolton-Maggs P. Childhood immune thrombocytopenic purpura: diagnosis and management.  Pediatr Clin North Am. 2008;  55 (2) 393-420
    Google Scholar
  • 10 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;  113 (11) 2386-2393
    Google Scholar
  • 11 Stasi R, Amadori S, Osborn J, Newland A C, Provan D. Long-term outcome of otherwise healthy individuals with incidentally discovered borderline thrombocytopenia.  PLoS Med. 2006;  3 (3) e24
    Google Scholar
  • 12 Dubansky A S, Boyett J M, Falletta J et al.. Isolated thrombocytopenia in children with acute lymphoblastic leukemia: a rare event in a Pediatric Oncology Group Study.  Pediatrics. 1989;  84 (6) 1068-1071
    Google Scholar
  • 13 Calpin C, Dick P, Poon A, Feldman W. Is bone marrow aspiration needed in acute childhood idiopathic thrombocytopenic purpura to rule out leukemia?.  Arch Pediatr Adolesc Med. 1998;  152 (4) 345-347
    Google Scholar
  • 14 Kühne T, Buchanan G R, Zimmerman S Intercontinental Childhood ITP Study Group et al. A prospective comparative study of 2540 infants and children with newly diagnosed idiopathic thrombocytopenic purpura (ITP) from the Intercontinental Childhood ITP Study Group.  J Pediatr. 2003;  143 (5) 605-608
    Google Scholar
  • 15 Imbach P, Kühne T, Müller D 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 (3) 351-356
    Google Scholar
  • 16 Lilleyman J S. Paediatric Haematology Forum of the British Society for Haematology . Intracranial haemorrhage in idiopathic thrombocytopenic purpura.  Arch Dis Child. 1994;  71 (3) 251-253
    Google Scholar
  • 17 Kühne T, Imbach P, Bolton-Maggs PHB, Berchtold W, Blanchette V, Buchanan G R. Intercontinental Childhood ITP Study Group . Newly diagnosed idiopathic thrombocytopenic purpura in childhood: an observational study.  Lancet. 2001;  358 (9299) 2122-2125
    Google Scholar
  • 18 Woerner S J, Abildgaard C F, French B N. Intracranial hemorrhage in children with idiopathic thrombocytopenic purpura.  Pediatrics. 1981;  67 (4) 453-460
    Google Scholar
  • 19 Butros L J, Bussel J B. Intracranial hemorrhage in immune thrombocytopenic purpura: a retrospective analysis.  J Pediatr Hematol Oncol. 2003;  25 (8) 660-664
    Google Scholar
  • 20 Neunert C E, Buchanan G R, Imbach P Intercontinental Childhood ITP Study Group Registry II Participants et al. Severe hemorrhage in children with newly diagnosed immune thrombocytopenic purpura.  Blood. 2008;  112 (10) 4003-4008
    Google Scholar
  • 21 Blanchette V, Imbach P, Andrew M et al.. Randomised trial of intravenous immunoglobulin G, intravenous anti-D, and oral prednisone in childhood acute immune thrombocytopenic purpura.  Lancet. 1994;  344 (8924) 703-707
    Google Scholar
  • 22 Carcao M D, Zipursky A, Butchart S, Leaker M, Blanchette V S. Short-course oral prednisone therapy in children presenting with acute immune thrombocytopenic purpura (ITP).  Acta Paediatr Suppl. 1998;  424 71-74
    Google Scholar
  • 23 Tarantino M D, Young G, Bertolone S J Acute ITP Study Group 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;  148 (4) 489-494
    Google Scholar
  • 24 Buchanan G R, Holtkamp C A. Prednisone therapy for children with newly diagnosed idiopathic thrombocytopenic purpura. A randomized clinical trial.  Am J Pediatr Hematol Oncol. 1984;  6 (4) 355-361
    Google Scholar
  • 25 Blanchette V S, Luke B, Andrew M et al.. A prospective, randomized trial of high-dose intravenous immune globulin G therapy, oral prednisone therapy, and no therapy in childhood acute immune thrombocytopenic purpura.  J Pediatr. 1993;  123 (6) 989-995
    Google Scholar
  • 26 Gaines A R. Disseminated intravascular coagulation associated with acute hemoglobinemia or hemoglobinuria following Rh(0)(D) immune globulin intravenous administration for immune thrombocytopenic purpura.  Blood. 2005;  106 (5) 1532-1537
    Google Scholar
  • 27 Imbach P, Akatsuka J, Blanchette V et al.. Immunthrombocytopenic purpura as a model for pathogenesis and treatment of autoimmunity.  Eur J Pediatr. 1995;  154 (9, Suppl 4) S60-S64
    Google Scholar
  • 28 Sobota A, Neufeld E J, Lapsia S, Bennett C M. Response to mercaptopurine for refractory autoimmune cytopenias in children.  Pediatr Blood Cancer. 2009;  52 (1) 80-84
    Google Scholar
  • 29 Hilgartner M W, Lanzkowsky P, Smith C H. The use of azathioprine in refractory idiopathic thrombocytopenic purpura in children.  Acta Paediatr Scand. 1970;  59 (4) 409-415
    Google Scholar
  • 30 Quiquandon I, Fenaux P, Caulier M T, Pagniez D, Huart J J, 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 (2) 223-228
    Google Scholar
  • 31 Andersen J C. Response of resistant idiopathic thrombocytopenic purpura to pulsed high-dose dexamethasone therapy.  N Engl J Med. 1994;  330 (22) 1560-1564
    Google Scholar
  • 32 Kühne T, Freedman J, Semple J W, Doyle J, Butchart S, Blanchette V S. Platelet and immune responses to oral cyclic dexamethasone therapy in childhood chronic immune thrombocytopenic purpura.  J Pediatr. 1997;  130 (1) 17-24
    Google Scholar
  • 33 Cuker A, Cines D B. Immune thrombocytopenia.  Hematology (Am Soc Hematol Educ Program). 2010;  2010 377-384 http://asheducationbook.hematology.org
    Google Scholar
  • 34 Arnold D M, Dentali F, Crowther M A et al.. Systematic review: efficacy and safety of rituximab for adults with idiopathic thrombocytopenic purpura.  Ann Intern Med. 2007;  146 (1) 25-33
    Google Scholar
  • 35 Bennett C M, Rogers Z R, Kinnamon D D Pediatric Rituximab/ITP Study Group and the Glaser Pediatric Research Network et al. Prospective phase 1/2 study of rituximab in childhood and adolescent chronic immune thrombocytopenic purpura.  Blood. 2006;  107 (7) 2639-2642
    Google Scholar
  • 36 Mueller B U, Bennett C M, Feldman H A Pediatric Rituximab/ITP Study Group et al. One year follow-up of children and adolescents with chronic immune thrombocytopenic purpura (ITP) treated with rituximab.  Pediatr Blood Cancer. 2009;  52 (2) 259-262
    Google Scholar
  • 37 Carson K R, Evens A M, Richey E A et al.. 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. 2009;  113 (20) 4834-4840
    Google Scholar
  • 38 Kaushansky K. Thrombopoietin.  N Engl J Med. 1998;  339 746-754
    Google Scholar
  • 39 Kaushansky K. Historical review: megakaryopoiesis and thrombopoiesis.  Blood. 2008;  111 (3) 981-986
    Google Scholar
  • 40 Bussel J B, Kuter D J, Pullarkat V, Lyons R M, Guo M, Nichol J L. Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP.  Blood. 2009;  113 (10) 2161-2171
    Google Scholar
  • 41 Kuter D J, Rummel M, Boccia R et al.. Romiplostim or standard of care in patients with immune thrombocytopenia.  N Engl J Med. 2010;  363 (20) 1889-1899
    Google Scholar
  • 42 Bussel J B, Cheng G, Saleh M N et al.. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura.  N Engl J Med. 2007;  357 (22) 2237-2247
    Google Scholar
  • 43 Price V E, Dutta S, Blanchette V S et al.. The prevention and treatment of bacterial infections in children with asplenia or hyposplenia: practice considerations at the Hospital for Sick Children, Toronto.  Pediatr Blood Cancer. 2006;  46 (5) 597-603
    Google Scholar
  • 44 Crary S E, Buchanan G R. Vascular complications after splenectomy for hematologic disorders.  Blood. 2009;  114 (14) 2861-2868
    Google Scholar
  • 45 van Hoff J, Ritchey A K. Pulse methylprednisolone therapy for acute childhood idiopathic thrombocytopenic purpura.  J Pediatr. 1988;  113 (3) 563-566
    Google Scholar
  • 46 Shatz D V, Schinsky M F, Pais L B, Romero-Steiner S, Kirton O C, Carlone G M. Immune responses of splenectomized trauma patients to the 23-valent pneumococcal polysaccharide vaccine at 1 versus 7 versus 14 days after splenectomy.  J Trauma. 1998;  44 (5) 760-765, discussion 765–766
    Google Scholar
  • 47 Williams J A, Boxer L A. Combination therapy for refractory idiopathic thrombocytopenic purpura in adolescents.  J Pediatr Hematol Oncol. 2003;  25 (3) 232-235
    Google Scholar
  • 48 Arnold D M, Nazi I, Santos A et al.. Combination immunosuppressant therapy for patients with chronic refractory immune thrombocytopenic purpura.  Blood. 2010;  115 (1) 29-31
    Google Scholar
  • 49 Cunningham-Rundles C. How I treat common variable immune deficiency.  Blood. 2010;  116 (1) 7-15
    Google Scholar
  • 50 Teachey D T, Seif A E, Grupp S A. Advances in the management and understanding of autoimmune lymphoproliferative syndrome (ALPS).  Br J Haematol. 2010;  148 (2) 205-216
    Google Scholar
  • 51 Oliveira J B, Bleesing J J, Dianzani U et al.. Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome (ALPS): report from the 2009 NIH International Workshop.  Blood. 2010;  116 (14) e35-e40
    Google Scholar
  • 52 Rao V K, Dugan F, Dale J K et al.. Use of mycophenolate mofetil for chronic, refractory immune cytopenias in children with autoimmune lymphoproliferative syndrome.  Br J Haematol. 2005;  129 (4) 534-538
    Google Scholar
  • 53 Teachey D T, Greiner R, Seif A et al.. Treatment with sirolimus results in complete responses in patients with autoimmune lymphoproliferative syndrome.  Br J Haematol. 2009;  145 (1) 101-106
    Google Scholar
  • 54 Seif A E, Manno C S, Sheen C, Grupp S A, Teachey D T. Identifying autoimmune lymphoproliferative syndrome in children with Evans syndrome: a multi-institutional study.  Blood. 2010;  115 (11) 2142-2145
    Google Scholar
  • 55 Beck C E, Nathan P C, Parkin P C, Blanchette V S, Macarthur C. Corticosteroids versus intravenous immune globulin for the treatment of acute immune thrombocytopenic purpura in children: a systematic review and meta-analysis of randomized controlled trials.  J Pediatr. 2005;  147 (4) 521-527
    Google Scholar
  • 56 Tamminga R, Berchtold W, Bruin M, Buchanan G R, Kühne T. Possible lower rate of chronic ITP after IVIG for acute childhood ITP an analysis from registry I of the Intercontinental Cooperative ITP Study Group (ICIS).  Br J Haematol. 2009;  146 (2) 180-184
    Google Scholar
  • 57 Najean Y, Rain J D, Billotey C. 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. 1997;  97 (3) 547-550
    Google Scholar
  • 58 Cuker A, Cines D B. Evidence-based mini-review: Is indium-labeled autologous platelet scanning predictive of response to splenectomy in patients with chronic immune thrombocytopenia?.  Hematology (Am Soc Hematol Educ Program). 2010;  2010 385-386 http://asheducationbook.hematology.org
    Google Scholar
  • 59 Buchanan G R, Adix L. Grading of hemorrhage in children with idiopathic thrombocytopenic purpura.  J Pediatr. 2002;  141 (5) 683-688
    Google Scholar
  • 60 Klaassen R J, Blanchette V S, Barnard D et al.. Validity, reliability, and responsiveness of a new measure of health-related quality of life in children with immune thrombocytopenic purpura: the Kids' ITP Tools.  J Pediatr. 2007;  150 (5) 510-515, 515, e1
    Google Scholar
  • 61 Mathias S D, Bussel J B, George J N, McMillan R, Okano G J, Nichol J L. A disease-specific measure of health-related quality of life for use in adults with immune thrombocytopenic purpura: its development and validation.  Health Qual Life Outcomes. 2007;  5 11
    Google Scholar
  • 62 Drachman J G. Inherited thrombocytopenia: when a low platelet count does not mean ITP.  Blood. 2004;  103 (2) 390-398
    Google Scholar
  • 63 Blanchette V S, Kirby M A, Turner C. Role of intravenous immunoglobulin G in autoimmune hematologic disorders.  Semin Hematol. 1992;  29 (3, Suppl 2) 72-82
    Google Scholar
  • 64 Ben-Yehuda D, Gillis S, Eldor A. Israeli ITP Study Group . Clinical and therapeutic experience in 712 Israeli patients with idiopathic thrombocytopenic purpura.  Acta Haematol. 1994;  91 (1) 1-6
    Google Scholar
  • 65 Mantadakis E, Buchanan G R. Elective splenectomy in children with idiopathic thrombocytopenic purpura.  J Pediatr Hematol Oncol. 2000;  22 (2) 148-153
    Google Scholar
  • 66 Kühne T, Blanchette V, Buchanan G R Intercontinental Childhood ITP Study Group 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;  49 (6) 829-834
    Google Scholar

Victor S. BlanchetteF.R.C.P. 

Medical Director, Pediatric Thrombosis and Hemostasis Program, Division of Hematology/Oncology, Hospital for Sick Children

555 University Avenue, Toronto, ON M5G 1X8, Canada

eMail: victor.blanchette@sickkids.ca