Semin Thromb Hemost 2003; 29(6): 605-618
DOI: 10.1055/s-2004-815628
Copyright © 2003 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Childhood Acute Immune Thrombocytopenic Purpura: 20 Years Later

Victor S. Blanchette1,2 , Manuel Carcao2
  • 1Chief, Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, and Department of Pediatrics, University of Toronto, Toronto, Canada
  • 2Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, and Department of Pediatrics, University of Toronto, Toronto, Canada
Further Information

Publication History

Publication Date:
13 January 2004 (online)

ABSTRACT

Childhood acute immune thrombocytopenic purpura (ITP) is a typically benign, self-limiting illness usually occurring after an infectious disease. Most affected children have platelet counts < 20 × 109/L at presentation and are at small, but definite risk for an intracranial hemorrhage. This feared complication occurs in < 1% of all children with acute ITP. There is consensus that a bone marrow aspirate should be performed in children with acute ITP and atypical features (e.g., hepatosplenomegaly), and most physicians continue to recommend this investigation before corticosteroids are administered. Issues such as hospitalization versus observation at home, and treatment versus no treatment continue to be debated; there is consensus, however, that children with extreme thrombocytopenia (platelet counts < 10 × 109/L) and/or clinically significant hemorrhage merit treatment with a regimen known to rapidly increase the circulating platelet count. Candidate regimens include high-dose intravenous (IV)/oral corticosteroids (≥ 4 mg/kg/day of prednisone or an equivalent corticosteroid preparation), IV immunoglobulin (IG; 0.8 to 1.0 g/kg once) or IV anti-D (75 μg/kg once) for Rhesus-positive patients. For those rare children with organ- or life-threatening hemorrhage (e.g., intracranial hemorrhage) multimodality therapy including platelet transfusion, IV high-dose methylprednisone (30 mg/kg, maximum 1 g) and IVIG (1 g/kg) is indicated with consideration of emergency splenectomy. Future prospective trials should include outcome measures other than the platelet count alone (e.g., bleeding scores) and health-related quality-of-life assessments. Key questions that remain to be addressed in children with acute ITP include the need for bone marrow aspiration in typical cases if corticosteroid therapy is planned, the role of hospitalization, and most important, the unresolved issue of treatment versus no treatment, especially in patients with typical features and mild clinical bleeding symptoms.

REFERENCES

  • 1 Imbach P, Barandun S, d'Apuzzo V. et al . High-dose intravenous gammaglobulin for idiopathic thrombocytopenic purpura in childhood.  Lancet . 1981;  i 1228-1231
  • 2 Salama A, Mueller-Eckhardt C, Kiefel V. Effect of intravenous immunoglobulin in immune thrombocytopenia. Competitive inhibition of reticuloendothelial system function by sequestration of autologous red blood cells?.  Lancet . 1983;  ii 193-195
  • 3 Zuelzer W W, Lusher J M. Childhood idiopathic thrombocytopenic purpura. To treat or not to treat.  Am J Dis Child . 1977;  131 360-362
  • 4 Kühne T, Imbach P, Bolton-Maggs P HB, Berchtold W, Blanchette V, Buchanan G R, for the Intercontinental ITP Study Group. Newly diagnosed idiopathic thrombocytopenic purpura in childhood: an observational study.  Lancet . 2001;  358 2122-2125
  • 5 Lusher J M, Zuelzer W W. Idiopathic thrombocytopenic purpura in childhood.  J Pediatr . 1966;  68 971-979
  • 6 Choi S I, McClure P D. Idiopathic thrombocytopenic purpura in childhood.  Can Med Assoc J . 1967;  97 562-568
  • 7 Blanchette V S. Unpublished observations . 
  • 8 Oski F A, Naiman J L. Effect of live measles vaccine on the platelet count.  New Engl J Med . 1966;  275 352-356
  • 9 Miller E, Waight P, Farrington P, Andrews N, Stowe J, Taylor B. Idiopathic thrombocytopenic purpura and MMR vaccine.  Arch Dis Child . 2001;  84 227-229
  • 10 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 3-40
  • 11 Dickerhoff R, von Ruecker A. The clinical course of immune thrombocytopenic purpura in children who did not receive intravenous immunoglobulin or sustained prednisone treatment.  J Pediatr . 2000;  137 629-632
  • 12 Imbach P, Akatsuka J, Blanchette V. et al . Immunocytopenic purpura as a model for pathogenesis and treatment of autoimmunity.  Eur J Pediatr . 1995;  154 (suppl 3) S60-S64
  • 13 Iyori H, Bessho F, Ookawa H, for the Japanese Study Group on childhood ITP. et al . Intracranial hemorrhage in children with immune thrombocytopenic purpura.  Ann Hematol . 2000;  79 691-695
  • 14 Lilleyman J S. on behalf of the Paediatric Haematology Forum of the British Society of Haematology. Intracranial hemorrhage in idiopathic thrombocytopenic purpura.  Arch Dis Child . 1994;  71 251-253
  • 15 Woerner S J, Abildgaard C F, French B N. Intracranial hemorrhage in children with idiopathic thrombocytopenic purpura.  Pediatrics . 1981;  67 453-460
  • 16 Blanchette V S, Turner C. Treatment of acute idiopathic thrombocytopenic purpura.  J Pediatr . 1986;  108 326-327
  • 17 Bolton-Maggs P HB, Dickerhoff R, Vora A J. The nontreatment of childhood ITP (or “The art of medicine consists of amusing the patient until nature cures the disease”).  Semin Thromb Hemost . 2001;  27 269-275
  • 18 Lee M S, Kim W G. Intracranial hemorrhage associated with idiopathic thrombocytopenic purpura: report of seven patients and a meta-analysis.  Neurology . 1998;  50 1160-1163
  • 19 De Mattia D, Del Principe D, Del Vecchio C G, and The AIEOP ITP Study Group. et al . Acute childhood idiopathic thrombocytopenic purpura: AIEOI concensus guidelines for diagnosis and treatment.  Haematologica . 2000;  85 420-424
  • 20 Working Party of the 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
  • 21 Lilleyman J S. Management of childhood idiopathic thrombocytopenic purpura.  Br J Haematol . 1999;  105 871-875
  • 22 Sartorius J A. Steroid treatment of idiopathic thrombocytopenic purpura in children. Preliminary results of a randomized cooperative study.  Am J Pediatr Hematol Oncol . 1984;  6 165-169
  • 23 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;  6 355-361
  • 24 Özsoylu S, Irken G, Karabent A. High-dose intravenous methylprednisolone for acute childhood idiopathic thrombocytopenic purpura.  Eur J Haematol . 1989;  42 431-435
  • 25 Özsoylu S, Sayli T R, Ozturk G. Oral megadose methylprednisolone versus intravenous immunoglobulin for acute childhood idiopathic thrombocytopenic purpura.  Pediatr Hematol Oncol . 1993;  10 317-321
  • 26 Gereige R S, Barrios N J. Treatment of childhood acute immune thrombocytopenic purpura with high-dose methylprednisolone, intravenous immunoglobulin, or the combination of both.  P R Health Sci J . 2000;  19 15-18
  • 27 Suarez C R, Rademaker D, Hasson A, Mangogna L. High-dose steroids in childhood acute idiopathic thrombocytopenia purpura.  Am J Pediatr Hematol Oncol . 1986;  8 111-115
  • 28 van Hoff J, Ritchey A K. Pulse methylprednisolone therapy for acute childhood idiopathic thrombocytopenic purpura.  J Pediatr . 1988;  113 563-566
  • 29 Jayabose S, Patel P, Inamdar S, Brillian R, Mamtani R. Use of intravenous methylprednisolone in acute idiopathic thrombocytopenic purpura.  Am J Pediatr Hematol Oncol . 1987;  9 133-135
  • 30 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 . 1998;  S424 71-74
  • 31 Imbach P, Wagner H P, Berchtold W. et al . Intravenous immunoglobulin versus oral corticosteroids in acute immune thrombocytopenic purpura in childhood.  Lancet . 1985;  ii 464-468
  • 32 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;  123 989-995
  • 33 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;  344 703-707
  • 34 Khalifa A S, Tolba K A, El-Alfy M S, Gadallah M, Ibrahim F H. Idiopathic thrombocytopenic purpura in Egyptian children.  Acta Haematol . 1993;  90 125-129
  • 35 Albayrak D, Islek I, Kalayci A G, Gürses N. Acute immune thrombocytopenic purpura: a comparative study of very high oral doses of methylprednisolone and intravenously administered immune globulin.  J Pediatr . 1994;  125 1004-1007
  • 36 Rosthoj S, Nielsen S, Pedersen F K, and the Danish ITP Study Group. Randomized trial comparing intravenous immunoglobulin with methylprednisolone pulse therapy in acute idiopathic thrombocytopenic purpura.  Acta Paediatr . 1996;  85 910-915
  • 37 Warrier I, Bussel J B, Valdez L, Barbosa J, Beardsley D S, and the Low-Dose IVIG Study Group. Safety and efficacy of low-dose intravenous immune globulin (IVIG) treatment for infants and children with immune thrombocytopenic purpura.  J Pediatr Hematol Oncol . 1997;  19 197-201
  • 38 Fujisawa K, Iyori H, Ohkawa H, for the Japanese Study Group on Childhood ITP. et al . A prospective, randomized trial of conventional, dose-accelerated corticosteroids and intravenous immunoglobulin in children with newly diagnosed idiopathic thrombocytopenic purpura.  Int J Hematol . 2000;  72 376-383
  • 39 Ancona K G, Parker R I, Atlas M P, Prakash D. Randomized trial of high-dose methylprednisolone versus intravenous immunoglobulin for the treatment of acute idiopathic thrombocytopenic purpura in children.  J Pediatr Hematol Oncol . 2002;  24 540-544
  • 40 Duru F, Fisgin T, Yarali N, Kara A. Clinical course of children with immune thrombocytopenic purpura treated with intravenous immunoglobulin G or megadose methylprednisolone or observed without therapy.  Pediatr Hematol Oncol . 2002;  19 219-225
  • 41 Eden O B, Lilleyman J S, on behalf of the British Paediatric Haematology Group. Guidelines for management of idiopathic thrombocytopenic purpura.  Arch Dis Child . 1992;  67 1056-1058
  • 42 Scaradavou A, Woo B, Woloski B MR. et al . Intravenous anti-D treatment of immune thrombocytopenic purpura: experience in 272 patients.  Blood . 1997;  89 2689-2700
  • 43 Tarantino M D, Madden R M, Fennewald D L, Patel C C, Bertolone S J. Treatment of chilhood acute immune thrombocytopenic purpura with anti-D immune globulin or pooled immunoglobulin.  J Pediatr . 1999;  134 21-26
  • 44 Newman G C, Nova M V, Fodero E M, Lesser M L, Woloski B MR, Bussel J B. A dose of 75 μg/kg/d of IV anti-D increases the platelet count more rapidly and for a longer period of time than 50 μg/kg/d in adults with immune thrombocytopenic purpura.  Br J Haematol . 2001;  112 1076-1078
  • 45 Gaines A R. Acute onset hemoglobinemia and/or hemoglobinuria and sequelae following Rho(D) immune globulin intravenous administration in immune thrombocytopenic purpura patients.  Blood . 2000;  95 2523-2529
  • 46 Baumann M A, Menitova J E, Aster R H, Anderson T. Urgent treatment of idiopathic thrombocytopenic purpura with single-dose gammaglobulin infusion followed by platelet transfusion.  Ann Intern Med . 1986;  104 808-809
  • 47 Bolton-Maggs P HB, Moon I. Assessment of UK practice for management of acute childhood idiopathic thrombocytopenic purpura against published guidelines.  Lancet . 1997;  350 620-623
  • 48 Dubansky A S, Oski F A. Controversies in the management of acute idiopathic thrombocytopenic purpura: a survey of specialists.  Pediatrics . 1986;  77 49-52
  • 49 Vesely S, Buchanan G R, Cohen A, Raskob G, George J. Self-reported diagnostic and management strategies in childhood idiopathic thrombocytopenic purpura. Results of a survey of practicing pediatric hematology/oncology specialists.  J Pediatr Hematol Oncol . 2000;  22 55-61
  • 50 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 1068-1071
  • 51 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 Adol Med . 1998;  152 345-347
  • 52 Halperin D S, Doyle J J. Is bone marrow examination justified in idiopathic thrombocytopenic purpura?.  Am J Dis Child . 1988;  142 508-511
  • 53 Vesely S K, Buchanan G R, Leah A. et al . Self-reported initial management of childhood idiopathic thrombocytopenic purpura: results of a survey of members of the American Society of Pediatric Hematology/Oncology, 2001.  J Pediatr Hematol Oncol . 2003;  25 130-133
  • 54 Sutor A H, Harms A, Kaufmehl K. Acute immune thrombocytopenia (ITP) in childhood: retrospective and prospective survey in Germany.  Semin Thromb Hemost . 2001;  27 253-267
  • 55 Buchanan G R, Adix L. Outcome measures and treatment endpoints other than platelet count in childhood idiopathic thrombocytopenic purpura.  Semin Thromb Hemost . 2001;  27 277-285
  • 56 Buchanan G, Adix L. Grading of hemorrhage in children with idiopathic thrombocytopenic purpura.  J Pediatr . 2002;  141 683-688
  • 57 Barnard D, Woloski M, Feeny D, for the Canadian Children's Platelet Study Group. et al . Development of disease-specific health-related quality-of-life instruments for children with immune thrombocytopenic purpura and their parents.  J Pediatr Hematol Oncol . 2003;  25 56-62
  • 58 Medeiros D, Buchanan G R. Major hemorrhage in children with idiopathic thrombocytopenic purpura: immediate response to therapy and long-term outcome.  J Pediatr . 1998;  133 334-339
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