ITP in Childhood: Predictors of Disease Duration

Chapter

Abstract

Most children with immune thrombocytopenic purpura have a favorable outcome. A small but significant minority have clinically significant chronic ITP that requires ongoing treatment. At presentation, it is not possible to differentiate between the patients who will have a short duration of thrombocytopenia from those who will develop chronic disease. Predictors of ITP outcome would help guide treatment decisions and ultimately improve quality of life. In this chapter, the current body of evidence regarding biomarker and genetic predictors of ITP duration is reviewed.

References

  1. Ahmed R, Devasia AJ, Viswabandya A, Lakshmi KM, Abraham A, Karl S, Mathai J, Jacob PM, Abraham D, Srivastava A, et al. Long-term outcome following splenectomy for chronic and persistent immune thrombocytopenia (ITP) in adults and children: splenectomy in ITP. Ann Hematol. 2016;95(9):1429–34.CrossRefPubMedGoogle Scholar
  2. Ahmed I, Rajpurkar M, Thomas R, Chitlur M. Initial lymphocyte count and the development of persistent/chronic immune thrombocytopenic purpura. Pediatr Blood Cancer. 2010;55(3):508–11.CrossRefPubMedGoogle Scholar
  3. Akbayram S, Dogan M, Ustyol L, Akgun C, Peker E, Bilici S, Caksen H, Oner AF. The clinical outcome of 260 pediatric ITP patients in one center. Clin Appl Thromb Hemost. 2011;17(6):E30–5.CrossRefPubMedGoogle Scholar
  4. Andrew M, Blanchette VS, Adams M, Ali K, Barnard D, Chan KW, DeVeber LB, Esseltine D, Israels S, Korbrinsky N, et al. A multicenter study of the treatment of childhood chronic idiopathic thrombocytopenic purpura with anti-D. J Pediatr. 1992;120(4 Pt 1):522–7.CrossRefPubMedGoogle Scholar
  5. Aronis S, Platokouki H, Avgeri M, Pergantou H, Keramidas D. Retrospective evaluation of long-term efficacy and safety of splenectomy in chronic idiopathic thrombocytopenic purpura in children. Acta Paediatr. 2004;93(5):638–42.CrossRefPubMedGoogle Scholar
  6. Aronis S, Platokouki H, Mitsika A, Haidas S, Constantopoulos A. Seventeen years of experience with chronic idiopathic thrombocytopenic purpura in childhood. Is therapy always better? Pediatr Hematol Oncol. 1994;11(5):487–98.CrossRefPubMedGoogle Scholar
  7. Bansal D, Bhamare TA, Trehan A, Ahluwalia J, Varma N, Marwaha RK. Outcome of chronic idiopathic thrombocytopenic purpura in children. Pediatr Blood Cancer. 2010;54(3):403–7.CrossRefPubMedGoogle Scholar
  8. Bennett CM, Neunert C, Grace RF, Buchanan G, Imbach P, Vesely SK, Kuhne T. Predictors of remission in children with newly diagnosed immune thrombocytopenia: data from the Intercontinental Cooperative ITP Study Group Registry II participants. Pediatr Blood Cancer. 2017. https://doi.org/10.1002/pbc.26736 [Epub ahead of print].
  9. Bennett CM, Rogers ZR, Kinnamon DD, Bussel JB, Mahoney DH, Abshire TC, Sawaf H, Moore TB, Loh ML, Glader BE et al. Prospective phase 1/2 study of rituximab in childhood and adolescent chronic immune thrombocytopenic purpura. In: 18th Annual Meeting of the American-Society-of-Pediatric-Hematology-Oncology: May 13–17 2005; Washington, DC; 2005. p. 2639–42.Google Scholar
  10. Bennett CM, Tarantino M. Chronic immune thrombocytopenia in children: epidemiology and clinical presentation. Hematol Oncol Clin North Am. 2009;23(6):1223–38.CrossRefPubMedGoogle Scholar
  11. Bergmann AK, Grace RF, Neufeld EJ. Genetic studies in pediatric ITP: outlook, feasibility, and requirements. Ann Hematol. 2010;89(Suppl 1):S95–103.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Blanchette V, Imbach P, Andrew M, Adams M, McMillan J, Wang E, Milner R, Ali K, Barnard D, Bernstein 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):703–7.CrossRefPubMedGoogle Scholar
  13. Blanchette VS, Luke B, Andrew M, Sommerville-Nielsen S, Barnard D, de Veber B, Gent M. 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):989–95.CrossRefPubMedGoogle Scholar
  14. Bruin M, Bierings M, Uiterwaal C, Revesz T, Bode L, Wiesman ME, Kuijpers T, Tamminga R, de Haas M. Platelet count, previous infection and FCGR2B genotype predict development of chronic disease in newly diagnosed idiopathic thrombocytopenia in childhood: results of a prospective study. Br J Haematol. 2004;127(5):561–7.CrossRefPubMedGoogle Scholar
  15. Chotsampancharoen T, Sripornsawan P, Duangchoo S, Wongchanchailert M, McNeil E. Predictive factors for resolution of childhood immune thrombocytopenia: experience from a single tertiary center in Thailand. Pediatr Blood Cancer. 2017;64(1):128–34.CrossRefPubMedGoogle Scholar
  16. Deel MD, Kong M, Cross KP, Bertolone SJ. Absolute lymphocyte counts as prognostic indicators for immune thrombocytopenia outcomes in children. Pediatr Blood Cancer. 2013;60(12):1967–74.CrossRefPubMedGoogle Scholar
  17. Despotovic JM, Polfus LM, Flanagan JM, Bennett CM, Lambert MP, Neunert C, Kumar M, Klaassen RJ, Thornburg C, Jeng M, et al. Genes influencing the development and severity of chronic ITP identified through whole exome sequencing. Blood. 2015;126(23):3.Google Scholar
  18. Donato H, Picon A, Martinez M, Rapetti MC, Rosso A, Gomez S, Rossi N, Bacciedoni V, Schvartzman G, Riccheri C, et al. Demographic data, natural history, and prognostic factors of idiopathic thrombocytopenic purpura in children: a multicentered study from Argentina. Pediatr Blood Cancer. 2009;52(4):491–6.CrossRefPubMedGoogle Scholar
  19. ElAlfy M, Farid S, Abdel Maksoud A. Predictors of chronic idiopathic thrombocytopenic purpura. Pediatr Blood Cancer. 2010;54(7):959–62.PubMedGoogle Scholar
  20. Foster CB, Zhu S, Erichsen HC, Lehrnbecher T, Hart ES, Choi E, Stein S, Smith MW, Steinberg SM, Imbach P, et al. Polymorphisms in inflammatory cytokines and Fcgamma receptors in childhood chronic immune thrombocytopenic purpura: a pilot study. Br J Haematol. 2001;113(3):596–9.CrossRefPubMedGoogle Scholar
  21. Glanz J, France E, Xu S, Hayes T, Hambidge S. A population-based, multisite cohort study of the predictors of chronic idiopathic thrombocytopenic purpura in children. Pediatrics. 2008;121(3):e506–12.CrossRefPubMedGoogle Scholar
  22. Grainger JD, Locatelli F, Chotsampancharoen T, Donyush E, Pongtanakul B, Komvilaisak P, Sosothikul D, Drelichman G, Sirachainan N, Holzhauer S, et al. Eltrombopag for children with chronic immune thrombocytopenia (PETIT2): a randomised, multicentre, placebo-controlled trial. Lancet. 2015;386(10004):1649–58.CrossRefPubMedGoogle Scholar
  23. Grimaldi-Bensouda L, Nordon C, Michel M, Viallard JF, Adoue D, Magy-Bertrand N, Durand JM, Quittet P, Fain O, Bonnotte B, et al. Immune thrombocytopenia in adults: a prospective cohort study of clinical features and predictors of outcome. Haematologica. 2016;101(9):1039–45.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 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):1–10.PubMedGoogle Scholar
  25. Heitink-Polle KM, Nijsten J, Boonacker CW, de Haas M, Bruin MC. Clinical and laboratory predictors of chronic immune thrombocytopenia in children: a systematic review and meta-analysis. Blood. 2014;124(22):3295–307.CrossRefPubMedGoogle Scholar
  26. Heitink-Polle KMJ, Uiterwaal CSPM, Porcelijn L, Tamminga RYJ, Smiers FJ, van Woerden NL, Wesseling J, Laarhoven AG, de Haas M, Bruin MCA. Treatment with Intravenous Immunoglobulin Does Not Prevent Chronic Immune Thrombocytopenia in Children: Results of a Randomized Controlled Trial. Blood. 2016;128(22):866.Google Scholar
  27. Hilgartner MW, Lanzkowsky P, Smith CH. The use of azathioprine in refractory idiopathic thrombocytopenic purpura in children. Acta Paediatr Scand. 1970;59(4):409–15.CrossRefPubMedGoogle Scholar
  28. Imbach P, Kuhne T, Muller D, Berchtold W, Zimmerman S, Elalfy M, Buchanan GR. 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):351–6.CrossRefPubMedGoogle Scholar
  29. Imbach P, Wagner HP, Berchtold W, Gaedicke G, Hirt A, Joller P, Mueller-Eckhardt C, Muller B, Rossi E, Barandun S. Intravenous immunoglobulin versus oral corticosteroids in acute immune thrombocytopenic purpura in childhood. Lancet. 1985;2(8453):464–8.CrossRefPubMedGoogle Scholar
  30. Kuhne T. Update on the Intercontinental Cooperative ITP Study Group (ICIS) and on the pediatric and Adult Registry on Chronic ITP (PARC ITP). Pediatr Blood Cancer. 2013;60(Suppl 1):S15–8.CrossRefPubMedGoogle Scholar
  31. Kuhne T, Berchtold W, Michaels LA, Wu R, Donato H, Espina B, Tamary H, Rodeghiero F, Chitlur M, Rischewski J, et al. Newly diagnosed immune thrombocytopenia in children and adults: a comparative prospective observational registry of the Intercontinental Cooperative Immune Thrombocytopenia Study Group. Haematologica. 2011;96(12):1831–7.CrossRefPubMedPubMedCentralGoogle Scholar
  32. Kuhne T, Blanchette V, Buchanan GR, Ramenghi U, Donato H, Tamminga RY, Rischewski J, Berchtold W, Imbach P. 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):829–34.CrossRefPubMedGoogle Scholar
  33. Kuhne T, Buchanan GR, Zimmerman S, Michaels LA, Kohan R, Berchtold W, Imbach P, Intercontinental Childhood ITPSG, Intercontinental Childhood ITPSG. 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):605–8.CrossRefPubMedGoogle Scholar
  34. McMillan R, Wang L, Tomer A, Nichol J, Pistillo J. Suppression of in vitro megakaryocyte production by antiplatelet autoantibodies from adult patients with chronic ITP. Blood. 2004;103(4):1364–9.CrossRefPubMedGoogle Scholar
  35. Montalvo J, Velazquez D, Pantoja JP, Sierra M, Lopez-Karpovitch X, Herrera MF. Laparoscopic splenectomy for primary immune thrombocytopenia: clinical outcome and prognostic factors. J Laparoendosc Adv Surg Tech A. 2014;24(7):466–70.CrossRefPubMedGoogle Scholar
  36. Neunert CE, Buchanan GR, Imbach P, Bolton-Maggs PH, Bennett CM, Neufeld EJ, Vesely SK, Adix L, Blanchette VS, Kuhne T, et al. Severe hemorrhage in children with newly diagnosed immune thrombocytopenic purpura. Blood. 2008;112(10):4003–8.CrossRefPubMedPubMedCentralGoogle Scholar
  37. Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA. American Society of H: The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117(16):4190–207.CrossRefPubMedGoogle Scholar
  38. Papagianni A, Economou M, Tragiannidis A, Karatza E, Tsatra I, Gombakis N, Athanassiadou-Piperopoulou F, Athanasiou-Metaxa M. Standard-dose intravenous anti-D immunoglobulin versus intravenous immunoglobulin in the treatment of newly diagnosed childhood primary immune thrombocytopenia. J Pediatr Hematol Oncol. 2011;33(4):265–9.CrossRefPubMedGoogle Scholar
  39. Provan D, Moss AJ, Newland AC, Bussel JB. Efficacy of mycophenolate mofetil as single-agent therapy for refractory immune thrombocytopenic purpura. Am J Hematol. 2006;81(1):19–25.CrossRefPubMedGoogle Scholar
  40. Provan D, Newland A, Norfolk D, Bolton-Maggs P, Lilleyman J, Greer I, May A, Murphy M, Ouwehand W, Watson S, et al. Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy. Br J Haematol. 2003;120(4):574–96.CrossRefGoogle Scholar
  41. Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, Chong BH, Cines DB, Gernsheimer TB, Godeau B, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010;115(2):168–86.CrossRefPubMedGoogle Scholar
  42. Psaila B, Petrovic A, Page LK, Menell J, Schonholz M, Bussel JB. Intracranial hemorrhage (ICH) in children with immune thrombocytopenia (ITP): study of 40 cases. Blood. 2009;114(23):4777–83.CrossRefPubMedPubMedCentralGoogle Scholar
  43. Rao VK, Dugan F, Dale JK, Davis J, Tretler J, Hurley JK, Fleisher T, Puck J, Straus SE. Use of mycophenolate mofetil for chronic, refractory immune cytopenias in children with autoimmune lymphoproliferative syndrome. Br J Haematol. 2005;129(4):534–8.CrossRefPubMedGoogle Scholar
  44. Revel-Vilk S, Yacobovich J, Frank S, Ben-Ami T, Yechieli M, Shkalim V, Lebel A, Semo-Oz R, Tamary H. Age and duration of bleeding symptoms at diagnosis best predict resolution of childhood immune thrombocytopenia at 3, 6, and 12 months. J Pediatr. 2013;163(5):1335–1339 e1331–1332.CrossRefPubMedGoogle Scholar
  45. Rijcken E, Mees ST, Bisping G, Krueger K, Bruewer M, Senninger N, Mennigen R. Laparoscopic splenectomy for medically refractory immune thrombocytopenia (ITP): a retrospective cohort study on longtime response predicting factors based on consensus criteria. Int J Surg. 2014;12(12):1428–33.CrossRefPubMedGoogle Scholar
  46. Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, Bussel JB, Cines DB, Chong BH, Cooper N, 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):2386–93.CrossRefPubMedGoogle Scholar
  47. Roganovic J, Letica-Crepulja M. Idiopathic thrombocytopenic purpura: a 15-year natural history study at the Children’s Hospital Rijeka, Croatia. Pediatr Blood Cancer. 2006;47(5 Suppl):662–4.CrossRefPubMedGoogle Scholar
  48. Rosthoj S, Rajantie J, Treutiger I, Zeller B, Tedgard U, Henter JI, NOPHO ITP Working Group. Duration and morbidity of chronic immune thrombocytopenic purpura in children: five-year follow-up of a Nordic cohort. Acta Paediatr. 2012;101(7):761–6.CrossRefPubMedGoogle Scholar
  49. Saleh MN, Gutheil J, Moore M, Feinberg B, Bunch P, Butler J, Lavelle P, Kunkel L, Benyunes K, Grillo-Lopez A, et al. A pilot study of anti-CD20 MoAb Rituximab in patients with refractory immune thrombocytopenic purpura (ITP). Blood. 2000;96(11):1086.Google Scholar
  50. Sobota A, Neufeld EJ, Lapsia S, Bennett CM. Response to mercaptopurine for refractory autoimmune cytopenias in children. Pediatr Blood Cancer. 2009;52(1):80–4.CrossRefPubMedPubMedCentralGoogle Scholar
  51. Sood R, Wong W, Gotlib J, Jeng M, Zehnder JL. Gene expression and pathway analysis of immune thrombocytopenic purpura. Br J Haematol. 2008;140(1):99–103.PubMedGoogle Scholar
  52. Stasi R, Stipa E, Masi M, Cecconi M, Scimo MT, Oliva F, Sciarra A, Perrotti AP, Adomo G, Amadori S, et al. Long-term observations of 208 adults with chronic idiopathic thrombocytopenic purpura. Am J Med. 1995;98(5):436–42.CrossRefPubMedGoogle Scholar
  53. Tamminga R, Berchtold W, Bruin M, Buchanan GR, Kuhne 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):180–4.CrossRefPubMedGoogle Scholar
  54. Tarantino MD, Bussel JB, Blanchette VS, Despotovic J, Bennett C, Raj A, Williams B, Beam D, Morales J, Rose MJ, et al. Romiplostim in children with immune thrombocytopenia: a phase 3, randomised, double-blind, placebo-controlled study. Lancet. 2016;388(10039):45–54.CrossRefPubMedGoogle Scholar
  55. Watts RG. Idiopathic thrombocytopenic purpura: a 10-year natural history study at the Children’s Hospital of Alabama. Clin Pediatr (Phila). 2004;43(8):691–702.CrossRefGoogle Scholar
  56. Zeller B, Rajantie J, Hedlund-Treutiger I, Tedgard U, Wesenberg F, Jonsson AG, Henter JI, Rosthoj S, Grp NIW, Five Natl Study G. Childhood idiopathic thrombocytopenic purpura in the Nordic countries: epidemiology and predictors of chronic disease. Acta Paediatr. 2005;94(2):178–84.CrossRefPubMedGoogle Scholar
  57. Zhang B, Lo C, Shen L, Sood R, Jones C, Cusmano-Ozog K, Park-Snyder S, Wong W, Jeng M, Cowan T, et al. The role of vanin-1 and oxidative stress-related pathways in distinguishing acute and chronic pediatric ITP. Blood. 2011;117(17):4569–79.CrossRefPubMedGoogle Scholar
  58. Zufferey A, Kapur R, Semple JW. Pathogenesis and therapeutic mechanisms in immune thrombocytopenia (ITP). J Clin Med. 2017;6(2):16.CrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Emory University School of MedicineAtlantaUSA
  2. 2.Aflac Cancer and Blood Disorder Center, Children’s Healthcare of AtlantaAtlantaUSA

Personalised recommendations