Immune thrombocytopenia (ITP) in children: Management of chronic disease
- James B Bussel, MD
James B Bussel, MD
- Emeritus Professor of Pediatrics, Pediatric Hematology
- Weill Medical College of Cornell University
Immune thrombocytopenia (ITP) of childhood is characterized by isolated thrombocytopenia (platelet count <100,000/microL, with normal white blood cell count and hemoglobin). The cause of ITP remains unknown in most cases, but it can be triggered by a preceding viral infection. ITP was previously known as idiopathic thrombocytopenic purpura or immune thrombocytopenic purpura. The current term Immune ThrombocytoPenia preserves the widely-recognized acronym "ITP" and acknowledges the immune-mediated mechanism of the disorder, while allowing that patients may have little or no signs of purpura or bleeding .
ITP in children often resolves spontaneously within three months. Up to 20 percent of affected children will go on to have chronic ITP, which is defined as thrombocytopenia for more than 12 months since presentation [1-3]. (See "Immune thrombocytopenia (ITP) in children: Initial management", section on 'Disease course'.)
The treatment and prognosis of chronic ITP and chronic refractory in children will be reviewed here. The epidemiology, diagnosis, and initial management of ITP in children are discussed separately. (See "Immune thrombocytopenia (ITP) in children: Clinical features and diagnosis" and "Immune thrombocytopenia (ITP) in children: Initial management".)
Approximately 10 to 20 percent of children who present with immune thrombocytopenia (ITP) will develop chronic ITP, defined as thrombocytopenia (platelet count <100,000/microL) continuing beyond 12 months from the time of presentation [4,5]. Risk factors for developing chronic ITP include older age, less severe thrombocytopenia at the initial diagnosis, insidious onset of symptoms, and lack of preceding infection or vaccination prior to development of ITP. (See "Immune thrombocytopenia (ITP) in children: Initial management", section on 'Disease course'.)
At the initial presentation of a child with symptoms suggestive of immune thrombocytopenia (ITP), a basic evaluation should be performed to exclude other causes of thrombocytopenia, including a focused history and physical examination, and laboratory testing consisting of a complete blood count (CBC) with a reticulocyte count, differential white blood cell count and red blood cell indices, and direct antiglobulin test (DAT, also known as a direct Coombs test) (table 1). Children with lymphadenopathy, splenomegaly, systemic symptoms, or any abnormalities in the CBC or peripheral blood smear, should promptly undergo further investigation to exclude other causes of thrombocytopenia. This initial diagnostic evaluation is discussed in detail in a separate topic review. (See "Immune thrombocytopenia (ITP) in children: Clinical features and diagnosis", section on 'Diagnosis'.)
- 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; 113:2386.
- Donato H, Picón A, Martinez M, et al. Demographic data, natural history, and prognostic factors of idiopathic thrombocytopenic purpura in children: a multicentered study from Argentina. Pediatr Blood Cancer 2009; 52:491.
- 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; 46:351.
- Rosthøj S, Rajantie J, Treutiger I, et al. Duration and morbidity of chronic immune thrombocytopenic purpura in children: five-year follow-up of a Nordic cohort. Acta Paediatr 2012; 101:761.
- Neunert CE, Buchanan GR, Imbach P, et al. Bleeding manifestations and management of children with persistent and chronic immune thrombocytopenia: data from the Intercontinental Cooperative ITP Study Group (ICIS). Blood 2013; 121:4457.
- Stasi R, Pagano A, Stipa E, Amadori S. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura. Blood 2001; 98:952.
- Wang J, Wiley JM, Luddy R, et al. Chronic immune thrombocytopenic purpura in children: assessment of rituximab treatment. J Pediatr 2005; 146:217.
- Parodi E, Rivetti E, Amendola G, et al. Long-term follow-up analysis after rituximab therapy in children with refractory symptomatic ITP: identification of factors predictive of a sustained response. Br J Haematol 2009; 144:552.
- Patel VL, Mahévas M, Lee SY, et al. Outcomes 5 years after response to rituximab therapy in children and adults with immune thrombocytopenia. Blood 2012; 119:5989.
- Bussel JB, Lee CS, Seery C, et al. Rituximab and three dexamethasone cycles provide responses similar to splenectomy in women and those with immune thrombocytopenia of less than two years duration. Haematologica 2014; 99:1264.
- Carson KR, Evens AM, Richey EA, 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; 113:4834.
- http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm459430.htm (Accessed on September 09, 2015).
- Grainger JD, Locatelli F, Chotsampancharoen T, et al. Eltrombopag for children with chronic immune thrombocytopenia (PETIT2): a randomised, multicentre, placebo-controlled trial. Lancet 2015; 386:1649.
- Bussel JB, de Miguel PG, Despotovic JM, et al. Eltrombopag for the treatment of children with persistent and chronic immune thrombocytopenia (PETIT): a randomised, multicentre, placebo-controlled study. Lancet Haematol 2015; 2:e315.
- Bussel JB, Buchanan GR, Nugent DJ, et al. A randomized, double-blind study of romiplostim to determine its safety and efficacy in children with immune thrombocytopenia. Blood 2011; 118:28.
- Bussel JB, Hsieh L, Buchanan GR, et al. Long-term use of the thrombopoietin-mimetic romiplostim in children with severe chronic immune thrombocytopenia (ITP). Pediatr Blood Cancer 2015; 62:208.
- Mokhtar GM, Tantawy AA, El Sherif NH. Romiplostim therapy in children with unresponsive chronic immune thrombocytopenia. Platelets 2012; 23:264.
- Escudero Vilaplana V, Aragonés JH, Fernández-Llamazares CM, et al. Use of romiplostim for primary immune thrombocytopenia in children. Pediatr Hematol Oncol 2012; 29:197.
- Pasquet M, Aladjidi N, Guiton C, et al. Romiplostim in children with chronic immune thrombocytopenia (ITP): the French experience. Br J Haematol 2014; 164:266.
- Ramaswamy K, Hsieh L, Leven E, et al. Thrombopoietic agents for the treatment of persistent and chronic immune thrombocytopenia in children. J Pediatr 2014; 165:600.
- Neunert C, Despotovic J, Haley K, et al. Thrombopoietin Receptor Agonist Use in Children: Data From the Pediatric ITP Consortium of North America ICON2 Study. Pediatr Blood Cancer 2016; 63:1407.
- Tarantino MD, Bussel JB, Blanchette VS, et al. Romiplostim in children with immune thrombocytopenia: a phase 3, randomised, double-blind, placebo-controlled study. Lancet 2016; 388:45.
- Hilgartner MW, Lanzkowsky P, Smith CH. The use of azathioprine in refractory idiopathic thrombocytopenic purpura in children. Acta Paediatr Scand 1970; 59:409.
- Boruchov DM, Gururangan S, Driscoll MC, Bussel JB. Multiagent induction and maintenance therapy for patients with refractory immune thrombocytopenic purpura (ITP). Blood 2007; 110:3526.
- Gombakis N, Trahana M, Athanassiou M, Kanakoudi-Tsakalidou F. Evans syndrome: successful management with multi-agent treatment including intermediate-dose intravenous cyclophosphamide. J Pediatr Hematol Oncol 1999; 21:248.
- Liu AP, Cheuk DK, Lee AH, et al. Cyclosporin A for persistent or chronic immune thrombocytopenia in children. Ann Hematol 2016; 95:1881.
- Perrotta S, Amendola G, Locatelli F, et al. Treatment with short-term, high-dose cyclosporin A in children with refractory chronic idiopathic thrombocytopenic purpura. Br J Haematol 2003; 121:143.
- Gesundheit B, Cividalli G, Freeman A, et al. Cyclosporin A in the treatment of refractory immune thrombocytopenia purpura in children. Eur J Haematol 2001; 66:347.
- Williams JA, Boxer LA. Combination therapy for refractory idiopathic thrombocytopenic purpura in adolescents. J Pediatr Hematol Oncol 2003; 25:232.
- Patel AP, Patil AS. Dapsone for immune thrombocytopenic purpura in children and adults. Platelets 2015; 26:164.
- Sobota A, Neufeld EJ, Lapsia S, Bennett CM. Response to mercaptopurine for refractory autoimmune cytopenias in children. Pediatr Blood Cancer 2009; 52:80.
- Panigrahi A, Clark A, Myers J, Raj A. A novel immunomodulatory treatment involving mycophenolate mofetil and corticosteroids for pediatric autoimmune cytopenias. Pediatr Blood Cancer 2017; 64:287.
- Miano M, Ramenghi U, Russo G, et al. Mycophenolate mofetil for the treatment of children with immune thrombocytopenia and Evans syndrome. A retrospective data review from the Italian association of paediatric haematology/oncology. Br J Haematol 2016; 175:490.
- Wood JH, Partrick DA, Hays T, Ziegler MM. Predicting response to splenectomy in children with immune thrombocytopenic purpura. J Pediatr Surg 2010; 45:140.
- Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 2011; 117:4190.
- Katkhouda N, Mavor E. Laparoscopic splenectomy. Surg Clin North Am 2000; 80:1285.
- Lilleyman JS. Management of childhood idiopathic thrombocytopenic purpura. Br J Haematol 1999; 105:871.
- Rørholt M, Ghanima W, Farkas DK, Nørgaard M. Risk of cardiovascular events and pulmonary hypertension following splenectomy - a Danish population-based cohort study from 1996-2012. Haematologica 2017; 102:1333.
- Schwartz J, Leber MD, Gillis S, et al. Long term follow-up after splenectomy performed for immune thrombocytopenic purpura (ITP). Am J Hematol 2003; 72:94.
- Medeiros D, Buchanan GR. Current controversies in the management of idiopathic thrombocytopenic purpura during childhood. Pediatr Clin North Am 1996; 43:757.
- 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.
- Psaila B, Petrovic A, Page LK, et al. Intracranial hemorrhage (ICH) in children with immune thrombocytopenia (ITP): study of 40 cases. Blood 2009; 114:4777.
- Supportive care
- Pharmacologic therapy
- - First-line therapies
- - Second-line therapies
- Thrombopoietin receptor agonists
- - Our approach
- - Specific agents
- Other agents
- Adjunctive therapies
- Spontaneous remission
- Bleeding risk
- CHRONIC REFRACTORY ITP
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