REVIEW PAPER
Immune thrombocytopaenia in children and adolescents – current management and Polish perspective
 
More details
Hide details
1
Department of Paediatric Oncology, Haematology, and Transplantology, Poznań University of Medical Sciences, Poznań, Poland
 
 
Submission date: 2024-02-29
 
 
Final revision date: 2024-04-04
 
 
Acceptance date: 2024-04-06
 
 
Publication date: 2024-09-20
 
 
Corresponding author
Marta Andrzejewska
Marta Andrzejewska, MD, Department of Paediatric Oncology, Haematology, and Transplantology, Poznań University of Medical Sciences, Poznań, Poland
 
 
Pediatr Pol 2024;99(3):225-232
 
KEYWORDS
TOPICS
ABSTRACT
Immune thrombocytopaenia (ITP) is the most common cause of acquired thrombocytopaenia diagnosed in paediatric patients. It is described as an isolated thrombocytopaenia without other factors, which may cause a decrease in platelets. Therefore, the diagnosis is of exclusion. Over the last few years, its management has significantly developed, and a paradigm switch in second-line treatment is being observed. Currently, thrombopoietin receptor agonists (TPO-RA) are available in Poland, which reduce the need for splenectomy in affected patients. The use of thrombopoietin receptor agonists has also provoked a change in definitions, especially concerning refractory ITP. This review focuses on an overview of currently recommended diagnostics and treatment of ITP, ongoing research concerning genetic predisposition, the use of TPO-RA, other immunosuppressive agents, and the role of splenectomy. We summarise congenital thrombocytopaenic disorders, which are the most often mistaken as ITP and need to be considered in the differential diagnosis.
REFERENCES (60)
1.
Provan D, Arnold DM, Bussel JB, et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv 2019; 3:3780-3817.
 
2.
Maria L. Lozano. New developments in the diagnosis of primary immune thrombocytopenia. Blood Coagul Fibrinolysis Int J Haemost Thromb 2022; 33: S5-7.
 
3.
Grace RF, Lambert MP. An update on pediatric ITP: differentiating primary ITP, IPD, and PID. Blood 2022; 140: 542-555.
 
4.
Ibrahim L, Dong SX, O’Hearn K, et al. Pediatric refractory immune thrombocytopenia: a systematic review. Pediatr Blood Cancer 2023; 70: e30173.
 
5.
Neunert C, Heitink-Polle KMJ, Lambert MP. A proposal for new definition (s) and management approach to paediatric refractory ITP: reflections from the Intercontinental ITP Study Group. Br J Haematol 2023; 203: 17-22.
 
6.
Yang LP, Fu HX, Zhao P, et al. High dimensional single-cell profiling identifies immune and metabolic heterogeneity in immune thrombocytopenia. Blood 2023; 142: 2585.
 
7.
Mingot-Castellano ME, Bastida JM, Caballero-Navarro G, et al. Novel therapies to address unmet needs in ITP. Pharmaceuticals 2022; 15: 779.
 
8.
Zufferey A, Kapur R, Semple JW. Pathogenesis and therapeutic mechanisms in immune thrombocytopenia (ITP). J Clin Med 2017; 6: 16.
 
9.
Imbach P, Crowther M. Thrombopoietin-receptor agonists for primary immune thrombocytopenia. N Engl J Med 2011; 365: 734-741.
 
10.
Li Y, Fu J, Ling Y, et al. Sialylation on O-glycans protects platelets from clearance by liver Kupffer cells. Proc Natl Acad Sci U S A 2017; 114: 8360-8365.
 
11.
Cooper N, Bussel J. The pathogenesis of immune thrombocytopaenic purpura. Br J Haematol 2006; 133: 364-374.
 
12.
Castelli R, Lambertenghi Delilliers G, Gidaro A, et al. Complement activation in patients with immune thrombocytopenic purpura according to phases of disease course. Clin Exp Immunol 2020; 201: 258-265.
 
13.
Zakaria M, Al-Akhras A, Hassan T, et al. FcγRIIa and FcγRIIIa genes polymorphism in Egyptian children with primary immune thrombocytopenia. Hematol Transfus Cell Ther 2023; 45: 58-65.
 
14.
Schmidt DE, Heitink-Pollé KMJ, Laarhoven AG, et al. Transient and chronic childhood immune thrombocytopenia are distinctly affected by Fc-γ receptor polymorphisms. Blood Adv 2019; 3: 2003-2012.
 
15.
Li G, Gao L, Ma R, et al. Associations between FCGR polymorphisms and immune thrombocytopenia: a meta-analysis. Scand J Immunol 2019; 89: e12758.
 
16.
Hesham M, Hassan T, Fawzy A, et al. PTPN22 gene polymorphism as a genetic risk factor for primary immune thrombocytopenia in Egyptian children. Expert Rev Hematol 2021; 14: 877-881.
 
17.
Kim TO, Geris JM, Grimes AB, et al. Genetic variants in canonical wnt signaling pathway associated with pediatric ITP. Blood 2023; 142: 2593.
 
18.
Ismail AM, Higazi AM, Nomeir HM, et al. IL-23/Th17 pathway and IL-17A gene polymorphism in Egyptian children with immune thrombocytopenic purpura. Ital J Pediatr 2021; 47: 178.
 
19.
Ou Y, Yang Y, Xiang X, et al. Relationship between the IL-10 (-1082 A/G) polymorphism and the risk of immune/idiopathic thrombocytopenic purpura: a meta-analysis. Cytokine 2020; 125: 154820.
 
20.
Elnaenaey WA, Omar OM, Aboelwafa RA. Increased expression of IL-17A and IL-17F Is correlated with RUNX1 and RORγT in pediatric patients with primary immune thrombocytopenia. J Pediatr Hematol Oncol 2021; 43: e320-327.
 
21.
Ferreira FLB, Colella MP, Medina SS, et al. Evaluation of the immature platelet fraction contribute to the differential diagnosis of hereditary, immune and other acquired thrombocytopenias. Sci Rep 2017; 7: 3355.
 
22.
Hillier K, MacMath D, Chumsky J, et al. Immunoglobulins as a predictor of chronicity in pediatric immune thrombocytopenia. Blood 2023; 142: 2370.
 
23.
Kim TO, Grimes AB, Kirk S, et al. Association of a positive direct antiglobulin test with chronic immune thrombocytopenia and use of second line therapies in children: a multi-institutional review. Am J Hematol 2019; 94: 461-466.
 
24.
Jones NL, Koletzko S, Goodman K, et al. Joint ESPGHAN/NASPGHAN Guidelines for the Management of Helicobacter pylori in Children and Adolescents (Update 2016). J Pediatr Gastroenterol Nutr 2017; 64: 991-1003.
 
25.
González-López TJ, Provan D, Bárez A, et al. Primary and secondary immune thrombocytopenia (ITP): time for a rethink. Blood Rev 2023; 61: 101112.
 
26.
Cines DB, Liebman H, Stasi R. Pathobiology of secondary immune thrombocytopenia. Semin Hematol 2009; 46: S2-14.
 
27.
Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv 2019; 3: 3829-3866.
 
28.
Li T, Liu Q, Pu T, et al. Efficacy and safety of thrombopoietin receptor agonists in children and adults with persistent and chronic immune thrombocytopenia: a meta-analysis. Expert Opin Pharmacother 2023; 24: 763-774.
 
29.
Wang Z, Wang N, Ouyang J, et al. Long-term eltrombopag in children with chronic immune thrombocytopenia: a single-center extended real-life observational study in China. Blood 2023; 142: 2590.
 
30.
Pines M, Degliuomini M, Kaicker S. Real world practices of thrombopoietin receptor agonist use and discontinuation in pediatric patients with immune thrombocytopenia (ITP): a single center retrospective review. Blood 2023; 142: 3960.
 
31.
Neunert CE, Rose MJ. Romiplostim for the management of pediatric immune thrombocytopenia: drug development and current practice. Blood Adv 2019; 3: 1907-1915.
 
32.
Nieto M, Calvo G, Hudson I, et al. The European Medicines Agency review of eltrombopag (Revolade) for the treatment of adult chronic immune (idiopathic) thrombocytopenic purpura: summary of the scientific assessment of the Committee for Medicinal Products for Human Use. Haematologica 2011; 96: e33-40.
 
33.
Qiu KY, Liao XY, Huang K, et al. Eltrombopag as first-line treatment for thrombocytopenia among paediatric patients after allogeneic haematopoietic stem cell transplantation. Br J Clin Pharmacol 2021; 87: 2023-2031.
 
34.
An Q, Liu L, Wang D. PB2623: avatrombopag for the treatment of children with persistent and chronic immune thrombocytopenia. HemaSphere 2023; 7: e96683e8.
 
35.
Cheng X, Wang Z, Dong S, et al. Outcomes of switching to avatrombopag following treatment failure with eltrombopag in paediatric immune thrombocytopenia: a real-world study in China. Br J Haematol 2023; 202: 636-644.
 
36.
Mingot Castellano ME, Pedrote Amador B, Tomasello R, et al. Avatrombopag plus fostamatinib combination efficacy and safety in patients with immune thrombocytopenia. Blood 2023; 142: 2596.
 
37.
Ruan Y, Cao W, Luo T, et al. Avatrombopag for the treatment of thrombocytopenia in children’s patients following allogeneic hematopoietic stem-cell transplantation: a pilot study. Front Pediatr 2023; 11: 1099372.
 
38.
Jiangsu HengRui Medicine Co., Ltd. Safety and efficacy of hetrombopag in children and adolescents with chronic primary immune thrombocytopenia: a randomized, multicenter, placebo-controlled trial. clinicaltrials.gov; 2022.
 
39.
Lei Z. A multicenter, randomized, open-label study to compare the efficacy and safety of TPO-RAs combining anti-CD 20 monoclonal antibody versus TPO-RAs in persistent or chronic pediatric ITP patients who failed or relapse after hormone therapy. clinicaltrials.gov; 2023.
 
40.
Lucchini E, Zaja F, Bussel J. Rituximab in the treatment of immune thrombocytopenia: what is the role of this agent in 2019? Haematologica 2019; 104: 1124-1135.
 
41.
Ay Y, Karapinar TH, Oymak Y, et al. Retrospective analysis of rituximab therapy and splenectomy in childhood chronic and refractory immune thrombocytopenic purpura. Blood Coagul Fibrinolysis Int J Haemost Thromb 2016; 27: 431-435.
 
42.
Nazi I, Kelton JG, Larché M, et al. The effect of rituximab on vaccine responses in patients with immune thrombocytopenia. Blood 2013; 122: 1946-1953.
 
43.
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: 490-495.
 
44.
Panigrahi A, Clark A, Myers J, et al. A novel immunomodulatory treatment involving mycophenolate mofetil and corticosteroids for pediatric autoimmune cytopenias. Pediatr Blood Cancer 2017; 64: 287-293.
 
45.
pKuwana M, Ito T, Kowata S, et al. Long-term treatment with fostamatinib in japanese patients with primary immune thrombocytopenia: an open-label extension study following a phase 3 placebo-controlled, double-blind, parallel-grou study. Blood 2023; 142: 2578.
 
46.
Pinedo-Rodríguez A, Pérez-Rojas AK, Rodriguez-Rodriguez S, et al. Determinants of relapse and treatment-free survival following splenectomy in patients with immune cytopenias. Blood 2023; 142: 2587.
 
47.
Matkowska-Kocjan A. Profilaktyka zakażeń u dzieci z asplenią 2020. Available from: http://www.mp.pl/social/articl... (accessed: 13.02.2024).
 
48.
Mikołuć B, Bernatowska E, Jackowska T. Profilaktyka zakażeń u pacjentów z asplenią wrodzoną, po splenektomii lub z dysfunkcją śledziony – aktualizacja standardów postępowania. Stand Med 2011; 8: 227-233.
 
49.
Choi YU, Dominguez EP, Sherman V, et al. laparoscopic accessory splenectomy for recurrent idiopathic thrombocytopenic purpura. JSLS 2008; 12: 314-317.
 
50.
Germeshausen M, Ballmaier M. CAMT-MPL: congenital amegakaryocytic thrombocytopenia caused by MPL mutations – heterogeneity of a monogenic disorder – a comprehensive analysis of 56 patients. Haematologica 2021; 106: 2439-2448.
 
51.
Tirthani E, Said MS, De Jesus O. Amegakaryocytic thrombocytopenia. StatPearls, Treasure Island (FL): StatPearls Publishing 2024.
 
52.
Bastida JM, Gonzalez-Porras JR, Rivera J, et al. Role of thrombopoietin receptor agonists in inherited Thrombocytopenia. Int J Mol Sci 2021; 22: 4330.
 
53.
Althaus K, Greinacher A. MYH-9 related platelet disorders: strategies for management and diagnosis. Transfus Med Hemotherapy 2010; 37: 260-267.
 
54.
Seri M, Pecci A, Di Bari F, et al. MYH9-related disease: May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but represent a variable expression of a single illness. Medicine (Baltimore) 2003; 82: 203-215.
 
55.
Chojnowski K, Klukowska A, Łętowska M, et al. Management of inherited thrombocytopenia. Recommendations of the Group on Hemostasis of the Polish Society of Hematology and Transfusion Medicine, 2019. J Transfus Med 2020; 13: 16-28.
 
56.
Malik MA, Masab M. Wiskott-Aldrich Syndrome. StatPearls, Treasure Island (FL): StatPearls Publishing 2024.
 
57.
Bildik HN, Cagdas D, Ozturk Kura A, et al. Clinical, laboratory features and clinical courses of patients with wiskott aldrich syndrome and X-linked thrombocytopenia – a single center study. Immunol Invest 2022; 51: 1272-1283.
 
58.
Almomani MH, Mangla A. Bernard-Soulier Syndrome. StatPearls, Treasure Island (FL): StatPearls Publishing 2024.
 
59.
Reisi N. Bernard-Soulier syndrome or idiopathic thrombocytopenic purpura: a case series. Casp J Intern Med 2020; 11: 105-109.
 
60.
Sarıdoğan E, Onat T, Arda Düz S, et al. Bernard-Soulier syndrome from the perspective of the obstetrician: a case report with a review of the literature. Z Geburtshilfe Neonatol 2023; 227: 168-178.
 
Journals System - logo
Scroll to top