OncohematologyOncohematologyОнкогематология1818-83462413-4023Publishing House ABV Press93510.17650/1818-8346-2024-19-3-34-44NEW DIRECTIONS, DIAGNOSTIC OPPORTUNITIES, AND TREATMENT ADVANCESНОВЫЕ НАПРАВЛЕНИЯ, ВОЗМОЖНОСТИ ДИАГНОСТИКИ И УСПЕХИ ЛЕЧЕНИЯImmune thrombocytopenia: literature reviewИммунная тромбоцитопения: обзор литературыhttps://orcid.org/0000-0003-2847-4374ZakharovS. G.ЗахаровС. Г.
Russian Federation

Sergey G. Zakharov 

61 / 2 Shchepkina St., Moscow 129110

Сергей Геннадьевич Захаров

129110 Москва, ул. Щепкина, 61 / 2

hematologymoniki@mail.ruM. F. Vladimirskiy Moscow Regional Research Clinical InstituteГБУЗ МО «Московский областной научно-исследовательский клинический институт им. М. Ф. Владимирского»0309202419334440109202401092024https://oncohematology.abvpress.ru/ongm/article/view/935

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by a decrease in platelet count, which often leads to bleeding. Evidence suggests that low platelet counts in ITP are the result of multiple factors, including impaired thrombocytopoiesis and changes in the immune response leading to platelet destruction. ITP is a heterogeneous disease with a course that is difficult to predict. In a significant number of cases, ITP becomes chronic, requiring long-term maintenance treatment, which leads to an increased risk of hemorrhagic complications and a decrease in quality of life. A deeper understanding ofthe etiology and pathogenesis ofthis disease makesit possible to identify potentialtherapeutic targets for the development of new effective treatments. This review summarizes recent advances in understanding the ITP pathophysiology, evaluating current therapeutic strategies and methods for predicting therapy response.

Иммунная тромбоцитопения (ИТП) – аутоиммунное заболевание, сопровождающееся снижением количества тромбоцитов, что зачастую приводит к развитию кровотечений. Имеющиеся данные свидетельствуют о том, что низкое количество тромбоцитов при ИТП – результат действия множества факторов, включая нарушение тромбоцитопоэза и изменения иммунного ответа, приводящих к разрушению тромбоцитов. ИТП – гетерогенное заболевание с трудно прогнозируемым течением. В значительном количестве случаев оно переходит в хроническую форму, требующую длительного поддерживающего лечения, что приводит к повышению риска геморрагических осложнений и снижению качества жизни. Более глубокое понимание этиологии и патогенеза этого заболевания позволяет выявить потенциальные терапевтические мишени для разработки новых эффективных методов лечения. В данном обзоре суммированы последние достижения в изучении патофизиологии ИТП, дана оценка текущих терапевтических стратегий и методов прогнозирования ответа на терапию.

idiopathic thrombocytopenic purpuraimmune thrombocytopeniaидиопатическая тромбоцитопеническая пурпураиммунная тромбоцитопения1. Vrbensky J. The Characterization of CD8+ T cells as a potential mechanism of disease in immune thrombocytopenia. PhD thesis, Hamilton, Ontario, Canada: McMaster University, 2022.Vrbensky J. The Characterization of CD8+ T cells as a potential mechanism of disease in immune thrombocytopenia. PhD thesis, Hamilton, Ontario, Canada: McMaster University, 2022.2. Neunert C., Lim W., Crowther M. et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 2011;117(16):4190–207. DOI: 10.1182/blood-2010-08-302984Neunert C., Lim W., Crowther M. et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 2011;117(16):4190–207. DOI: 10.1182/blood-2010-08-3029843. Moulis G., Palmaro A., Montastruc J.L. et al. Epidemiology of incident immune thrombocytopenia: a nationwide populationbased study in France. Blood 2014;124(22):3308–15. DOI: 10.1182/blood-2014-05-578336Moulis G., Palmaro A., Montastruc J.L. et al. Epidemiology of incident immune thrombocytopenia: a nationwide populationbased study in France. Blood 2014;124(22):3308–15. DOI: 10.1182/blood-2014-05-5783364. Neunert C., Terrell D.R., Arnold D.M. et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia [published correction appears in Blood Adv 2020;4(2):252]. Blood Adv 2019;3(23):3829–66. DOI: 10.1182/bloodadvances.2019000966Neunert C., Terrell D.R., Arnold D.M. et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia [published correction appears in Blood Adv 2020;4(2):252]. Blood Adv 2019;3(23):3829–66. DOI: 10.1182/bloodadvances.20190009665. Bakchoul T., Sachs U.J. Platelet destruction in immune thrombocytopenia. Understanding the mechanisms. Hamostaseologie 2016;36(3):187–94. DOI: 10.5482/HAMO-14-09-0043Bakchoul T., Sachs U.J. Platelet destruction in immune thrombocytopenia. Understanding the mechanisms. Hamostaseologie 2016;36(3):187–94. DOI: 10.5482/HAMO-14-09-00436. Zhao Z., Yang L., Yang G. et al. Contributions of T lymphocyte abnormalities to therapeutic outcomes in newly diagnosed patients with immune thrombocytopenia. PLoS One 2015;10(5):e0126601. DOI: 10.1371/journal.pone.0126601Zhao Z., Yang L., Yang G. et al. Contributions of T lymphocyte abnormalities to therapeutic outcomes in newly diagnosed patients with immune thrombocytopenia. PLoS One 2015;10(5):e0126601. DOI: 10.1371/journal.pone.01266017. Ji X., Zhang L., Peng J., Hou M. T cell immune abnormalities in immune thrombocytopenia. J Hematol Oncol 2014;7:72. DOI: 10.1186/s13045-014-0072-6Ji X., Zhang L., Peng J., Hou M. T cell immune abnormalities in immune thrombocytopenia. J Hematol Oncol 2014;7:72. DOI: 10.1186/s13045-014-0072-68. Marini I., Bakchoul T. Pathophysiology of autoimmune thrombocytopenia: current insight with a focus on thrombopoiesis. Hamostaseologie 2019;39(3):227–37. DOI: 10.1055/s-0039-1678732Marini I., Bakchoul T. Pathophysiology of autoimmune thrombocytopenia: current insight with a focus on thrombopoiesis. Hamostaseologie 2019;39(3):227–37. DOI: 10.1055/s-0039-16787329. Zhang F., Chu X., Wang L. et al. Cell-mediated lysis of autologous platelets in chronic idiopathic thrombocytopenic purpura. Eur J Haematol 2006;76(5):427–31. DOI: 10.1111/j.1600-0609.2005.00622.xZhang F., Chu X., Wang L. et al. Cell-mediated lysis of autologous platelets in chronic idiopathic thrombocytopenic purpura. Eur J Haematol 2006;76(5):427–31. DOI: 10.1111/j.1600-0609.2005.00622.x10. Bakchoul T., Walek K., Krautwurst A. et al. Glycosylation of autoantibodies: insights into the mechanisms of immune thrombocytopenia. Thromb Haemost 2013;110(6):1259–66. DOI: 10.1160/TH13-04-0294Bakchoul T., Walek K., Krautwurst A. et al. Glycosylation of autoantibodies: insights into the mechanisms of immune thrombocytopenia. Thromb Haemost 2013;110(6):1259–66. DOI: 10.1160/TH13-04-029411. Vrbensky J.R., Nazy I., Clare R. et al. T cell-mediated autoimmunity in immune thrombocytopenia. Eur J Haematol 2022;108(1):18–27. DOI: 10.1111/ejh.13705Vrbensky J.R., Nazy I., Clare R. et al. T cell-mediated autoimmunity in immune thrombocytopenia. Eur J Haematol 2022;108(1):18–27. DOI: 10.1111/ejh.1370512. Nieswandt B., Bergmeier W., Schulte V. et al. Expression and function of the mouse collagen receptor glycoprotein VI is strictly dependent on its association with the FcRgamma chain. J Biol Chem 2000;275(31):23998–4002. DOI: 10.1074/jbc.M003803200Nieswandt B., Bergmeier W., Schulte V. et al. Expression and function of the mouse collagen receptor glycoprotein VI is strictly dependent on its association with the FcRgamma chain. J Biol Chem 2000;275(31):23998–4002. DOI: 10.1074/jbc.M00380320013. Webster M.L., Sayeh E., Crow M. et al. Relative efficacy of intravenous immunoglobulin G in ameliorating thrombocytopenia induced by antiplatelet GPIIbIIIa versus GPIbalpha antibodies. Blood 2006;108(3):943–6. DOI: 10.1182/blood-2005-06-009761Webster M.L., Sayeh E., Crow M. et al. Relative efficacy of intravenous immunoglobulin G in ameliorating thrombocytopenia induced by antiplatelet GPIIbIIIa versus GPIbalpha antibodies. Blood 2006;108(3):943–6. DOI: 10.1182/blood-2005-06-00976114. Li J., van der Wal D.E., Zhu G. et al. Desialylation is a mechanism of Fc-independent platelet clearance and a therapeutic target in immune thrombocytopenia. Nat Commun 2015;6:7737. DOI: 10.1038/ncomms8737Li J., van der Wal D.E., Zhu G. et al. Desialylation is a mechanism of Fc-independent platelet clearance and a therapeutic target in immune thrombocytopenia. Nat Commun 2015;6:7737. DOI: 10.1038/ncomms873715. Qiu J., Liu X., Li X. et al. CD8(+) T cells induce platelet clearance in the liver via platelet desialylation in immune thrombocytopenia. Sci Rep 2016;6:27445. DOI: 10.1038/srep27445Qiu J., Liu X., Li X. et al. CD8(+) T cells induce platelet clearance in the liver via platelet desialylation in immune thrombocytopenia. Sci Rep 2016;6:27445. DOI: 10.1038/srep2744516. Tao L., Zeng Q., Li J. et al. Platelet desialylation correlates with efficacy of first-line therapies for immune thrombocytopenia. J Hematol Oncol 2017;10(1):46. DOI: 10.1186/s13045-017-0413-3Tao L., Zeng Q., Li J. et al. Platelet desialylation correlates with efficacy of first-line therapies for immune thrombocytopenia. J Hematol Oncol 2017;10(1):46. DOI: 10.1186/s13045-017-0413-317. Quach M.E., Dragovich M.A., Chen W. et al. Fc-independent immune thrombocytopenia via mechanomolecular signaling in platelets. Blood 2018;131(7):787–96. DOI: 10.1182/blood-2017-05-784975Quach M.E., Dragovich M.A., Chen W. et al. Fc-independent immune thrombocytopenia via mechanomolecular signaling in platelets. Blood 2018;131(7):787–96. DOI: 10.1182/blood-2017-05-78497518. Marini I., Zlamal J., Faul C. et al. Autoantibody-mediated desialylation impairs human thrombopoiesis and platelet lifespan. Haematologica 2021;106(1):196–207. DOI: 10.3324/haematol.2019.236117Marini I., Zlamal J., Faul C. et al. Autoantibody-mediated desialylation impairs human thrombopoiesis and platelet lifespan. Haematologica 2021;106(1):196–207. DOI: 10.3324/haematol.2019.23611719. Mason K.D., Carpinelli M.R., Fletcher J.I. et al. Programmed anuclear cell death delimits platelet life span. Cell 2007;128(6):1173–86. DOI: 10.1016/j.cell.2007.01.037Mason K.D., Carpinelli M.R., Fletcher J.I. et al. Programmed anuclear cell death delimits platelet life span. Cell 2007;128(6):1173–86. DOI: 10.1016/j.cell.2007.01.03720. Van der Wal D.E., Gitz E., Du V.X. et al. Arachidonic acid depletion extends survival of cold-stored platelets by interfering with the [glycoprotein Ibα-14-3-3ζ] association. Haematologica 2012;97(10):1514–22. DOI: 10.3324/haematol.2011.059956Van der Wal D.E., Gitz E., Du V.X. et al. Arachidonic acid depletion extends survival of cold-stored platelets by interfering with the [glycoprotein Ibα-14-3-3ζ] association. Haematologica 2012;97(10):1514–22. DOI: 10.3324/haematol.2011.05995621. Li J.Q., Tian J.M., Fan X.R. et al. miR-106b-5p induces immune imbalance of Treg/Th17 in immune thrombocytopenic purpura through NR4A3/Foxp3 pathway [published correction appears in Cell Cycle 2020;19(15):1994–5]. Cell Cycle 2020;19(11): 1265–74. DOI:10.1080/15384101.2020.1746485Li J.Q., Tian J.M., Fan X.R. et al. miR-106b-5p induces immune imbalance of Treg/Th17 in immune thrombocytopenic purpura through NR4A3/Foxp3 pathway [published correction appears in Cell Cycle 2020;19(15):1994–5]. Cell Cycle 2020;19(11): 1265–74. DOI:10.1080/15384101.2020.174648522. Wu D., Liu Y., Pang N. et al. PD-1/PD-L1 pathway activation restores the imbalance of Th1/Th2 and Treg/Th17 cells subtypes in immune thrombocytopenic purpura patients. Medicine (Baltimore) 2019;98(43):e17608. DOI: 10.1097/MD.0000000000017608Wu D., Liu Y., Pang N. et al. PD-1/PD-L1 pathway activation restores the imbalance of Th1/Th2 and Treg/Th17 cells subtypes in immune thrombocytopenic purpura patients. Medicine (Baltimore) 2019;98(43):e17608. DOI: 10.1097/MD.000000000001760823. Li Q., Liu Y., Wang X. et al. Regulation of Th1/Th2 and Th17/Treg by pDC/mDC imbalance in primary immune thrombocytopenia. Exp Biol Med (Maywood) 2021;246(15):1688–97. DOI: 10.1177/15353702211009787Li Q., Liu Y., Wang X. et al. Regulation of Th1/Th2 and Th17/Treg by pDC/mDC imbalance in primary immune thrombocytopenia. Exp Biol Med (Maywood) 2021;246(15):1688–97. DOI: 10.1177/1535370221100978724. Alvarez Román M.T., Fernández Bello I., Arias-Salgado E.G. et al. Effects of thrombopoietin receptor agonists on procoagulant state in patients with immune thrombocytopenia. Thromb Haemost 2014;112(1):65–72. DOI: 10.1160/TH13-10-0873Alvarez Román M.T., Fernández Bello I., Arias-Salgado E.G. et al. Effects of thrombopoietin receptor agonists on procoagulant state in patients with immune thrombocytopenia. Thromb Haemost 2014;112(1):65–72. DOI: 10.1160/TH13-10-087325. Winkler J., Kroiss S., Rand M.L. et al. Platelet apoptosis in paediatric immune thrombocytopenia is ameliorated by intravenous immunoglobulin. Br J Haematol 2012;156(4):508–15. DOI: 10.1111/j.1365-2141.2011.08973.xWinkler J., Kroiss S., Rand M.L. et al. Platelet apoptosis in paediatric immune thrombocytopenia is ameliorated by intravenous immunoglobulin. Br J Haematol 2012;156(4):508–15. DOI: 10.1111/j.1365-2141.2011.08973.x26. Goette N.P., Glembotsky A.C., Lev P.R. et al. Platelet apoptosis in adult immune thrombocytopenia: insights into the mechanism of damage triggered by auto-antibodies. PLoS One 2016;11(8):e0160563. DOI: 10.1371/journal.pone.0160563Goette N.P., Glembotsky A.C., Lev P.R. et al. Platelet apoptosis in adult immune thrombocytopenia: insights into the mechanism of damage triggered by auto-antibodies. PLoS One 2016;11(8):e0160563. DOI: 10.1371/journal.pone.016056327. McMillan R., Luiken G.A., Levy R. et al. Antibody against megakaryocytes in idiopathic thrombocytopenic purpura. JAMA 1978;239(23):2460–2. DOI: 10.1001/jama.239.23.2460McMillan R., Luiken G.A., Levy R. et al. Antibody against megakaryocytes in idiopathic thrombocytopenic purpura. JAMA 1978;239(23):2460–2. DOI: 10.1001/jama.239.23.246028. Takahashi R., Sekine N., Nakatake T. Influence of monoclonal antiplatelet glycoprotein antibodies on in vitro human megakaryocyte colony formation and proplatelet formation. Blood 1999;93(6):1951–8.Takahashi R., Sekine N., Nakatake T. Influence of monoclonal antiplatelet glycoprotein antibodies on in vitro human megakaryocyte colony formation and proplatelet formation. Blood 1999;93(6):1951–8.29. Zeng D.F., Chen F., Wang S. et al. Autoantibody against integrin αv β3 contributes to thrombocytopenia by blocking the migration and adhesion of megakaryocytes. J Thromb Haemost 2018;16(9):1843–56. DOI: 10.1111/jth.14214Zeng D.F., Chen F., Wang S. et al. Autoantibody against integrin αv β3 contributes to thrombocytopenia by blocking the migration and adhesion of megakaryocytes. J Thromb Haemost 2018;16(9):1843–56. DOI: 10.1111/jth.1421430. McMillan R., Wang L., Tomer A. et al. Suppression of in vitro megakaryocyte production by antiplatelet autoantibodies from adult patients with chronic ITP. Blood 2004;103(4):1364–9. DOI: 10.1182/blood-2003-08-2672McMillan R., Wang L., Tomer A. et al. Suppression of in vitro megakaryocyte production by antiplatelet autoantibodies from adult patients with chronic ITP. Blood 2004;103(4):1364–9. DOI: 10.1182/blood-2003-08-267231. Yang L., Wang L., Zhao C.H. et al. Contributions of TRAILmediated megakaryocyte apoptosis to impaired megakaryocyte and platelet production in immune thrombocytopenia. Blood 2010;116(20):4307–16. DOI: 10.1182/blood-2010-02-267435Yang L., Wang L., Zhao C.H. et al. Contributions of TRAILmediated megakaryocyte apoptosis to impaired megakaryocyte and platelet production in immune thrombocytopenia. Blood 2010;116(20):4307–16. DOI: 10.1182/blood-2010-02-26743532. Radley J.M., Haller C.J. Fate of senescent megakaryocytes in the bone marrow. Br J Haematol 1983;53(2):277–87. DOI: 10.1111/j.1365-2141.1983.tb02022.xRadley J.M., Haller C.J. Fate of senescent megakaryocytes in the bone marrow. Br J Haematol 1983;53(2):277–87. DOI: 10.1111/j.1365-2141.1983.tb02022.x33. Houwerzijl E.J., Blom N.R., van der Want J.J. et al. Ultrastructural study shows morphologic features of apoptosis and para-apoptosis in megakaryocytes from patients with idiopathic thrombocytopenic purpura. Blood 2004;103(2):500–6. DOI: 10.1182/blood-2003-01-0275Houwerzijl E.J., Blom N.R., van der Want J.J. et al. Ultrastructural study shows morphologic features of apoptosis and para-apoptosis in megakaryocytes from patients with idiopathic thrombocytopenic purpura. Blood 2004;103(2):500–6. DOI: 10.1182/blood-2003-01-027534. Vrbensky J.R., Nazy I., Toltl L.J. et al. Megakaryocyte apoptosis in immune thrombocytopenia. Platelets 2018;29(7):729–32. DOI: 10.1080/09537104.2018.1475637Vrbensky J.R., Nazy I., Toltl L.J. et al. Megakaryocyte apoptosis in immune thrombocytopenia. Platelets 2018;29(7):729–32. DOI: 10.1080/09537104.2018.147563735. Hou Y., Feng Q., Xu M. et al. High-dose dexamethasone corrects impaired myeloid-derived suppressor cell function via Ets1 in immune thrombocytopenia. Blood 2016;127(12):1587–97. DOI: 10.1182/blood-2015-10-674531Hou Y., Feng Q., Xu M. et al. High-dose dexamethasone corrects impaired myeloid-derived suppressor cell function via Ets1 in immune thrombocytopenia. Blood 2016;127(12):1587–97. DOI: 10.1182/blood-2015-10-67453136. Hou Y., Xie J., Wang S. et al. Glucocorticoid receptor modulates myeloid-derived suppressor cell function via mitochondrial metabolism in immune thrombocytopenia. Cell Mol Immunol 2022;19(7):764–76. DOI: 10.1038/s41423-022-00859-0Hou Y., Xie J., Wang S. et al. Glucocorticoid receptor modulates myeloid-derived suppressor cell function via mitochondrial metabolism in immune thrombocytopenia. Cell Mol Immunol 2022;19(7):764–76. DOI: 10.1038/s41423-022-00859-037. Dai L., He L., Wang Z. et al. Altered circulating T follicular helper cells in patients with chronic immune thrombocytopenia. Exp Ther Med 2018;16(3):2471–7. DOI: 10.3892/etm.2018.6508Dai L., He L., Wang Z. et al. Altered circulating T follicular helper cells in patients with chronic immune thrombocytopenia. Exp Ther Med 2018;16(3):2471–7. DOI: 10.3892/etm.2018.650838. Chen Y., Luo L., Zheng Y. et al. Association of platelet desialylation and circulating follicular helper T cells in patients with thrombocytopenia. Front Immunol 2022;13:810620. DOI: 10.3389/fimmu.2022.810620Chen Y., Luo L., Zheng Y. et al. Association of platelet desialylation and circulating follicular helper T cells in patients with thrombocytopenia. Front Immunol 2022;13:810620. DOI: 10.3389/fimmu.2022.81062039. Hassan T., Abdel Rahman D., Raafat N. et al. Contribution of interleukin 27 serum level to pathogenesis and prognosis in children with immune thrombocytopenia. Medicine (Baltimore) 2022;101(25):e29504. DOI: 10.1097/MD.0000000000029504Hassan T., Abdel Rahman D., Raafat N. et al. Contribution of interleukin 27 serum level to pathogenesis and prognosis in children with immune thrombocytopenia. Medicine (Baltimore) 2022;101(25):e29504. DOI: 10.1097/MD.000000000002950440. Neylon A.J., Saunders P.W., Howard M.R. et al. Clinically significant newly presenting autoimmune thrombocytopenic purpura in adults: a prospective study of a population-based cohort of 245 patients. Br J Haematol 2003;122(6):966–74. DOI: 10.1046/j.1365-2141.2003.04547.xNeylon A.J., Saunders P.W., Howard M.R. et al. Clinically significant newly presenting autoimmune thrombocytopenic purpura in adults: a prospective study of a population-based cohort of 245 patients. Br J Haematol 2003;122(6):966–74. DOI: 10.1046/j.1365-2141.2003.04547.x41. Lee J.Y., Lee J.H., Lee H. et al. Epidemiology and management of primary immune thrombocytopenia: a nationwide populationbased study in Korea. Thromb Res 2017;155:86–91. DOI: 10.1016/j.thromres.2017.05.010Lee J.Y., Lee J.H., Lee H. et al. Epidemiology and management of primary immune thrombocytopenia: a nationwide populationbased study in Korea. Thromb Res 2017;155:86–91. DOI: 10.1016/j.thromres.2017.05.01042. Schoonen W.M., Kucera G., Coalson J. et al. Epidemiology of immune thrombocytopenic purpura in the General Practice Research Database [published correction appears in Br J Haematol 2009;147(1):157]. Br J Haematol 2009;145(2):235–44. DOI: 10.1111/j.1365-2141.2009.07615.xSchoonen W.M., Kucera G., Coalson J. et al. Epidemiology of immune thrombocytopenic purpura in the General Practice Research Database [published correction appears in Br J Haematol 2009;147(1):157]. Br J Haematol 2009;145(2):235–44. DOI: 10.1111/j.1365-2141.2009.07615.x43. Kühne T., Buchanan G.R., Zimmerman S. 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):605–8. DOI: 10.1067/s0022-3476(03)00535-3Kühne T., Buchanan G.R., Zimmerman S. 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):605–8. DOI: 10.1067/s0022-3476(03)00535-344. 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):351–6. DOI: 10.1002/pbc.20453Imbach 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):351–6. DOI: 10.1002/pbc.2045345. Jaime-Pérez J.C., Aguilar-Calderón P., Jiménez-Castillo R.A. et al. Treatment outcomes and chronicity predictors for primary immune thrombocytopenia: 10-year data from an academic center. Ann Hematol 2020;99(11):2513–20. DOI: 10.1007/s00277-020-04257-2Jaime-Pérez J.C., Aguilar-Calderón P., Jiménez-Castillo R.A. et al. Treatment outcomes and chronicity predictors for primary immune thrombocytopenia: 10-year data from an academic center. Ann Hematol 2020;99(11):2513–20. DOI: 10.1007/s00277-020-04257-246. Matzdorff A., Meyer O., Ostermann H. et al. Immune thrombocytopenia – current diagnostics and therapy: recommendations of a Joint Working Group of DGHO, ÖGHO, SGH, GPOH and DGTI. Oncol Res Treat 2018;41(Suppl 5):1–30. DOI: 10.1159/000492187Matzdorff A., Meyer O., Ostermann H. et al. Immune thrombocytopenia – current diagnostics and therapy: recommendations of a Joint Working Group of DGHO, ÖGHO, SGH, GPOH and DGTI. Oncol Res Treat 2018;41(Suppl 5):1–30. DOI: 10.1159/00049218747. Adelborg K., Kristensen N.R., Nørgaard M. et al. Cardiovascular and bleeding outcomes in a population-based cohort of patients with chronic immune thrombocytopenia. J Thromb Haemost 2019;17(6):912–24. DOI: 10.1111/jth.14446Adelborg K., Kristensen N.R., Nørgaard M. et al. Cardiovascular and bleeding outcomes in a population-based cohort of patients with chronic immune thrombocytopenia. J Thromb Haemost 2019;17(6):912–24. DOI: 10.1111/jth.1444648. Mithoowani S., Cervi A., Shah N. et al. Management of major bleeds in patients with immune thrombocytopenia. J Thromb Haemost 2020;18(7):1783–90. DOI: 10.1111/jth.14809Mithoowani S., Cervi A., Shah N. et al. Management of major bleeds in patients with immune thrombocytopenia. J Thromb Haemost 2020;18(7):1783–90. DOI: 10.1111/jth.1480949. Cohen Y.C., Djulbegovic B., Shamai-Lubovitz O., Mozes B. The bleeding risk and natural history of idiopathic thrombocytopenic purpura in patients with persistent low platelet counts. Arch Intern Med 2000;160(11):1630–8. DOI: 10.1001/archinte.160.11.1630Cohen Y.C., Djulbegovic B., Shamai-Lubovitz O., Mozes B. The bleeding risk and natural history of idiopathic thrombocytopenic purpura in patients with persistent low platelet counts. Arch Intern Med 2000;160(11):1630–8. DOI: 10.1001/archinte.160.11.163050. Neunert C., Noroozi N., Norman G. et al. Severe bleeding events in adults and children with primary immune thrombocytopenia: a systematic review. J Thromb Haemost 2015;13(3):457–64. DOI: 10.1111/jth.12813Neunert C., Noroozi N., Norman G. et al. Severe bleeding events in adults and children with primary immune thrombocytopenia: a systematic review. J Thromb Haemost 2015;13(3):457–64. DOI: 10.1111/jth.1281351. Forsythe A., Schneider J., Pham T. et al. Real-world evidence on clinical outcomes in immune thrombocytopenia treated with thrombopoietin receptor agonists. J Comp Eff Res 2020;9(7): 447–57. DOI: 10.2217/cer-2019-0177Forsythe A., Schneider J., Pham T. et al. Real-world evidence on clinical outcomes in immune thrombocytopenia treated with thrombopoietin receptor agonists. J Comp Eff Res 2020;9(7): 447–57. DOI: 10.2217/cer-2019-017752. Arnold D.M., Nazy I., Clare R. et al. Misdiagnosis of primary immune thrombocytopenia and frequency of bleeding: lessons from the McMaster ITP Registry. Blood Adv 2017;1(25):2414–20. DOI: 10.1182/bloodadvances.2017010942Arnold D.M., Nazy I., Clare R. et al. Misdiagnosis of primary immune thrombocytopenia and frequency of bleeding: lessons from the McMaster ITP Registry. Blood Adv 2017;1(25):2414–20. DOI: 10.1182/bloodadvances.201701094253. Piel-Julian M.L., Mahévas M., Germain J. et al. Risk factors for bleeding, including platelet count threshold, in newly diagnosed immune thrombocytopenia adults. J Thromb Haemost 2018;16(9):1830–42. DOI: 10.1111/jth.14227Piel-Julian M.L., Mahévas M., Germain J. et al. Risk factors for bleeding, including platelet count threshold, in newly diagnosed immune thrombocytopenia adults. J Thromb Haemost 2018;16(9):1830–42. DOI: 10.1111/jth.1422754. Hato T., Shimada N., Kurata Y. et al. Risk factors for skin, mucosal, and organ bleeding in adults with primary ITP: a nationwide study in Japan. Blood Adv 2020;4(8):1648–55. DOI: 10.1182/bloodadvances.2020001446Hato T., Shimada N., Kurata Y. et al. Risk factors for skin, mucosal, and organ bleeding in adults with primary ITP: a nationwide study in Japan. Blood Adv 2020;4(8):1648–55. DOI: 10.1182/bloodadvances.202000144655. Newton J.L., Reese J.A., Watson S.I. et al. Fatigue in adult patients with primary immune thrombocytopenia. Eur J Haematol 2011;86(5):420–9. DOI: 10.1111/j.1600-0609.2011.01587.xNewton J.L., Reese J.A., Watson S.I. et al. Fatigue in adult patients with primary immune thrombocytopenia. Eur J Haematol 2011;86(5):420–9. DOI: 10.1111/j.1600-0609.2011.01587.x56. Kuter D.J., Mathias S.D., Rummel M. et al. Health-related quality of life in nonsplenectomized immune thrombocytopenia patients receiving romiplostim or medical standard of care. Am J Hematol 2012;87(5):558–61. DOI: 10.1002/ajh.23163Kuter D.J., Mathias S.D., Rummel M. et al. Health-related quality of life in nonsplenectomized immune thrombocytopenia patients receiving romiplostim or medical standard of care. Am J Hematol 2012;87(5):558–61. DOI: 10.1002/ajh.2316357. Blatt J., Weston B., Gold S. Fatigue as marker of thrombocytopenia in childhood idiopathic thrombocytopenic purpura. Pediatr Hematol Oncol 2010;27(1):65–7. DOI: 10.3109/08880010903426767Blatt J., Weston B., Gold S. Fatigue as marker of thrombocytopenia in childhood idiopathic thrombocytopenic purpura. Pediatr Hematol Oncol 2010;27(1):65–7. DOI: 10.3109/0888001090342676758. Hill Q.A., Newland A.C. Fatigue in immune thrombocytopenia. Br J Haematol 2015;170(2):141–9. DOI: 10.1111/bjh.13385Hill Q.A., Newland A.C. Fatigue in immune thrombocytopenia. Br J Haematol 2015;170(2):141–9. DOI: 10.1111/bjh.1338559. Severinsen M.T., Engebjerg M.C., Farkas D.K. et al. Risk of venous thromboembolism in patients with primary chronic immune thrombocytopenia: a Danish population-based cohort study. Br J Haematol 2011;152(3):360–2. DOI: 10.1111/j.1365-2141.2010.08418.xSeverinsen M.T., Engebjerg M.C., Farkas D.K. et al. Risk of venous thromboembolism in patients with primary chronic immune thrombocytopenia: a Danish population-based cohort study. Br J Haematol 2011;152(3):360–2. DOI: 10.1111/j.1365-2141.2010.08418.x60. Doobaree I.U., Nandigam R., Bennett D. et al. Thromboembolism in adults with primary immune thrombocytopenia: a systematic literature review and meta-analysis. Eur J Haematol 2016;97(4):321–30. DOI: 10.1111/ejh.12777Doobaree I.U., Nandigam R., Bennett D. et al. Thromboembolism in adults with primary immune thrombocytopenia: a systematic literature review and meta-analysis. Eur J Haematol 2016;97(4):321–30. DOI: 10.1111/ejh.1277761. Moulis G., Audemard-Verger A., Arnaud L. et al. Risk of thrombosis in patients with primary immune thrombocytopenia and antiphospholipid antibodies: a systematic review and metaanalysis. Autoimmun Rev 2016;15(3):203–9. DOI: 10.1016/j.autrev.2015.11.001Moulis G., Audemard-Verger A., Arnaud L. et al. Risk of thrombosis in patients with primary immune thrombocytopenia and antiphospholipid antibodies: a systematic review and metaanalysis. Autoimmun Rev 2016;15(3):203–9. DOI: 10.1016/j.autrev.2015.11.00162. Peerschke E.I., Yin W., Ghebrehiwet B. Complement activation on platelets: implications for vascular inflammation and thrombosis. Mol Immunol 2010;47(13):2170–5. DOI: 10.1016/j.molimm.2010.05.009Peerschke E.I., Yin W., Ghebrehiwet B. Complement activation on platelets: implications for vascular inflammation and thrombosis. Mol Immunol 2010;47(13):2170–5. DOI: 10.1016/j.molimm.2010.05.00963. Kuter D.J., Bussel J.B., Newland A. et al. Long-term treatment with romiplostim in patients with chronic immune thrombocytopenia: safety and efficacy. Br J Haematol 2013;161(3):411–23. DOI: 10.1111/bjh.12260Kuter D.J., Bussel J.B., Newland A. et al. Long-term treatment with romiplostim in patients with chronic immune thrombocytopenia: safety and efficacy. Br J Haematol 2013;161(3):411–23. DOI: 10.1111/bjh.1226064. Rodeghiero F., Stasi R., Giagounidis A. et al. Long-term safety and tolerability of romiplostim in patients with primary immune thrombocytopenia: a pooled analysis of 13 clinical trials. Eur J Haematol 2013;91(5):423–36. DOI: 10.1111/ejh.12181Rodeghiero F., Stasi R., Giagounidis A. et al. Long-term safety and tolerability of romiplostim in patients with primary immune thrombocytopenia: a pooled analysis of 13 clinical trials. Eur J Haematol 2013;91(5):423–36. DOI: 10.1111/ejh.1218165. Frederiksen H., Maegbaek M.L., Nørgaard M. Twenty-year mortality of adult patients with primary immune thrombocytopenia: a Danish population-based cohort study. Br J Haematol 2014;166(2):260–7. DOI: 10.1111/bjh.12869Frederiksen H., Maegbaek M.L., Nørgaard M. Twenty-year mortality of adult patients with primary immune thrombocytopenia: a Danish population-based cohort study. Br J Haematol 2014;166(2):260–7. DOI: 10.1111/bjh.1286966. Vollenberg R., Jouni R., Norris P.A.A. et al. Glycoprotein V is a relevant immune target in patients with immune thrombocytopenia. Haematologica 2019;104(6):1237–43. DOI: 10.3324/haematol.2018.211086Vollenberg R., Jouni R., Norris P.A.A. et al. Glycoprotein V is a relevant immune target in patients with immune thrombocytopenia. Haematologica 2019;104(6):1237–43. DOI: 10.3324/haematol.2018.21108667. Kiefel V., Freitag E., Kroll H. et al. Platelet autoantibodies (IgG, IgM, IgA) against glycoproteins IIb/IIIa and Ib/IX in patients with thrombocytopenia. Ann Hematol 1996;72(4):280–5. DOI: 10.1007/s002770050173Kiefel V., Freitag E., Kroll H. et al. Platelet autoantibodies (IgG, IgM, IgA) against glycoproteins IIb/IIIa and Ib/IX in patients with thrombocytopenia. Ann Hematol 1996;72(4):280–5. DOI: 10.1007/s00277005017368. Lu J., Sun L., Wu X. et al. Diagnostic value of peripheral blood lymphocytes for primary immune thrombocytopenia. Contrast Media Mol Imaging 2022;2022:9833941. DOI: 10.1155/2022/9833941Lu J., Sun L., Wu X. et al. Diagnostic value of peripheral blood lymphocytes for primary immune thrombocytopenia. Contrast Media Mol Imaging 2022;2022:9833941. DOI: 10.1155/2022/983394169. Wang W., Tao S., Zhang X. et al. The value of combined detection of megakaryocyte and platelet parameters for the diagnosis of primary immune thrombocytopenia. Clin Appl Thromb Hemost 2022;28:10760296221106779. DOI: 10.1177/10760296221106779Wang W., Tao S., Zhang X. et al. The value of combined detection of megakaryocyte and platelet parameters for the diagnosis of primary immune thrombocytopenia. Clin Appl Thromb Hemost 2022;28:10760296221106779. DOI: 10.1177/1076029622110677970. Pehlivan M., Okan V., Sever T. et al. Investigation of TNF-alpha, TGF-beta 1, IL-10, IL-6, IFN-gamma, MBL, GPIA, and IL1A gene polymorphisms in patients with idiopathic thrombocytopenic purpura. Platelets 2011;22(8):588–95. DOI: 10.3109/09537104.2011.577255Pehlivan M., Okan V., Sever T. et al. Investigation of TNF-alpha, TGF-beta 1, IL-10, IL-6, IFN-gamma, MBL, GPIA, and IL1A gene polymorphisms in patients with idiopathic thrombocytopenic purpura. Platelets 2011;22(8):588–95. DOI: 10.3109/09537104.2011.57725571. Page L.K., Psaila B., Provan D. et al. The immune thrombocytopenic purpura (ITP) bleeding score: assessment of bleeding in patients with ITP. Br J Haematol 2007;138(2):245–8. DOI: 10.1111/j.1365-2141.2007.06635.xPage L.K., Psaila B., Provan D. et al. The immune thrombocytopenic purpura (ITP) bleeding score: assessment of bleeding in patients with ITP. Br J Haematol 2007;138(2):245–8. DOI: 10.1111/j.1365-2141.2007.06635.x72. Palau J., Jarque I., Sanz M.A. Long-term management of chronic immune thrombocytopenic purpura in adults. Int J Gen Med 2010;3:305–11. DOI: 10.2147/IJGM.S4722Palau J., Jarque I., Sanz M.A. Long-term management of chronic immune thrombocytopenic purpura in adults. Int J Gen Med 2010;3:305–11. DOI: 10.2147/IJGM.S472273. McGrath L.J., Kilpatrick K., Overman R.A. et al. Treatment patterns among adults with primary immune thrombocytopenia diagnosed in hematology clinics in the United States. Clin Epidemiol 2020;12:435–45. DOI: 10.2147/CLEP.S229266McGrath L.J., Kilpatrick K., Overman R.A. et al. Treatment patterns among adults with primary immune thrombocytopenia diagnosed in hematology clinics in the United States. Clin Epidemiol 2020;12:435–45. DOI: 10.2147/CLEP.S22926674. Branehög I., Weinfeld A. Platelet survival and platelet production in idiopathic thrombocytopenic purpura (ITP) before and during treatment with corticosteroids. Scand J Haematol 1974;12(1): 69–79. DOI: 10.1111/j.1600-0609.1974.tb00182.xBranehög I., Weinfeld A. Platelet survival and platelet production in idiopathic thrombocytopenic purpura (ITP) before and during treatment with corticosteroids. Scand J Haematol 1974;12(1): 69–79. DOI: 10.1111/j.1600-0609.1974.tb00182.x75. Gernsheimer T., Stratton J., Ballem P.J., Slichter S.J. Mechanisms of response to treatment in autoimmune thrombocytopenic purpura. N Engl J Med 1989;320(15):974–80. DOI: 10.1056/NEJM198904133201505Gernsheimer T., Stratton J., Ballem P.J., Slichter S.J. Mechanisms of response to treatment in autoimmune thrombocytopenic purpura. N Engl J Med 1989;320(15):974–80. DOI: 10.1056/NEJM19890413320150576. Wang L., Xu L., Hao H. et al. First line treatment of adult patients with primary immune thrombocytopenia: a real-world study. Platelets 2020;31(1):55–61. DOI: 10.1080/09537104.2019.1572875Wang L., Xu L., Hao H. et al. First line treatment of adult patients with primary immune thrombocytopenia: a real-world study. Platelets 2020;31(1):55–61. DOI: 10.1080/09537104.2019.157287577. Provan D., Arnold D.M., Bussel J.B. et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv 2019;3(22):3780–817. DOI: 10.1182/bloodadvances.2019000812Provan D., Arnold D.M., Bussel J.B. et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv 2019;3(22):3780–817. DOI: 10.1182/bloodadvances.201900081278. Mithoowani S., Gregory-Miller K., Goy J. et al. High-dose dexamethasone compared with prednisone for previously untreated primary immune thrombocytopenia: a systematic review and metaanalysis. Lancet Haematol 2016;3(10):e489–96. DOI: 10.1016/S2352-3026(16)30109-0Mithoowani S., Gregory-Miller K., Goy J. et al. High-dose dexamethasone compared with prednisone for previously untreated primary immune thrombocytopenia: a systematic review and metaanalysis. Lancet Haematol 2016;3(10):e489–96. DOI: 10.1016/S2352-3026(16)30109-079. Frederiksen H., Ghanima W. Response of first line treatment with corticosteroids in a population-based cohort of adults with primary immune thrombocytopenia. Eur J Intern Med 2017;37:e23–5. DOI: 10.1016/j.ejim.2016.09.001Frederiksen H., Ghanima W. Response of first line treatment with corticosteroids in a population-based cohort of adults with primary immune thrombocytopenia. Eur J Intern Med 2017;37:e23–5. DOI: 10.1016/j.ejim.2016.09.00180. Wang J., Li Y., Wang C. et al. Efficacy and safety of the combination treatment of rituximab and dexamethasone for adults with primary immune thrombocytopenia (ITP): a meta-analysis. Biomed Res Int 2018;2018:1316096. DOI: 10.1155/2018/1316096Wang J., Li Y., Wang C. et al. Efficacy and safety of the combination treatment of rituximab and dexamethasone for adults with primary immune thrombocytopenia (ITP): a meta-analysis. Biomed Res Int 2018;2018:1316096. DOI: 10.1155/2018/131609681. Imbach P. Treatment of immune thrombocytopenia with intravenous immunoglobulin and insights for other diseases. A historical review. Swiss Med Wkly 2012;142:w13593. DOI: 10.4414/smw.2012.13593Imbach P. Treatment of immune thrombocytopenia with intravenous immunoglobulin and insights for other diseases. A historical review. Swiss Med Wkly 2012;142:w13593. DOI: 10.4414/smw.2012.1359382. Lazarus A.H., Crow A.R. Mechanism of action of IVIG and anti-D in ITP. Transfus Apher Sci 2003;28(3):249–55. DOI: 10.1016/S1473-0502(03)00043-0Lazarus A.H., Crow A.R. Mechanism of action of IVIG and anti-D in ITP. Transfus Apher Sci 2003;28(3):249–55. DOI: 10.1016/S1473-0502(03)00043-083. Beck C.E., Nathan P.C., Parkin P.C. et al. 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):521–7. DOI: 10.1016/j.jpeds.2005.04.032Beck C.E., Nathan P.C., Parkin P.C. et al. 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):521–7. DOI: 10.1016/j.jpeds.2005.04.03284. Zhou Z., Qiao Z., Li H. et al. Different dosages of intravenous immunoglobulin (IVIg) in treating immune thrombocytopenia with long-term follow-up of three years: results of a prospective study including 167 cases. Autoimmunity 2016;49(1):50–7. DOI: 10.3109/08916934.2015.1104671Zhou Z., Qiao Z., Li H. et al. Different dosages of intravenous immunoglobulin (IVIg) in treating immune thrombocytopenia with long-term follow-up of three years: results of a prospective study including 167 cases. Autoimmunity 2016;49(1):50–7. DOI: 10.3109/08916934.2015.110467185. Qin Y.H., Zhou T.B., Su L.N. et al. The efficacy of different dose intravenous immunoglobulin in treating acute idiopathic thrombocytopenic purpura: a meta-analysis of 13 randomized controlled trials. Blood Coagul Fibrinolysis 2010;21(8):713–21. DOI: 10.1097/MBC.0b013e3283401490Qin Y.H., Zhou T.B., Su L.N. et al. The efficacy of different dose intravenous immunoglobulin in treating acute idiopathic thrombocytopenic purpura: a meta-analysis of 13 randomized controlled trials. Blood Coagul Fibrinolysis 2010;21(8):713–21. DOI: 10.1097/MBC.0b013e328340149086. Jacobs P., Wood L., Novitzky N. Intravenous gammaglobulin has no advantages over oral corticosteroids as primary therapy for adults with immune thrombocytopenia: a prospective randomized clinical trial. Am J Med 1994;97(1):55–9. DOI: 10.1016/0002-9343(94)90048-5Jacobs P., Wood L., Novitzky N. Intravenous gammaglobulin has no advantages over oral corticosteroids as primary therapy for adults with immune thrombocytopenia: a prospective randomized clinical trial. Am J Med 1994;97(1):55–9. DOI: 10.1016/0002-9343(94)90048-587. Godeau B., Chevret S., Varet B. et al. Intravenous immunoglobulin or high-dose methylprednisolone, with or without oral prednisone, for adults with untreated severe autoimmune thrombocytopenic purpura: a randomised, multicentre trial. Lancet 2002;359(9300):23–9. DOI: 10.1016/S0140-6736(02)07275-6Godeau B., Chevret S., Varet B. et al. Intravenous immunoglobulin or high-dose methylprednisolone, with or without oral prednisone, for adults with untreated severe autoimmune thrombocytopenic purpura: a randomised, multicentre trial. Lancet 2002;359(9300):23–9. DOI: 10.1016/S0140-6736(02)07275-688. Peng J., Ma S.H., Liu J. et al. Association of autoantibody specificity and response to intravenous immunoglobulin G therapy in immune thrombocytopenia: a multicenter cohort study. J Thromb Haemost 2014;12(4):497–504. DOI: 10.1111/jth.12524Peng J., Ma S.H., Liu J. et al. Association of autoantibody specificity and response to intravenous immunoglobulin G therapy in immune thrombocytopenia: a multicenter cohort study. J Thromb Haemost 2014;12(4):497–504. DOI: 10.1111/jth.1252489. Al-Samkari H., Rosovsky R.P., Karp Leaf R.S. et al. A modern reassessment of glycoprotein-specific direct platelet autoantibody testing in immune thrombocytopenia. Blood Adv 2020;4(1):9–18. DOI: 10.1182/bloodadvances.2019000868Al-Samkari H., Rosovsky R.P., Karp Leaf R.S. et al. A modern reassessment of glycoprotein-specific direct platelet autoantibody testing in immune thrombocytopenia. Blood Adv 2020;4(1):9–18. DOI: 10.1182/bloodadvances.201900086890. Dash C.H., Gillanders K.R., Stratford Bobbitt M.E. et al. Safety and efficacy of Gammaplex® in idiopathic thrombocytopenic purpura (ClinicalTrials.gov-NCT00504075). PLoS One 2014;9(6):e96600. DOI: 10.1371/journal.pone.0096600Dash C.H., Gillanders K.R., Stratford Bobbitt M.E. et al. Safety and efficacy of Gammaplex® in idiopathic thrombocytopenic purpura (ClinicalTrials.gov-NCT00504075). PLoS One 2014;9(6):e96600. DOI: 10.1371/journal.pone.009660091. Bonilla F.A. Intravenous immunoglobulin: adverse reactions and management. J Allergy Clin Immunol 2008;122(6):1238–9. DOI: 10.1016/j.jaci.2008.08.033Bonilla F.A. Intravenous immunoglobulin: adverse reactions and management. J Allergy Clin Immunol 2008;122(6):1238–9. DOI: 10.1016/j.jaci.2008.08.03392. Almizraq R.J., Branch D.R. Efficacy and mechanism of intravenous immunoglobulin treatment for immune thrombocytopenia in adults. Ann Blood 2021;6:2. DOI: 10.21037/aob-20-87Almizraq R.J., Branch D.R. Efficacy and mechanism of intravenous immunoglobulin treatment for immune thrombocytopenia in adults. Ann Blood 2021;6:2. DOI: 10.21037/aob-20-8793. Safapour A., Alghasi A., Abolnezhadian F. Recurrence rate in patients with acute immune thrombocytopenic purpura in Ahvaz, southwest of Iran: corticosteroids versus intravenous immunoglobulin. J Prev Epidemiol 2021;6(1):e03. DOI: 10.34172/jpe.2021.03Safapour A., Alghasi A., Abolnezhadian F. Recurrence rate in patients with acute immune thrombocytopenic purpura in Ahvaz, southwest of Iran: corticosteroids versus intravenous immunoglobulin. J Prev Epidemiol 2021;6(1):e03. DOI: 10.34172/jpe.2021.0394. Yoshida Y. Historical review. The light and shadow of Paul Kaznelson: his life and contribution to hematology. Ann Hematol 2008;87(11):877–9. DOI: 10.1007/s00277-008-0553-1Yoshida Y. Historical review. The light and shadow of Paul Kaznelson: his life and contribution to hematology. Ann Hematol 2008;87(11):877–9. DOI: 10.1007/s00277-008-0553-195. Kojouri K., Vesely S.K., Terrell D.R., George J.N. Splenectomy for adult patients with idiopathic thrombocytopenic purpura: a systematic review to assess long-term platelet count responses, prediction of response, and surgical complications. Blood 2004;104(9):2623–34. DOI: 10.1182/blood-2004-03-1168Kojouri K., Vesely S.K., Terrell D.R., George J.N. Splenectomy for adult patients with idiopathic thrombocytopenic purpura: a systematic review to assess long-term platelet count responses, prediction of response, and surgical complications. Blood 2004;104(9):2623–34. DOI: 10.1182/blood-2004-03-116896. Park Y.H., Yi H.G., Kim C.S. et al. Clinical outcome and predictive factors in the response to splenectomy in elderly patients with primary immune thrombocytopenia: a multicenter retrospective study. Acta Haematol 2016;135(3):162–71. DOI: 10.1159/000442703Park Y.H., Yi H.G., Kim C.S. et al. Clinical outcome and predictive factors in the response to splenectomy in elderly patients with primary immune thrombocytopenia: a multicenter retrospective study. Acta Haematol 2016;135(3):162–71. DOI: 10.1159/00044270397. Kristinsson S.Y., Gridley G., Hoover R.N. et al. Long-term risks after splenectomy among 8,149 cancer-free American veterans: a cohort study with up to 27 years follow-up. Haematologica 2014;99(2):392–8. DOI: 10.3324/haematol.2013.092460Kristinsson S.Y., Gridley G., Hoover R.N. et al. Long-term risks after splenectomy among 8,149 cancer-free American veterans: a cohort study with up to 27 years follow-up. Haematologica 2014;99(2):392–8. DOI: 10.3324/haematol.2013.09246098. Cooper N., Evangelista M.L., Amadori S., Stasi R. Should rituximab be used before or after splenectomy in patients with immune thrombocytopenic purpura? Curr Opin Hematol 2007;14(6):642–6. DOI: 10.1097/MOH.0b013e3282c8ca50Cooper N., Evangelista M.L., Amadori S., Stasi R. Should rituximab be used before or after splenectomy in patients with immune thrombocytopenic purpura? Curr Opin Hematol 2007;14(6):642–6. DOI: 10.1097/MOH.0b013e3282c8ca5099. Bussel J.B., Kuter D.J., Pullarkat V. et al. Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP [published correction appears in Blood 2009;113(19):4822]. Blood 2009;113(10):2161–71. DOI: 10.1182/blood-2008-04-150078Bussel J.B., Kuter D.J., Pullarkat V. et al. Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP [published correction appears in Blood 2009;113(19):4822]. Blood 2009;113(10):2161–71. DOI: 10.1182/blood-2008-04-150078100. Zhan Y., Cao J., Ji L. et al. Impaired mitochondria of Tregs decreases OXPHOS-derived ATP in primary immune thrombocytopenia with positive plasma pathogens detected by metagenomic sequencing. Exp Hematol Oncol 2022;11(1):48. DOI: 10.1186/s40164-022-00304-yZhan Y., Cao J., Ji L. et al. Impaired mitochondria of Tregs decreases OXPHOS-derived ATP in primary immune thrombocytopenia with positive plasma pathogens detected by metagenomic sequencing. Exp Hematol Oncol 2022;11(1):48. DOI: 10.1186/s40164-022-00304-y101. Zhu J.J., Shan N.N. Immunomodulatory cytokine interleukin-35 and immune thrombocytopaenia. J Int Med Res 2020;48(12):300060520976477. DOI: 10.1177/0300060520976477Zhu J.J., Shan N.N. Immunomodulatory cytokine interleukin-35 and immune thrombocytopaenia. J Int Med Res 2020;48(12):300060520976477. DOI: 10.1177/0300060520976477102. Okamoto N., Homma M., Kawaguchi Y. et al. Increased expression of interleukin-17 is associated with macrophages in chronic immune thrombocytopenia. Int J Clin Exp Pathol 2018;11(5):2419–29.Okamoto N., Homma M., Kawaguchi Y. et al. Increased expression of interleukin-17 is associated with macrophages in chronic immune thrombocytopenia. Int J Clin Exp Pathol 2018;11(5):2419–29.103. McKenzie C.G., Guo L., Freedman J., Semple J.W. Cellular immune dysfunction in immune thrombocytopenia (ITP). Br J Haematol 2013;163(1):10–23. DOI: 10.1111/bjh.12480McKenzie C.G., Guo L., Freedman J., Semple J.W. Cellular immune dysfunction in immune thrombocytopenia (ITP). Br J Haematol 2013;163(1):10–23. DOI: 10.1111/bjh.12480104. Shulman N.R., Marder V.J., Weinrach R.S. Similarities between known antiplatelet antibodies and the factor responsible for thrombocytopenia in idiopathic purpura. Physiologic, serologic and isotopic studies. Ann N Y Acad Sci 1965;124(2):499–542. DOI: 10.1111/j.1749-6632.1965.tb18984.xShulman N.R., Marder V.J., Weinrach R.S. Similarities between known antiplatelet antibodies and the factor responsible for thrombocytopenia in idiopathic purpura. Physiologic, serologic and isotopic studies. Ann N Y Acad Sci 1965;124(2):499–542. DOI: 10.1111/j.1749-6632.1965.tb18984.x105. Rank A., Weigert O., Ostermann H. Management of chronic immune thrombocytopenic purpura: targeting insufficient megakaryopoiesis as a novel therapeutic principle. Biologics 2010;4:139–45. DOI: 10.2147/btt.s3436Rank A., Weigert O., Ostermann H. Management of chronic immune thrombocytopenic purpura: targeting insufficient megakaryopoiesis as a novel therapeutic principle. Biologics 2010;4:139–45. DOI: 10.2147/btt.s3436106. Cines D.B., Liebman H.A. The immune thrombocytopenia syndrome: a disorder of diverse pathogenesis and clinical presentation. Hematol Oncol Clin North Am 2009;23(6):1155–61. DOI: 10.1016/j.hoc.2009.09.003Cines D.B., Liebman H.A. The immune thrombocytopenia syndrome: a disorder of diverse pathogenesis and clinical presentation. Hematol Oncol Clin North Am 2009;23(6):1155–61. DOI: 10.1016/j.hoc.2009.09.003107. D’Orazio J.A., Neely J., Farhoudi N. ITP in children: pathophysiology and current treatment approaches. J Pediatr Hematol Oncol 2013;35(1):1–13. DOI: 10.1097/MPH.0b013e318271f457D’Orazio J.A., Neely J., Farhoudi N. ITP in children: pathophysiology and current treatment approaches. J Pediatr Hematol Oncol 2013;35(1):1–13. DOI: 10.1097/MPH.0b013e318271f457