儿童免疫性血小板减少症相关机制研究进展及药物评价
Research Progress and Drug Evaluation of Immunological Thrombocytopenia in Children
DOI: 10.12677/PI.2021.105032, PDF,   
作者: 岳登媛, 沈 婷, 钱明霞, 徐柳红：浙江中医药大学公共卫生学院，浙江 杭州；陈梦婷：浙江中医药大学医学技术学院，浙江 杭州；胡梦娇*：浙江中医药大学基础医学院，浙江 杭州
关键词: 儿童；免疫性血小板减少症；发病机制；药物评价；Child； Immune Thrombocytopenia； Etiology and Pathogenesis； Drug-Evaluation
摘要: 免疫性血小板减少症是儿童最常见的获得性免疫介导出血性疾病之一，其异质性明显，在儿童中尤其突出，具体发病机制、自然病程、并发症及治疗方案因人而异。随着免疫性血小板减少症(Immune Thrombocytopenic Purpura, ITP)在治疗的研究进展中，儿童ITP的治疗获得了一定突破，一般认为治疗儿童ITP的常见用药包括肾上腺糖皮质激素类药物、丙种球蛋白以及刺激血小板生成类药物等，新型药物以免疫抑制剂及生物制品等，本文探讨了国内外儿童免疫性血小板减少症的流行特征、发病机制及治疗进展，以此展开综述。
Abstract: Immune thrombocytopenia is one of the most common acquired immune-mediated hemorrhagic diseases in children. Its heterogeneity is obvious, especially prominent in children. The specific pathogenesis, natural course, complications and treatment plan vary from person to person. As immune thrombocytopenia (ITP) in the diagnosis, treatment, the progress of the treatment of ITP in children to obtain a breakthrough, it is generally believed to treat common medication of ITP in children include sugar cortical hormone drugs, gamma globulin and stimulate platelet production drugs, new drugs to immunosuppressants and biological products, etc., This article will review the epidemiological characteristics, pathogenesis and treatment progress of immune thrombocytopenia in children at home and abroad.
文章引用：岳登媛, 陈梦婷, 沈婷, 钱明霞, 徐柳红, 胡梦娇. 儿童免疫性血小板减少症相关机制研究进展及药物评价[J]. 药物资讯, 2021, 10(5): 252-260. https://doi.org/10.12677/PI.2021.105032

参考文献

[1] Rodeghiero, F., Stasi, R., Gernsheimer, T., Michel, M., Provan, D., Arnold, D.M., et al. (2009) Standardization of Ter-minology, Definitions and Outcome Criteria in Immune Thrombocytopenic Purpura of Adults and Children: Report from an International Working Group. Blood, 113, 2386-2393. [Google Scholar] [CrossRef] [PubMed]
[2] Cines, D.B. and Blanchette, V.S. (2002) Immune Thrombo-cytopenic Purpura. The New England Journal of Medicine, 346, 995-1008. [Google Scholar] [CrossRef] 
[3] 国家卫生健康委. 儿童原发性免疫性血小板减少症诊疗规范(2019年版) [J]. 全科医学临床与教育, 2019, 17(12): 1059-1062.
[4] Neunert, C., Lim, W., Crowther, M., Cohen, A., Solberg Jr., L. and Crowther, M.A. (2011) The American Society of Hematology 2011 Evidence-Based Practice Guideline for Immune Thrombocytopenia. Blood, 117, 4190-4207. [Google Scholar] [CrossRef] [PubMed]
[5] 谢幸娟, 陈振萍. 儿童免疫性血小板减少症发病机制研究进展[J]. 中国实用儿科杂志, 2021; 36(2): 90-94.
[6] Youssef, M.A.M., Salah Eldeen, E., Elsayh, K.I., Taha, S.F. and Abo-Elela, M.G.M. (2019) High Dose Dexamethasone as an Alternative Rescue Therapy for Active Bleeding in Children with Chronic ITP: Clinical and Immunological Effects. Platelets, 30, 886-892. [Google Scholar] [CrossRef] [PubMed]
[7] Portielje, J.E., Westendorp, R.G., Kluin-Nelemans, H.C. and Brand, A. (2001) Morbidity and Mortality in Adults with Idiopathic Thrombocytopenic Purpura. Blood, 97, 2549-2554. [Google Scholar] [CrossRef] 
[8] Mithoowani, S., Gregory-Miller, K., Goy, J., Miller, M.C., Wang, G., Noroozi, N., et al. (2016) High-Dose Dexamethasone Compared with Prednisone for Previously Untreated Primary Immune Thrombocytopenia: A Systematic Review and Meta-Analysis. The Lancet Haematology, 3, e489-e496. [Google Scholar] [CrossRef] 
[9] Arai, Y., Matsui, H., Jo, T., Kondo, T. and Takaori-Kondo, A. (2017) Efficacy of Dexamethasone for Acute Primary Immune Thrombocytopenia Compared to Prednisolone: A Sys-tematic Review and Meta-Analysis. TH Open, 1, e73-e81. [Google Scholar] [CrossRef] [PubMed]
[10] 王丽媛, 刘亢亢, 储金华, 杨林海, 谢志伟, 张坤龙, 等. 儿童免疫性血小板减少症病程慢性化影响因素的研究[J]. 中国实验血液学杂志, 2021, 29(3): 881-886.
[11] Balch, A., Wilkes, J., Thorell, E., Pavia, A., Sherwin, C.M.T. and Enioutina, E.Y. (2019) Changing Trends in IVIG Use in Pediatric Patients: A Retrospective Review of Practices in a Network of Major USA Pediatric Hospitals. International Im-munopharmacology, 76, Article ID: 105868. [Google Scholar] [CrossRef] [PubMed]
[12] Benesch, M., Kerbl, R., Lackner, H., Berghold, A., Schwinger, W., Triebl-Roth, K., et al. (2003) Low-Dose versus High-Dose Im-munoglobulin for Primary Treatment of Acute Immune Thrombocytopenic Purpura in Children: Results of a Prospective, Randomized Single-Center Trial. Journal of Pediatric Hematology/Oncology, 25, 797-800. [Google Scholar] [CrossRef] [PubMed]
[13] 李蓉蔚, 付荣凤, 陈云飞, 刘葳, 薛峰, 李慧媛, 等. 原发免疫性血小板减少症住院患儿临床分析[J]. 中国实验血液学杂志, 2021, 29(2): 574-580.
[14] 覃薇, 黄少玲, 李婷婷. 抗-D免疫球蛋白治疗儿童免疫性血小板减少症疗效的Meta分析[J]. 中国当代儿科杂志, 2017, 19(10): 1070-1076.
[15] Shahgholi, E., Vosough, P., Sotoudeh, K., Arjomandi, K., Ansari, S., Salehi, S., et al. (2008) Intrave-nous Immune Globulin versus Intravenous Anti-D Immune Globulin for the Treatment of Acute Immune Thrombocyto-penic Purpura. Indian Journal of Pediatrics, 75, 1231-1235. [Google Scholar] [CrossRef] [PubMed]
[16] Oray, M., Abu Samra, K., Ebrahimiadib, N., Meese, H. and Foster, C.S. (2016) Long-Term Side Effects of Glucocorticoids. Expert Opinion on Drug Safety, 15, 457-465. [Google Scholar] [CrossRef] [PubMed]
[17] Despotovic, J.M., Lambert, M.P., Herman, J.H., Gernsheimer, T.B., McCrae, K.R., Tarantino, M.D., et al. (2012) RhIG for the Treatment of Immune Thrombocytopenia: Consensus and Controversy (CME). Transfusion, 52, 1126-1136. [Google Scholar] [CrossRef] [PubMed]
[18] 黄月婷, 刘晓帆, 陈云飞, 付荣凤, 刘葳, 薛峰, 等. 艾曲泊帕治疗儿童原发免疫性血小板减少症23例临床观察[J]. 中华血液学杂志, 2019, 40(12): 1031-1034.
[19] Bussel, J.B., de Miguel, P.G., Despotovic, J.M., Grainger, J.D., Sevilla, J., Blanchette, V.S., et al. (2015) Eltrombopag for the Treatment of Children with Persistent and Chronic Immune Thrombocytopenia (PETIT): A Randomised, Multicentre, Placebo-Controlled Study. The Lancet Haematology, 2, e315-e325. [Google Scholar] [CrossRef] 
[20] Escudero Vilaplana, V., Aragonés, J.H., Fernán-dez-Llamazares, C.M., Bieler, C.B., Rodríguez, S.M. and Sáez, M.S. (2012) Use of Romiplostim for Primary Immune Thrombocytopenia in Children. Pediatric Hematology and Oncology, 29, 197-205. [Google Scholar] [CrossRef] [PubMed]
[21] Bussel, J.B., Hsieh, L., Buchanan, G.R., Stine, K., Kalpatthi, R., Gnarra, D.J., et al. (2015) Long-Term Use of the Thrombopoietin-Mimetic Romiplostim in Children with Severe Chronic Immune Thrombocytopenia (ITP). Pediatric Blood & Cancer, 62, 208-213. [Google Scholar] [CrossRef] [PubMed]
[22] 黄月婷, 刘晓帆, 薛峰, 陈云飞, 刘葳, 付荣凤, 等. 重组人血小板生成素治疗41例儿童原发免疫性血小板减少症的疗效及安全性[J]. 中华血液学杂志, 2015, 36(6): 511-514.
[23] 卢园园, 管娜, 孟庆红, 李明磊, 刘云云, 王莹. rhTPO联合大剂量地塞米松治疗儿童难治性免疫性血小板减少症的临床分析[J]. 中国当代儿科杂志, 2018, 20(7): 534-537.
[24] 刘亚璐, 宋玉琴, 朱军. PD-1通路抑制剂在淋巴瘤临床治疗中的研究进展[J]. 中华血液学杂志, 2016, 37(9): 829-832.
[25] Wang, J., Wiley, J.M., Luddy, R., Green-berg, J., Feuerstein, M.A. and Bussel, J.B. (2005) Chronic Immune Thrombocytopenic Purpura in Children: Assessment of Rituximab Treatment. The Journal of Pediatrics, 146, 217-221. [Google Scholar] [CrossRef] [PubMed]
[26] Choi, P.Y., Roncolato, F., Badoux, X., Ramanathan, S., Ho, S.J. and Chong, B.H. (2015) A Novel Triple Therapy for ITP Using High-Dose Dexamethasone, Low-Dose Rituximab, and Cyclosporine (TT4). Blood, 126, 500-503. [Google Scholar] [CrossRef] [PubMed]
[27] 牛子冉, 左玮, 邹羽真, 梅丹, 赵蕾蕾, 张波. 艾曲泊帕治疗儿童慢性免疫性血小板减少症的临床效果[J]. 临床药物治疗杂志, 2020, 18(7): 62-66.
[28] 冯永, 董志兴, 左一红, 李明坤. 治疗慢性免疫性血小板减少症新药罗米司汀[J]. 中国药师, 2009, 12(7): 965-966.
[29] 桑宝华. 利妥昔单抗对儿童难治性ITP的疗效观察[J]. 世界最新医学信息文摘, 2019, 19(11): 109.
[30] Liang, Y., Zhang, L., Gao, J., Hu, D. and Ai, Y. (2012) Rituximab for Children with Immune Thrombocytopenia: A Systematic Review. PLoS ONE, 7, e36698. [Google Scholar] [CrossRef] [PubMed]
[31] Liu, A.P., Cheuk, D.K., Lee, A.H., Lee, P.P., Chiang, A.K., Ha, S.Y., et al. (2016) Cyclosporin A for Persistent or Chronic Immune Thrombocytopenia in Children. Annals of Hematology, 95, 1881-1886. [Google Scholar] [CrossRef] [PubMed]
[32] Gesundheit, B., Cividalli, G., Freeman, A., Yatziv, S., Koren, G. and Baruchel, S. (2001) Cyclosporin A in the Treatment of Refractory Immune Thrombocytopenia Purpura in Children. European Journal of Haematology, 66, 347-351. [Google Scholar] [CrossRef] [PubMed]
[33] Schreiber, A.D., Chien, P., Tomaski, A. and Cines, D.B. (1987) Effect of Danazol in Immune Thrombocytopenic Purpura. The New England Journal of Medicine, 316, 503-508. [Google Scholar] [CrossRef] 
[34] 蔡艳. 达那唑对ITP患者血小板数量的影响[J]. 实用药物与临床, 2012, 15(2): 86-87.
[35] Panigrahi, A., Clark, A., Myers, J. and Raj, A. (2017) A Novel Immuno-modulatory Treatment Involving Mycophenolate Mofetil and Corticosteroids for Pediatric Autoimmune Cytopenias. Pe-diatric Blood & Cancer, 64, 287-293. [Google Scholar] [CrossRef] [PubMed]
[36] Zhou, H., Hou, Y., Liu, X., Qiu, J., Feng, Q., Wang, Y., et al. (2015) Low-Dose Decitabine Promotes Megakaryocyte Maturation and Platelet Production in Healthy Controls and Immune Thrombocytopenia. Thrombosis and Haemostasis, 113, 1021-1034. [Google Scholar] [CrossRef] 
[37] Vaughan, C.J., Murphy, M.B. and Buckley, B.M. (1996) Statins Do More than Just Lower Cholesterol. Lancet, 348, 1079-1082. [Google Scholar] [CrossRef] 
[38] Li, D.W., Li, J.H., Wang, Y.D. and Li, G.R. (2015) Atorvastatin Protects Endothelial Colony-Forming Cells against H2O2-Induced Oxidative Damage by Regulating the Ex-pression of Annexin A2. Molecular Medicine Reports, 12, 7941-7948. [Google Scholar] [CrossRef] [PubMed]
[39] Dobrucki, L.W., Kalinowski, L., Dobrucki, I.T. and Malinski, T. (2001) Statin-Stimulated Nitric Oxide Release from Endothelium. Medical Science Monitor, 7, 622-627.
[40] Kong, Y., Cao, X.N., Zhang, X.H., Shi, M.M., Lai, Y.Y., Wang, Y., et al. (2018) Atorvastatin Enhances Bone Marrow Endothelial Cell Function in Corticosteroid-Resistant Immune Thrombocytopenia Patients. Blood, 131, 1219-1233. [Google Scholar] [CrossRef] [PubMed]
[41] 潘月芬, 方遒, 吴霞雯. 免疫抑制剂联合应用治疗慢性难治性ITP效果分析[J]. 实用药物与临床, 2013, 16(6): 487-489.
[42] 杨青, 宋元华, 吕瑜, 宋春艳, 张翼宇. 免疫抑制剂治疗儿童慢性免疫性血小板减少症的临床研究[J]. 中国医刊 2021, 56(2): 209-212.
[43] 董中明, 周朝阳, 李培斌, 杨国彪. 成人原发免疫性血小板减少症二线药物应用[J]. 大理大学学报, 2019, 4(2): 44-48.
[44] Tang, Y., Chen, J., Liu, Q., Chu, T., Pan, T., Liang, J., et al. (2021) Low-Dose Decitabine for Refractory Prolonged Isolated Thrombocytopenia after HCT: A Randomized Multicenter Trial. Blood Advances, 5, 1250-1258.