アブストラクト
Japanese
| Title | 小児免疫性血小板減少症 (ITP) の病態生理と臨床課題および今後 |
|---|---|
| Subtitle | 【第62回日本小児血液・がん学会学術集会】 シンポジウム6 : 非腫瘍性血液疾患診療のupdate |
| Authors | 東川正宗1, 森麻希子2, 石黒精3, 日本小児血液・がん学会血小板委員会4 |
| Authors (kana) | |
| Organization | 1伊勢赤十字病院小児科 / 新生児科 (日本小児血液・がん学会血小板委員会委員長), 2埼玉県立小児医療センター血液・腫瘍科, 3国立成育医療研究センター教育研修センター血液内科, 4日本小児血液・がん学会血小板委員会 |
| Journal | 日本小児血液・がん学会雑誌 |
| Volume | 58 |
| Number | 3 |
| Page | 233-239 |
| Year/Month | 2021 / |
| Article | 報告 |
| Publisher | 日本小児血液・がん学会 |
| Abstract | 「要旨」ITPは血小板の破壊と産生障害により血小板減少をきたす自己免疫性疾患である. 小児ITPはウイルス感染などが契機となり, 抗原提示細胞から血小板抗原由来の潜在性ペプチドがCD4+ T細胞に提示され, 反応したB細胞から産生される自己抗体により発症する. 小児ITPに対してエビデンスがある治療は大量ガンマグロブリン療法, 副腎皮質ステロイド, トロンボポエチン受容体作動薬, リツキシマブ, 脾摘の5つである. ITPの病態に基づいて, それぞれの薬剤の作用部位が解明されてきている. 小児ITPの多くは自然治癒するが, 1)治療対象患者の選択基準, 2)初期治療の選択, 3)初期治療に抵抗・難治例に対する治療, 4)患者・家族の健康に関連した生活の質(HRQoL)を考慮した治療, 5)新規薬剤導入後の脾摘の位置づけが課題である. 欧米では, 血小板数にかかわらず出血の重症度に基づいて治療が行われている. 出血の重症度評価には, Buchanan出血Gradeが多用されている. Buchanan分類のGrade 0〜2は無治療経過観察, Grade 4, 5は治療を行うことに異論は少ない. Grade 3を治療するか否かは今後の課題である. 血小板数に生活様式を合わせるのでなく, 患者のHRQoLを改善する治療を選択できる時代となっている. 小児ITPの病態生理, 臨床的課題, ASH 2019 ITPガイドラインと慢性ITPに対する治療について概説した. |
| Practice | 臨床医学：一般 |
| Keywords | 小児免疫性血小板減少症, 病態生理, 出血重症度分類, 治療, 健康に関連した生活の質, childhood immune thrombocytopenia (ITP), pathophysiology, grading of hemorrhage, treatment, health-related quality of life (HRQoL) |
English
| Title | Pathophysiology and clinical challenges of childhood immune thrombocytopenia and future directions |
|---|---|
| Subtitle | |
| Authors | Masamune Higashigawa1, Makiko Mori2, Akira Ishiguro3, the Platelet Committee in 2020, Japanese Society of Pediatric Hematology/Oncology4 |
| Authors (kana) | |
| Organization | 1Department of Pediatrics/Neonatology, Japanese Red Cross Ise Hospital (Chair of the Platelet Committee in 2020, Japanese Society of Pediatric Hematology/Oncology), 2Saitama Children's Medical Center, Department of Hematology/Oncology (Vice-chair of the Platelet Committee in 2020), 3National Center for Child Health and Development, Center for Postgraduate Education and Training/Division of Hematology (Former Chair of the Platelet Committee in 2019), 4the Platelet Committee in 2020, Japanese Society of Pediatric Hematology/Oncology |
| Journal | The Japanese Journal of Pediatric Hematology/Oncology |
| Volume | 58 |
| Number | 3 |
| Page | 233-239 |
| Year/Month | 2021 / |
| Article | Report |
| Publisher | The Japanese Society of Pediatric Hematology/Oncology |
| Abstract | [Abstract] Immune thrombocytopenia (ITP) is an autoimmune disease that causes thrombocytopenia due to platelet destruction and impaired platelet production. Pathological triggers such as viral infections induce the presentation of cryptic peptides derived from platelet antigens from antigen-presenting cells to CD4+ T cells, resulting in anti-platelet autoantibody production in B cells. There are five established treatment options for childhood ITP: high-dose gamma globulin therapy, corticosteroids, thrombopoietin receptor agonists, rituximab, and splenectomy. The underlying pathophysiology of ITP helps in elucidating the site of action of each drug. Many children with ITP undergo remission spontaneously. However, the following issues arise: (1) selection criteria for patients to be treated, (2) selection of initial treatment, (3) treatment of refractory patients, (4) treatment selection considering patient/family health-related quality of life (HRQoL), and (5) clinical positioning of splenectomy after introduction of new drugs. In Europe and the United States, treatment is selected on the basis of the severity of bleeding symptoms regardless of the platelet count. Buchanan's bleeding grade is often used to assess the severity of bleeding. Conventionally, patients with the Buchanan classification Grades 0 to 2 are carefully monitored, whereas those with and Grades 4 and 5 should be treated. Whether or not to treat patients with Grade 3 classification is an issue for consideration. We are in an era where treatments that improve the patient's HRQoL can be selected instead of patients adjusting their lifestyle on the basis of their platelet count. In this paper, an overview of the pathophysiology of childhood ITP, clinical issues, the American Society of Hematology (ASH) 2019 ITP guidelines, and treatment of chronic ITP are presented. |
| Practice | Clinical medicine |
| Keywords | childhood immune thrombocytopenia (ITP), pathophysiology, grading of hemorrhage, treatment, health-related quality of life (HRQoL) |
- 全文ダウンロード： 従量制、基本料金制の方共に770円(税込) です。
参考文献
- 1) Cooper N, Bussel J: The pathogenesis of immune thrombocytopenic purpura. Br J Haematol 133: 364-374, 2006.
- 2) Berchtold P, McMillan R, Tani P, et al: Autoantibodies against platelet membrane glycoproteins in children with acute and chronic immune thrombocytopenic purpura. Blood 74: 1600-1602, 1989.
- 3) Taub JW, Warrier I, Holtkamp C, et al: Characterization of autoantibodies against the platelet glycoprotein antigens IIb/IIIa in childhood idiopathic thrombocytopenia purpura. Am J Hematol 48: 104-107, 1995.
- 4) Winiarski J: Platelet antigens in varicella associated thrombocytopenia. Arch Dis Child 65: 137-139, 1990.
- 5) Kuwana M, Kaburaki J, Ikeda Y: Autoreactive T cells to platelet GPIIb-IIIa in immune thrombocytopenic purpura: role in production of antiplatelet autoantibody. J Clin Invest 102: 1393-1402, 1998.
残りの32件を表示する
- 6) Chang M, Nakagawa PA, Shirley A, et al: Immune thrombocytopenic purpura (ITP) plasma and purified ITP monoclonal autoantibodies inhibit megakaryocytopoiesis in vitro. Blood 102: 887-895, 2003.
- 7) Houweijl EJ, Blom NR, van der Want JJL, et al: Ultrastructural study shows morphologic features of apoptosis and para-apoptosis in megakaryocyotes from patients with idiopathic thrombocytopenic purpura. Blood 103: 500-506, 2004.
- 8) Kurata Y, Curd JG, Tamerius JD, et al: Platelet-associated complement in chronic ITP thrombocytopenia. Br J Haematol 60: 723-733, 1985.
- 9) Njaoui A, Bakchoul T, Stoy J, et al: Autoantibody-mediated complement activation on platelets is a common finding in patients with immune thrombocytopenic purpura (ITP). Eur J Haematol 88: 167-174, 2012.
- 10) Liu B, Zhao H, Poon MC, et al: Abnormality of CD4+CD25+ regulatory T cells in idiopathic thrombocytopenic purpura. Eur J Haematol 78: 139-143, 2007.
- 11) Yu J, Heck S, Patel V, et al: Defective circulating CD25 regulatory T cells in patients with chronic immune thrombocytopenic purpura. Blood 112: 1325-1328, 2008.
- 12) Li X, Zhong H, Bao W, et al: Defective regulatory B-cell compartment in patients with immune thrombocyotopenia. Blood 120: 3318-3325, 2012.
- 13) Olsson B, Andersson PO, Jernas M, et al: T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nat Med 9: 1123-1124, 2003.
- 14) Bussel J, Arnold DM, Grossbard E, et al: Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: Results of two phase 3, randomized, placebo-controlled trials. Am J Hematol 93: 921-930, 2018.
- 15) Zefferey A, Kapur R, Semple JW: Pathogenesis and therapeutic mechanisms in immune thrombocytopenia (ITP). J Clin Med 6: 16, 2017.
- 16) Neunert C, Terrell DR, Arnold DM, et al: American society of hematology 2019 guidelines for immune thrombocytopenia. Blood Adv 3: 3829-3866, 2019.
- 17) Provan D, Amold DM, Bussel JB, et al: Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv 3: 3780-3817, 2019.
- 18) Grainger JD, Rees JL, Reeves M, et al: Changing trends in the UK management of childhood ITP. Ach Dis Child 97: 8-11, 2012.
- 19) Buchanan GR, Adix L: Grading of hemorrhage in children with idiopathic thrombocytopenic purpura. J Pediatr 141: 683-688, 2002.
- 20) Heitink-Polle KMJ, Uiterwaal CSPM, Porcelijn L. et al: Intravenous immunoglobulin vs observation in childhood immune thrombocytopenia: a randomized controlled trial. Blood 132: 883-891, 2018.
- 21) Neunert C, Lim W, Crowther M, et al: The American society hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 117: 4190-4207, 2011.
- 22) Schultz CL, Mitra N, Schapira MM, et al: Influence of the American Society of Hematology guidelines on the management of newly diagnosed childhood immune thrombocytopenia. JAMA Pediatr 168: e142214, 2014.
- 23) Schoettler M, Graham D, Tao W, et al: Increasing observation rates in low-risk pediatric immune thrombocytopenia using a standardized clinical assessment and management plan (SCAMP(R)). Pediatr Blood Cancer 64: e26303, 2017.
- 24) 白幡聡,石井榮一,江口春彦,他:小児特発性血小板減少性紫斑病-診断・治療・管理ガイドライン-.日小児血液会誌 18: 210-218, 2004.
- 25) Shirahata A, Fujisawa K, Ishii E, et al: A nationwide survey of newly diagnosed childhood idiopathic thrombocytopenic purpura in Japan. J Pediatr Hematol Oncol 31: 27-32, 2009.
- 26) Higashigawa M, Yamamoto T, Yoshino A, et al: Evaluation of Japanese practice guidelines for newly diagnosed childhood idiopathic thrombocytopenic purpura. Pediatr Int 53: 701-705, 2011.
- 27) Okubo Y, Michihata N, Morisaki N, et al: Recent trends in practice patterns and comparisons between immunoglobulin and corticosteroid in pediatric immune thrombocytopenia. Int J Hematol 107: 75-82, 2018.
- 28) 高橋幸博,宮川義隆,森麻希子,他:日本小児血液・がん学会血小板委員会:小児難治性ITP治療ガイド2019.日小児血がん会誌 56: 61-68, 2019.
- 29) Kim TO, Despotovic J, Lambert MP: Eltrombopag for use in children with immune thrombocytopenia. Blood Adv 2: 454-461, 2018.
- 30) Grainger JD, Locatelli F, Chotsampancharoen T, et al: Eltrombopag for children with chronic immune thrombocytopenia (PETIT2): a randomised, multicentre, placebo-controlled trial. Lancet 386: 1649-1658, 2015.
- 31) Neunert CE, Rose MJ: Romiplostim for the management of pediatric immune thrombocytopenia: drug development and current practice. Blood Adv 3: 1907-1915, 2019.
- 32) 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 118: 28-36, 2011.
- 33) Matsubara K, Takahashi Y, Hayakawa A, et al: Long-term follow-up of children with refractory immune thrombocytopenia treated with rituximab. Int J Hematol 99: 429-436, 2014.
- 34) Bhatt NS, Bhatt P, Donda K, et al: Temporal trends of splenectomy in pediatric hospitalizations with immune thrombocytopenia. Pediatr Blood Cancer 65: e27072, 2018.
- 35) Chaturvedi S, Arnold DM, McCrae KR: Splenectomy for immune thrombocytopenia: down but not out. Blood 131: 1172-1182, 2018.
- 36) Klaassen RJ, Blanchette V, Burke TA, et al: Quality of life in childhood immune thrombocytopenia: international validation of the kids' ITP tools. Pediatr Blood Cancer 60: 95-100, 2013.
- 37) Kumar M, Lambert MP, Breakey V, et al: ITP Consortium of North America. Sports Participation in Children and Adolescents with Immune Thrombocytopenia (ITP). Pediatr Blood Cancer 62: 2223-2225, 2015.
