ITP共识解读PPT演示课件

成人原发免疫性血小板减少症诊治中国专家共识解读,.,.,提纲,概述诊断要点治疗原则与方案疗效判断,,.,.,概述,获得性自身免疫性出血性疾病占出血性疾病1/3，60岁以上老年人高发皮肤黏膜出血为主，出血风险随年龄增加部分患者没有出血症状患者可有明显乏力症状,,.,.,Epidemiology and incidence of ITP,.,.,Life Quality in Chronic ITP Patients,,Healthy,General Population,Cancer,Hypertension,Arthritis,ITP,ITP,Diabetes,Limo,CHF,McMillan et al. American Journal of Hematology DOI 10.1002/ajh/20992,.,.,临床表现,出血症状一般与血小板计数负相关部分重度血小板减少患者无出血症状或仅轻度出血老年患者出血发生率明显高于年轻患者注意：乏力与血栓形成,,.,.,Estimated annual rate of bleeding according to age group,,.,.,ITP 出血评分量表,.,.,概述发病机制,对自身抗原免疫耐受缺失血小板生成减少血小板破坏增多,,.,.,Oligoclonal expansions of GP-specific CD4+T cells Fogarty PF, et al. Clin Adv Hematol Oncol 2003;1:365-71T-cell activation in ITPSemple et al. Blood 1991;78:2619-25Semple et al. Blood 1996;87:4245-54Lost of T-cell tolerance to self antigen in ITPPeng，et al. Blood 2003；101：2721-26 Zhang，et al. J Thrombosis Haemostasis 2007；6:15865Disturbed apoptosis of T cellsOlsson, et al. Thromb Haemost 2005;93:139-44,T细胞免疫失耐受,.,.,发病机制,对自身抗原免疫耐受缺失血小板生成减少血小板破坏增多,,.,.,ITP患者血小板生成减少,,Autologous 111In-platelet studies show platelet production normal in 2/3 patientsTPO levels normal in 75% of ITP patients (relative TPO deficiency) Autoantibodies inhibit both Mk growth and Mk apoptosisTrail-mediated megakaryocyte para-apoptosis leading to in vitro dysmegakaryocytopoiesis and impaired platelet production,.,.,Thrombopoietin levels in ITP patients,,Hou et al. Br J Haematol 1998;101:420-4,.,.,,血小板生成减少,Trail-mediated megakaryocyte para-apoptosis leading to in vitro dysmegakaryocytopoiesis,plasma,antibody,Removal of antibody,The number of megakaryocytes,Megakaryocyte apoptosis,Antibodies inhibit the Generation of megakaryocytes,Yang, et al. Blood 2010;116:4307-16,.,.,发病机制,对自身抗原免疫耐受缺失血小板生成减少血小板破坏增多,,.,.,血小板破坏增加,Autoantibody-mediated platelet clearance Zucker-Franklin, et al. N Engl J Med 1977;297:517-23CTL-mediated platelet lysisOlsson, et al. Nat Med 2003;9:1123-27GPIb desialyation leading to platelet apoptosis Heyu Ni, et al. JCI. 2013 on published,.,.,Increased platelet destruction,Chow, et al. Blood 2010;115:1247-53,GPIIIa knockout miceImmunized with platelets,CD19(+)Splenocytes,CD8(+)Splenocytes,SCID mice,Thrombo-cytopenia,Thrombo-cytopenia,Mouse model of ITP,.,.,提纲,概述诊断要点治疗原则与方案疗效判断,,.,.,诊断要点,至少2次血小板计数减少，形态无异常脾脏一般不增大骨髓检查：巨核细胞增多/正常，成熟障碍排除继发性血小板减少,,.,.,排除继发性血小板减少,EDTA诱导的假性血小板减少 遗传/先天性血小板减少综合症 继发性血小板减少- 免疫性： 药物相关性血小板减少 病毒（HIV、HCV）相关性血小板减少 继发于自免病、淋巴增殖性疾病等血小板减少- 非免疫性：再障、MDS、脾亢、DIC、TTP等,.,.,诊断要点,特殊实验室检查： 血小板抗体检测（MAIPA法和流式微球法） 检测抗原特异性自身抗体的特异性较高 鉴别免疫性与非免疫性血小板减少 血小板生成素（TPO）不作为常规检测 有助于鉴别ITP与不典型AA或低增生性MDS,,.,.,诊断要点疾病分期与分型,新诊断ITP：确诊后3个月以内持续性ITP：确诊后312个月血小板持续减少慢性ITP：血小板减少持续超过12个月重症ITP：血小板10109/L，出血症状难治性ITP：进行诊断再评估仍然确诊为ITP 脾切除无效或复发,,.,.,,.,.,提纲,概述诊断要点治疗原则与方案疗效判断,,.,.,治疗原则,治疗原则紧急治疗新诊断ITP的一线治疗成人ITP的二线治疗,,.,.,治疗原则,随访观察：血小板30109/L，无出血表现，不从事增加出血危险的工作或活动增加出血风险的危险因素：年龄和患病时间血小板功能缺陷凝血因子缺陷未被控制的高血压外科手术或外伤感染必须服用抗凝药物,,.,.,紧急治疗,重症ITP（血小板计数10109/L），活动性出血或需要急诊手术方案：血小板输注IVIg1.0 g/(kgd)12天和/或甲基强的松龙(1.0 g/d3天)促血小板生成药物 重组人活化因子（rhFa）,,.,.,新诊断ITP的一线治疗,肾上腺糖皮质激素： HD-DXM，40mg/d4d，无效者半月后可重复泼尼松剂量从1.0mg/(kgd)，稳定后剂量快速减少至最小维持量（15mg/d），不能维持考虑二线治疗静脉输注丙种球蛋白（IVIg）治疗,,Wei Y, Blood. 2016.127(3):296-302,.,.,Conventional PDN vs HD-DXM,One or two courses of HD-DXM demonstrated higher CR rate, shorter time to response and less adverse events than PDN.,Wei Y, et al, Conventional Oral Prednisone Versus High-Dose Dexamethasone for Management of Adult Immune Thrombocytopenia: A Prospective Randomized Multicenter Clinical Trial, Blood. 2016.127(3):296-302,NCT01356511,.,.,成人ITP的二线治疗,2016版共识1. 促血小板生成药物2. 抗-CD20单克隆抗体3. 脾切除4. 其他二线药物：硫唑嘌呤、环孢素A、达那唑、长春碱类等5. 临床试验,,2012版共识1.脾切除2.药物治疗（按字母顺序）硫唑嘌呤环孢素达那唑利妥昔单抗TPO 和 TPO 受体激动剂 长春碱类,.,.,促血小板生成药物 - 重组人血小板生成素（rhTPO）- 艾曲波帕（Eltrombopag）- 罗米司亭（Romiplostim）起效快（1-2周）个体化维持治疗,N Engl J Med. 2007; 357(22):2237-47. Lancet. 2008;371(9610):395-403.Lancet. 2009;373(9664):641-8. N Engl J Med. 2010;363(20):1889-99.Int J Hematol. 2012;96(2):222-8. Blood. 2015;125(10):1541-7.,成人ITP的二线治疗- 1,.,.,rhTPO,rhTPO (1.0 ug/kg) was given to patients in the rhTPO group daily for 14 days and stopped.,Wang S, et al, A multicenter randomized controlled trial of recombinant human thrombopoietin treatment in patients with primary immune thrombocytopenia, Int J Hematol. 2012;96(2):222-8.,.,.,Bussel et al. N Engl J Med. 2007;357:2237.Bussel et al. Blood .2008;112: 1176.Bussel et al. Lancet. 2009;373:641. Cheng et al. Lancet. 2011;377:393. Saleh et al. Blood. 2013;121:537.,Eltrombopag,.,.,Eltrombopag,Saleh MN, et al. Blood. 2013;121(3):537-545.,NCT00351468,.,.,艾曲波帕停药,Platelet response following eltrombopag cessation may be sustained in nearly half of adult patients with primary ITP after CR with eltrombopag.,260 ITP patients,77% (201/260) CR,80/201 Eltrombopag was discontinued,49 evaluble patients,45% (22/49) immediate relapse,12% (30/260) R,11% (29/260) NR,2% (1/49) relapse at 10 mo,53% (26/49) sustained response,Toms Jos Gonzlez-Lpez, et al, Successful Discontinuation of Eltrombopag after Complete Remission in Patients with Primary Immune Thrombocytopenia, 2014 ASH abstract, 1465,.,.,Romiplostim,Kuter, et al.Lancet.2008;371:395403. Kuter et al. N Engl J Med. 2010;363:18891899. Kuter et al. Br J Haematol. 2013;161:411423. Khellaf, et al. Blood. 2011; 118:43384345. George, et al. Br J Haematol. 2009;144:409415. Bussel et al. Blood. 2009; 113: 21612171,.,.,Platelet Response and Romiplostim Dose Remained Stable Over Time,Kuter, et al. Br J Haematol. 2013;161:411-423.,.,.,Romiplostim 停药,Carpenedo, et al. Hematology Reports.2015;7:5673.,.,.,成人ITP的二线治疗- 2,Rituximablong TTRhigh sustained response rate,Blood. 2001;98(4):952-7. Ann Intern Med. 2007;146(1):25-33. Haematologica. 2008; 93(6):930-3. Blood. 2012;119(25):5989-95. Blood. 2015;125(10):1541-7. Lancet. 2015;385(9978):1653-61.,.,.,Rituximab,Blood. 2001;98:952-957. Ann Intern Med. 2007;146:25-33. Haematologica. 2008; 93:930-3. Blood. 2012;119:5989-95. Br J Haematol. 2012;158:386-398Blood 2014;124:3228-3236 Blood. 2015;125:1541-7. Lancet. 2015;385:1653-61.,.,.,Rituximab(Standard dose),Auger, et al. Br J Haematol. 2012;158:386-398.,.,.,Long-term follow-up analysis after rituximab salvage therapy,Zaja, F., et al. (2012). Am J Hematol 87(9): 886-889.,.,.,Long term response to rituximab,,Patel, V. L., et al. (2012). Blood 119(25): 5989-5995.Libor Cervinek, et al. Int J Hematol. 2012 87(9): 886-889.,Estimated event-free survival curves with standard dose or low dose,.,.,Ghanima W et al. Lancet. 2015 25;385(9978):1653-61.,Rituximab as second-line treatment for adult immune thrombocytopenia (the RITP trial): a multicentre, random