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;1:365-71 T-cell activation in ITP Semple et al. Blood 1991;78:2619-25 Semple et al. Blood 1996;87:4245-54 Lost of T-cell tolerance to self antigen in ITP Peng，et al. Blood 2003；101：2721-26 Zhang，et al. J Thrombosis Haemostasis 2007；6:15865 Disturbed apoptosis of T cells Olsson, 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 patients TPO levels normal in 75% of ITP patients (relative TPO deficiency) Autoantibodies inhibit both Mk growth and Mk apoptosis Trail-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;297:517-23 CTL-mediated platelet lysis Olsson, et al. Nat Med 2003;9:1123-27 GPIb 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 mice Immunized 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,,.,.,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,Rituximab long TTR high 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;158:386-398 Blood 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, randomis