成人原发免疫性血小板减少症诊治中国专家共识2修订版解读ppt课件.ppt

成人原发免疫性血小板减少症诊治中国专家共识 2012修订版 解读 1 提纲 概述诊断要点疾病分期治疗原则疗效判断 2 概述 获得性自身免疫性出血性疾病占出血性疾病1 3 老年人高发以皮肤黏膜出血为主患者可有明显乏力症状 3 AverageannualITPincidencebyagegroupandgender n 1145 4 LifeQualityinChronicITPPatients Healthy GeneralPopulation Cancer Hypertension Arthritis ITP ITP Diabetes Limo CHF McMillanetal AmericanJournalofHematologyDOI10 1002 ajh 20992 5 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 6 Estimatedannualrateofbleedingaccordingtoagegroup 7 ITP出血评分量表 王琳侯明 原发免疫性血小板减少症出血评分系统临床应用分析 中华血液学杂志 2012 8 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 9 OligoclonalexpansionsofGP specificCD4 TcellsFogartyPF etal ClinAdvHematolOncol2003 1 365 71T cellactivationinITPSempleetal Blood1991 78 2619 25Sempleetal Blood1996 87 4245 54LostofT celltolerancetoselfantigeninITPPeng etal Blood2003 101 2721 26Zhang etal JThrombosisHaemostasis2007 6 158 65DisturbedapoptosisofTcellsOlsson etal ThrombHaemost2005 93 139 44 LossofT celltolerance 10 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 11 PlateletproductionissuboptimalinITPpatients Autologous111In plateletstudiesshowplateletproduction normalin2 3patientsTPOlevelsnormalin75 ofITPpatients relativeTPOdeficiency AutoantibodiesinhibitbothMkgrowthandMkapoptosisTrail mediatedmegakaryocytepara apoptosisleadingtoinvitrodysmegakaryocytopoiesisandimpairedplateletproduction 12 ThrombopoietinlevelsinITPpatients Houetal BrJHaematol1998 101 420 4 13 Decreasedplateletproduction Trail mediatedmegakaryocytepara apoptosisleadingtoinvitrodysmegakaryocytopoiesis plasma antibody Removalofantibody Thenumberofmegakaryocytes Megakaryocyteapoptosis AntibodiesinhibittheGenerationofmegakaryocytes Yang etal Blood2010 116 4307 16 14 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 15 Increasedplateletdestruction Autoantibody mediatedplateletclearanceZucker Franklin etal NEnglJMed1977 297 517 23CTL mediatedplateletlysisOlsson etal NatMed2003 9 1123 27GPIb desialyationleadingtoplateletapoptosisHeyuNi etal JCI 2013onpublished 16 Increasedplateletdestruction Chow etal Blood2010 115 1247 53 GPIIIaknockoutmiceImmunizedwithplatelets CD19 Splenocytes CD8 Splenocytes SCIDmice Thrombo cytopenia Thrombo cytopenia MousemodelofITP 17 提纲 概述诊断要点疾病分期治疗原则疗效判断 18 诊断要点 血小板计数减少 形态无异常脾脏不大骨髓检查 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SLE MPD的血小板减少 19 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 20 提纲 概述诊断要点疾病分期治疗原则疗效判断 21 疾病分期 新诊断ITP 确诊后3个月以内持续性ITP 确诊后3 12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 10 109 L 出血症状难治性ITP 脾切除无效或复发 需治疗以降低出血危险 除外其他原因 22 23 提纲 概述诊断要点疾病分期治疗原则疗效判断 24 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 25 治疗原则 随访观察 血小板 30 109 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 26 紧急治疗 重症ITP 血小板计数 10 109 L 活动性出血或需要急诊手术方案 血小板输注IVIg 1 0g kg d 2 3天 和 或甲基强的松龙 1 0g d 3天 其他方案重组人活化因子 rhF a 27 新诊断ITP的一线治疗 短程肾上腺糖皮质激素 泼尼松剂量从1 0mg kg d 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 HD DXM 40mg d 4d 无效者半月后可重复静脉输注丙种球蛋白 IVIg 治疗 28 Antibodyspeciesonresponsetosteroid R Response NR Noresponse ITPpatientswithanti GPIbantibodiesarelessresponsivetosteroidtherapy Zeng etal AmericanJournalofHematology2011 29 Overallresponserate 64 5 GPIb IX responserate 41 8 GPIb IX responserate 79 5 responserate 83 7 Ourunpublisheddata AntibodyspeciesonresponsetoIVIg 30 成人ITP的二线治疗 脾切除 正规糖皮质激素治疗无效 病程迁延6个月以上强的松有效 维持量 30mg d糖皮质激素禁忌药物治疗利妥昔单抗 TPO和TPO受体激动剂 硫唑嘌呤 环孢素A 达那唑 长春碱类 GodeauB etal Blood 2008 112 999 1004 GudbrandsdottirS etal Blood 2013 121 1976 81 SalehMN etal Blood 2013 121 537 45 31 Zaja etal Haematologica2008 93 930 33Taube etal Haematologica2005 90 281 3 Decreasethedestructionofplatelet Rituximab Standarddose 32 Long termfollow upanalysisafterrituximabsalvagetherapy Zaja F etal 2012 AmJHematol87 9 886 889 33 Longtermresponsetorituximab Patel V L etal 2012 Blood119 25 5989 5995 LiborCervinek etal IntJHematol 201287 9 886 889 Estimatedevent freesurvivalcurveswithstandarddoseorlowdose 34 PlateletResponseandRomiplostimDoseRemainedStableOverTime Note datapointswithn 5notplotted D Kuteretal ASH2010 35 299adultITPpatientswereinvolved 87 ofpatientsachievedaPC 50 109 L MedianPCincreasedtoPC 50 109 Lbyweek2andremainedconsistentlythrough164weeks Theincidenceofanybleedingsymptomsdeclinedfrom56 atbaselineto16 and20 atweek52andweek104respectively Salehetal ASH2010 Abstract 67 Eltrombopag 36 不同措施治疗ITP的起效时间 BusselJB ProvanD KovalevaL etal Lancet 2009 373 9664 641 648 KuterDJ BusselJB LyonsRM SenecalFM etal Lancet 2008 371 9610 395 403 WangSJ YangRC ZouP etal IntJHematol 2012 96 2 222 2228 ArnoldDM DentaliF CrowtherMA MeyerRM CookRJ SigouinC etalAnnInternMed 2007 146 25 33 37 联合治疗 地塞米松联合利妥昔单抗血小板生成素联合利妥昔单抗地塞米松联合血小板生成素 38 Dexamethasoneplusrituximab Zaja etal Blood2010 115 2755 62 Dexamethasoneplusrituximabyieldshighersustainedresponseratesthandexamethasonemonotherapyinadultswithprimaryimmunethrombocytopenia 39 rhTPOplusRituximab Rituximab rhTPO Decreaseplateletdestruction Increaseplateletproduction HighresponseratewithalongTTRandSR HighresponseratewithashortTTR andrelapsesoonafterwithdrawal 40 Open label non randomized non placebo controlled rhTPO 300U Kg d d1 14 Rituximab 375mg m2 qw 4 d1 8 15 22 RituximabcombinedrhTPOincorticosteroidnon responsiveITP rhTPOplusRituximab Unpublisheddata Arnold etal AnnofInternMed2007 146 25 33 Wang etal ChinJThrombHaemost2010 15 149 53 41 EfficacyComparison OR overallresponse CR completeresponse R response rhTPOplusRituximab Unpublisheddata Arnold etal AnnofInternMed2007 146 25 33 Wang etal ChinJThrombHaemost2010 15 149 53115 2755 62 42 HD DexplusrhT