危重患者血小板减少的诊治课件

危重患者血小板减少的诊治 概述血小板减少的定义 机制 诊断思路 常用的检查方法危重患者中血小板减少的诊断和治疗总结病例讨论 血小板减少 thrombocytopenia 定义为各种遗传或获得性因素导致的血小板减少 血小板计数 150 0 x10 9 L 通常小于100 0 x10 9 L 其主要机制为破坏增加 hyperdestructive 生成减少 hypoproductive 和分布异常 altereddistribution 常见于充血性脾大或低体温 Hospital acquiredthrombocytopenia HospPract 2014Oct 42 4 142 52 血小板减少的病因多样 涉及多个学科 常规检查特异性和敏感性不高 特异性检查受到技术条件和标准化的制约难以开展 导致诊断及鉴别诊断困难 同一病因导致血小板减少的时间 程度个体差异大 发生严重出血受到患者年龄 基础疾病 心 肝 肾等 和有创操作等的影响 及时评估 干预非常重要 相关病史 基础疾病 药物史 出血事件 查体 出血倾向 肝脾淋巴结 免疫相关疾病 皮肤巩膜黄染 外周血涂片 EDTA抗凝剂导致的血小板聚集 clumping 自动血细胞计数仪中血小板计数下降 称为假性血小板减少 pseudothrombocytopenia 人工计数或枸橼酸抗凝可以识别 裂红细胞 破碎红细胞 球形红细胞 骨髓涂片 活检 了解巨核细胞系 巨核细胞数量及产板情况 还可发现粒系 红系异常 破坏增多骨髓检查巨核细胞数量正常或增加 部分ITP可见巨核细胞成熟障碍 产板少 生成减少骨髓涂片巨核细胞减少 再障患者活检增生极度低下 造血组织少 即Coombs直接试验 将洗涤过的红细胞2 混悬液加入Coombs试剂 混和后离心一分钟促进凝集 如果肉眼或显微镜下能见到红细胞凝集 即为阳性 说明红细胞表面有抗体或补体 Coombs间接试验 先将受试的血清加入等量5 适当的正常红细胞 Rh阳性的O型红细胞 在37 温育30 60分钟 以促使血清中的半抗体结合于红细胞上 致敏 将红细胞充分洗涤 以后同直接试验 抗人球蛋白试验 血小板减少诊断简易流程 以下的实验室方法能帮助我们进一步明确诊断 平均血小板容积 MPV meanplateletvolume Onehundredtwopatientswerecompletelyevaluated WhencomparedwiththeBMexamination theMPVof 7 9flcouldpredicthyperdestructivesensitivityof82 3 95 CI 70 5 90 8 specificityof92 5 95 CI 79 6 98 4 positivepredictivevalueof94 4 95 CI 84 6 98 8 negativepredictivevalueof77 1 95 CI 62 7 88 0 Aprospectiveevaluationofnormalmeanplateletvolumeindiscriminatinghyperdestructivethrombocytopeniafromhypoproductive0thrombocytopenia Internationaljournaloflaboratoryhematology 2008Oct 30 5 408 14 血小板指数 plateletindices 包括MPV 血小板体积变异宽度 plateletsizedeviationwidth PDW 和大血小板比率 platelet to large cellratio P LCR Thestudygroupwasdividedintotwocategories hypoproliferativeanddestructivethrombocytopeniaAllthethreeplateletindicesweresignificantlyhigherindestructivegroupascomparedtothehypoproliferativecategory 134thrombocytopenicpatients 69men 65women whoweredividedintotwogroupsgroupI n 63 includedITPpatientsgroupII n 71 includedpatientswithHTduetomyelosuppressionsecondarytochemotherapyConcerningMPVandPDWindices sensitivity specificity positiveprognosticvalue negativeprognosticvalue efficiencyandYoudenindexwere100 forthediagnosisofITP Onthecontrary thevaluesforP LCRweresignificantlylower 血小板指数的局限性在于血小板严重下降的患者 10 x10 9 L 结果有较大的偏差 输血等治疗措施影响对结果的判断 在ICU的应用价值需要再评估 Roleofplateletvolumeindicesinthedifferentialdiagnosisofthrombocytopenia asimpleandinexpensivemethod Hematology Amsterdam Netherlands 2009Jun 14 3 182 6 Increasedvaluesofmeanplateletvolumeandplateletsizedeviationwidthmayprovideasafepositivediagnosisofidiopathicthrombocytopenicpurpura ActaHaematol 2008 119 3 173 7 未成熟血小板比例和网织血小板比例Group1 CentralthrombocytopeniaIPF8 67 6 49 10 46 RP4 08 2 86 5 30 Group2 Thrombocytopeniaasaresultofenhancedperipheralplateletdestruction6 80 12 20 21 39 16 14 9 89 22 40 P 0 01 Group3 Peripheralnon immunethrombocytopeniabyabnormaldistribution9 04 6 95 11 14 5 23 3 41 7 05 Correlationbetweenimmatureplateletfractionandreticulatedplatelets Usefulnessintheetiologydiagnosisofthrombocytopenia EurJHaematol 2010Aug 85 2 158 63 促血小板生成素 Thrombopoietin TPO 在生成障碍患者 特别是再障患者明显升高 但在鉴别诊断中的价值有限 血小板相关抗体在免疫性血小板减少中有一定的价值 但检测方法的标准化和特异性需要再评估 Isthethrombopoietinassayusefulfordifferentialdiagnosisofthrombocytopenia Analysisofacohortof160patientswiththrombocytopeniaanddefinedplateletlifespan ClinChem 2001Sep 47 9 1660 5 Attempttoimprovethediagnosisofimmunethrombocytopeniabycombineduseoftwodifferentplateletautoantibodiesassays PAIgGandMACE Haematologica 2002Oct 87 10 1046 52 Quantificationofplatelet associatedIgGfordifferentialdiagnosisofpatientswiththrombocytopenia ThrombHaemost 2000Nov 84 5 779 83 以上是简易流程 最常见的几种疾病 针对住院特别是ICU患者情况可能更复杂 更多的是基础疾病和治疗性因素导致的血小板减少 医院获得性血小板减少 Hospital acquiredthrombocytopenia Hospital acquiredthrombocytopenia HospPract 1995 2014Oct 42 4 142 52 Thrombocytopeniaintheintensivecareunitpatient HematologyAmSocHematolEducProgram 2010 2010 135 43 Infectionisacommoncauseofthrombocytopenia Viralinfectionsassociatedwiththrombocytopeniaincludethehumanimmunodeficiencyvirus hepatitisCvirus andEpstein Barrvirus cytomegalovirusThrombocytopeniaisalsofrequentinpatientswithbacterialinfectionsandsepsisorseveresepsis Mechanismsofinfection inducedthrombocytopeniaaremultipleandmayincludebonemarrowsuppression peripheralimmunedestruction andactivationandconsumption Thefallinplateletcountassociatedwithsepsisistypicallygradual occurringover5to7days andthethrombocytopeniaischaracteristicallymild Managementconsistsoftreatmentoftheunderlyinginfectionandsupportivecare 1 感染 2primarymechanisms decreasedplateletproductionsecondarytobonemarrowsuppression eg chemotherapeuticagents andincreasedplateletdestructioncausedbydrug inducedimmunethrombocytopenia DITP 后者更难以识别 2 药物诱导免疫性血小板减少 Drug inducedimmunethrombocytopeniatypicallypresentsinadelayedfashion 5to10daysafterinitiationoftheoffendingdrug Thereare2exceptionstothisrule 1 patientspreviouslyexposedtoadrug 2 patientsmaydevelopthrombocytopeniaimmediatelyafterinitiationofaglycoproteinIIb IIIainhibitor eg eptifibatide tirofiban andabciximab ThefollowingclinicalcriteriahavebeenproposedtoestimatethelikelihoodthatagivendrugisthecauseofDITP 1 thrombocytopeniaoccursafterexposuretothedrugandimprovesafterthedrugisstopped 2 thecandidatedrugistheonlydrugusedbeforetheonsetofthrombocytopenia orotherdrugsarecontinuedorreintroducedwithoutaffectingtheplateletcount 3 othercausesofthrombocytopeniaareexcluded 4 thrombocytopeniarecursifthedrugisrestarted但在ICU的环境下 多种药物使用 合并多种疾病 可能难以判断 万古霉素青霉素哌拉西林头孢曲松甲氧苄氨嘧啶 磺胺甲恶唑利福平卡马西平苯妥英丙戊酸阿昔单抗替罗非班依替巴肽奎宁对乙酰氨基酚布洛芬米氮平雷尼替丁 SuspectedDITPistreatedbydiscontinuingthepotentiallyoffendingdrug Theplateletcounttypicallybeginstoimprovewithin1to2daysafterthedrugisstopped Themediantimetorecoveryofplateletcountis7days Patientswithseverethrombocytopeniaandbleedingmaybetreatedwithplatelettransfusion Inparticularlyseverecases corticosteroids intravenousimmunoglobulin andplasmaexchangehavebeenused althoughthereislimitedevidenceofefficacywiththese Heparin inducedthrombocytopenia HIT isanimmune mediateddisorderthatoccursafterexposuretounfractionatedheparinorlowmolecularweightheparin UnlikemostotherformsofDITP HITisgenerallyprothromboticratherthanprohemorrhagic Thromboticcomplications includedeepvenousthrombosis pulmonaryembolism peripheralarterialthrombosis ischemicstroke andmyocardialinfarction 肝素诱导的血小板减少 anintermediateorhighprobabilityofHIT heparinshouldbediscontinuedthepatientshouldbetreatedwithanonheparinanticoagulant argatroban danaparoid bivalirudinfondaparinux Oncetheplateletcounthasrecovered patientsmaybetransitionedtowarfarin Disseminatedintravascularcoagulation DIC occursnotinisolationbutsecondarytoanunderlyingdisorderTheseconditionsmaygenerateprocoagulantsubstances leadingtowidespreadactivationofcoagulationanddepositionoffibrininthemicrovasculature Theendresultisthrombosisofsmallvesselsandend organischemicinjury Acceleratedconsumptionofcoagulationfactorsandplateletsmayalsoproduceaconcomitantbleedingtendency 3 弥散性血管内凝血 DIC的病理生理机制 ThecornerstoneoftherapyforDICistreatmentoftheunderlyingcondition Transfusionisindicatedinpatientswhoarebleedingorotherwiseathighriskforbleeding TherapeuticheparinshouldbeconsideredinpatientswithDICcomplicatedbyovertthrombosis AntifibrinolytictreatmentsaregenerallycontraindicatedinpatientswithDICduetoanincreasedriskofthrombosis Thromboticthrombocytopenicpurpura TTP isathromboticmicroangiopathyItischaracterizedbythrombocytopeniaandmicroangiopathichemolyticanemiaandmayalsoincludeneurologicsymptoms fevers andrenalimpairmentTTPiscausedbyadeficiencyofADAMTS13 aproteasethatcleavesvonWillebrandfactor IntheabsenceofADAMTS13 ultralargevonWillebrandfactormultimerspromoteformationofplateletaggregatesinthemicrovasculature causingshearstressandmechanicalfragmentationoferythrocytesinareasofhighflow 4 血栓性血小板减少性紫癜 TTP患者肺栓塞病理 TTP患者肾小球病变 DiagnosisofTTPisbasedonacombinationofclinicalsignsandsymptomsandlaboratoryvalues Themedianplateletcountatpresentationis10to30 109 L Themedianhemoglobinis8to10g dLandisaccompaniedbymarkersofintravascularhemolysis Schistocytes andoftennucleatedredcells arefoundintheperipheralbloodsmear ThePTandaPTTaretypicallynormal andthedirectCoombstestisnegative Patientsmayhaveacutekidneyinjuryorproteinuria Thromboticthrombocytopenicpurpuraisamedicalemergency andtreatmentofsuspectedTTPmustbecommencedimmediately dailyplasmaexchange PEX decreasesmortalityratesfrom80 90 tounder20 plasmainfusionwhileawaitingexchangetherapy Plasmaexchangeiscontinueduntilplateletcountrecovery high dosecorticosteroids whichhavebeenshowninsomestudiestoimproveoutcomes Rituximab amonoclonalantibodythattargetsCD20onBlymphocytes iswidelyusedinpatientswithrefractoryorrelapseddisease platelettransfusionisrelativelycontraindicatedunlessseriousbleedingispresent Posttransfusionpurpura PTP isararecomplicationofbloodtransfusionthatcausesacute severethrombocytopeniawithamediannadirplateletcount 10 109 L occurs5to10daysaftertransfusioncaus