危重患者血小板减少的诊治.ppt

危重患者血小板减少的诊治Hospital-acquiredthrombocytopenia.HospPract,2014Oct;42(4):142-52.234血小板减少的病因多样，涉与多个学科，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，导致诊断与鉴别诊断困难。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，与时评估、干预非常重要。5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）6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7裂红细胞（破碎红细胞）8球形红细胞9骨髓涂片/活检了解巨核细胞系（巨核细胞数量与产板情况），还可发现粒系/红系异常10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。11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。12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3060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13血小板减少诊断简易流程14以下的实验室方法能帮助我们进一步明确诊断15平均血小板容积（MPV，meanplateletvolume）Onehundredtwopatientswerecompletelyevaluated.WhencomparedwiththeBMexamination,theMPVof7.9flcouldpredicthyperdestructivesensitivityof82.3%(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):408-14.16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:hypoproliferativeanddestructivethrombocytopeniaAllthethreeplateletindicesweresignificantlyhigherindestructivegroupascomparedtothehypoproliferativecategory17134thrombocytopenicpatients(69men,65women)whoweredividedintotwogroupsgroupI(n=63)includedITPpatientsgroupII(n=71)includedpatientswithHTduetomyelosuppressionsecondarytochemotherapyConcerningMPVandPDWindices,sensitivity,specificity,positiveprognosticvalue,negativeprognosticvalue,efficiencyandYoudenindexwere100%forthediagnosisofITP.Onthecontrary,thevaluesforP-LCRweresignificantlylower。18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):173-7.19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%).(P0.01).Group3.Peripheralnon-immunethrombocytopeniabyabnormaldistribution9.04%(6.95-11.14%)，5.23%(3.41-7.05%).Correlationbetweenimmatureplateletfractionandreticulatedplatelets.Usefulnessintheetiologydiagnosisofthrombocytopenia.EurJHaematol.2010Aug;85(2):158-63.20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。IsthethrombopoietinassayusefulfordifferentialdiagnosisofthrombocytopeniaAnalysisofacohortof160patientswiththrombocytopeniaanddefinedplateletlifespan.ClinChem.2001Sep;47(9):1660-5.Attempttoimprovethediagnosisofimmunethrombocytopeniabycombineduseoftwodifferentplateletautoantibodiesassays(PAIgGandMACE).Haematologica.2002Oct;87(10):1046-52.Quantificationofplatelet-associatedIgGfordifferentialdiagnosisofpatientswiththrombocytopenia.ThrombHaemost.2000Nov;84(5):779-83.21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;2010:135-43.22Infectionisacommoncauseofthrombocytopenia.Viralinfectionsassociatedwiththrombocytopeniaincludethehumanimmunodeficiencyvirus,hepatitisCvirus,andEpstein-Barrvirus，cytomegalovirusThrombocytopeniaisalsofrequentinpatientswithbacterialinfectionsandsepsisorseveresepsis.Mechanismsofinfection-inducedthrombocytopeniaaremultipleandmayincludebonemarrowsuppression,peripheralimmunedestruction,andactivationandconsumption.Thefallinplateletcountassociatedwithsepsisistypicallygradual,occurringover5to7days,andthethrombocytopeniaischaracteristicallymild.Managementconsistsoftreatmentoftheunderlyinginfectionandsupportivecare.1.感染232primarymechanisms：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24Drug-inducedimmunethrombocytopeniatypicallypresentsinadelayedfashion,5to10daysafterinitiationoftheoffendingdrug.Thereare2exceptionstothisrule:(1)patientspreviouslyexposedtoadrug（2）patientsmaydevelopthrombocytopeniaimmediatelyafterinitiationofaglycoproteinIIb/IIIainhibitor(eg,eptifibatide,tirofiban,andabciximab)25ThefollowingclinicalcriteriahavebeenproposedtoestimatethelikelihoodthatagivendrugisthecauseofDITP:(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。26万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27SuspectedDITPistreatedbydiscontinuingthepotentiallyoffendingdrug.Theplateletcounttypicallybeginstoimprovewithin1to2daysafterthedrugisstopped.Themediantimetorecoveryofplateletcountis7days.Patientswithseverethrombocytopeniaandbleedingmaybetreatedwithplatelettransfusion.Inparticularlyseverecases,corticosteroids,intravenousimmunoglobulin,andplasmaexchangehavebeenused,althoughthereislimitedevidenceofefficacywiththese28Heparin-inducedthrombocytopenia(HIT)isanimmune-mediateddisorderthatoccursafterexposuretounfractionatedheparinorlowmolecularweightheparin.UnlikemostotherformsofDITP,HITisgenerallyprothromboticratherthanprohemorrhagic.Thromboticcomplications,includedeepvenousthrombosis,pulmonaryembolism,peripheralarterialthrombosis,ischemicstroke,andmyocardialinfarction.肝素诱导的血小板减少2930anintermediateorhighprobabilityofHIT,heparinshouldbediscontinuedthepatientshouldbetreatedwithanonheparinanticoagulant（argatroban,danaparoid，bivalirudinfondaparinux）Oncetheplateletcounthasrecovered,patientsmaybetransitionedtowarfarin.31Disseminatedintravascularcoagulation(DIC)occursnotinisolationbutsecondarytoanunderlyingdisorderTheseconditionsmaygenerateprocoagulantsubstances,leadingtowidespreadactivationofcoagulationanddepositionoffibrininthemicrovasculature.Theendresultisthrombosisofsmallvesselsandend-organischemicinjury.Acceleratedconsumptionofcoagulationfactorsandplateletsmayalsoproduceaconcomitantbleedingtendency3.弥散性血管内凝血32DIC的病理生理机制333435ThecornerstoneoftherapyforDICistreatmentoftheunderlyingcondition.Transfusionisindicatedinpatientswhoarebleedingorotherwiseathighriskforbleeding.TherapeuticheparinshouldbeconsideredinpatientswithDICcomplicatedbyovertthrombosis.AntifibrinolytictreatmentsaregenerallycontraindicatedinpatientswithDICduetoanincreasedriskofthrombosis.36Thromboticthrombocytopenicpurpura(TTP)isathromboticmicroangiopathyItischaracterizedbythrombocytopeniaandmicroangiopathichemolyticanemiaandmayalsoincludeneurologicsymptoms,fevers,andrenalimpairmentTTPiscausedbyadeficiencyofADAMTS13,aproteasethatcleavesvonWillebrandfactor.IntheabsenceofADAMTS13,ultralargevonWillebrandfactormultimerspromoteformationofplateletaggregatesinthemicrovasculature,causingshearstressandmechanicalfragmentationoferythrocytesinareasofhighflow.4.血栓性血小板减少性紫癜3738TTP患者肺栓塞病理TTP患者肾小球病变39DiagnosisofTTPisbasedonacombinationofclinicalsignsandsymptomsandlaboratoryvalues.Themedianplateletcountatpresentationis10to30109/L.Themedianhemoglobinis8to10g/dLandisaccompaniedbymarkersofintravascularhemolysis.Schistocytes,andoftennucleatedredcells,arefoundintheperipheralbloodsmear.ThePTandaPTTaretypicallynormal,andthedirectCoombstestisnegative.Patientsmayhaveacutekidneyinjuryorproteinuria.40Thromboticthrombocytopenicpurpuraisamedicalemergency,andtreatmentofsuspectedTTPmustbecommencedimmediately.dailyplasmaexchange(PEX)decreasesmortalityratesfrom80%90%tounder20%.plasmainfusionwhileawaitingexchangetherapy.Plasmaexchangeiscontinueduntilplateletcountrecovery.high-dosecorticosteroids,whichhavebeenshowninsomestudiestoimproveoutcomes.Rituximab,amonoclonalantibodythattargetsCD20onBlymphocytes,iswidelyusedinpatientswithrefractoryorrelapseddisease.platelettransfusionisrelativelycontraindicatedunlessseriousbleedingispresent.41Posttransfusionpurpura(PTP)isararecomplicationofbloodtransfusionthatcausesacute,severethrombocytopeniawithamediannadirplateletcount,10109/L.occurs5to10daysaftertransfusioncausedbyalloantibodiesagainstaplateletantigen，alloantibodiesinduceclearanceofdonorplateletsandrecipientsownplatelets,resultinginseverethrombocytopeniaandapronouncedbleedingdiathesis5.输血后紫癜42Posttransfusionpurpuramaybetreatedwithintravenousimmunoglobulin,whichoftenincreasesplateletcountsto100109/Lwithinseveraldays.Thedisorderisself-limitedandplateletcountstypicallyrecoverwithin3weeks.43ExtracorporealCircuitsandIntra-ArterialDevices，suchasextracorporealmembraneoxygenation(ECMO),Intra-aorticballoonpumps(IABPs).plateletactivationandconsumptionMajorSurgery.plateletconsumptionandhemodilution6.其它4445461.重视血涂片在诊断中的价值2.综合考虑临床环境（普通ICU、儿童、产科差异性），血小板下降的时间和严重程度，血栓和（或）出血表现3.治疗基于与时、正确的诊断4.HIT和TTP是输血小板的禁忌症summary47患者，男，68岁，因“便血1月，腹痛20天”入院。查体贫血貌，右上腹扪与2*3cm包块，有压痛，余无阳性发现。肠镜与病检提示结肠肝曲腺癌。术前检查未发现肺、肝等转移，于2009年11月行根治性右半结肠切除术，术后病理检查示低分化腺癌侵与结肠全层，淋巴结转移。术后1月出现意识淡漠，昏睡与清醒交替出现，体温38.5度，双下肢散在瘀斑，神经系统检查颅神经与周围神经感觉运动正常，肌张力正常，病理征阴性。血常规白细胞9.8*109/L，中性粒细胞86%，HGB74g/L，HCT21%，PLT38*109/L病例讨论48还需要重点查体的地方？血小板减少的原因？安排哪些检查？治疗手段？49医学资料仅供参考,用药方面谨遵医嘱