危重患者血小板减少的诊治.pptx

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%).(P0.01).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.Themedianplateletcountatpresentationis10to30109/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,10109/L.occurs5to10daysaftertransfusioncausedbyalloantibodiesagainstaplateletantigen，alloantibodiesinduceclearanceofdonorplateletsandrecipientso