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.1.概述血小板减少的定义、机制、诊断思路、常用的检查方法2.危重患者中血小板减少的诊断和治疗3.总结4.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:hypoproliferativeanddestructivethrombocytopeniaAllthethreeplateletindicesweresignificantlyhigherindestructivegroupascomparedtothehypoproliferativecategory134thrombocytopenicpatients(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)thrombocytopeniarecursifthedrugis restarted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,althoughthereislimitedevidenceofefficacywiththeseHeparin-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.Acceleratedconsumptionofcoagulationfactorsandplateletsmayalsoproduceaconcomitantbleedingtendency3.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,andthedirectCoombs testisnegative.Patientsmayhaveacutekidneyinjuryorproteinuria.Thromboticthrombocytopenicpurpuraisamedicalemergency,andtreatmentofsuspectedTTPmustbecommencedimmediately.dailyplasmaexchange(PEX)decreasesmortalityratesfrom80%90%tounder20%.plasmainfusionwhileawaitingexchangetherapy.Plasmaexchangeiscontinueduntilplateletcountrecovery.high-dosecorticosteroids,whichhavebeenshowninsomestudiestoimproveoutcomes.Rituximab,amonoclonalantibodythattargetsCD20onBlymphocytes,iswidelyusedinpatientswithrefractoryorrelapseddisease.platelettransfusionisrelativelycontraindicatedunlessseriousbleedingispresent.Posttransfusionpurpura(PTP)isararecomplicationofbloodtransfusionthatcausesacute,severethrombocytopeniawithamediannadirplateletcount,10109/L.occurs5to10daysaftertransfusioncausedbyalloantibodiesagainstaplateletantigen，alloantibodiesinduceclearanceofdonorplateletsandrecipientsownplatelets,resultinginseverethrombocytopeniaandapronouncedbleedingdiathesis5.输血后紫癜Posttransfusionpurpuramaybetreatedwithintravenousimmunoglobulin,whichoftenincreasesplateletcountsto100109/Lwithinseveraldays.Thedisorderisself-limitedandplateletcountstypicallyrecoverwithin3weeks.ExtracorporealCircuitsandIntra-ArterialDevices，suchasextracorporealmembraneoxygenation(ECMO),Intra-aorticballoonpumps(IABPs).plateletactivationandconsumption MajorSurgery.plateletconsumptionandhemodilution6.其它1.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.治疗基于及时、正确的诊断4.HIT和TTP是输血小板的禁忌症summary 患者，男，68岁，因“便血1月，腹痛20天”入院。查体贫血貌，右上腹扪及2*3cm包块，有压痛，余无阳性发现。肠镜及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及结肠全层，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及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？