危重患者血小板减少的诊治

危重患者血小板减少的诊治四川省肿瘤医院ICU刘真君2022.4第一页，共五十二页。整理ppt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第二页，共五十二页。整理ppt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<150.0x10(9)/L，通常小于100.0x10(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〕

。第三页，共五十二页。整理pptHospital-acquiredthrombocytopenia.HospPract,2022Oct;42(4):142-52.第四页，共五十二页。整理ppt第五页，共五十二页。整理ppt第六页，共五十二页。整理ppt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、根底疾病〔心、肝、肾等〕和有创操作等的影响，及时评估、干预非常重要。第七页，共五十二页。整理ppt相关病史〔根底疾病、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〕第八页，共五十二页。整理ppt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

第九页，共五十二页。整理ppt裂红细胞〔破碎红细胞〕第十页，共五十二页。整理ppt球形红细胞第十一页，共五十二页。整理ppt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/红系异常第十二页，共五十二页。整理ppt破坏增多骨髓检查巨核细胞数量正常或增加。局部ITP可见巨核细胞成熟障碍，产板少。第十三页，共五十二页。整理ppt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。

第十四页，共五十二页。整理ppt即Coombs直接试验:将洗涤过的红细胞2%混悬液参加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，说明红细胞外表有抗体或补体。Coombs间接试验:先将受试的血清参加等量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。抗人球蛋白试验第十五页，共五十二页。整理ppt血小板减少诊断简易流程第十六页，共五十二页。整理ppt

以下的实验室方法能帮助我们进一步明确诊断第十七页，共五十二页。整理ppt平均血小板容积〔MPV，mean

platelet

volume〕Onehundredtwopatientswerecompletelyevaluated.WhencomparedwiththeBMexamination,theMPVof>7.9flcouldpredicthyperdestructive

sensitivityof82.3%(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,2022Oct;30(5):408-14.第十八页，共五十二页。整理ppt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:hypoproliferativeanddestructivethrombocytopeniaAllthethree

platelet

indices

weresignificantlyhigherindestructivegroupascomparedtothehypoproliferativecategory第十九页，共五十二页。整理ppt134thrombocytopenicpatients(69men,65women)whoweredividedintotwogroups

groupI(n=63)includedITPpatientsgroupII(n=71)includedpatientswithHTduetomyelosuppressionsecondarytochemotherapy

ConcerningMPVandPDWindices,sensitivity,specificity,positiveprognosticvalue,negativeprognosticvalue,efficiencyandYoudenindexwere100%forthe

diagnosis

ofITP.Onthecontrary,thevaluesforP-LCRweresignificantlylower。

第二十页，共五十二页。整理ppt血小板指数的局限性在于血小板严重下降的患者〔<10x10(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),2022Jun;14(3):182-6.Increasedvaluesofmeanplateletvolumeandplateletsizedeviationwidthmayprovideasafepositivediagnosisofidiopathicthrombocytopenicpurpura.ActaHaematol.2022;119(3):173-7.第二十一页，共五十二页。整理ppt未成熟血小板比例和网织血小板比例Group1.Central

thrombocytopenia

IPF8.67%(6.49-10.46%)RP4.08%(2.86-5.30%)Group2.Thrombocytopeniaasaresultofenhancedperipheral

platelet

destruction6.80%(12.20-21.39%)，16.14%(9.89-22.40%).

(P<0.01).Group3.Peripheralnon-immunethrombocytopeniabyabnormal

distribution

9.04%(6.95-11.14%)，5.23%(3.41-7.05%).Correlationbetweenimmatureplateletfractionandreticulatedplatelets.Usefulnessintheetiologydiagnosisofthrombocytopenia.EurJHaematol.2022Aug;85(2):158-63.第二十二页，共五十二页。整理ppt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.第二十三页，共五十二页。整理ppt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，更多的是根底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).2022Oct;42(4):142-52.Thrombocytopeniaintheintensivecareunitpatient.HematologyAmSocHematolEducProgram.2022;2022:135-43.第二十四页，共五十二页。整理ppt

Infectionisacommoncauseofthrombocytopenia.

Viralinfectionsassociatedwiththrombocytopeniaincludethehumanimmunodeficiencyvirus,hepatitisCvirus,andEpstein-Barrvirus，cytomegalovirusThrombocytopeniaisalsofrequentinpatientswithbacterialinfectionsandsepsisorseveresepsis.

Mechanismsofinfection-inducedthrombocytopeniaaremultipleandmayincludebonemarrowsuppression,peripheralimmunedestruction,andactivationandconsumption.

Thefallinplateletcountassociatedwithsepsisistypicallygradual,occurringover5to7days,andthethrombocytopeniaischaracteristicallymild.

Managementconsistsoftreatmentoftheunderlyinginfectionandsupportivecare.1.感染第二十五页，共五十二页。整理ppt2primarymechanisms：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第二十六页，共五十二页。整理pptDrug-inducedimmunethrombocytopeniatypicallypresentsinadelayedfashion,5to10daysafterinitiationoftheoffendingdrug.Thereare2exceptionstothisrule:(1)patientspreviouslyexposedtoadrug〔2〕patientsmaydevelopthrombocytopeniaimmediatelyafterinitiationofaglycoproteinIIb/IIIainhibitor(eg,eptifibatide,tirofiban,andabciximab)第二十七页，共五十二页。整理pptThefollowingclinicalcriteriahavebeenproposedtoestimatethelikelihoodthatagivendrugisthecauseofDITP:(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。

第二十八页，共五十二页。整理ppt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

雷尼替丁第二十九页，共五十二页。整理pptSuspectedDITPistreatedbydiscontinuingthepotentiallyoffendingdrug.Theplateletcounttypicallybeginstoimprovewithin1to2daysafterthedrugisstopped.Themediantimetorecoveryofplateletcountis7days.Patientswithseverethrombocytopeniaandbleedingmaybetreatedwithplatelettransfusion.Inparticularlyseverecases,corticosteroids,intravenousimmunoglobulin,andplasmaexchangehavebeenused,althoughthereislimitedevidenceofefficacywiththese第三十页，共五十二页。整理pptHeparin-inducedthrombocytopenia(HIT)isanimmune-mediateddisorderthatoccursafterexposuretounfractionatedheparinorlowmolecularweightheparin.UnlikemostotherformsofDITP,HITisgenerallyprothromboticratherthanprohemorrhagic.Thromboticcomplications,includedeepvenousthrombosis,pulmonaryembolism,peripheralarterialthrombosis,ischemicstroke,andmyocardialinfarction.肝素诱导的血小板减少第三十一页，共五十二页。整理ppt第三十二页，共五十二页。整理pptanintermediateorhighprobabilityofHIT,heparinshouldbediscontinuedthepatientshouldbetreatedwithanonheparinanticoagulant〔argatroban,danaparoid，bivalirudinfondaparinux〕Oncetheplateletcounthasrecovered,patientsmaybetransitionedtowarfarin.

第三十三页，共五十二页。整理ppt

Disseminatedintravascularcoagulation(DIC)occursnotinisolationbutsecondarytoanunderlyingdisorderTheseconditionsmaygenerateprocoagulantsubstances,leadingtowidespreadactivationofcoagulationanddepositionoffibrininthemicrovasculature.Theendresultisthrombosisofsmallvesselsandend-organischemicinjury.Acceleratedconsumptionofcoagulationfactorsandplateletsmayalsoproduceaconcomitantbleedingtendency3.弥散性血管内凝血第三十四页，共五十二页。整理pptDIC的病理生理机制第三十五页，共五十二页。整理ppt第三十六页，共五十二页。整理ppt第三十七页，共五十二页。整理pptThecornerstoneoftherapyforDICistreatmentoftheunderlyingcondition.Transfusionisindicatedinpatientswhoarebleedingorotherwiseathighriskforbleeding.TherapeuticheparinshouldbeconsideredinpatientswithDICcomplicatedbyovertthrombosis.AntifibrinolytictreatmentsaregenerallycontraindicatedinpatientswithDICduetoanincreasedriskofthrombosis.第三十八页，共五十二页。整理pptThromboticthrombocytopenicpurpura(TTP)isathromboticmicroangiopathyItischaracterizedbythrombocytopeniaandmicroangiopathichemolyticanemiaandmayalsoincludeneurologicsymptoms,fevers,andrenalimpairmentTTPiscausedbyadeficiencyofADAMTS13,aproteasethatcleavesvonWillebrandfactor.IntheabsenceofADAMTS13,ultralargevonWillebrandfactormultimerspromoteformationofplateletaggregatesinthemicrovasculature,causingshearstressandmechanicalfragmentationoferythrocytesinareasofhighflow.4.血栓性血小板减少性紫癜第三十九页，共五十二页。整理ppt第四十页，共五十二页。整理pptTTP患者肺栓塞病理TTP患者肾小球病变第四十一页，共五十二页。整理pptDiagnosisofTTPisbasedonacombinationofclinicalsignsandsymptomsandlaboratoryvalues.Themedianplateletcountatpresentationis10to30×109/L.Themedianhemoglobinis8to10g/dLandisaccompaniedbymarkersofintravascularhemolysis.Schistocytes,andoftennucleatedredcells,arefoundintheperipheralbloodsmear.

ThePTandaPTTaretypicallynormal,andthedirectCoombs

testisnegative.Patientsmayhaveacutekidneyinjuryorproteinuria.第四十二页，共五十二页。整理pptThromboticthrombocytopenicpurpuraisamedicalemergency,andtreatmentofsuspectedTTPmustbecommencedimmediately.dailyplasmaexchange(PEX)decreasesmortalityratesfrom80%–90%tounder20%.plasmainfusionwhileawaitingexchangetherapy.Plasmaexchangeiscontinueduntilplateletcountrecovery.high-dosecorticosteroids,whichhavebeenshowninsomestudiestoimproveoutcomes.Rituximab,amonoclonalantibodythattargetsCD20onBlymphocytes,iswidelyusedinpatientswithrefractoryorrelapseddisease.

platelettransfusionisrelativelycontraindicatedunlessseriousbleedingispresent.第四十三页，共五十二页。整理ppt

Posttransfusionpurpura(PTP)isararecomplicationofbloodtransfusionthatcausesacute,severethrombocytopeniawithamediannadirplateletcount,10×109/L.occurs5to10daysaftertransfusioncausedbyalloantibodiesagainstaplateletantigen，alloantibodiesinduceclearanceofdonorplateletsand