危重患者血小板減少的診治

危重患者血小板減少的診治1整理ppt概述血小板減少的定義、機(jī)制、診斷思路、常用的檢查方法危重患者中血小板減少的診斷和治療總結(jié)病例討論2整理ppt血小板減少〔thrombocytopenia〕

定義為各種遺傳或獲得性因素導(dǎo)致的血小板減少，血小板計(jì)數(shù)<150.0x10(9)/L，通常小于100.0x10(9)/L.其主要機(jī)制為破壞增加〔hyperdestructive

〕、生成減少〔hypoproductive

〕和分布異?！瞐ltereddistribution,常見(jiàn)于充血性脾大或低體溫〕

。3整理pptHospital-acquiredthrombocytopenia.HospPract,2021Oct;42(4):142-52.4整理ppt5整理ppt6整理ppt血小板減少的病因多樣，涉及多個(gè)學(xué)科，常規(guī)檢查特異性和敏感性不高，特異性檢查受到技術(shù)條件和標(biāo)準(zhǔn)化的制約難以開(kāi)展，導(dǎo)致診斷及鑒別診斷困難。同一病因?qū)е卵“鍦p少的時(shí)間、程度個(gè)體差異大，發(fā)生嚴(yán)重出血受到患者年齡、根底疾病〔心、肝、腎等〕和有創(chuàng)操作等的影響，及時(shí)評(píng)估、干預(yù)非常重要。7整理ppt相關(guān)病史〔根底疾病、藥物史、出血事件〕查體〔出血傾向、肝脾淋巴結(jié)、免疫相關(guān)疾病、皮膚鞏膜黃染〕8整理ppt外周血涂片EDTA抗凝劑導(dǎo)致的血小板聚集〔clumping〕，自動(dòng)血細(xì)胞計(jì)數(shù)儀中血小板計(jì)數(shù)下降，稱(chēng)為假性血小板減少〔pseudothrombocytopenia〕人工計(jì)數(shù)或枸櫞酸抗凝可以識(shí)別

9整理ppt裂紅細(xì)胞〔破碎紅細(xì)胞〕10整理ppt球形紅細(xì)胞11整理ppt骨髓涂片/活檢了解巨核細(xì)胞系〔巨核細(xì)胞數(shù)量及產(chǎn)板情況〕，還可發(fā)現(xiàn)粒系/紅系異常12整理ppt破壞增多骨髓檢查巨核細(xì)胞數(shù)量正?；蛟黾?。局部ITP可見(jiàn)巨核細(xì)胞成熟障礙，產(chǎn)板少。13整理ppt生成減少骨髓涂片巨核細(xì)胞減少。再障患者活檢增生極度低下，造血組織少。

14整理ppt即Coombs直接試驗(yàn):將洗滌過(guò)的紅細(xì)胞2%混懸液參加Coombs試劑，混和后離心一分鐘促進(jìn)凝集。如果肉眼或顯微鏡下能見(jiàn)到紅細(xì)胞凝集，即為陽(yáng)性，說(shuō)明紅細(xì)胞外表有抗體或補(bǔ)體。Coombs間接試驗(yàn):先將受試的血清參加等量5%適當(dāng)?shù)恼＜t細(xì)胞(Rh陽(yáng)性的O型紅細(xì)胞)，在37℃溫育30~60分鐘，以促使血清中的半抗體結(jié)合于紅細(xì)胞上(致敏)，將紅細(xì)胞充分洗滌，以后同直接試驗(yàn)?？谷饲虻鞍自囼?yàn)15整理ppt血小板減少診斷簡(jiǎn)易流程16整理ppt

以下的實(shí)驗(yàn)室方法能幫助我們進(jìn)一步明確診斷17整理ppt平均血小板容積〔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,2021Oct;30(5):408-14.18整理ppt血小板指數(shù)

〔plateletindices〕，包括MPV,血小板體積變異寬度〔plateletsizedeviationwidth，PDW)和大血小板比率〔platelet-to-large-cellratio，P-LCR)

Thestudygroupwasdividedintotwocategories:hypoproliferativeanddestructivethrombocytopeniaAllthethree

platelet

indices

weresignificantlyhigherindestructivegroupascomparedtothehypoproliferativecategory19整理ppt134thrombocytopenicpatients(69men,65women)whoweredividedintotwogroups

groupI(n=63)includedITPpatients

groupII(n=71)includedpatientswithHTduetomyelosuppressionsecondarytochemotherapy

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

diagnosis

ofITP.Onthecontrary,thevaluesforP-LCRweresignificantlylower。

20整理ppt血小板指數(shù)的局限性在于血小板嚴(yán)重下降的患者〔<10x10(9)/L〕結(jié)果有較大的偏差，輸血等治療措施影響對(duì)結(jié)果的判斷。在ICU的應(yīng)用價(jià)值需要再評(píng)估。

Roleofplateletvolumeindicesinthedifferentialdiagnosisofthrombocytopenia:asimpleandinexpensivemethod.Hematology(Amsterdam,Netherlands),2021Jun;14(3):182-6.Increasedvaluesofmeanplateletvolumeandplateletsizedeviationwidthmayprovideasafepositivediagnosisofidiopathicthrombocytopenicpurpura.ActaHaematol.2021;119(3):173-7.21整理ppt未成熟血小板比例和網(wǎng)織血小板比例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.2021Aug;85(2):158-63.22整理ppt促血小板生成素〔Thrombopoietin

，TPO)在生成障礙患者，特別是再障患者明顯升高，但在鑒別診斷中的價(jià)值有限。血小板相關(guān)抗體在免疫性血小板減少中有一定的價(jià)值，但檢測(cè)方法的標(biāo)準(zhǔn)化和特異性需要再評(píng)估。

Isthethrombopoietinassayusefulfordifferentialdiagnosisofthrombocytopenia?Analysisofacohortof160patientswiththrombocytopeniaanddefinedplateletlifespan.ClinChem.2001Sep;47(9):1660-5.Attempttoimprovethediagnosisofimmunethrombocytopeniabycombineduseoftwodifferentplateletautoantibodiesassays(PAIgGandMACE).Haematologica.2002Oct;87(10):1046-52.Quantificationofplatelet-associatedIgGfordifferentialdiagnosisofpatientswiththrombocytopenia.ThrombHaemost.2000Nov;84(5):779-83.23整理ppt以上是簡(jiǎn)易流程，最常見(jiàn)的幾種疾病。針對(duì)住院特別是ICU患者情況可能更復(fù)雜，更多的是根底疾病和治療性因素導(dǎo)致的血小板減少，醫(yī)院獲得性血小板減少〔Hospital-acquiredthrombocytopenia〕。Hospital-acquiredthrombocytopenia.HospPract(1995).2021Oct;42(4):142-52.Thrombocytopeniaintheintensivecareunitpatient.HematologyAmSocHematolEducProgram.2021;2021:135-43.24整理ppt

Infectionisacommoncauseofthrombocytopenia.

Viralinfectionsassociatedwiththrombocytopeniaincludethehumanimmunodeficiencyvirus,hepatitisCvirus,andEpstein-Barrvirus，cytomegalovirus

Thrombocytopeniaisalsofrequentinpatientswithbacterialinfectionsandsepsisorseveresepsis.

Mechanismsofinfection-inducedthrombocytopeniaaremultipleandmayincludebonemarrowsuppression,peripheralimmunedestruction,andactivationandconsumption.

Thefallinplateletcountassociatedwithsepsisistypicallygradual,occurringover5to7days,andthethrombocytopeniaischaracteristicallymild.

Managementconsistsoftreatmentoftheunderlyinginfectionandsupportivecare.1.感染25整理ppt2primarymechanisms：decreasedplateletproductionsecondarytobonemarrowsuppression(eg,chemotherapeuticagents)andincreasedplateletdestructioncausedbydrug-inducedimmunethrombocytopenia(DITP)

后者更難以識(shí)別。2.藥物誘導(dǎo)免疫性血小板減少26整理pptDrug-inducedimmunethrombocytopeniatypicallypresentsinadelayedfashion,5to10daysafterinitiationoftheoffendingdrug.Thereare2exceptionstothisrule:(1)patientspreviouslyexposedtoadrug〔2〕patientsmaydevelopthrombocytopeniaimmediatelyafterinitiationofaglycoproteinIIb/IIIainhibitor(eg,eptifibatide,tirofiban,andabciximab)27整理pptThefollowingclinicalcriteriahavebeenproposedtoestimatethelikelihoodthatagivendrugisthecauseofDITP:

(1)thrombocytopeniaoccursafterexposuretothedrugandimprovesafterthedrugisstopped;

(2)thecandidatedrugistheonlydrugusedbeforetheonsetofthrombocytopenia,orotherdrugsarecontinuedorreintroducedwithoutaffectingtheplateletcount;

(3)othercausesofthrombocytopeniaareexcluded;

(4)thrombocytopeniarecursifthedrugis

restarted

但在ICU的環(huán)境下，多種藥物使用，合并多種疾病，可能難以判斷。

28整理ppt萬(wàn)古霉素青霉素哌拉西林頭孢曲松甲氧芐氨嘧啶/磺胺甲惡唑利福平卡馬西平苯妥英丙戊酸阿昔單抗替羅非班依替巴肽奎寧對(duì)乙酰氨基酚布洛芬米氮平

雷尼替丁29整理pptSuspectedDITPistreatedbydiscontinuingthepotentiallyoffendingdrug.

Theplateletcounttypicallybeginstoimprovewithin1to2daysafterthedrugisstopped.Themediantimetorecoveryofplateletcountis7days.

Patientswithseverethrombocytopeniaandbleedingmaybetreatedwithplatelettransfusion.

Inparticularlyseverecases,corticosteroids,intravenousimmunoglobulin,andplasmaexchangehavebeenused,althoughthereislimitedevidenceofefficacywiththese30整理pptHeparin-inducedthrombocytopenia(HIT)isanimmune-mediateddisorderthatoccursafterexposuretounfractionatedheparinorlowmolecularweightheparin.

UnlikemostotherformsofDITP,HITisgenerallyprothromboticratherthanprohemorrhagic.

Thromboticcomplications,includedeepvenousthrombosis,pulmonaryembolism,peripheralarterialthrombosis,ischemicstroke,andmyocardialinfarction.肝素誘導(dǎo)的血小板減少31整理ppt32整理pptanintermediateorhighprobabilityofHIT,heparinshouldbediscontinuedthepatientshouldbetreatedwithanonheparinanticoagulant〔argatroban,danaparoid，bivalirudinfondaparinux〕Oncetheplateletcounthasrecovered,patientsmaybetransitionedtowarfarin.

33整理ppt

Disseminatedintravascularcoagulation(DIC)occursnotinisolationbutsecondarytoanunderlyingdisorderTheseconditionsmaygenerateprocoagulantsubstances,leadingtowidespreadactivationofcoagulationanddepositionoffibrininthemicrovasculature.

Theendresultisthrombosisofsmallvesselsandend-organischemicinjury.

Acceleratedconsumptionofcoagulationfactorsandplateletsmayalsoproduceaconcomitantbleedingtendency3.彌散性血管內(nèi)凝血34整理pptDIC的病理生理機(jī)制35整理ppt36整理ppt37整理pptThecornerstoneoftherapyforDICistreatmentoftheunderlyingcondition.

Transfusionisindicatedinpatientswhoarebleedingorotherwiseathighriskforbleeding.TherapeuticheparinshouldbeconsideredinpatientswithDICcomplicatedbyovertthrombosis.AntifibrinolytictreatmentsaregenerallycontraindicatedinpatientswithDICduetoanincreasedriskofthrombosis.38整理ppt

Thromboticthrombocytopenicpurpura(TTP)isathromboticmicroangiopathy

Itischaracterizedbythrombocytopeniaandmicroangiopathichemolyticanemiaandmayalsoincludeneurologicsymptoms,fevers,andrenalimpairmentTTPiscausedbyadeficiencyofADAMTS13,aproteasethatcleavesvonWillebrandfactor.

IntheabsenceofADAMTS13,ultralargevonWillebrandfactormultimerspromoteformationofplateletaggregatesinthemicrovasculature,causingshearstressandmechanicalfragmentationoferythrocytesinareasofhighflow.4.血栓性血小板減少性紫癜39整理ppt40整理pptTTP患者肺栓塞病理TTP患者腎小球病變41整理pptDiagnosisofTTPisbasedonacombinationofclinicalsignsandsymptomsandlaboratoryvalues.

Themedianplateletcountatpresentationis10to30×109/L.Themedianhemoglobinis8to10g/dLandisaccompaniedbymarkersofintravascularhemolysis.

Schistocytes,andoftennucleatedredcells,arefoundintheperipheralbloodsmear.

ThePTandaPTTaretypicallynormal,andthedirectCoombs

testisnegative.Patientsmayhaveacutekidneyinjuryorproteinuria.42整理pptThromboticthrombocytopenicpurpuraisamedicalemergency,andtreatmentofsuspectedTTPmustbecommencedimmediately.

dailyplasmaexchange(PEX)decreasesmortalityratesfrom80%–90%tounder20%.

plasmainfusionwhileawaitingexchangetherapy.

Plasmaexchangeiscontinueduntilplateletcountrecovery.

high-dosecorticosteroids,whichhavebeenshowninsomestudiestoimproveoutcomes.

Rituximab,amonoclonalantibodythattargetsCD20onBlymphocytes,iswidelyusedinpatientswithrefractoryorrelapseddisease.

platelettransfusionisrelativelycontraindicatedunlessseriousbleedingispresent.43整理ppt

Posttransfusionpurpura(PTP)isararecomplicationofbloodtransfusionthatcausesacute,severethrombocytopeniawithamediannadirplateletcount,10×109/L.occurs5to10daysafter