危重患者血小板減少的診治課件

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)病例討論概述血小板減少的定義、機(jī)制、診斷思路、常用的檢查方法2

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

）和分布異常（altereddistribution,常見于充血性脾大或低體溫）

。血小板減少（thrombocytopenia）

3Hospital-acquiredthrombocytopenia.HospPract,2014Oct;42(4):142-52.Hospital-acquiredthrombocytop4危重患者血小板減少的診治課件5危重患者血小板減少的診治課件6

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、基礎(chǔ)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。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7

相關(guān)病史（基礎(chǔ)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）相關(guān)病史（基礎(chǔ)疾病、藥物史、8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

外周血涂片EDTA抗凝劑導(dǎo)致的血小板9裂紅細(xì)胞（破碎紅細(xì)胞）裂紅細(xì)胞（破碎紅細(xì)胞）10球形紅細(xì)胞球形紅細(xì)胞11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12破壞增多骨髓檢查巨核細(xì)胞數(shù)量正常或增加。部分ITP可見巨核細(xì)胞成熟障礙，產(chǎn)板少。破壞增多骨髓檢查巨核細(xì)胞數(shù)量正常或增加。部分IT13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。

生成減少骨髓涂片巨核細(xì)胞減少。14

即Coombs直接試驗(yàn):將洗滌過的紅細(xì)胞2%混懸液加入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到紅細(xì)胞凝集，即為陽性，說明紅細(xì)胞表面有抗體或補(bǔ)體。

Coombs間接試驗(yàn):先將受試的血清加入等量5%適當(dāng)?shù)恼＜t細(xì)胞(Rh陽性的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)。抗人球蛋白試驗(yàn)即Coombs直接試驗(yàn):將洗滌過的紅細(xì)胞2%混15血小板減少診斷簡(jiǎn)易流程血小板減少診斷簡(jiǎn)易流程16

以下的實(shí)驗(yàn)室方法能幫助我們進(jìn)一步明確診斷以下的實(shí)驗(yàn)室方法能幫助我們進(jìn)一步明確診斷17

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)

Aprospectiveevaluationofnormalmeanplateletvolumeindiscriminatinghyperdestructivethrombocytopeniafromhypoproductive

0thrombocytopenia.Internationaljournaloflaboratoryhematology,2008Oct;30(5):408-14.平均血小板容積（MPV，mean

platelet

vol18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:hypoproliferativeanddestructivethrombocytopenia

Allthethree

platelet

indices

weresignificantlyhigherindestructivegroupascomparedtothehypoproliferativecategory血小板指數(shù)

（plateletindices），19134thrombocytopenicpatients(69men,65women)whoweredividedintotwogroups

groupI(n=63)includedITPpatients

groupII(n=71)includedpatientswithHTduetomyelosuppressionsecondarytochemotherapy

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

diagnosis

ofITP.Onthecontrary,thevaluesforP-LCRweresignificantlylower。

134thrombocytopenicpat20

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),2009Jun;14(3):182-6.Increasedvaluesofmeanplateletvolumeandplateletsizedeviationwidthmayprovideasafepositivediagnosisofidiopathicthrombocytopenicpurpura.ActaHaematol.2008;119(3):173-7.血小板指數(shù)的局限性在于血小板嚴(yán)重下降的患者（<121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.2010Aug;85(2):158-63.未成熟血小板比例和網(wǎng)織血小板比例22

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.促血小板生成素（Thrombopoietin

，T23以上是簡(jiǎn)易流程，最常見的幾種疾病。針對(duì)住院特別是ICU患者情況可能更復(fù)雜，更多的是基礎(chǔ)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).2014Oct;42(4):142-52.Thrombocytopeniaintheintensivecareunitpatient.HematologyAmSocHematolEducProgram.2010;2010:135-43.以上是簡(jiǎn)易流程，最常見的幾種疾病。針對(duì)住院特別是24

Infectionisacommoncauseofthrombocytopenia.

Viralinfectionsassociatedwiththrombocytopeniaincludethehumanimmunodeficiencyvirus,hepatitisCvirus,andEpstein-Barrvirus，cytomegalovirus

Thrombocytopeniaisalsofrequentinpatientswithbacterialinfectionsandsepsisorseveresepsis.

Mechanismsofinfection-inducedthrombocytopeniaaremultipleandmayincludebonemarrowsuppression,peripheralimmunedestruction,andactivationandconsumption.

Thefallinplateletcountassociatedwithsepsisistypicallygradual,occurringover5to7days,andthethrombocytopeniaischaracteristicallymild.

Managementconsistsoftreatmentoftheunderlyinginfectionandsupportivecare.1.感染Infectionisacommonca252primarymechanisms：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2primarymechanisms：dec26Drug-inducedimmunethrombocytopeniatypicallypresentsinadelayedfashion,5to10daysafterinitiationoftheoffendingdrug.

Thereare2exceptionstothisrule:(1)patientspreviouslyexposedtoadrug（2）patientsmaydevelopthrombocytopeniaimmediatelyafterinitiationofaglycoproteinIIb/IIIainhibitor(eg,eptifibatide,tirofiban,andabciximab)Drug-inducedimmunethrom27ThefollowingclinicalcriteriahavebeenproposedtoestimatethelikelihoodthatagivendrugisthecauseofDITP:

(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。

危重患者血小板減少的診治課件28萬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

雷尼替丁萬古霉素29SuspectedDITPistreatedbydiscontinuingthepotentiallyoffendingdrug.

Theplateletcounttypicallybeginstoimprovewithin1to2daysafterthedrugisstopped.Themediantimetorecoveryofplateletcountis7days.

Patientswithseverethrombocytopeniaandbleedingmaybetreatedwithplatelettransfusion.

Inparticularlyseverecases,corticosteroids,intravenousimmunoglobulin,andplasmaexchangehavebeenused,althoughthereislimitedevidenceofefficacywiththese危重患者血小板減少的診治課件30Heparin-inducedthrombocytopenia(HIT)isanimmune-mediateddisorderthatoccursafterexposuretounfractionatedheparinorlowmolecularweightheparin.

UnlikemostotherformsofDITP,HITisgenerallyprothromboticratherthanprohemorrhagic.

Thromboticcomplications,includedeepvenousthrombosis,pulmonaryembolism,peripheralarterialthrombosis,ischemicstroke,andmyocardialinfarction.肝素誘導(dǎo)的血小板減少Heparin-inducedthrombocyt31危重患者血小板減少的診治課件32anintermediateorhighprobabilityofHIT,heparinshouldbediscontinued

thepatientshouldbetreatedwithanonheparinanticoagulant（argatroban,danaparoid，bivalirudin

fondaparinux）

Oncetheplateletcounthasrecovered,patientsmaybetransitionedtowarfarin.

危重患者血小板減少的診治課件33

Disseminatedintravascularcoagulation(DIC)occursnotinisolationbutsecondarytoanunderlyingdisorderTheseconditionsmaygenerateprocoagulantsubstances,leadingtowidespreadactivationofcoagulationanddepositionoffibrininthemicrovasculature.

Theendresultisthrombosisofsmallvesselsandend-organischemicinjury.

Acceleratedconsumptionofcoagulationfactorsandplateletsmayalsoproduceaconcomitantbleedingtendency3.彌散性血管內(nèi)凝血Disseminatedintravascular34DIC的病理生理機(jī)制DIC的病理生理機(jī)制35危重患者血小板減少的診治課件36危重患者血小板減少的診治課件37ThecornerstoneoftherapyforDICistreatmentoftheunderlyingcondition.

Transfusionisindicatedinpatientswhoarebleedingorotherwiseathighriskforbleeding.TherapeuticheparinshouldbeconsideredinpatientswithDICcomplicatedbyovertthrombosis.AntifibrinolytictreatmentsaregenerallycontraindicatedinpatientswithDICduetoanincreasedriskofthrombosis.危重患者血小板減少的診治課件38

Thromboticthrombocytopenicpurpura(TTP)isathromboticmicroangiopathy

Itischaracterizedbythrombocytopeniaandmicroangiopathichemolyticanemiaandmayalsoincludeneurologicsymptoms,fevers,andrenalimpairmentTTPiscausedbyadeficiencyofADAMTS13,aproteasethatcleavesvonWillebrandfactor.

IntheabsenceofADAMTS13,ultralargevonWillebrandfactormultimerspromoteformationofplateletaggregatesinthemicrovasculature,causingshearstressandmechanicalfragmentationoferythrocytesinareasofhighflow.4.血栓性血小板減少性紫癜Thromboticthrombocytopeni39危重患者血小板減少的診治課件40TTP患者肺栓塞病理TTP患者腎小球病變TTP患者肺栓塞病理TTP患者腎小球病變41DiagnosisofTTPisbasedonacombinationofclinicalsignsandsymptomsandlaboratoryvalues.

Themedianplateletcountatpresentationis10to30×109/L.Themedianhemoglobinis8to10g/dLandisaccompaniedbymarkersofintravascularhemolysis.

Schistocytes,andoftennucleatedredcells,arefoundintheperipheralbloodsmear.

ThePTandaPTTaretypicallynormal,andthedirectCoombs

testisnegative.Patientsmayhaveacutekidneyinjuryorproteinuria.危重患者血小板減少的診治課件42Thromboticthrombocytopenicpurpuraisamedicalemergency,andtreatmentofsuspectedTTPmustbecommencedimmediately.

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

plasmainfusionwhileawaitingexchangetherapy.

Plasmaexchangeiscontinueduntilplateletcountrecovery.

high-dosecorticosteroids,whichhavebeenshowninsomestudiestoimproveoutcomes.

Rituximab,amonoclonalantibodythattargetsCD20onBlymphocytes,iswidelyusedinpatientswithrefractoryorrelapseddisease.

platelettransfusionisrelativelycontraindicatedunlessseriousbleedingispresent.危重患者血小板減少的診治課件43

Posttransfusionpurpura(PTP)isararecomplicationofbloodtransfusionthatcausesacute,severethrombocytopeniawithamediannadirplateletcount,10×109/L.occurs5to10daysaftertransfusion

causedbyalloantibodiesagainstaplateletantigen，alloantibodiesinduceclearanceofdonorplateletsandrecipient’sownplatelets,resultinginseverethrombocytopeniaandapronouncedbleedingdiathesis5.輸血后紫癜Posttransfusionpurpura(P44

Posttransfusionpurpuramaybetreatedwithintravenousimmunoglobulin,whichoftenincreasesplateletcountsto100×109/Lwithinseveraldays.

Thedisorderisself-limitedandplateletcountstypicallyrecoverwithin3weeks.Posttransfusionpurpurama45

ExtracorporealCircuitsandIntra-ArterialDevices，suchasextracorporealmembraneoxygenation(ECMO),Intra-aorticballoonpumps(IABPs).

plateletactivationandconsumption

MajorSurgery.

plateletconsumptionandhemodilution6.其它ExtracorporealCircuits46危重患者血小板減少的診治課件47危重患者血小板減少的診治課件48重視血涂片在診斷中的價(jià)值綜合考慮臨床環(huán)境（普通ICU、兒童、產(chǎn)科差異性），血小板下降的時(shí)間和嚴(yán)重程度，血栓和（或）出血表現(xiàn)治療基于及時(shí)、正確的診斷HIT和TTP是輸血小板的禁忌癥summary重視血涂片在診斷中的價(jià)值summary49患者，男，68歲，因“便血1月，腹痛20天”入院。查體貧血貌，右上腹捫及2*3cm包塊，有壓痛，余無陽性發(fā)現(xiàn)。腸鏡及病檢提示結(jié)腸肝曲腺癌。術(shù)前檢查未發(fā)現(xiàn)肺、肝等轉(zhuǎn)移，于2009年11月行根治性右半結(jié)腸切除術(shù)，術(shù)后病理檢查示低分化腺癌侵及結(jié)腸全層，淋巴結(jié)轉(zhuǎn)移。術(shù)后1月出現(xiàn)意識(shí)淡漠，昏睡與清醒交替出現(xiàn)，體溫38.5度，雙下肢散在瘀斑，神經(jīng)系統(tǒng)檢查顱神經(jīng)及周圍神經(jīng)感覺運(yùn)動(dòng)正常，肌張力正常，病理征陰性。

血常規(guī)白細(xì)胞9.8*109/L，中性粒細(xì)胞86%，HGB74g/L，HCT21%，PLT38*109/L病例討論患者，男，68歲，因“便血1月，腹痛20天”50

還需要重點(diǎn)查體的地方？血小板減少的原因？安排哪些檢查？治療手段？還需要重點(diǎn)查體的地方？血小板減少的原因？安排哪些檢51危重患者血小板減少的診治.危重患者血小板減少的診治.52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)病例討論概述血小板減少的定義、機(jī)制、診斷思路、常用的檢查方法53

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

）和分布異常（altereddistribution,常見于充血性脾大或低體溫）

。血小板減少（thrombocytopenia）

54Hospital-acquiredthrombocytopenia.HospPract,2014Oct;42(4):142-52.Hospital-acquiredthrombocytop55危重患者血小板減少的診治課件56危重患者血小板減少的診治課件57

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、基礎(chǔ)疾?。ㄐ摹⒏?、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。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58

相關(guān)病史（基礎(chǔ)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）相關(guān)病史（基礎(chǔ)疾病、藥物史、59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

外周血涂片EDTA抗凝劑導(dǎo)致的血小板60裂紅細(xì)胞（破碎紅細(xì)胞）裂紅細(xì)胞（破碎紅細(xì)胞）61球形紅細(xì)胞球形紅細(xì)胞62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63破壞增多骨髓檢查巨核細(xì)胞數(shù)量正?；蛟黾?。部分ITP可見巨核細(xì)胞成熟障礙，產(chǎn)板少。破壞增多骨髓檢查巨核細(xì)胞數(shù)量正常或增加。部分IT64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。

生成減少骨髓涂片巨核細(xì)胞減少。65

即Coombs直接試驗(yàn):將洗滌過的紅細(xì)胞2%混懸液加入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到紅細(xì)胞凝集，即為陽性，說明紅細(xì)胞表面有抗體或補(bǔ)體。

Coombs間接試驗(yàn):先將受試的血清加入等量5%適當(dāng)?shù)恼＜t細(xì)胞(Rh陽性的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)即Coombs直接試驗(yàn):將洗滌過的紅細(xì)胞2%混66血小板減少診斷簡(jiǎn)易流程血小板減少診斷簡(jiǎn)易流程67

以下的實(shí)驗(yàn)室方法能幫助我們進(jìn)一步明確診斷以下的實(shí)驗(yàn)室方法能幫助我們進(jìn)一步明確診斷68

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)

Aprospectiveevaluationofnormalmeanplateletvolumeindiscriminatinghyperdestructivethrombocytopeniafromhypoproductive

0thrombocytopenia.Internationaljournaloflaboratoryhematology,2008Oct;30(5):408-14.平均血小板容積（MPV，mean

platelet

vol69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:hypoproliferativeanddestructivethrombocytopenia

Allthethree

platelet

indices

weresignificantlyhigherindestructivegroupascomparedtothehypoproliferativecategory血小板指數(shù)

（plateletindices），70134thrombocytopenicpatients(69men,65women)whoweredividedintotwogroups

groupI(n=63)includedITPpatients

groupII(n=71)includedpatientswithHTduetomyelosuppressionsecondarytochemotherapy

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

diagnosis

ofITP.Onthecontrary,thevaluesforP-LCRweresignificantlylower。

134thrombocytopenicpat71

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),2009Jun;14(3):182-6.Increasedvaluesofmeanplateletvolumeandplateletsizedeviationwidthmayprovideasafepositivediagnosisofidiopathicthrombocytopenicpurpura.ActaHaematol.2008;119(3):173-7.血小板指數(shù)的局限性在于血小板嚴(yán)重下降的患者（<172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.2010Aug;85(2):158-63.未成熟血小板比例和網(wǎng)織血小板比例73

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.促血小板生成素（Thrombopoietin

，T74以上是簡(jiǎn)易流程，最常見的幾種疾病。針對(duì)住院特別是ICU患者情況可能更復(fù)雜，更多的是基礎(chǔ)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).2014Oct;42(4):142-52.Thrombocytopeniaintheintensivecareunitpatient.HematologyAmSocHematolEducProgram.2010;2010:135-43.以上是簡(jiǎn)易流程，最常見的幾種疾病。針對(duì)住院特別是75

Infectionisacommoncauseofthrombocytopenia.

Viralinfectionsassociatedwiththrombocytopeniaincludethehumanimmunodeficiencyvirus,hepatitisCvirus,andEpstein-Barrvirus，cytomegalovirus

Thrombocytopeniaisalsofrequentinpatientswithbacterialinfectionsandsepsisorseveresepsis.

Mechanismsofinfection-inducedthrombocytopeniaaremultipleandmayincludebonemarrowsuppression,peripheralimmunedestruction,andactivationandconsumption.

Thefallinplateletcountassociatedwithsepsisistypicallygradual,occurringover5to7days,andthethrombocytopeniaischaracteristicallymild.

Managementconsistsoftreatmentoftheunderlyinginfectionandsupportivecare.1.感染Infectionisacommonca762primarymechanisms：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2primarymechanisms：dec77Drug-inducedimmunethrombocytopeniatypicallypresentsinadelayedfashion,5to10daysafterinitiationoftheoffendingdrug.

Thereare2exceptionstothisrule:(1)patientspreviouslyexposedtoadrug（2）patientsmaydevelopthrombocytopeniaimmediatelyafterinitiationofaglycoproteinIIb/IIIainhibitor(eg,eptifibatide,tirofiban,andabciximab)Drug-inducedimmunethrom78ThefollowingclinicalcriteriahavebeenproposedtoestimatethelikelihoodthatagivendrugisthecauseofDITP:

(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。

危重患者血小板減少的診治課件79萬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

雷尼替丁萬古霉素80SuspectedDITPistreatedbydiscontinuingthepotentiallyoffendingdrug.

Theplateletcounttypicallybeginstoimprovewithin1to2daysafterthedrugisstopped.Themediantimetorecoveryofplateletcountis7days.

Patientswithseverethrombocytopeniaandbleedingmaybetreatedwithplatelettransfusion.

Inparticularlyseverecases,corticosteroids,intravenousimmunoglobulin,andplasmaexchangehavebeenused,althoughthereislimitedevidenceofefficacywiththese危重患者血小板減少的診治課件81Heparin-inducedthrombocytopenia(HIT)isanimmune-mediateddisorderthatoccursafterexposuretounfractionatedheparinorlowmolecularweightheparin.

UnlikemostotherformsofDITP,HITisgenerallyprothromboticratherthanprohemorrhagic.

Thromboticcomplications,includedeepvenousthrombosis,pulmonaryembolism,peripheralarterialthrombosis,ischemicstroke,andmyocardialinfarction.肝素誘導(dǎo)的血小板減少Heparin-inducedthrombocyt82危重患者血小板減少的診治課件83anintermediateorhighprobabilityofHIT,heparinshouldbediscontinued

thepatientshouldbetreatedwithanonheparinanticoagulant（argatroban,danaparoid，bivalirudin

fondaparinux）

Oncetheplateletcounthasrecovered,patientsmaybetransitionedtowarfarin.

危重患者血小板減少的診治課件84

Disseminatedintravascularcoagulation(DIC)occursnotinisolationbutsecondarytoanunderlyingdisorderTheseconditionsmaygenerateprocoagulantsubstances,leadingtowidespreadactivationofcoagulationanddepositionoffibrininthemicrovasculature.

Theendresultisthrombosisofsmallvesselsandend-organischemicinjury.

Acceleratedconsumptionofcoagulationfactorsandplateletsmayalsoproduceaconcomitantbleedingtendency3.彌散性血管內(nèi)凝血Disseminatedintravascular85DIC的病理生理機(jī)制DIC的病理生理機(jī)制86危重患者血小板減少的診治課件87危重患者血小板減少的診治課件88ThecornerstoneoftherapyforDICistreatmentoftheunderlyingcondition.

Transfusionisindicatedinpatientswhoarebleedingorotherwiseathighriskforbleeding.TherapeuticheparinshouldbeconsideredinpatientswithDICcomplicatedbyovertthrombosis.AntifibrinolytictreatmentsaregenerallycontraindicatedinpatientswithDICduetoanincreasedriskofthrombosis.危重患者血小板減少的診治課件89

Thromboticthrombocytopenicpurpura(TTP)isathromboticmicroangiopathy

Itischaracterizedbythrombocytopeniaandmicroangiopathichemolyticanemiaandmayalsoincludeneurologicsymptoms,fevers,andrenalimpairmentTTPiscausedbyadeficiencyofADAMTS13,aproteasethatcleavesvonWillebrandfactor.

IntheabsenceofADAMTS13,ultralargevonWillebrandfactormultimerspromoteformationofplateletaggregatesinthemicrovasculature,causingshearstressandmechanicalfragmentationoferythrocytesinareasofhighflow.4.血栓性血小板減少性紫癜Thromboticthrombocytopeni90危重患者血小板減少的診治課件91TTP患者肺栓塞病理TTP患者腎小球病變TTP患者肺栓塞病理TTP患者腎小球病變92DiagnosisofTTPisbasedonacombinationofclinicalsignsandsymptomsandlaboratoryvalues.

Themedianplateletcountatpresentationis10to30×109/L.