危重患者血小板减少的诊治课件

危重患者血小板减少的诊治.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、常用的检查方法危重患者中血小板减少的诊断和治疗总结病例讨论概述血小板减少的定义、机制、诊断思路、常用的检查方法2

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）

。血小板减少（thrombocytopenia）

3Hospital-acquiredthrombocytopenia.HospPract,2014Oct;42(4):142-52.Hospital-acquiredthrombocytop4危重患者血小板减少的诊治课件5危重患者血小板减少的诊治课件6

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、基础疾病（心、肝、肾等）和有创操作等的影响，及时评估、干预非常重要。血小板减少的病因多样，涉及多个学科，常规检查特异7

相关病史（基础疾病、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）相关病史（基础疾病、药物史、8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

外周血涂片EDTA抗凝剂导致的血小板9裂红细胞（破碎红细胞）裂红细胞（破碎红细胞）10球形红细胞球形红细胞11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12破坏增多骨髓检查巨核细胞数量正常或增加。部分ITP可见巨核细胞成熟障碍，产板少。破坏增多骨髓检查巨核细胞数量正常或增加。部分IT13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。

生成减少骨髓涂片巨核细胞减少。14

即Coombs直接试验:将洗涤过的红细胞2%混悬液加入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，说明红细胞表面有抗体或补体。

Coombs间接试验:先将受试的血清加入等量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。抗人球蛋白试验即Coombs直接试验:将洗涤过的红细胞2%混15血小板减少诊断简易流程血小板减少诊断简易流程16

以下的实验室方法能帮助我们进一步明确诊断以下的实验室方法能帮助我们进一步明确诊断17

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)

Aprospectiveevaluationofnormalmeanplateletvolumeindiscriminatinghyperdestructivethrombocytopeniafromhypoproductive

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

platelet

vol18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:hypoproliferativeanddestructivethrombocytopenia

Allthethree

platelet

indices

weresignificantlyhigherindestructivegroupascomparedtothehypoproliferativecategory血小板指数

（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),2009Jun;14(3):182-6.Increasedvaluesofmeanplateletvolumeandplateletsizedeviationwidthmayprovideasafepositivediagnosisofidiopathicthrombocytopenicpurpura.ActaHaematol.2008;119(3):173-7.血小板指数的局限性在于血小板严重下降的患者（<121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.2010Aug;85(2):158-63.未成熟血小板比例和网织血小板比例22

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.促血小板生成素（Thrombopoietin

，T23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.以上是简易流程，最常见的几种疾病。针对住院特别是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)

后者更难以识别。2.药物诱导免疫性血小板减少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的环境下，多种药物使用，合并多种疾病，可能难以判断。

危重患者血小板减少的诊治课件28万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

雷尼替丁万古霉素29SuspectedDITPistreatedbydiscontinuingthepotentiallyoffendingdrug.

Theplateletcounttypicallybeginstoimprovewithin1to2daysafterthedrugisstopped.Themediantimetorecoveryofplateletcountis7days.

Patientswithseverethrombocytopeniaandbleedingmaybetreatedwithplatelettransfusion.

Inparticularlyseverecases,corticosteroids,intravenousimmunoglobulin,andplasmaexchangehavebeenused,althoughthereislimitedevidenceofefficacywiththese危重患者血小板减少的诊治课件30Heparin-inducedthrombocytopenia(HIT)isanimmune-mediateddisorderthatoccursafterexposuretounfractionatedheparinorlowmolecularweightheparin.

UnlikemostotherformsofDITP,HITisgenerallyprothromboticratherthanprohemorrhagic.

Thromboticcomplications,includedeepvenousthrombosis,pulmonaryembolism,peripheralarterialthrombosis,ischemicstroke,andmyocardialinfarction.肝素诱导的血小板减少Heparin-inducedthrombocyt31危重患者血小板减少的诊治课件32anintermediateorhighprobabilityofHIT,heparinshouldbediscontinued

thepatientshouldbetreatedwithanonheparinanticoagulant（argatroban,danaparoid，bivalirudin

fondaparinux）

Oncetheplateletcounthasrecovered,patientsmaybetransitionedtowarfarin.

危重患者血小板减少的诊治课件33

Disseminatedintravascularcoagulation(DIC)occursnotinisolationbutsecondarytoanunderlyingdisorderTheseconditionsmaygenerateprocoagulantsubstances,leadingtowidespreadactivationofcoagulationanddepositionoffibrininthemicrovasculature.

Theendresultisthrombosisofsmallvesselsandend-organischemicinjury.

Acceleratedconsumptionofcoagulationfactorsandplateletsmayalsoproduceaconcomitantbleedingtendency3.弥散性血管内凝血Disseminatedintravascular34DIC的病理生理机制DIC的病理生理机制35危重患者血小板减少的诊治课件36危重患者血小板减少的诊治课件37ThecornerstoneoftherapyforDICistreatmentoftheunderlyingcondition.

Transfusionisindicatedinpatientswhoarebleedingorotherwiseathighriskforbleeding.TherapeuticheparinshouldbeconsideredinpatientswithDICcomplicatedbyovertthrombosis.AntifibrinolytictreatmentsaregenerallycontraindicatedinpatientswithDICduetoanincreasedriskofthrombosis.危重患者血小板减少的诊治课件38

Thromboticthrombocytopenicpurpura(TTP)isathromboticmicroangiopathy

Itischaracterizedbythrombocytopeniaandmicroangiopathichemolyticanemiaandmayalsoincludeneurologicsymptoms,fevers,andrenalimpairmentTTPiscausedbyadeficiencyofADAMTS13,aproteasethatcleavesvonWillebrandfactor.

IntheabsenceofADAMTS13,ultralargevonWillebrandfactormultimerspromoteformationofplateletaggregatesinthemicrovasculature,causingshearstressandmechanicalfragmentationoferythrocytesinareasofhighflow.4.血栓性血小板减少性紫癜Thromboticthrombocytopeni39危重患者血小板减少的诊治课件40TTP患者肺栓塞病理TTP患者肾小球病变TTP患者肺栓塞病理TTP患者肾小球病变41DiagnosisofTTPisbasedonacombinationofclinicalsignsandsymptomsandlaboratoryvalues.

Themedianplateletcountatpresentationis10to30×109/L.Themedianhemoglobinis8to10g/dLandisaccompaniedbymarkersofintravascularhemolysis.

Schistocytes,andoftennucleatedredcells,arefoundintheperipheralbloodsmear.

ThePTandaPTTaretypicallynormal,andthedirectCoombs

testisnegative.Patientsmayhaveacutekidneyinjuryorproteinuria.危重患者血小板减少的诊治课件42Thromboticthrombocytopenicpurpuraisamedicalemergency,andtreatmentofsuspectedTTPmustbecommencedimmediately.

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

plasmainfusionwhileawaitingexchangetherapy.

Plasmaexchangeiscontinueduntilplateletcountrecovery.

high-dosecorticosteroids,whichhavebeenshowninsomestudiestoimproveoutcomes.

Rituximab,amonoclonalantibodythattargetsCD20onBlymphocytes,iswidelyusedinpatientswithrefractoryorrelapseddisease.

platelettransfusionisrelativelycontraindicatedunlessseriousbleedingispresent.危重患者血小板减少的诊治课件43

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

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

Posttransfusionpurpuramaybetreatedwithintravenousimmunoglobulin,whichoftenincreasesplateletcountsto100×109/Lwithinseveraldays.

Thedisorderisself-limitedandplateletcountstypicallyrecoverwithin3weeks.Posttransfusionpurpurama45

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

plateletactivationandconsumption

MajorSurgery.

plateletconsumptionandhemodilution6.其它ExtracorporealCircuits46危重患者血小板减少的诊治课件47危重患者血小板减少的诊治课件48重视血涂片在诊断中的价值综合考虑临床环境（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）出血表现治疗基于及时、正确的诊断HIT和TTP是输血小板的禁忌症summary重视血涂片在诊断中的价值summary49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病例讨论患者，男，68岁，因“便血1月，腹痛20天”50

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？还需要重点查体的地方？血小板减少的原因？安排哪些检51危重患者血小板减少的诊治.危重患者血小板减少的诊治.52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概述血小板减少的定义、机制、诊断思路、常用的检查方法53

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）

。血小板减少（thrombocytopenia）

54Hospital-acquiredthrombocytopenia.HospPract,2014Oct;42(4):142-52.Hospital-acquiredthrombocytop55危重患者血小板减少的诊治课件56危重患者血小板减少的诊治课件57

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、基础疾病（心、肝、肾等）和有创操作等的影响，及时评估、干预非常重要。血小板减少的病因多样，涉及多个学科，常规检查特异58

相关病史（基础疾病、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）相关病史（基础疾病、药物史、59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

外周血涂片EDTA抗凝剂导致的血小板60裂红细胞（破碎红细胞）裂红细胞（破碎红细胞）61球形红细胞球形红细胞62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63破坏增多骨髓检查巨核细胞数量正常或增加。部分ITP可见巨核细胞成熟障碍，产板少。破坏增多骨髓检查巨核细胞数量正常或增加。部分IT64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。

生成减少骨髓涂片巨核细胞减少。65

即Coombs直接试验:将洗涤过的红细胞2%混悬液加入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，说明红细胞表面有抗体或补体。

Coombs间接试验:先将受试的血清加入等量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。抗人球蛋白试验即Coombs直接试验:将洗涤过的红细胞2%混66血小板减少诊断简易流程血小板减少诊断简易流程67

以下的实验室方法能帮助我们进一步明确诊断以下的实验室方法能帮助我们进一步明确诊断68

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)

Aprospectiveevaluationofnormalmeanplateletvolumeindiscriminatinghyperdestructivethrombocytopeniafromhypoproductive

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

platelet

vol69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:hypoproliferativeanddestructivethrombocytopenia

Allthethree

platelet

indices

weresignificantlyhigherindestructivegroupascomparedtothehypoproliferativecategory血小板指数

（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),2009Jun;14(3):182-6.Increasedvaluesofmeanplateletvolumeandplateletsizedeviationwidthmayprovideasafepositivediagnosisofidiopathicthrombocytopenicpurpura.ActaHaematol.2008;119(3):173-7.血小板指数的局限性在于血小板严重下降的患者（<172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.2010Aug;85(2):158-63.未成熟血小板比例和网织血小板比例73

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.促血小板生成素（Thrombopoietin

，T74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.以上是简易流程，最常见的几种疾病。针对住院特别是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)

后者更难以识别。2.药物诱导免疫性血小板减少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的环境下，多种药物使用，合并多种疾病，可能难以判断。

危重患者血小板减少的诊治课件79万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

雷尼替丁万古霉素80SuspectedDITPistreatedbydiscontinuingthepotentiallyoffendingdrug.

Theplateletcounttypicallybeginstoimprovewithin1to2daysafterthedrugisstopped.Themediantimetorecoveryofplateletcountis7days.

Patientswithseverethrombocytopeniaandbleedingmaybetreatedwithplatelettransfusion.

Inparticularlyseverecases,corticosteroids,intravenousimmunoglobulin,andplasmaexchangehavebeenused,althoughthereislimitedevidenceofefficacywiththese危重患者血小板减少的诊治课件81Heparin-inducedthrombocytopenia(HIT)isanimmune-mediateddisorderthatoccursafterexposuretounfractionatedheparinorlowmolecularweightheparin.

UnlikemostotherformsofDITP,HITisgenerallyprothromboticratherthanprohemorrhagic.

Thromboticcomplications,includedeepvenousthrombosis,pulmonaryembolism,peripheralarterialthrombosis,ischemicstroke,andmyocardialinfarction.肝素诱导的血小板减少Heparin-inducedthrombocyt82危重患者血小板减少的诊治课件83anintermediateorhighprobabilityofHIT,heparinshouldbediscontinued

thepatientshouldbetreatedwithanonheparinanticoagulant（argatroban,danaparoid，bivalirudin

fondaparinux）

Oncetheplateletcounthasrecovered,patientsmaybetransitionedtowarfarin.

危重患者血小板减少的诊治课件84

Disseminatedintravascularcoagulation(DIC)occursnotinisolationbutsecondarytoanunderlyingdisorderTheseconditionsmaygenerateprocoagulantsubstances,leadingtowidespreadactivationofcoagulationanddepositionoffibrininthemicrovasculature.

Theendresultisthrombosisofsmallvesselsandend-organischemicinjury.

Acceleratedconsumptionofcoagulationfactorsandplateletsmayalsoproduceaconcomitantbleedingtendency3.弥散性血管内凝血Disseminatedintravascular85DIC的病理生理机制DIC的病理生理机制86危重患者血小板减少的诊治课件87危重患者血小板减少的诊治课件88ThecornerstoneoftherapyforDICistreatmentoftheunderlyingcondition.

Transfusionisindicatedinpatientswhoarebleedingorotherwiseathighriskforbleeding.TherapeuticheparinshouldbeconsideredinpatientswithDICcomplicatedbyovertthrombosis.AntifibrinolytictreatmentsaregenerallycontraindicatedinpatientswithDICduetoanincreasedriskofthrombosis.危重患者血小板减少的诊治课件89

Thromboticthrombocytopenicpurpura(TTP)isathromboticmicroangiopathy

Itischaracterizedbythrombocytopeniaandmicroangiopathichemolyticanemiaandmayalsoincludeneurologicsymptoms,fevers,andrenalimpairmentTTPiscausedbyadeficiencyofADAMTS13,aproteasethatcleavesvonWillebrandfactor.

IntheabsenceofADAMTS13,ultralargevonWillebrandfactormultimerspromoteformationofplateletaggregatesinthemicrovasculature,causingshearstressandmechanicalfragmentationoferythrocytesinareasofhighflow.4.血栓性血小板减少性紫癜Thromboticthrombocytopeni90危重患者血小板减少的诊治课件91TTP患者肺栓塞病理TTP患者肾小球病变TTP患者肺栓塞病理TTP患者肾小球病变92DiagnosisofTTPisbasedonacombinationofclinicalsignsandsymptomsandlaboratoryvalues.

Themedianplateletcountatpresentationis10to30×109/L.