肝素誘導(dǎo)的血小板減少癥

肝素誘導(dǎo)的血小板減少癥演示文稿當(dāng)前第1頁\共有41頁\編于星期五\12點(diǎn)（優(yōu)選）肝素誘導(dǎo)的血小板減少癥當(dāng)前第2頁\共有41頁\編于星期五\12點(diǎn)Epidemiologythechanceofsignificantexposuretoheparinexceeds50%inhospitalizedpatientsacutecoronarysyndrome(UA/MI)pulmonaryembolismdeepvenousthrombosisandprophylaxisatrialfibrillation/strokeheparinizedpulmonarywedgecathetersPCIIABPSemiThrombHemost1999;25Suppl1:57-60當(dāng)前第3頁\共有41頁\編于星期五\12點(diǎn)U.S.EstimatedCausesofAccidentalDeaths〈100040,00090,000Deathsperyear當(dāng)前第4頁\共有41頁\編于星期五\12點(diǎn)MedicationErrors–HospitalAudit%REFERENCE當(dāng)前第5頁\共有41頁\編于星期五\12點(diǎn)血小板減少癥（HIT/HITS）

美國每年有1200萬人因肢體或肺部血栓、心臟病或血管成型術(shù)而接受肝素治療36萬人發(fā)生HIT12萬人出現(xiàn)血栓并發(fā)癥（靜脈、動脈）3.6萬人死亡

當(dāng)前第6頁\共有41頁\編于星期五\12點(diǎn)Heparin-inducedThrombocytopeniaHeparin-inducedthrombocytopenia(HIT),anantibody-mediatedsyndrome,isassociatedwithsignificantmorbidityandmortalityconsideredararityinthepastunrecognizedbymanycliniciansdiagnosescanbedifficulttoconfirmuntilrecentlytherewasnotherapeuticoptionsotherthandiscontinuationofheparin當(dāng)前第7頁\共有41頁\編于星期五\12點(diǎn)EpidemiologythrombocytopeniaisoneofthemostcommonlaboratoryabnormalitiesfoundamonghospitalizedpatientsserologicallyprovenHIToccursin1.5%to3%ofpatientswithheparinexposureNEnglJMed1995;332:1330-5當(dāng)前第8頁\共有41頁\編于星期五\12點(diǎn)CascadeofeventsleadingtoformationofHITantibodiesandprothromboticcomponents當(dāng)前第9頁\共有41頁\編于星期五\12點(diǎn)BleedingandClottingthemostfearedconsequenceinthesepatientswithalowplateletcountisnotbleedingbutclottingpresentwithmucocutaneousbleeding,rangingfrompetechiaeandecchymosestolife-threateninggastrointestinalandintracranialhemorrhage

當(dāng)前第10頁\共有41頁\編于星期五\12點(diǎn)Thrombosisthrombosisismostlyvenousnotarterialmayresultinbilateraldeepvenousthrombosisofthelegspulmonaryembolismvenousgangreneoffingers,toes,penis,ornipplesmyocardialinfarction,strokemesentericarterialthrombosislimbischemiaandamputationCirculation1999;100:587-93

AmJMed1996;101:502-7

ThrombHaemost1993;70:554-61當(dāng)前第11頁\共有41頁\編于星期五\12點(diǎn)OtherClinicalFeaturesSkinlesionsatheparininjectionsiteSkinnecrosisAcuteplateletactivationAcuteinflammatoryreactions(fever,chills,etc.)當(dāng)前第12頁\共有41頁\編于星期五\12點(diǎn)SkinNecrosisUsedwithpermissionfromWarkentinTE.BrJHaematol.1996;92:494–497.當(dāng)前第13頁\共有41頁\編于星期五\12點(diǎn)VenousLimbGangrene

UsedwithpermissionfromWarkentinTE,ElavathilLJ,HaywardCPM,JohnstonMA,RussettJI,KeltonJG.AnnInternMed.1997;127:804–812.當(dāng)前第14頁\共有41頁\編于星期五\12點(diǎn)MorbidityandMortalityHIT-associatedmortalityishigh(about18%)5%ofaffectedpatientsrequirelimbamputationOvertbleedingorbruisingisrareevenwithseverethrombocytopeniaAppropriatemanagementcanlimitmorbidityandmortality當(dāng)前第15頁\共有41頁\編于星期五\12點(diǎn)HITSyndromeTypeInonimmunologicmechanisms(milddirectplateletactivationbyheparin)associatedwithanearly(within4days)andusuallymilddecreaseinplateletcount(rarely<100x109/L)typicallyrecoverswithin3daysdespitecontinueduseofheparinnotassociatedwithanymajorclinicalsequelaeoccursprimarilywithhighdoseivheparin當(dāng)前第16頁\共有41頁\編于星期五\12點(diǎn)HITSyndromeTypeIIinducedbyimmunologicmechanismssubstantialfallinplateletcount(>50%)countinthe50,000-80,000/mmrangetypicalonsetof4-14daysoccurswithanydosebyanyroutepotentialfordevelopmentoflife-threateningthromboemboliccomplicationsrarelycausesbleeding當(dāng)前第17頁\共有41頁\編于星期五\12點(diǎn)RisksforHITTypeIintravenoushigh-doseheparinTypeIIvarieswithdoseofheparinunfractionatedheparin>LMWHbovine>porcinesurgical>medicalpatients當(dāng)前第18頁\共有41頁\編于星期五\12點(diǎn)DiagnosisofHITabsenceofanotherclearcauseforthrombocytopeniathetimingofthrombocytopeniathedegreeofthrombocytopeniaadverseclinicalevents(mostoftenthrombocytpenia)positivelaboratorytestsforHITantibodies當(dāng)前第19頁\共有41頁\編于星期五\12點(diǎn)Pathogenesisof

Drug-inducedthrombocytopeniaCertaindrugs(quinine,quinidine,sulfaantibiotics)linknon-covalentlytoplateletmembraneglycoproteinsveryrarely,IgGantibodiesareproducedthatrecognizethesedrug-glycoproteincomplexesmacrophagesremovethecomplexescausingseverethrombocytopenia當(dāng)前第20頁\共有41頁\編于星期五\12點(diǎn)ComparisonofHITandother

Drug-InducedThrombocytopenia

HIT

Quinine/SulfaFrequency ~1/100 ~1/10,000Onset 5-8days 7daysPlateletcount 20-150x109/L <20x109/LSequelae Thrombosis BleedingLaboratory Immunoassay Platelet- (heparin/PF4) associatedIgG

當(dāng)前第21頁\共有41頁\編于星期五\12點(diǎn)UnusualClinicalEventsSuspiciousforHITmildtomoderatethrombocytopenia,ofteninconjunctionwiththrombosisadrenalhemorrhagicinfarction(causedbyadrenalveinthrombosis)warfarin-inducedvenouslimbgangrenefever,chills,beginning5to30minutesafteranIVheparinbolusheparin-inducedskinlesionsassociatedwithHITantibodies,evenintheabsenceofthrombocytopania

當(dāng)前第22頁\共有41頁\編于星期五\12點(diǎn)OtherClinicalFeatures

SuspiciousforHITarapiddropinplateletsmayalsobeindicativeofHIT,particularlyifthepatientsreceivedheparinwithintheprevious3monthsafallinplateletcountof>50%thatbeginsafter5daysofheparintherapy,butwiththeplateletcount>150x109/L,shouldalsoraisethesuspicionofHIT

當(dāng)前第23頁\共有41頁\編于星期五\12點(diǎn)CommonLaboratoryTestsforHITTest Advantages DisadvantagesPAA Rapidandsimple Lowsensitivity-notsuitablefor testingmultiplesamplesSRA Sensitivity>90% Washedplatelet(technically demanding),needsradiolabeled material14CHIPA Rapid,sensitivity>90%WashedplateletsELISA Highsensitivity, Highcost,lowerspecificityfor clinicallysignificantHIT ThrombHaemost1998;79:1-7plateletaggregationassay(PAA)serotoninreleaseassay(SRA)heparininducedplateletactivation(HIPA)當(dāng)前第24頁\共有41頁\編于星期五\12點(diǎn)FunctionalAssayPlateletaggregationassay(PAA)performedbymanylaboratoriesincubateplatelet-richplasmafromnormaldonorswithpatientplasmaandheparinlimitedbypoorsensitivityandspecificitybecauseheparincanactivateplateletsundertheseconditions,evenintheabsenceofHITantibodies當(dāng)前第25頁\共有41頁\編于星期五\12點(diǎn)AntigenAssayAntibodiesagainstheparin/PF4complexes(themajorantigenofHIT)aremeasuredbycolorimetricabsorbanceTwoELISAhavebeendevelopedStagoGTIlimitedbyhighcost當(dāng)前第26頁\共有41頁\編于星期五\12點(diǎn)ManagementofHITriskforthrombosisishighinHIT,preventionofthrombosisisthegoalofinterventionhepariniscontraindicatedinpatientswithHITdiscontinuationofheparin-allsourcesofheparinmustbeeliminatedmostpatientswillrequiretreatmentwithanalternateanticoagulantforinitialclinicalproblemHITinducedthrombosis當(dāng)前第27頁\共有41頁\編于星期五\12點(diǎn)HIT處理措施

藥物 可用

禁用

評價

華法令

x warfarinintheabsenceofananticoagulant

canprecipitatevenouslimbgangrene

補(bǔ)充血小板

x infusingplateletsmerely“addsfueltothefire”

靜脈濾器

x

oftenresultsindevastatingcaval,pelvic,and

lowerlegvenousthrombosis

低分子肝素

x lowmolecularweightheparinusuallycross-

reactwithunfractionatedheparinafterHITor

HITTS(HITthrombosissyndrome)hasoccurred

水蛭素/阿加曲班

x Bewarerenalinsufficiency,antibodyformation

血漿置換

x removesmicro-particlesformedfromplatelet

activation;notastandardindication

阿司匹林

xcaninhibitplateletactivationbyHIT

氯吡格雷

xantibodies

Gp2b/3a受體

x

阻滯劑當(dāng)前第28頁\共有41頁\編于星期五\12點(diǎn)StepstoPreventHITporcineheparinpreferredoverbovineheparinLMWHpreferredoverunfractionatedheapirnoralanticoagulationshouldbestartedasearlyaspossibletoreducethedurationofheparinexposureintravenousadaptersshouldnotbeflushwithheparinmonitoringserialplatecountsfordevelopingthrombocytopenia當(dāng)前第29頁\共有41頁\編于星期五\12點(diǎn)第七次ACCP抗栓和溶栓會議

肝素誘導(dǎo)的血小板減少癥防治指南

當(dāng)前第30頁\共有41頁\編于星期五\12點(diǎn)HIT監(jiān)測—血小板計(jì)數(shù)接受治療劑量UFH患者，建議隔日血小板計(jì)數(shù)，直到第14天或直至停用UFH(2C級)100天內(nèi)接受過UFH治療的患者或既往是否使用過UFH的病史不詳者，再次開始使用UFH或LMWH時，建議先進(jìn)行血小板計(jì)數(shù)，隨后在肝素治療后的24小時以內(nèi)再次血小板計(jì)數(shù)(2C級)當(dāng)前第31頁\共有41頁\編于星期五\12點(diǎn)HIT監(jiān)測—血小板計(jì)數(shù)

靜脈UFH注射后30min內(nèi)出現(xiàn)發(fā)熱、寒戰(zhàn)、呼吸困難、或其他不常見的癥狀體征，建議立即進(jìn)行血小板計(jì)數(shù)，并與先前的計(jì)數(shù)值進(jìn)行比較(1C級)

當(dāng)前第32頁\共有41頁\編于星期五\12點(diǎn)HIT監(jiān)測—血小板計(jì)數(shù)

HIT發(fā)生率不高患者（0.1-1%）下列患者建議術(shù)后4-14天，至少隔2-3天進(jìn)行血小板計(jì)數(shù)（或直到停用UFH）(2C級)

內(nèi)科/產(chǎn)科患者預(yù)防性使用UFH術(shù)后患者預(yù)防性使用LMWHUFH沖洗穿刺導(dǎo)管或內(nèi)科/產(chǎn)科患者使用過UFH后接受LMWH治療當(dāng)前第33頁\共有41頁\編于星期五\12點(diǎn)HIT監(jiān)測—血小板計(jì)數(shù)

HIT發(fā)生率很低患者（<0.1%）僅接受LMWH治療的內(nèi)科/產(chǎn)科患者或僅在血管內(nèi)介入治療中使用UFH的患者（HIT危險(xiǎn)<0.1%），建議臨床醫(yī)師不常規(guī)使用血小板監(jiān)測(2C級)

當(dāng)前第34頁\共有41頁\編于星期五\12點(diǎn)HIT監(jiān)測—血小板計(jì)數(shù)

HIT抗體篩查使用肝素的患者，如果無血小板減少癥、血栓形成、肝素誘發(fā)