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Laboratory

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LaboratoryLabora

    Laboratory

29年第15卷第4

    ;LaboratoryDetectionforAntiplateletTherapy ;

    ;?

    ;147?

    ;?(Commentaries)

    ;BAOChengxin包承鑫

    ;fInstituteofHematolpgyChineseAcademyofMedicalSciences.Tianjin,300020,China)

    ;Keywords:Laboratorydetection;Antiplatelettherapy ;[CLCnumber]R446[Documentcode]C[Article]10096213(2009)04_14702

    ;Lowresponsivenesstoantiplateletdrugsisanemer

    ;gingclinicalentitywithpotentiallysevereconsequences ;suchasrecurrentmyocardialinfactionordeath,butthe ;pathoph~rsiologicalmechanismofindividualinadequate ;responseremainincompletelydefined.Inrecentyears, ;theissueofresistancetoantiplateletagents,inparticular ;aspirinandthienopyridines,hasbeenlargelyemphasized ;inthemedicalliterature.

    ;Thereforeidentificationofpatientswithhighresidual ;plateletreactivitymaybeusefultopredicttheirriskof ;atherothromboticevents.

    ;Avarietyofmethodshavebeenutilizedtoassess ;plateletfunctionandinhibitionduringantiplateletthera

     ;PY.Amongtheavailablemethods,lighttransmissionag

    ;gregometry(LTA)hasbeenthemostwidelyused. ;LTAmeasureslightpassingthroughasampleof ;PRP.Asplateletsaggregate,morelightpassesthrough ;thesample.Maximumlighttransmittanceissetonthe ;aggregometerwithplateketpoorplasma.Minimumlight

    ;transmittanceissetwithallaliquotofPRPbeforeaggre

    ;gation.Thesedetermine100%and0%aggregation.The ;mostcommonmethodemployedtodetermineaplatelet ;DharmacodynamicresponseisIJrrA.Thismethodhas ;beenwidelyappliedtothecharacterizationandclinical ;developmentofantiplateletagents.However,prospective ;andretrospectivestudieshaveshownthatLTAisnotide- ;alfortestingplateletsensitivitytoaspirinorthienopyri

    ;dines.BecauseLTAhasseverallimitations,including ;theneedforaspecializedlaboratoryandalackofstand

    ;ardizationinreagents,protocols,andequipment,soits ;routineusetoguideantiplatelettherapyisunproven? ;Therefore.somenewtechniqueshavebeendeveloped. ;Theincidenceofaspirinresistancevariedbetween ;5.5%61%thatusedunspecifictestsplateletaggrega

    ;tiontomonitoraspirineffect.However,theincidenceof ;aspirinresistancerangedbetween1%;1.7%instud

    ;ies.whentestedwitharachidonicacidinducedplatelwt

    ;aggregation.Themethodstopredictandidentifyaspirin ;resistancearestillunclear.

    ;Inrecentyears,itisfoundthatsubjectsaremore ;sensitivetostimulationwithsubmaximalconcentrationof ;agonistcomparedtononaspirinresistance.Therefore,it ;issuggestedthatplateletaggregationtestwithsubmaxi? ;malstimulationcouldpredictresponsestoaspirin.The ;resuItsformGuthikondaeta1.hasshownwhichthenega

    ;tivepredictivevalue(93%)andsensitivity(80%)were ;highpredictingplateletresistanceusingasubmaximal ;stimulationwitharachidonicacid(0.75mM). ;Wholebloodaggregometrymeasuresthechangein ;electricalimpedancewhichoccurswhenplateletsforman ;aggregateonplatinumelectrodesaftertheadditionofago ;nists.Inthe2006s.Dynabyte(Munich,Germany)de

    ;velopedanewgenerationimpedanceaggregometer.The ;deviceiscalledMultiplateanalyzer(MEA),indicating ;themultiplicityofchannelsandsensorsperchannelof ;thedevice.OneMuhiplatetestcellincorporatestwoin

    ;dependentsensorunits.Oneunitconsistsoftwosilver

    ;coatedhighlyconductivecopperwireswithalengthof3. ;2mm.TheresultsofMEAcorrelatewellwithLTAand ;maybehelpfulinantiplateletregimesinpatientssched ;uledf0rPCI.However,veryfewexperiencewiththis ;techniqueisavailableforassaymentoftheeffectsofanti? ;plateletagentsonplateletaggregation.

    ;Wholebloodplateletaggregationmeasuredbyplate- ;letcountingisaneasyandextremelysensitivemethodto ;studyplateletaggregation.Itisbasedontheprinciple ;?

    ;l48?

    ;thatsingleplateletcountsinsamplewithEDTAandsam

    ;plethathasbeenactivatedwithADP,itispossibletoas- ;sessplateletfunctionandmoresensitivethanIJTA.How

    ;ever,nowveryfewexperiencewiththistechniqueisa

    ;vailable,anditshouldnotbeusedtoevaluatetheeffects

;ofantiplateletagents.

    ;VerifyNow,formerlyknownastheUltegraRapid ;PlateletFunctionAnalyzer(RPFAAccumetrics,SanDie

    ;go,CA.USA),isapointofcare(POC)devicedesigned ;tomeasureplateletaggregationinwholeblood.Thisde

    ;viceisbasedupontheprinciplethatfibrinogencoated

    ;beadswillagglutinateinwholebloodinpropo~iontothe ;numberofplateletGPI1b/nlareceptors.Adisposable ;cartridgecantainsfibrinogencoatedbeadsandaplatelet

    ;activator(TRAP,thrombinreceptoractivatingpeptide) ;withinreactionwel1.Resultsareobtainedwithin1rain, ;theinstrumentmirrorsbothplateletaggregometryandthe ;degreeofGPI1b/llIablockade,andthisinstrumentmay ;alsobeusefulformonitoringaspirinandelopidogre1. ;ThreeVerifyNowassaysareavailable:theVerifyNow ;GPIIb/IIIaassay,theVerifyNowaspirinassayandthe ;VerifyNowP2Y12assay.RPFA-VerifyNowisprobably ;morespecificthanagonistinducedplateletaggregation

    ;withLTAformonitoringaspirinandclopidogreltreat? ;ment.

    ;ThebleedingtimeinventedbyDuke(1912)wasthe ;firstinvivotestofplateletfunction,itispoorlyrepro

    ;ducible,invasive,insensitiveandtimeconsuming.Itdis

    ;playslowsensitivitytodruginduceddefectofplatelet

    ;functionandshouldnotbeusedtoevaluatetheeffectsof ;antiplateletagents.

    ;Inthemid-1990s,Dade/Behringdevelopeda

    ;commercialanalyzercalledthePFA100.Theprinciple

    ;ofthemethodistoexposeplateletswithincitratedwhole ;bloodtohighshear(5000;6O00/s)withinacapillary

    ;andthenmonitorthedropinflowrateastheplateletform ;ahaemostatieplugwithinanaperturewithinthecentreof ;amembranecoatedwithcollagenandeitherADPorepi

    ;nephrine.Thetestrecordsthevalidatedparametercalled ;theclosuretimeandthein.flowrateandtotalvolumeof ;bloodusedinthetest.Itssensitivitytodruginducedde

    ;feetsofplateletfunctionislow,closuretimesofcollagen ;plusepinephrinecartridgemaybeprolongedinsome, ;ChineseJournalofThrombosisandHemostasis2009Vol15No4 ;butnotallpatientsonaspirintreatment,whilevariable ;butoftennormalclosuretimehavebeenobservedoncar. ;tridgesinsamplesfrompatientsreceivingclopidogrel ;therapy.Therefore,thePFA100systemisnotanade

    ;quatemethodtomeasureplateletinhibitionbyaspirinor

;thienopyridines.

    ;Vasodilatorstimulatedphosphoprotein(VASP)isa ;relativelynewassaythatmeasuresP2Yl2functionmore ;directlyandislessdependentthanADP-inducedLTAon ;otherpathwaystoyieldthefinalassayendpoint.There- ;fore,itrepresentsahighlyspecificassayformeasuring ;theeffectsofthienopyridinesandotherdrugsinhibiting ;theplateletP2Yl2receptor.Therewasagoodcorrelation ;betweenADP?-inducedplateletaggregationandVASP?- ;phosphorylationassayindetecingP2Y12inhibition.The ;VASPassayismoredirectmeasureofP2Y12function. ;Morerecentlypreliminarydatasuggestasimilarrelation- ;shipbetweenhighVASPPRIandadversecardiovascular

    ;eventsafterpercutaneouscoronaryinterventions,inclu? ;dingstentthrombosis.Therefore,VASPassayisamore ;usefulmethodformonitoringofantiplatelettherapy. ;Thromboelastography(TEG)measurestheclots ;physicalproperty.Itssensitivitytoaspirinandclopidogrel ;Wasshowntobeacceptable.SerumthromboxaneB2 ;(TXB2)isthemostspecifictesttomeasurethepharma- ;eologiealeffectofaspirin,.The11dehydrothromboxane

    ;B2isaTXB2metaboliteintheurineandreflectssystem- ;icTXA2formation,butabout30%oftheurinarymetab- ;olitederivesfromextraplateletsources.Therefore,de-

    ;tectionof11dehydrothromboxaneB2isnothighlyspeeiG ;icformonitoringtheeffectsofaspirinoffplateletCOX?1. ;Uptonow,themethodsformonitoryingofantiplate

    ;lettherapyhasseveraldrawbacks,andwedontknow ;howtoaddressfollowingtwoquestions:

    ;(1)Ismonitoringwiththislaboratorytestclinically ;effective?

    ;(2)Islaboratorymonitoringofantiplatelettherapy ;costeffeetive.

    ;9

    ;Therefore,peoplethinkthatmonitoringofantiplate

    ;lettherapyshouldbeconsideredforinvestigationalpur

    ;posesonly.

    ;(收稿13:2008.10.11)

    ;

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