D-dimerassaysMethodologyandApplication北京大学第一医院检验科王建中JianzhongWang,Prof.jw4ub@yahoo.com.cnDdimerD-dimerAmarkerofcoagulationandfibrinolysisactivationAmarkerofacutethrombosisfhbblidiiforthromboembolismdiagnosisJianzhongWang,Prof.jw4ub@yahoo.com.cnAcuteThrombosislocationinthecirculationAcutethromboticeventsinthebloodcirculationCVTAcutethromboticeventsinthebloodcirculationVenousArterialMicrocirculationDeepvenousAcutecoronaryDisseminatedStrokePEDeepvenousthrombosis(DVT)Pulmonaryembolism(PE)Acutecoronarysyndromes(ACS)Disseminatedintravascularcoagulation(DIC);dtiACSe.g.duetosepsisCerebralvenousthrombosis(CVT)StrokeCross-linkedFibrinDegradationPdtProducts(D-dimer)DVTJianzhongWang,Prof.jw4ub@yahoo.com.cnDdiftiD-dimerformationJianzhongWang,Prof.jw4ub@yahoo.com.cnCoagulationFXIIIgThrombinFXIIIaDDEFibrinogenFibrinMonomerCross-linkedFibrinClotDDPlasminFragmentXEFragmentYFragmentDDDD-DimerFibrinolysisFragmentEDDDDDDDDDDEFDPJianzhongWang,Prof.jw4ub@yahoo.com.cn3.53.5FPAFPAHalfHalf--life(min)ofcoagulationlife(min)ofcoagulation1515TATTATHalfHalflife(min)ofcoagulationlife(min)ofcoagulationActivationmarkersActivationmarkers1515IXactiv.peptideIXactiv.peptide90903030F1+2(II)F1+2(II)Xactiv.peptideXactiv.peptide1501509090VIIaVIIaF1+2(II)F1+2(II)480480DD--dimerdimer0100200300400500600JianzhongWang,Prof.jw4ub@yahoo.com.cnMeasurementMeasurementofD-dimerlevelfmJianzhongWang,Prof.jw4ub@yahoo.com.cnD-dimerAssayMethodologyimmunoassayprinciplesELISATwoanti-D-dimermonoclonalantibodies:catchingandenzyme-labelledtaggingManual(microplateimmunefiltration)Manual(microplate,immunefiltration)Automated(ELFA,enzyme-linkedfluorescenceassay;VIDAS®)RedbloodcellagglutinationBi-specificmonoclonalantibody(redcellsandD-dimer)Manual,wholeblood(SimpliRED®)LatexparticleagglutinationSingleanti-D-dimermonoclonalantibodyManual(slide)Automated(immunoturbidimetric;variousanalyzers)JianzhongWang,Prof.jw4ub@yahoo.com.cnAutomated(immunoturbidimetric;variousanalyzers)EifthDEifthDdilldillExpressionoftheDExpressionoftheD--dimerleveldimerlevelDDU:DDDU:D--dimerunit,dimerunit,µg/ml(orµg/ml(orngng/ml,mg/L)/ml,mg/L)FEU:FibrinogenEquivalentUnit.FEU:FibrinogenEquivalentUnit.µg/ml(orµg/ml(orngng/ml/ml,,mg/Lmg/L)),theDDUconcentrationisapproximatelyhalfof,theDDUconcentrationisapproximatelyhalfofmg/Lmg/L)),thDDconcntratonsappromatyhafof,thDDconcntratonsappromatyhafoftheFEUtheFEUhfhfTheuseofSIunitsTheuseofSIunitsJianzhongWang,Prof.jw4ub@yahoo.com.cnDditD-dimermeasurementDdiiidifliii•D-dimerisanindicatorofcoagulationactivation,cross-linkedfibrinformationandhyperfibrinolysisinvivoinvivo•MolecularweightofD-dimerisaround180kD•Monoclonalantibodiesweredeveloped,whichp,recongizeepitopesforD-dimer•ArapidsampleturnaroundtimeforD-dimertestissstilisessential•D-dimermeasurementshouldbereachedwithinminutesratherthanhoursminutesratherthanhoursJianzhongWang,Prof.jw4ub@yahoo.com.cnJTH2008,6:1059-1071JianzhongWang,Prof.jw4ub@yahoo.com.cnJTH2007,5:296-304JianzhongWang,Prof.jw4ub@yahoo.com.cnStandardizationofStandardizationoftheD-dimerassaystheDdimerassaysJianzhongWang,Prof.jw4ub@yahoo.com.cnStandardizationoftheD-dimerassays•ThecalibratorsforDDunitsWithithi•Withvarioustechniques•Differentcut-offs•SystemsofunitsOtilhtiti•Operationalcharacteristics•ClinicalvaliditynaayJianzhongWang,Prof.jw4ub@yahoo.com.cnStandardizationoftheD-dimerassays•Comprehensivereferencesystem:–referencemethod–Primarystandard–UseofSIunitsUseofSIunts•D-dimerisnotasingleentity•D-dimerisacomplexmixtureofdegradationDdimerisacomplexmixtureofdegradationproductsofdifferentsize•ResultsofD-dimerassayisamethod-specificyp•TomaketestresultscomparableJianzhongWang,Prof.jw4ub@yahoo.com.cnDdimerisnotasingleanalyteD-dimerisnotasingleanalyteHeterogeneouscompositionoffibrindegradationproductsMultipleDdimerepitopesDDMultipleD-dimerepitopesQuantityandsizedistributionariesbeteenindiidalsandDDvariesbetweenindividualsandbetweendiseasestatesHihllihfDDHighmolecularweightfragmentsaremostabundantDDDDDDDDDDEJianzhongWang,Prof.jw4ub@yahoo.com.cnD-dimerasadiagnostictest•D-Dimerforrulingoutvenousthromboembolism•D-Dimerfordiagnosing(rulingin)venousthbblithromboembolism•UseofDDtestinginspecialpopulations–ElderlypatientsElderlypatients–Cancerpatients–PatientswithpreviousDVT/PE–Pregnantwomen–PatientswithasmallthrombusburdenPtitldtiltttt–Patientsalreadyonanticoagulanttreatment•D-dimerasaprognosticmarkerinpatientswithVTEJianzhongWang,Prof.jw4ub@yahoo.com.cnInterpretationoftheDInterpretationoftheD--dimerleveldimerlevelInterpretationoftheDInterpretationoftheDdimerleveldimerlevelDD--dimer0.5mg/Ldimer0.5mg/LÎÎfurtherinvestigationsfurtherinvestigationsDVT/PE/ATEDVT/PE/ATE→→DVT/PE/ATEDVT/PE/ATE→→DICDIC→→CancerCancer→→CancerCancer→→SepsisSepsis→→Elderly,inflammation,postElderly,inflammation,post--surgery…surgery…ypypgygy→→OACefficacyOACefficacy0.5mg/L………………………….cutoffforVTEexclusion0.5mg/L………………………….cutoffforVTEexclusionJianzhongWang,Prof.jw4ub@yahoo.com.cnDD--dimertests:clinicalperformancedimertests:clinicalperformanceatacutoffof0.5mg/Latacutoffof0.5mg/L