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D-dimer - Wikipedia, the free encyclopedia

Ddimer
FromWikipedia,thefreeencyclopedia

Ddimerisafibrindegradationproduct(orFDP),asmallproteinfragmentpresentinthebloodaftera bloodclotisdegradedbyfibrinolysis.ItissonamedbecauseitcontainstwocrosslinkedDfragmentsof thefibrinprotein.[1] Ddimerconcentrationmaybedeterminedbyabloodtesttohelpdiagnosethrombosis.Sinceits introductioninthe1990s,ithasbecomeanimportanttestperformedinpatientssuspectedofthrombotic disorders.Whileanegativeresultpracticallyrulesoutthrombosis,apositiveresultcanindicatethrombosis butdoesnotruleoutotherpotentialcauses.Itsmainuse,therefore,istoexcludethromboembolicdisease wheretheprobabilityislow.Inaddition,itisusedinthediagnosisoftheblooddisorderdisseminated intravascularcoagulation.[1]

Contents
1Principles 2Indications 3Testproperties 4History 5References

Principles
Coagulation,theformationofabloodclotorthrombus,occurswhentheproteinsofthecoagulation cascadeareactivated,eitherbycontactwithdamagedbloodvesselwall(intrinsicpathway)orby activationoffactorVIIbytissueactivatingfactors.Bothpathwaysleadtothegenerationofthrombin,an enzymethatturnsthesolublebloodproteinfibrinogenintofibrin,whichaggregatesintoproteofibrils. Anotherthrombingeneratedenzyme,factorXIII,thencrosslinksthefibrinproteofibrilsattheDfragment site,leadingtotheformationofaninsolublegelwhichservesasascaffoldforbloodclotformation.[1] Thecirculatingenzymeplasmin,themainenzymeoffibrinolysis,cleavesthefibringelinanumberof places.Theresultantfragments,"highmolecularweightpolymers",aredigestedseveraltimesmoreby plasmintoleadtointermediateandthentosmallpolymers(fibrindegradationproductsorFDPs).The crosslinkbetweentwoDfragmentsremainsintact,however,andtheseareexposedonthesurfacewhen thefibrinfragmentsaresufficientlydigested.ThetypicalDdimercontainingfragmentcontainstwoD domainsandoneEdomainoftheoriginalfibrinogenmolecule.[1] Ddimersarenotnormallypresentinhumanbloodplasma,exceptwhenthecoagulationsystemhasbeen activated,forinstancebecauseofthepresenceofthrombosisordisseminatedintravascularcoagulation. TheDdimerassaydependsonthebindingofamonoclonalantibodytoaparticularepitopeontheD dimerfragment.Severaldetectionkitsarecommerciallyavailableallofthemrelyonadifferent monoclonalantibodyagainstDdimer.Forsomeofthese,theareaoftheDdimertowhichtheantibody bindsisknown.Thebindingoftheantibodyisthenmeasuredquantitativelybyoneofvariouslaboratory methods.[1]

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Indications
Ddimertestingisofclinicalusewhenthereisasuspicionofdeepvenousthrombosis(DVT),pulmonary embolism(PE)ordisseminatedintravascularcoagulation(DIC).[2]Itisunderinvestigationinthediagnosis ofaorticdissection.[3][4] ForDVTandPE,therearepossiblevariousscoringsystemsthatareusedtodeterminetheaprioriclinical probabilityofthesediseasesthebestknownwereintroducedbyWellsetal.(2003). Foraveryhighscore,orpretestprobability,aDdimerwillmakelittledifferenceandanticoagulant therapywillbeinitiatedregardlessoftestresults,andadditionaltestingforDVTorpulmonary embolismmaybeperformed. Foramoderateorlowscore,orpretestprobability:[5] AnegativeDdimertestwillvirtuallyruleoutthromboembolism:thedegreetowhichtheD dimerreducestheprobabilityofthromboticdiseaseisdependentonthetestpropertiesofthe specifictestusedintheclinicalsetting:mostavailableDdimertestswithanegativeresultwill reducetheprobabilityofthromboembolicdiseasetolessthan1%ifthepretestprobabilityis lessthan1520% IftheDdimerreadshigh,thenfurthertesting(ultrasoundofthelegveinsorlungscintigraphy orCTscanning)isrequiredtoconfirmthepresenceofthrombus.Anticoagulanttherapymay bestartedatthispointorwithhelduntilfurthertestsconfirmthediagnosis,dependingonthe clinicalsituation. Insomehospitals,theyaremeasuredby laboratoriesafteraformiscompleted showingtheprobabilityscoreandonlyif theprobabilityscoreislowor intermediate.Thisreducestheneedfor unnecessarytestsinthosewhoarehigh probability.[6]PerformingtheDdimertest firstcanavoidasignificantproportionof imagingtestsandislessinvasive.Since theDdimercanexcludetheneedfor imaging,specialtyprofessional organizationsrecommendthatphysicians useDdimertestingasaninitial diagnostic.[7][8][9][10]

Testproperties
Variouskitshavea9395%sensitivityand about50%specificityinthediagnosisof thromboticdisease.[11] Falsepositivereadingscanbedue tovariouscauses:liverdisease,high rheumatoidfactor,inflammation, malignancy,trauma,pregnancy, recentsurgeryaswellasadvanced
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PrinciplesofDdimertesting

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age[citationneeded ] Falsenegativereadingscanoccurifthesampleistakeneithertooearlyafterthrombusformationor iftestingisdelayedforseveraldays.Additionally,thepresenceofanticoagulationcanrenderthe testnegativebecauseitpreventsthrombusextension. Falsevaluesmaybeobtainedifthespecimencollectiontubeisnotsufficientlyfilled(falselowvalue ifunderfilledandfalsehighvalueifoverfilled).Thisisduetothedilutionaleffectofthe anticoagulant(thebloodmustbecollectedina9:1bloodtoanticoagulantratio). Likelihoodratiosarederivedfromsensitivityandspecificitytoadjustpretestprobability. Ininterpretationoftheddimer,forpatientsoverage50avalueofageX10maybeabnormal.[12][13]

History
Ddimerwasoriginallydescribedinthe1970s,andfounditsdiagnosticapplicationinthe1990s.[1]

References
1. ^ a b c d e fAdamSS,KeyNS,GreenbergCS(March2009)."Ddimerantigen:currentconceptsandfuture prospects"(http://bloodjournal.hematologylibrary.org/cgi/content/full/113/13/2878). Blood 113(13):2878 2887.doi:10.1182/blood200806165845(http://dx.doi.org/10.1182%2Fblood200806165845). PMID19008457(//www.ncbi.nlm.nih.gov/pubmed/19008457). 2. ^GeneralPracticeNotebook>Ddimer(http://www.gpnotebook.co.uk/simplepage.cfm?ID=26869806) RetrievedSeptember2011 3. ^Suzuki,T.Distante,A.Eagle,K.(2010)."Biomarkerassisteddiagnosisofacuteaorticdissection:Howfar wehavecomeandwhattoexpect". CurrentOpinioninCardiology 25(6):541545. doi:10.1097/HCO.0b013e32833e6e13(http://dx.doi.org/10.1097%2FHCO.0b013e32833e6e13). PMID20717014(//www.ncbi.nlm.nih.gov/pubmed/20717014). 4. ^Ranasinghe,A.M.Bonser,R.S.(2010)."BiomarkersinAcuteAorticDissectionandOtherAortic Syndromes". JournaloftheAmericanCollegeofCardiology 56(19):15351541. doi:10.1016/j.jacc.2010.01.076(http://dx.doi.org/10.1016%2Fj.jacc.2010.01.076).PMID21029872 (//www.ncbi.nlm.nih.gov/pubmed/21029872). 5. ^WellsPS,AndersonDR,RodgerMetal.(2003)."EvaluationofDdimerinthediagnosisofsuspecteddeep veinthrombosis"(http://content.nejm.org/cgi/content/full/349/13/1227). N.Engl.J.Med. 349(13):1227 1235.doi:10.1056/NEJMoa023153(http://dx.doi.org/10.1056%2FNEJMoa023153).PMID14507948 (//www.ncbi.nlm.nih.gov/pubmed/14507948). 6. ^Rathbun,SWTLWhitsett,SKVesely,GERaskob(2004)."ClinicalutilityofDdimerinpatientswith suspectedpulmonaryembolismandnondiagnosticlungscansornegativeCTfindings". Chest 125(3):851 855.doi:10.1378/chest.125.3.851(http://dx.doi.org/10.1378%2Fchest.125.3.851).PMC1215466 (//www.ncbi.nlm.nih.gov/pmc/articles/PMC1215466).PMID15006941 (//www.ncbi.nlm.nih.gov/pubmed/15006941). 7. ^AmericanCollegeofPhysicians,"FiveThingsPhysiciansandPatientsShouldQuestion" (http://choosingwisely.org/wpcontent/uploads/2012/04/5things_12_factsheet_Amer_College_Phys.pdf), presentedbyABIMFoundation, ChoosingWisely(AmericanCollegeofPhysicians),retrievedAugust14,2012 8. ^Fesmire,F.M.Brown,M.D.Espinosa,J.A.Shih,R.D.Silvers,S.M.Wolf,S.J.Decker,W.W. AmericanCollegeofEmergencyPhysicians(2011)."CriticalIssuesintheEvaluationandManagementof AdultPatientsPresentingtotheEmergencyDepartmentwithSuspectedPulmonaryEmbolism". Annalsof EmergencyMedicine 57(6):628652.e75.doi:10.1016/j.annemergmed.2011.01.020 (http://dx.doi.org/10.1016%2Fj.annemergmed.2011.01.020).PMID21621092 (//www.ncbi.nlm.nih.gov/pubmed/21621092). 9. ^Torbicki,A.Perrier,A.Konstantinides,S.Agnelli,G.Gali,N.Pruszczyk,P.Bengel,F.Brady,A.J. B.Ferreira,D.Janssens,U.Klepetko,W.Mayer,E.RemyJardin,M.Bassand,J.P.Vahanian,A. Camm,J.DeCaterina,R.Dean,V.Dickstein,K.Filippatos,G.FunckBrentano,C.Hellemans,I.
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Kristensen,S.D.McGregor,K.Sechtem,U.Silber,S.Tendera,M.Widimsky,P.Zamorano,J.L. Zamorano,J.L.(2008)."Guidelinesonthediagnosisandmanagementofacutepulmonaryembolism:The TaskForcefortheDiagnosisandManagementofAcutePulmonaryEmbolismoftheEuropeanSocietyof Cardiology(ESC)". EuropeanHeartJournal 29(18):22762315.doi:10.1093/eurheartj/ehn310 (http://dx.doi.org/10.1093%2Feurheartj%2Fehn310).PMID18757870 (//www.ncbi.nlm.nih.gov/pubmed/18757870). ^Qaseem,A.Snow,V.Barry,P.Hornbake,E.R.Rodnick,J.E.Tobolic,T.Ireland,B.Segal,J.Bass, E.Weiss,K.B.Green,L.Owens,D.K.(2007)."CurrentDiagnosisofVenousThromboembolismin PrimaryCare:AClinicalPracticeGuidelinefromtheAmericanAcademyofFamilyPhysiciansandthe AmericanCollegeofPhysicians". TheAnnalsofFamilyMedicine 5:57.doi:10.1370/afm.667 (http://dx.doi.org/10.1370%2Fafm.667). ^SchrecengostJE,LeGalloRD,BoydJCetal.(September2003)."Comparisonofdiagnosticaccuraciesin outpatientsandhospitalizedpatientsofDdimertestingfortheevaluationofsuspectedpulmonaryembolism". ClinicalChemistry 49(9):14831490.doi:10.1373/49.9.1483(http://dx.doi.org/10.1373%2F49.9.1483). PMID12928229(//www.ncbi.nlm.nih.gov/pubmed/12928229). ^vanEsJ,MosI,DoumaR,ErkensP,DurianM,NizetTetal.(2012)."Thecombinationoffourdifferent clinicaldecisionrulesandanageadjustedDdimercutoffincreasesthenumberofpatientsinwhomacute pulmonaryembolismcansafelybeexcluded."(http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi? dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22072293). ThrombHaemost 107 (1):16771.doi:10.1160/TH11080587(http://dx.doi.org/10.1160%2FTH11080587).PMID22072293 (//www.ncbi.nlm.nih.gov/pubmed/22072293). ^DoumaRA,leGalG,ShneM,RighiniM,KamphuisenPW,PerrierAetal.(2010)."Potentialofanage adjustedDdimercutoffvaluetoimprovetheexclusionofpulmonaryembolisminolderpatients:a retrospectiveanalysisofthreelargecohorts."(http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi? dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=20354012). BMJ 340:c1475. doi:10.1136/bmj.c1475(http://dx.doi.org/10.1136%2Fbmj.c1475).PMID20354012 (//www.ncbi.nlm.nih.gov/pubmed/20354012).

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