Approach to the Diagnosis and Management of Transfusion ...

Current management of TRALI consists of respiratory and circulatory support based on clinical severity. Oxygen supplementation is required ... SkiptoMainContent Advertisement Close ASHClinicalNews ASHNewsDaily ASH-SAP Blood BloodAdvances Hematology TheHematologist International BloodChineseEdition BloodJapaneseEdition BloodItalianEdition BloodLatinAmericaEdition BloodSpanishEdition ASH ASHHome Research Education Advocacy Meetings Publications ASHStore Cart UserToolsDropdown Cart SignIn SearchDropdownMenu headersearch searchinput Searchinputautosuggest filteryoursearch AllContentAllJournalsTheHematologist Search ToggleMenuMenu Issues CurrentIssue AllIssues Columns Multimedia Multimedia Podcasts Videos About AboutTheHematologist EditorialBoard Permissions Alerts App SkipNavDestination ContentMenu Close TheQuestion OurResponse References ArticleNavigation AsktheHematologist| July1,2013 ApproachtotheDiagnosisandManagementofTransfusion-RelatedAcuteLungInjury StevenL.Spitalnik,MD, StevenL.Spitalnik,MD ProfessorofPathologyandCellBiologyandViceChairmanofLaboratoryMedicine CollegeofPhysiciansandSurgeons,ColumbiaUniversity Searchforotherworksbythisauthoron: ThisSite PubMed GoogleScholar HuyP.Pham,MD HuyP.Pham,MD AssistantProfessorofPathology UABMedicine,BaptistHealth Searchforotherworksbythisauthoron: ThisSite PubMed GoogleScholar TheHematologist(2013)10(4) https://doi.org/10.1182/hem.V10.4.1046 ShareIcon Share Twitter LinkedIn RequestPermissions Citation StevenL.Spitalnik,HuyP.Pham;ApproachtotheDiagnosisandManagementofTransfusion-RelatedAcuteLungInjury.TheHematologist2013;10(4):NoPaginationSpecified.doi:https://doi.org/10.1182/hem.V10.4.1046 Downloadcitationfile: Ris(Zotero) ReferenceManager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbarsearch SearchDropdownMenu toolbarsearch searchinput Searchinputautosuggest filteryoursearch AllContentAllJournalsTheHematologist Search TheQuestion Whatisyourapproachtothediagnosisandmanagementoftransfusion-relatedacutelunginjury(TRALI)? OurResponse Epidemiology ThebloodsupplyintheUnitedStatesissafe.Althoughnon-life-threateningadverseeventssuchasallergicandfebriletransfusionreactionsareencounteredregularlybyclinicians,transfusion-relatedfatalitiesarerare.From2007through2011,212fatalitiesfollowingbloodcollectionandtransfusionwerereportedtotheFDA.1  Non-infectiouscomplicationsposethegreatestmortalityrisktothetransfusedpatientwithTRALIaccountingfor43percentofdeathsandhemolytictransfusionreactionsduetoABO(10%)andnon-ABO(13%)incompatibilityaccountingfor23percent.1  Incomparison,11percentoftransfusion-relateddeathswereduetomicrobialinfections.Althoughusuallyassociatedwithinfusionofbloodproductscontaininghighvolumesofplasma(e.g.,freshfrozenplasmaandplatelets),TRALIhasalsobeenlinkedtoredbloodcelltransfusions.EstimatesoftheincidenceofTRALImaybeinfluencedbyfactorssuchastransfusionpolicy.Forexample,theincidencefellfrom2.57to0.81per10,000transfusionsconcurrentwithreductionintheuseofplasmafromfemaledonors.2  ClinicalPresentationandDiagnosis ThediagnosisofTRALIismadeonclinicalgrounds,andnosinglelaboratoryorradiologictestdefinitivelyidentifiesorexcludesthisentity.WecurrentlyusethecriteriaandcasedefinitionsproposedbyaCanadianConsensusConference(Table).3  Thus,TRALIisanacuteeventpresentingduringatransfusionorwithinsixhoursofitscompletion.Characteristicsignsandsymptomsincludefever,chills,dypsnea,hypoxemia,hypotension(orpossibletransienthypertension),andthenewonsetofbilateralnoncardiogenicpulmonaryedema(e.g.,chestx-rayshowingbilateralalveolarandinterstitialinfiltratesintheabsenceofcardiomegaly).TRALIisoftenassociatedwithtransientleukopeniaorneutropenia.Adiagnosisof“PossibleTRALI”ismadebasedonthesamecriteriaasTRALIexceptthatanalternativeriskfactorforacutelunginjuryispresentconcurrently(Table). Table1.CanadianConsensusConferenceontheDefinitionofTRALI Table1.CanadianConsensusConferenceontheDefinitionofTRALITRALI: . AcutelunginjuryAcuteonsetHypoxemiaResearchsetting:PaO2/FlO2<300and/orSpO2<90%onroomairNon-researchsetting:PaO2/FlO2<300and/orSpO2<90%onroomairand/orotherclinicalsymptomsofhypoxiaBilateralinfiltratesonfrontalchestx-rayNoevidenceofleftatrialhypertension(i.e.,nocirculatoryoverload)Nopre-existingacutelunginjurybeforetransfusionDuringorwithin6hoursoftransfusionNotemporalrelationshiptoanalternativeriskfactorforacutelunginjury PossibleTRALI: . AcutelunginjuryNopre-existingacutelunginjurypriortotransfusionDuringorwithin6hoursoftransfusionAcleartemporalrelationshiptoanalternativeriskfactorforacutelunginjury TRALI: . AcutelunginjuryAcuteonsetHypoxemiaResearchsetting:PaO2/FlO2<300and/orSpO2<90%onroomairNon-researchsetting:PaO2/FlO2<300and/orSpO2<90%onroomairand/orotherclinicalsymptomsofhypoxiaBilateralinfiltratesonfrontalchestx-rayNoevidenceofleftatrialhypertension(i.e.,nocirculatoryoverload)Nopre-existingacutelunginjurybeforetransfusionDuringorwithin6hoursoftransfusionNotemporalrelationshiptoanalternativeriskfactorforacutelunginjury PossibleTRALI: . AcutelunginjuryNopre-existingacutelunginjurypriortotransfusionDuringorwithin6hoursoftransfusionAcleartemporalrelationshiptoanalternativeriskfactorforacutelunginjury KleinmanSetal.Transfusion.2004;44:1774-1789.ViewLarge ThedifferentialdiagnosisofTRALIincludesthefollowing:transfusion-associatedcirculatoryoverload(TACO),anaphylaxis,andsepsis.4  DistinguishingTACOfromTRALImaybechallengingbecausesomeofthesignsandsymptomsofthetwoentitiesoverlap;inaddition,thetwoprocessescanoccurconcurrentlyinagivenpatient.Thekeydifferencebetweenthesetwoconditionsisthepathophysiologicoriginofthepulmonaryedema(i.e.,cardiogenicinthecaseofTACOandnon-cardiogenicinthecaseofTRALI).Thus,clinicalimprovementaftertreatmentwithadiureticand/oraninotropicagentischaracteristicofTACO,butnotTRALI.OtherfindingssuggestiveofTACOincludepersistenthypertension,apost-transfusionbrainnatriureticpeptide(BNP)levelofatleast100pg/mL,andapost-transfusion:pre-transfusionBNPratioof>1.5.5  Althoughanaphylaxiscanpresentwithhypotension,cyanosis,andhypoxiaduetobronchospasmandlaryngealedema,theabsenceoffeverandpulmonaryedemadistinguishthisprocessfromTRALI.Althoughtransfusion-inducedsepsis,particularlyafteraplatelettransfusion,typicallypresentswithpyrexiaandhypotension,respiratorydistressisaninfrequentcomplication.Otherentities,suchasmyocardialinfarction,pulmonaryembolism,andothercausesofacutelunginjuryshareclinicalfeatureswithTRALIandshouldbeconsideredinthedifferentialdiagnosis. ThediagnosisofTRALIisparticularlychallengingincomplexinpatientssuchasthoseencounteredintheintensivecareunitsetting,giventhatsuchpatientsoftenhavemultiplemedicalproblemsandmayexhibitsomesymptomsofTRALIevenbeforetransfusion. Pathophysiology AlthoughtheexactmechanismofTRALIisuncertain,a“two-hit”processhasbeenproposed.6-8  Accordingtothishypothesis,thefirst“hit”isinducedbyanunderlyingcondition,suchastraumaorsepsis,whichprimesgranulocytesand/oractivatesendothelialcells,therebycausingneutrophilstobecomesequesteredinthepulmonaryvasculature.Thesecond“hit”resultsfrompassiveinfusionofdonorantibodiesinthebloodproductthatrecognizeeitherhumanleukocyteantigens(HLA)onrecipientendothelialcellsorhumanneutrophilantigens(HNA)onrecipientneutrophils.Alternatively(orinaddition),infusionofbiologicresponsemodifiers(e.g.,CD40ligand)intheplasmaportionofthedonorproductcouldinducethesecondhit.Together,theseprocessesinducecapillaryendothelialdamage,resultinginvascularpermeabilityandpulmonaryedema.6-8  Basedonthisproposedmechanism,onemighthypothesizethattheincidenceofTRALIwouldbehigherforplasmarichtransfusionproductsandthattheincidencewouldbelowerwhenplasmaderivedfromfemaledonors(whohaveahigherprevalenceofanti-HLAantibodies)isrestricted;availabledatasupportthesetwohypotheses.2  Inaddition,recentstudiesindicatethatcirculatingplateletsareinvolvedinTRALIpathophysiology,suggestingthatanti-platelettherapymaybebeneficialclinically.7,9  Management Thefirststepinmanaginganysuspectedtransfusionreactionistostopthetransfusion.Oncethepatientisstabilized,theepisodeshouldbereportedtothetransfusionmedicineservicesothatatransfusionreactionevaluationcanbegin.Becausehemolytictransfusionreactionsareassociatedwithsignificantmorbidityandmortality,thetransfusionmedicineservicewillfirstperforma“clericalcheck”toensurethatthecorrectunitwastransfusedintothecorrectpatient.Next,theABOtypeofthepatientandthetransfusedunitwillbeconfirmed,thepost-transfusionbloodsamplewillbeinspectedforvisibleevidenceofhemolysis,andanindirectanddirectanti-globulintestwillbeperformedonthepost-transfusionsampletodetermineifcirculatingand/orredbloodcell-boundantibodiesarepresent.Additionallaboratoryteststoinvestigateforhemolysis,includingacompletebloodcount,urinalysis,andplasmaconcentrationofbilirubin,lactatedehydrogenase,andhaptoglobin,areoftenneeded.TodiagnoseTRALI,physicalexam,chestx-ray,andarterialbloodgasstudiesarerecommended.IndistinguishingTRALIfromTACO,anechocardiogrammaybeusefulindeterminingwhethertheobservedpulmonaryedemaisofcardiogenicorigin.OthercausesofadverseeventsthatshareclinicalfeatureswithTRALI(e.g.,sepsis,myocardialinfarction,andpulmonaryembolus)shouldbepromptlyinvestigated. CurrentmanagementofTRALIconsistsofrespiratoryandcirculatorysupportbasedonclinicalseverity.Oxygensupplementationisrequiredinalmostallpatients;inseverecases,mechanicalventilationmaybenecessary.Hypotensiveepisodescanbetreatedwithpressors.Corticosteroidtreatmenthasnotimprovedoutcome.10 Intheory,thenoncardiogenicpulmonaryedemaofTRALIshouldnotrespondtodiuresis.Mostpatientsimprovewithintwotothreedays,butthosewhodonotimproveoverthisperiodtypicallyhaveaprotractedclinicalcourseorafataloutcome.8  PatientswhohaveexperiencedanepisodeofTRALIarenotatgreaterriskforasecondepisode,assumingthattheinitialeventwasaconsequenceofinfusionofdonorantibodiesthatwerepresentinthetransfusionproductandthatsubsequentbloodproductsdonotcomefromtheinitialdonor.However,notificationofthetransfusionmedicineserviceaboutapossibleTRALIepisodehasimportantimplicationsforthedonorandthesafetyofthebloodsupply.IfTRALIissuggestedbybothclinicalpresentationandlaboratoryresults(e.g.,findinganti-HLAand/oranti-HNAantibodiesinthetransfusedbloodproductthatmatchthecorrespondingantigensinthepatient),thedonormustbeevaluatedforconsiderationoftheircontinuedeligibilitytodonate.Indeed,manycenterschoosetoexcludesuchdonorspermanently.ThattheproductfromaparticulardonorcausedanepisodeofTRALImaybedifficulttoproveunequivocally,however,becausepatientsoftenreceiveproductsfrommultipledonors. Prevention ApproachestoreducingtheriskofTRALIhaveincludedavoidingtheuseofplasmafromfemaledonors,usingplasmaderivedonlyfrommalesorfromnever-pregnantfemales,andtestingfemaledonorsforanti-HLAantibodies.1,2  Althoughthesemeasuresreducetheincidence,theydonotcompletelyeliminateriskbecauseTRALIcanbeinducedbyotherbloodproducts(e.g.,redbloodcells,plateletconcentrates,cryoprecipitate).Inadditiontoavoidingtheuseofhigh-riskbloodproducts,conservativetransfusionstrategiesandinterventionsthataddressthe“firsthit”couldalsohelpreduceTRALIincidence.Nonetheless,TRALIcontinuestobethemostcommoncauseoftransfusion-relatedmortality,makingrapidrecognitionandinstitutionofappropriatesupportivecareimperative.1,7  References 1.FatalitiesReportedtoFDAFollowingBloodCollectionandTransfusion:AnnualSummaryforFiscalYear2011.FDAUSFoodandDrugAdm.2011.http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/ReportaProblem/TransfusionDonationFatalities/ucm302847.htm2.ToyP,GajicO,BacchettiP,etal.Transfusion-relatedacutelunginjury:incidenceandriskfactors.Blood.2012;119:1757-1767.http://www.bloodjournal.org/content/119/7/1757.abstract?sid=d09b2415-e72a-4748-b50f-f0d934a32dff&sso-checked=trueGoogleScholar 3.KleinmanS,CaulfieldT,ChanP,etal.Towardanunderstandingoftransfusion-relatedacutelunginjury:statementofaconsensuspanel.Transfusion.2004;44:1774-1789.http://www.ncbi.nlm.nih.gov/pubmed/15584994GoogleScholar 4.MazzeiCA,PopovskyMA,KopkoPM.Noninfectiouscomplicationsofbloodtransfusion.In:RobackJD,GrossmanBJ,HarrisT,etal.(Eds).TechnicalManual,17thed.AABB.2011:272-762.GoogleScholar 5.ZhouL,GiacherioD,CoolingL,etal.UseofB-natriureticpeptideasadiagnosticmarkerinthedifferentialdiagnosisoftransfusion-associatedcirculatoryoverload.Transfusion.2005;45:1056-1063.http://www.ncbi.nlm.nih.gov/pubmed/15987348GoogleScholar 6.SillimanCC,BoshkovLK,MehdizadehkashiZ,etal.Transfusion-relatedacutelunginjury:epidemiologyandaprospectiveanalysisofetiologicfactors.Blood.2003;101:454-462.http://www.bloodjournal.org/content/101/2/454.abstract?sid=d4b4ca57-09e8-4bfc-ae15-2cd1bacfa39dGoogleScholar 7.GillissBM,LooneyMR.Experimentalmodelsoftransfusion-relatedacutelunginjury.TransfusMedRev.2011;25:1-11.http://www.ncbi.nlm.nih.gov/pubmed/21134622GoogleScholar 8.PopovskyMA,MooreSB.Diagnosticandpathogeneticconsiderationsintransfusion-relatedacutelunginjury.Transfusion.1985;25:573-577.http://www.ncbi.nlm.nih.gov/pubmed/4071603GoogleScholar 9.CaudrillierA,KessenbrockK,GillissBM,etal.Plateletsinduceneutrophilextracellulartrapsintransfusion-relatedacutelunginjury.JClinInvest.2012;122:2661-2671.http://www.ncbi.nlm.nih.gov/pubmed/22684106GoogleScholar 10.SteinbergKP,HudsonLD,GoodmanRB,etal.Efficacyandsafetyofcorticosteroidsforpersistentacuterespiratorydistresssyndrome.NEnglJMed.2006;354:1671-1684.http://www.ncbi.nlm.nih.gov/pubmed/16625008GoogleScholar  Authornotes In2016,thisarticlewasincludedintheAsktheHematologistCompendium.Atthattime,theauthorsindicatedthattherehadbeennoupdateregardingthecontentofthisarticlesincetheoriginalpublicationdatein2013. CompetingInterests Dr.PhamandDr.Spitalnikindicatednorelevantconflictsofinterest. Volume10,Issue4 July-August2013 PreviousArticle NextArticle Advertisement 0 Citations ViewMetrics × Emailalerts LatestIssueAlert ContinuousPublishingAlert NewJournalContentAlert CloseModal Advertisement CurrentIssue AllIssues AboutTheHematologist AdvertisinginTheHematologist Columns Podcasts Videos EditorialBoard Permissions Submissions EmailAlerts ASHPublicationsApp AmericanSocietyofHematology 2021LStreetNW,Suite900 Washington,DC20036 TEL+1202-776-0544 FAX+1202-776-0545 ASHPublications Blood BloodAdvances Hematology,ASHEducationProgram ASHClinicalNews ASH-SAP TheHematologist AmericanSocietyofHematology ASHHome Research Education Advocacy Meetings Publications ASHStore Copyright©2022byAmericanSocietyofHematology   PrivacyPolicy CookiePolicy TermsofUse ContactUs CloseModal CloseModal ThisFeatureIsAvailableToSubscribersOnly SignInorCreateanAccount CloseModal CloseModal