Transfusion Related Acute Lung Injury (TRALI) | FDA

TRALI is a well-characterized clinical constellation of symptoms including dyspnea, hypotension, and fever. The radiological picture is of ... Skiptomaincontent SkiptoFDASearch Skiptointhissectionmenu Skiptofooterlinks Inthissection: Safety&Availability(Biologics) Safety&Availability(Biologics) BiologicProductSecurity BloodSafety&Availability CBER-RegulatedProducts:ShortagesandDiscontinuations Pandemics&EmergingDiseases TissueSafety&Availability VaccineSafety&Availability HIVHomeTestKits Recalls(Biologics) ReportaProblemtotheCenterforBiologicsEvaluation&Research Home Vaccines,Blood&Biologics Safety&Availability(Biologics) TransfusionRelatedAcuteLungInjury(TRALI) Safety&Availability(Biologics) DepartmentofHealthandHumanServices PublicHealthService FoodandDrugAdministration 1401RockvillePike Rockville,MD20852-1448 October19,2001 DearColleague: Thisistoalertyoutothepossibilitythatpatientswhoreceivebloodproducts,particularlyplasma-containingproducts,maybeatriskforTransfusionRelatedAcuteLungInjury(TRALI),aseriouspulmonarysyndromethatcanleadtodeathifnotrecognizedandtreatedappropriately.EvensmallamountsofplasmainpackedredbloodcellsmayinduceTRALI.Recognitionofsymptomsandimmediatetreatmentareimperative. Reports ThefirstTRALIfatalitywasreportedtotheCenterforBiologicsEvaluationandResearch(CBER)in1992.Sincethen,CBERhasreceivedmorethan45fatalityreportsofTRALI.AsofFY2000thisrepresented13percentofalltransfusionfatalities.TRALIisthoughttobethethirdleadingcauseoftransfusionrelateddeath.Themajorityofdeathswereassociatedwithfreshfrozenplasmatransfusions;fewerwerecausedbypackedredbloodcelltransfusionsandplatelettransfusions.Inmostcases,follow-updonorantibodyscreensimplicateddonorswhoweremultiparousfemalesandwerepositiveforanti-HLAoranti-granulocyteantibodies.Non-fatalTRALIeventsreportedbylicensedbloodestablishmentsthroughMedWatchorasBiologicalProductDeviationreportsarealsoontheincrease.Therehavebeen26suchreportssince1999.Thisfindingmaybeattributabletobetterrecognitionandreportingofevents.Becauseofmisdiagnosisand/orunderreporting,thefullscopeofTRALIisnotknown. DescriptionandCauseofProblem TRALIisawell-characterizedclinicalconstellationofsymptomsincludingdyspnea,hypotension,andfever.Theradiologicalpictureisofbilateralpulmonaryinfiltrateswithoutevidenceofcardiaccompromiseorfluidoverload.Symptomstypicallybegin1-2hoursaftertransfusionandarefullymanifestwithin1-6hours.ProductstypicallyimplicatedinTRALIarewholeblood,packedredbloodcells,freshfrozenplasma,cryoprecipitate,plateletconcentrates,apheresisplatelets,andrarelyIGIV1.TheetiologyofTRALImaybeattributabletothepresenceofanti-HLAand/oranti-granulocyteantibodiesintheplasmaofmultiparousfemalesordonorswhohavereceivedprevioustransfusions.TRALIrecipientshavenospecificdemographicssuchasage,gender,orprevioustransfusionhistory.AlthoughTRALIdoesnotalwaysoccurthroughtransfusionsfromdonorswithanti-HLAoranti-granulocyteantibodies,oneorbothoftheseantibodytypeshavebeenfoundin89%ofTRALIcases.2   1 RizkA,GorsonK,KennyL,andWeinsteinR:Transfusion-relatedacutelunginjuryaftertheinfusionofIVIG.Transfusion2001;41:264-268. 2 Popovsky,MA,Chaplin,HC,andMoore,SB.Transfusion-relatedlunginjury:aneglectedseriouscomplicationofhemotherapy.Transfusion1992;32:589-592.   DiagnosisandTreatment Itappearsthatunlikeallergicoranaphylacticimmune-mediatedtransfusionreactions,antibodiesimplicatedinTRALIareusuallyofdonororigin.Oncetransferredtotherecipient,theseantibodiesmaycausecomplementactivationresultinginneutrophilicinfluxintothelungsanddamagetothepulmonarymicrovasculature.Theclinicalresultmaybesubtleorsignificant.Ineithercase,thereistypicallyamarkedhypoxemia,hypotension,fever,andseverebilateralpulmonaryedema.Respiratorysupportshouldbeasintensiveasdictatedbytheclinicalpicture.DiureticsplaynoroleinTRALIastheunderlyingpathologyinvolvesmicrovascularinjury,ratherthanfluidoverload. Recommendations Bealertthatanyrespiratorydistressoccurringduringorfollowingbloodorbloodcomponent(s)transfusioncouldpotentiallybeTRALI.Discontinuethetransfusionimmediately.Beginoxygenandsupportivetherapy.   NotifytheBloodCenterthatsuppliedthebloodcomponentandreturnremainingproducttobetestedforanti-HLAand/oranti-granulocyteantibodiesinthedonor.   1.FatalitiesfromTRALIshouldbereportedtoCBERinaccordancewith21CFR606.170(b).FDAencouragesvoluntaryreportingofTRALIasaseriousadversereactiontotransfusions.ReportscanbefiledviaMedWatchbyphoneat1-800-FDA-1088,byfaxat1-800-FDA-0178,byUSmailatMedWatch,HF-2,5600FishersLane,Rockville,MD20852,orbyemailathttp://www.fda.gov/medwatch. ForMoreInformation Ifyouhavequestionsregardingthisalert,pleasecontactDr.LeslieHolness,CenterforBiologicsEvaluationandResearch,FDA,1401RockvillePike,MailStopHFM-375,Rockville,MD20852-1448,byfaxat301-827-3534,[email protected]. Sincerely, ----signature--- KathrynC.Zoon,Ph.D. Director CenterforBiologicsEvaluationandResearch FoodandDrugAdministration Contentcurrentasof: 03/23/2018 RegulatedProduct(s) Biologics BloodProducts Safety&Availability(Biologics) BiologicProductSecurity BloodSafety&Availability CBER-RegulatedProducts:ShortagesandDiscontinuations Pandemics&EmergingDiseases TissueSafety&Availability VaccineSafety&Availability HIVHomeTestKits Recalls(Biologics) ReportaProblemtotheCenterforBiologicsEvaluation&Research BacktoTop