201768 RedbloodcelltransfusionsinthenewbornUpToDate

OfficialreprintfromUpToDate
www.uptodate.com2017UpToDate

Redbloodcelltransfusionsinthenewborn

Author: RobinOhls,MD
SectionEditors: DonaldHMahoney,Jr,MD,JosephAGarciaPrats,MD
DeputyEditor: MelanieSKim,MD

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:May2017.|Thistopiclastupdated:Jan12,2017.

INTRODUCTIONRedbloodcell(RBC)transfusionprovidesanimmediateincreaseinoxygendeliveryto
tissuesandisaneffectiveandrapidinterventiontotreatacuteanemia.RBCtransfusionsmayreducethe
morbidityassociatedwithchronicanemia,suchastheanemiaofprematurity,andcanbelifesavinginneonates
withseverebloodloss.

TheindicationsforneonatalRBCtransfusionsandtheselectionoftheproperbloodproductwillbereviewed
here.Anemiaofprematurityandindicationsforredcelltransfusionininfantsandchildrenarediscussed
separately.(See"Anemiaofprematurity"and"Redbloodcelltransfusionininfantsandchildren:Indications".)

INDICATIONS

OverviewSymptomaticanemiaoccurswhentheRBCmassdoesnotadequatelymeettheoxygendemands
oftissues.Signsincludeincreasedrestingheartrate,acidosis,poorgrowth,decreasedenergytonipplefeed,
apnea,andincreasedneedforrespiratorysupport.

Oxygensupplytotissuesisdefinedastheproductofcardiacoutputandarterialoxygencontent.Thearterial
oxygencontentisdependentuponthehemoglobinconcentration,arterialoxygensaturation,oxygencarrying
capacityofhemoglobin(1.34mL/gmhemoglobin),and,toaminorextent,thesolubilityofoxygen.Oxygensupply
isincreasedbyincreasingcardiacoutput,arterialoxygensaturation,orhemoglobinconcentration.

TheindicationsforneonatalRBCtransfusionsdifferbasedupontherateoffallinhemoglobin(acuteversus
chronicanemia).Theneedfortransfusioninaninfantwithacutebloodlossisgenerallydependentupon
persistentclinicalsignsofinadequateoxygendeliveryfollowingintravascularvolumerestoration.Inchronic
anemia,theneedforRBCtransfusionis,likewise,baseduponclinicalsignsofinadequateoxygendelivery(such
asincreasedrestingheartrate,acidosis,poorgrowth,andapnea)andthedegreeofrespiratorysupportneeded
bytheinfant.Althoughtargethemoglobinandhematocrit(HCT)(valuesbelowwhichaRBCtransfusionis
administered)havebeenusedasclinicalindicatorsforRBCtransfusion,itremainsuncertainwhattargetHCTor
hemoglobinwilloptimallybalancetheriskandbenefitsofthisintervention.

Transfusionsareatemporarymeasureandhavethedisadvantagesoffurtherinhibitingerythropoiesisandbeing
associatedwithrisksofinfection[1],graftversushostdisease,transfusionrelatedacutelunginjury(TRALI),
transfusionassociatedcirculatoryoverload(TACO),andtoxiceffectsofanticoagulantsorpreservatives.RBC
transfusionshavebeenreportedtobeassociatedwithanincreasedriskofdeath,necrotizingenterocolitis(NEC),
extensionofintraventricularhemorrhage(IVH),ortransientincreaseinrespiratorysupporthowever,highquality
evidenceforacausalrelationshipwithanyoftheseadverseeventsislacking[25].Thesepotentialcomplications
underscoretheneedtocarefullyevaluateaneonate'sabilitytodeliveroxygentotissuespriortoorderinga
nonemergenttransfusion,andtodocumentbenefitfollowingthetransfusion.(See"Transfusionassociatedgraft

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versushostdisease"and"Immunologictransfusionreactions"and"Pathologyandpathogenesisofnecrotizing
enterocolitisinnewborns",sectionon'AnemiaandRBCtransfusion'.)

Oneofthemajorchallengesindecidingwhentotransfuseisdistinguishingtheneonatewhoisanemicand
requiresanRBCtransfusionfromonewhohasadaptedtoalowHCT,andisbesttreatedconservativelytoavoid
theassociatedrisksoftransfusion.

DeterminingoptimalHCTlevelsforneonatesandyounginfantshasbeenanactiveareaofinvestigation.Various
factorsinfluencethethreshold,includingacuityofbloodloss,gestationalage,needforrespiratorysupport,orif
theinfantwillundergomajorsurgerywithin72hours(table1).

Thediagnosticapproachtoanemiainnewbornsisdiscussedseparately(algorithm1).(See"Approachtothe
childwithanemia",sectionon'Ageofpatient'.)

AcutebloodlossNeonateswithsignificantacutebloodlossrequireimmediatefluidresuscitation,butmayor
maynotrequireaRBCtransfusion.Forexample,someterminfantsmaytolerateperinatalbloodlossuptoone
thirdoftheirtotalbloodvolume.Infantswithahemoglobinlevel10gm/dLfollowingvolumeexpansionmayhave
adequateoxygendeliveryandgenerallyonlyrequireironsupplementationtoreplaceironlossesduetothe
hemorrhage.

IndicationsforaRBCtransfusioninatermorpretermneonateaftervolumeresuscitationwithrestorationofthe
effectivecirculatingvolumefollowinganacutebloodlossincludeoneormoreofthefollowing:

>20percentbloodloss
10to20percentbloodwithevidenceofinadequateoxygendelivery,suchaspersistentacidosis
Ongoinghemorrhage

Percentofexternalbloodlossisusuallydeterminedbydividingthevolumeofbloodloss(measuringthe
differenceinweightofbandages,gauze,andblanketsbeforeandaftersurgery[bloodsoaked])bythevolumeof
theinfant'stotalbloodvolume(85mL/kg).However,internalbloodlossismoredifficulttoestimatesome
calculationshavebeendeterminedbasedonclinicalcontext.Forexample,thevolumelossduetoasubgaleal
hemorrhagecanbeestimatedat38mLforevery1cmincreaseinheadcircumference.

Priortotransfusion,itiscriticaltodeterminewhetherasignificantlylowHCTofaninfantatbirthisduetoan
acutefallnearthetimeofdeliveryortoachronicinuteroprocess,becausethismayalterthetypeoftransfusion
administered(ie,simpleversusexchange).Forexample,intwintwintransfusionsyndromeorfetomaternal
hemorrhage,thedegreeandtimingofbleedingisvariable.Bleedingmayoccurjustbeforedeliveryormighthave
beguninthesecondtrimesterandbelongstandingatthetimeofdelivery,bothofwhichmayresultinaHCT
below20percentatbirth.Inthelattercase,apartialexchangetransfusionshouldbeconsideredinaninfantin
whomanincreaseintissueoxygendeliveryisnecessary.Asimpletransfusionmaycauseasignificantincreasein
bloodvolume,resultinginheartfailure,becausetheseinfantsoftenhaveelevatedcirculatingbloodvolumes.
Exchangetransfusionsshouldbeconsideredininfantswithseverehemolyticanemia.(See"Postnataldiagnosis
andmanagementofhemolyticdiseaseofthefetusandnewborn",sectionon'Postnatalmanagement'.)

ChronicanemiaAllnewborninfantshaveagradualfallintheirHCTafterbirthduetodecreasedproduction
oferythropoietin(EPO),referredtoasphysiologicanemia.Inpreterminfants,thisdeclineoccursearlierandis
morepronouncedinitsseveritythaninterminfants.ThishyporegenerativeanemiaassociatedwithlowEPO
concentrationsisdefinedasanemiaofprematurity.(See"Anemiaofprematurity",sectionon'Pathogenesis'.)

Inaddition,infantscaredforintheneonatalintensivecareunit(NICU)areatriskfordevelopingchronicanemia
becauseofbloodlossfromphlebotomy.Thisisespeciallytrueforverylowbirthweight(VLBW)infants(BW
<1500g)whoareoftenmoreseverelyillandrequirefrequentbloodtests,andwhohavealowertotalvolumeof
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bloodthanmoremature,largerneonates.Inaddition,RBCsinpreterminfantshaveareducedlifespan
comparedwithfullterminfants,whichcontributestotheanemiaofprematurity.

TargethemoglobinorhematocritItremainsunclearwhattheminimaltargetHCTorhemoglobinisin
neonatesthatoptimallybalancestheriskandbenefitsoftransfusion.Arestrictive(low)transfusionthreshold
comparedwithaliberal(high)threshold(HCTgreaterthan40percent)resultsinlessexposuretotransfusions
withnoincreaseinmortalityorseriousmorbidity[617].Weusearestrictiveapproachforneonataltransfusions
thatisbaseduponHCTtriggersandtherespiratorysupportrequiredbytheinfant(table1).Thisapproachis
supportedbyrandomizedcontrolledtrialsandmetaanalyses.

Ina2011metaanalysisbasedonfourtrialswith614infants,thefollowingoutcomeswerenoted[10]:

Infantsinthelowhemoglobinthresholdgroupreceivedfewertransfusionsthanthoseinthehighhemoglobin
thresholdgroup,anddonorexposuresperinfantwerealsolowerinthelowhemoglobinthresholdgroup.

Infantsinthelowthresholdgroupweretransfusedatalaterage.

Therewasnodifferenceintherateofmortalitybetweenthelowandhighhemoglobinthresholdgroups
(relativerisk[RR]1.23,95%CI0.861.76).

Therewasnodifferenceinthecompositeoutcomeofdeathandseriousmorbidityatthetimeofdischarge,
definedassevereretinopathyofprematurity(ROP),bronchopulmonarydysplasia(BPD),orbraininjuryon
ultrasound(RR1.07,95%CI0.961.2).Inaseparateanalysis,therewasalsonodifferenceinthecomposite
outcomeofdeathandseverebraininjuryathospitaldischarge(RR1.12,95%CI0.811.55).

Inonetrial(ThePrematureInfantsinNeedofTransfusion[PINT]Study[8]),therewasnodifference
betweenthelowandhightargetHCTgroupsat18to21monthscorrectedageinthecompositeoutcomeof
deathorneurodevelopmentimpairment,definedascerebralpalsy(CP),significantvisualandhearing
impairment,andaBayleyScalesofInfantDevelopmentIIMentalDevelopmentIndex(MDI)score<70(45
versus39percent,oddsratio[OR]1.45,95%CI0.942.21)[11].Inaposthocanalysis,MDIscore<85was
morelikelyinthelowHCTgroupcomparedwiththehighHCTgroup(45versus34percent,adjustedOR
1.81,95%CI1.122.93).Ofnote,thiswasthelargesttrialandaccountedfor73percentofthepatientsinthe
metaanalysis.

TherewerenosignificantdifferencesforsurvivorsinsecondaryoutcomesincludingROP,braininjurybased
onultrasonography,BPD,neurosensoryimpairmentat18to21monthsofcorrectedage,apnearequiring
intervention,differenceinweightgain,lengthofhospitalization,patentductusarteriosus(PDA),andNEC.

Therewasafairdegreeofheterogeneity,asthetrialsdifferedinthehighhemoglobintargetthresholds(although
thelowthresholdsweresimilar)andtheBWoftheenrolledinfants.Itshouldbenotedthatinthreeofthetrials
thatincludedalmostallofthepatients(n=580patients),EPOwasnotgiven.Nevertheless,theauthors
concludedthattherestrictive(low)transfusionthresholdscomparedwithaliberal(high)thresholdresultedin
modestreductionsinexposuretotransfusions,andtherewerenodifferencesinmortality,majormorbidities,and
seriousneurodevelopmentalimpairmentat18to21monthscorrectedage.Becausethelowthresholdswere
similaramongstthefourtrials,theauthorsrecommendedthefollowinglowerlevelsofhemoglobin(g/dL)based
onthepatientageandrequirementforrespiratorysupport:

Week1

Withrespiratorysupport11.5
Norespiratorysupport10

Week2
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Withrespiratorysupport10
Norespiratorysupport8.5

Week3

Withrespiratorysupport8.5
Norespiratorysupport7.5

A2012metaanalysisthatincludedtwoadditionaltrialsthatdidnotmeetinclusioncriteriafortheabovestudy
reportedsimilarfindingsofnodifferenceinmortalityratesbetweenhighandlowthresholdtransfusiongroups
[12].Inalongtermfollowupstudy,cognitivefunctionbasedondevelopmentalassessmentandmagnetic
resonanceimaging(MRI)outcomewerebetterinthelowHCTtargetgroup[13,14].Inaddition,asystematic
reviewoftheliteraturethatincludedbothrandomizedclinicaltrialsandnonrandomizedstudiesreportedno
differencesinharmfuloutcomes(eg,mortality,NEC,BPD,IVHorretinopathyofprematurity)betweenrestrictive
andliberaltransfusion[18].

Indevelopedcountries,thenumberoftransfusionsgiventoneonateshasdecreasedfromanaverageofseven
transfusionsinthelate1980stotwotransfusionsperinfantin2009duringtheirinitialbirthhospitalizationduetoa
morerestrictiveapproachtotransfusions[15,16].Despitethisdecrease,mostextremelylowbirthweight(ELBW)
infantsstillreceiveatleastonebloodtransfusion.Intheabovemetaanalysis,only11percentofinfantsinthe
lowthresholdgroupand9percentinthehighthresholdgroupreceivednotransfusions[10].Asnotedabove,
mostofthepatientsinthissystematicreviewdidnotreceiveEPO.

PreoperativetargetItremainsuncertainwhattheoptimalpreoperativetargethemoglobinshouldbefor
neonateswhoundergomajorsurgery.Inastudyofneonatesundergoingnoncardiacsurgerybasedondata
fromtheAmericanCollegeofSurgeonsNationalSurgicalQualityImprovementProgram,multipleregression
analysisdemonstratedthatpreoperativeHCTwasanindependentriskfactorformortality[19].

ErythropoietinInfantswhoreceiveappropriateandtimelydosesofEPOordarbepoetin(alongacting
EPO)therapyrequirefewertransfusionsandareexposedtofewerdonors[2022].Ongoingstudiesare
evaluatingdosinganddosingschedulestomaximizeincreasesinredcellmass.However,guidelinespublished
fromsomeorganizations,forexample,the2016guidelinesoftheBritishCommitteeforStandardsin
Haematologydonotrecommendtheuseoferythropoiesisstimulatingagentsinneonates[17].

Asystematicreviewoftheliteraturereportedthatearlyadministrationoferythropoietin(before8daysoflife)
reducedthenumberofRBCtransfusionsbyoneormore,reducedthetotalvolumeoftransfusedblood,and
reduceddonorexposureinpreterminfantswithabirthweight<2500g[22].However,thesmallreductions
arelikelytobeoflimitedclinicalimportance.EarlyEPOdidnotsignificantlyreduceorincreaseanyclinically
adverseoutcomes.

AsystematicreviewoflateadministrationofEPOshowedadecreasedtotalnumberoftransfusionsbuthad
noaffectonthetotalvolumeofRBCstransfusedperinfantsortheriskofdonorexposure[20,22].Late
administrationofEPOwasassociatedwithatrendforanincreasedriskforROPthatwasnotstatistically
significant.

Inasubsequenttrialofpreterminfants500to1250g,infantswhowererandomlyselectedtoreceiveeither
EPOordarbepoetinwerelesslikelytorequiretransfusionsandwereexposedtofewerdonorsthanthe
placebocontrolgroup[21].

Asaresult,EPOhasbeenusedtomanageinfantswithanemiaofprematurity(see"Anemiaofprematurity",
sectionon'Erythropoiesisstimulatingagents').Inaddition,prophylacticEPOisbeingevaluatedasapotential

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neuroprotectiveagent(see"Longtermneurodevelopmentaloutcomeofpreterminfants:Epidemiologyandrisk
factors",sectionon'Potentialneuroprotectiveagents').

SearchforothertransfusionmarkersAlthoughHCTandhemoglobinhaveprimarilybeenthetriggersto
indicatewhentransfusionisindicatedinneonates,theyarenotadequatemeasures.Thisisillustratedbythe
observationthatsomeinfantsremainasymptomaticatagivenlowHCT(hemoglobin),whileothersexhibitsigns
thatmightreflectanemia(tachycardia,poorweightgain,increasedrequirementofsupplementaloxygen,or
increasedfrequencyofapneaorbradycardia)atasimilarorhigherconcentration.

Researcheffortshavefocusedonidentifyingamoreaccurateindicatorfortransfusionshowever,areliableand
sensitivemarkerhasyettobeidentified.Investigationstotestamoreaccuratemarkerfortransfusionhave
includedstudiesofdirectorindirectoxygendelivery(eg,peripheralfractionaloxygenextractionandoxygen
consumption)[2325],echocardiographicchangesincardiovascularcirculation[2628],andtheuseof
biochemicalmarkers,suchasserumlactateorvascularendothelialgrowthfactor[29,30].

OurapproachBasedupontheavailabledata,thefollowingtransfusionguidelineshavebeenadoptedin
severalNICUs,includingourown(table1):

Acutebloodlossthatisgreaterthan20percentofbloodvolume.

Acutebloodlossthatisgreaterthan10percentofbloodvolumewithsymptomsofdecreasedoxygen
delivery,suchaspersistentacidosisaftervolumeresuscitation.

Thefollowingguidelinesforinfantswithchronicanemiasuggestthattransfusionsshouldbeconsidered
basedupontherespiratorysupportneededbytheinfant.TheyaredependentuponaHCT(hemoglobin)
valuethatispreferablymeasuredfromeitheracentralvenousorarterialsample.Thesehemoglobinvalues
arebasedonarestrictivehemoglobintransfusionthresholdandareconsistentwiththerecommendations
outlinedbythepreviouslydiscussedmetaanalysis.(See'Targethemoglobinorhematocrit'above.)

Ifaheelstickspecimenisused,itshouldbeobtainedafteradequatewarmingoftheheel.Thefinaldecision
foratransfusionisatthediscretionoftheneonatologyteam.

Forinfantsrequiringmoderateorsignificantmechanicalventilation,definedasfractionofinspired
oxygen(FiO2)0.4,andmeanairwaypressure(MAP)>8cmH2OonaconventionalventilatororMAP
>14onahighfrequencyventilator,theHCTtriggeris<30percent(hemoglobin10g/dL).

Forinfantsrequiringminimalmechanicalventilation,definedasfractionofinspiredoxygen(FiO2)<0.4,
andMAP8cmH2OonaconventionalventilatororMAP14onahighfrequencyventilator,theHCT
triggeris<25percent(hemoglobin8g/dL).

TheHCTtriggeris<25percent(hemoglobin8g/dL)forinfantsrequiringsupplementalloworhighflow
oxygenbutnotmechanicalventilation,andoneormoreofthefollowing:tachycardia(heartrate180
beatsperminute)for24hours,tachypnea(respiratoryrate60breathsperminute)for24hours,
doublingofoxygenrequirementfromtheprevious48hours,metabolicacidosisasindicatedbyapH7.2
orserumlactate2.5mEq/L,weightgain<10g/kgperdayoverthepreviousfourdayswhilereceiving
120kcal/kgperday,oriftheinfantundergoesmajorsurgerywithin72hours.Forinfantsrequiring
oxygenwithoutanysigns,atransfusionisnotconsidereduntilsignsoccur.

Inasymptomaticinfants,theHCTtriggeris18percent(hemoglobin6g/dL)withanabsolute
reticulocyte<100,000/microL(<2percent).Infantswithoutsignsoroxygenrequirementswhoare
activelyproducingnewredcellsandhaveanelevatedreticulocytecountlikelydonotrequirearedcell
transfusion.ThislastthresholdfortransfusionissimilartocriteriapublishedbytheCanadianPaediatric

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Society.Intheirguideline,criteriafortransfusionwereforasymptomaticinfantwitha"hemoglobinfalling
below6gm/dLwithanabsolutereticulocytecountlessthan100,000to150,000/microL,whichsuggests
lowplasmaconcentrationoferythropoietin"[31].

OthercentersandsocietieshavetransfusionguidelineswithhigherHCT(hemoglobin)triggers,whicharebased
uponsimilarrequirementsforrespiratorysupport[17,3234].

SELECTIONOFREDBLOODCELLPRODUCTSOncethedecisiontotransfuseRBCshasbeenmade,the
appropriateRBCproductischosenbasedupontheclinicalsetting.Donatedwholebloodusedfortransfusion
maybemodifiedinseveralwaysthatremovevaryingproportionsofnonredcellcomponents.These
modificationsareparticularlyimportantintheneonatebecauseoftheirincreasedvulnerabilitytocertain
infections,suchascytomegalovirus,potentialincreasedriskofgraftversushostdiseaseduetotransfusion,and
thepossibilityofalloimmunehemolyticdiseaseofthenewborn.

ProductsforacutelifethreateningbloodlossInthesettingofacutebloodloss,especiallyinlife
threateningcircumstances,anyavailableRBCproductthatiscompatiblewiththeinfant'sbloodtypecanbe
administered.IfOnegativeRBCsareavailableinthedeliveryroomasanemergencytransfusionforthemother,
thisbloodalsocanbeusedintheneonate.Onegativewholebloodshouldnotbeusedasitcontainsantibodies
directedagainstAorBbloodgroup,andagainstleukocytes.Onegativewholebloodshouldonlybeusedasa
lastresortincriticallyillneonates.

HemolyticdiseaseofthenewbornAlloimmunehemolyticdiseaseofthefetusandnewborn(HDFN)isa
conditioninwhichtheredcellsofthefetusornewbornaredestroyedbymaternallyderivedalloantibodies.These
antibodiesariseinthemotherasthedirectresultofabloodgroupincompatibilitybetweenthemotherandfetus.
Infantsoftenrequireexchangetransfusiontoremovethematernalalloantibodies,reducetherateofhemolysis,
andpreventsignificanthyperbilirubinemia.Insomecases,asimpletransfusionisadministeredbecausean
exchangetransfusioncannotbedoneinatimelymanner.(See"Postnataldiagnosisandmanagementof
hemolyticdiseaseofthefetusandnewborn",sectionon'Antenatalmanagement'.)

ThedifferenttypesofHDFNinclude(table2):

RhesusD(Rh(D))ThemostsignificantsetupforHDFNoccursintheRhpositiveinfant(ie,Dantigen
positive)ofanRhnegativemotherwhohasbecomesensitizedandhasproducedRh(D)antibodies.An
infantwhoneedseithersimpletransfusionorexchangetransfusionbecauseofHDFNshouldreceiveRh(D)
negativeredcellsoftheappropriateABOtype.

ABOincompatibilityHumanshavefourmajorbloodgroupsintheABOsystem(A,B,AB,andO)named
fortheantigen(s)ontheredcell.TheABOsystemmaycauseHDFN,althoughmostcasesarelesssevere
thanthatcausedbyDantigenisoimmunization.IninfantswithHDFNduetoABOincompatibility,donorO
cellsarewashedtoremoveanyplasmathatcontainsalloantibodies.Thesecellsmaybesuspendedin
plasmathatiscompatiblewithboththeinfant'sredcellsandthetransfused(donor)cells.ABplasmais
compatibleinallcases,sinceitdoesnotcontainantiAorantiBalloantibodies.

OtherRhantibodiesOtherantibodiesincludingRhantibodiesintheCandEsystems,andKellantibodies
cancauseHDFNoracuteordelayedhemolytictransfusionreaction.Inthesecases,redcellsthatare
negativefortheantigen,againstwhichtheantibodyisdirected,areused.

RedbloodcellsRBCsareusedforreplacementduringsurgery,RBCloss,andsporadictransfusiontherapy.
Thehematocrit(HCT)oftheunitvariesdependinguponthepreservativesolution.IntheUnitedStates,
commonlyusedsolutionsincludeCPDA1(citrate,phosphate,dextrose,adenine)withaHCTof65to70percent,
andnutrientpreparations,suchasAdsol(AS1adenine,glucose,mannitol,andsodiumchloride)andNutricel
(AS2citrate,phosphate,glucose,adenine,andsodiumchloride),withaHCTof50to60percent.RBCsinthe
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nutrientsolutions(AS1andAS2)canbeusedforupto42daysaftercollection,andthosepreservedinCPDA
1forupto28days[3537].(See"Redbloodcelltransfusioninadults:Storage,specializedmodifications,and
infusionparameters".)

IthasbeensuggestedthattheuseoffreshRBCtransfusionsinpreterminfantswouldresultinlowerratesof
organdysfunction,nosocomialinfection,andlengthofstay.However,aCanadianmulticentertrialofpreterm
infants(birthweight[BW]<1250g)demonstratednobenefitintheuseoffreshRBC(storedforsevendaysor
less)transfusioncomparedwithtransfusionsusingRBCsstoredunderstandardbloodbankpractice[38].
Specifically,therewasnodifferenceintheprimarycompositeoutcomeofmajorneonatalmorbiditiesthatincluded
necrotizingenterocolitis(NEC),retinopathyofprematurity(ROP),bronchopulmonarydysplasia(BPD),and
intraventricularhemorrhage(IVH)betweengroupsofinfantswhoreceivedfreshRBCs(meanageofRBCs,5.1
2.1days)andthoseadministeredstandardtransfusions(meanageofRBCs,14.68.3days).Infantsinthe
freshRBCgroupwereexposedtoagreaternumberofdonorscomparedwiththestandardRBCgroup(3.72.7
donorsversus2.11.6donors).ThesefindingsshowthatnoalterationforthestandardRBCsstoragetime
practicesisneededforpreterminfantsofneonatalRBCtransfusedproducts.

LeukoreducedandirradiatedredcellsLeukoreductionfiltersremoveapproximately99.9percentof
whitebloodcellsfrompackedredbloodcells(PRBCs),whichreducesfebrilenonhemolytictransfusionreactions,
preventsalloimmunization,andreduces(butdoesnotcompletelyprevent)thetransmissionofcertaininfections
(notablycytomegalovirus[CMV]).However,leukoreductiondoesnoteliminatealllymphocytesandcannot
preventtransfusionassociatedgraftversushostdisease(TAGVHD).

IrradiationpreventsTAGVHDinsusceptiblerecipients.Thedoseofradiationisnotsufficienttokillvirusesand
irradiationdoesnotprovideaCMVsafeproduct.

LeukoreducedPRBCsshouldbeusedinallneonates.Inaddition,mostbloodbankswillalsoirradiate
leukoreducedPRBCspriortoneonataltransfusion.

CMVsaferedcellsCytomegalovirus(CMV)safeproducts(includingCMVseronegativeandleukoreduced
redcells)reducethetransmissionofCMVinseronegativerecipients.Inourpractice,weuseCMVseronegative
PRBCsforallneonates.Incentersinwhichthispracticeisnotavailable,CMVseronegativePRBCsshouldbe
usedforthefollowingpopulations:

Infantsawaitingorundergoingtransplantation
Immunocompromisedinfants
PreterminfantsofCMVseronegativemothers

CordbloodAlthoughcordbloodhasbeensuggestedasaformofautologousblooddonation,mostbirthing
institutionsarenotpreparedforthecollectionandstorageofneonatalcordblood.Evenwithaprogramthat
collectsandprocessesumbilicalcordblood,autologousbloodwasonlyavailableinonethirdofneonatesthat
requiredtransfusion[39].Althoughthecollectionofcordbloodforautologoustransfusioninneonatesrequires
furtherstudy,theuseofcordbloodforinitialbloodtestscanbeeasilyinstituted.Inonestudy,theuseofcord
bloodforinitiallaboratoryevaluationresultedinanincreasedinitialHCTat12to24hoursafterbirth,and
decreasedtherateofearlytransfusionsandvasopressorsinverylowbirthweight(VLBW)infants(BW<1500g)
[40].

Anothermethodthatmayreduceerythrocytetransfusionsisdelayedclampingoftheumbilicalcord,especiallyin
preterminfants.(See"Managementofnormallaboranddelivery",sectionon'Cordclamping'and"Management
ofnormallaboranddelivery",sectionon'Cordblood'.)

ADMINISTRATIONThevolumeoftransfusionisdependentuponthedesiredriseinhematocrit(Hct).

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ThevolumeoftransfusioninmLisequaltothefollowingcalculation:

Wt(kg)XbloodvolumeperkgX(DesiredHCTObservedHCT)/HCTPRBCs

Inthenewborn,thebloodvolumeisapproximately85mL/kg(or90mL/kginverylowbirthweight[VLBW]
infants).Transfusionsgenerallyaregivenaspackedredbloodcells(PRBCs),inaliquotsof10to20mL/kg,over
twotofourhours.Insomecircumstances,suchashemodynamicinstabilityorhypovolemiaduetobloodloss,a
smallervolume(10mL/kg)isgivenmorerapidly(overonetotwohours).Dataareinconclusiveregardingthe
optimalvolumeforneonatalPRBCtransfusion.Inasystematicreviewoftheliterature,therewereonlyfourtrials
with146infantsthatcomparedtransfusionvolumesof10versus20mL/kg[12].Althoughtherewerenoreports
ofdifferenceinneonataloutcomesincludingmortality,thenumberofpatientsistoosmalltoreachanydefinitive
conclusionregardingchoiceofaliquotvolumeforPRBCtransfusion.

Inextremelylowbirthweight(ELBW)andVLBWinfants,thesmallvolumes,whichmaybeaslowas7mLof
bloodforasingletransfusion,requiretheuseofspecialequipmenttomaximizetheuseofasingleunitfroma
donor.Inaddition,thesesystemsallowforserialtransfusionstoanindividualneonatefromthesamedonor.

Theseincludethefollowingtwosystems:

Smallbagsmaycomeaspartofatransfusionset(referredtoassatellitepacks)inwhichfourorsixaliquots
canbemadefromasingleredcellunit.Ifthebloodbankhasasterileconnectingdevice,thesmallbagscan
beconnectedtothelargebloodunit,andanappropriateamountwithdrawnatanytime.

Anotherconvenientdeviceforsmallvolumetransfusionsisasyringesetinwhichthesyringeissterilely
connectedtotheoriginalunit.Bloodisdrawnthroughafilterintoasyringe,andcanbeusedwithinfour
hourswithoutfurtherfiltration.Suchsystemshavebeenshowntobesafe[41]andcanincreasethenumber
oftransfusionsfromasingleunit.

Withbothsystems,theoriginalexpirationdateoftheunitismaintainedifthesamplingdeviceremainsconnected
totheoriginalunitinasterilemanner.Thisperiodmaybeuptosixweeksforuseofasingleunitinanutrient
solutionsuchasAdsol(AS1)andNutricel(AS2).Ifasingleunitisdesignatedforaprematureinfantandisused
untilitsexpirationdate,asmanyas13individualtransfusionscanbemadefromasingledonorunit,which
markedlydecreasesdonorexposure[42].

SUMMARYANDRECOMMENDATIONSAnemiaoccurswhentheredbloodcell(RBC)massdoesnot
adequatelymeettheoxygendemandsoftissues.NeonatesmayrequireRBCtransfusionsbecauseofsignificant
anemiaduetoacutebloodlossorchronicanemiaduetophysiologicanemiaandbloodlossfromphlebotomy.In
particular,anemiainpreterminfants(referredtoasanemiaofprematurity)ismoresevereandpresentsearlierin
life.(See"Anemiaofprematurity".)

Neonateswithsignificantacutebloodlossrequireimmediatefluidresuscitation.IndicationsforRBC
transfusioninaneonatewithacutebloodlossfollowingvolumeresuscitationincludepersistentacidosis
indicatinginadequateoxygendelivery,ongoingbleeding,andanestimatedbloodlossgreaterthan20
percentoftheinfant'sbloodvolume.(See'Acutebloodloss'above.)

Intheacutesettingofbloodloss,especiallyinlifethreateningcircumstances,anyavailableRBCproductthat
iscompatiblewiththeinfant'sbloodtypecanbeadministered.Onegativewholebloodshouldnotbeusedas
itcontainsantibodiesdirectedagainstAorBbloodgroup,andleukocytes.Onegativewholebloodshould
onlybeusedasalastresortincriticallyillneonates.(See'Productsforacutelifethreateningbloodloss'
above.)

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TargethemoglobinandhematocrithavebeenuseduniversallyasclinicalindicatorsforRBCtransfusionin
neonatesduetochronicanemia.However,itremainsunclearwhattheminimaltargethematocrit(HCT)or
hemoglobinisinneonatesthatoptimallybalancestheriskandbenefitsoftransfusion.Basedontheavailable
data,itappearsthatarestrictiveapproachresultsinfewertransfusionsanddoesnotincreasetheriskof
deathorseriousmorbidity.Inourpractice,weusearestrictiveapproachforneonataltransfusionsthatis
baseduponHCTtriggersandtherespiratorysupportrequiredbytheinfant(table1).(See'Target
hemoglobinorhematocrit'above.)

Bloodproductsforneonateswithhemolyticdiseaseofthefetusandnewborn(HDFN)whorequireeither
exchangeorsimpletransfusionneedtobecompatiblewiththeinfant'sbloodtype.(See'Hemolyticdisease
ofthenewborn'above.)

Wesuggestthatleukoreducedpackedredbloodcells(PRBCs)shouldbeusedinallneonataltransfusions
becauseitreducesfebrilenonhemolytictransfusionreactions,preventsalloimmunization,andreducesthe
transmissionofcertaininfections(notablycytomegalovirus[CMV])(Grade2C).Mostneonatalintensivecare
units(NICUs)alsouseirradiatedRBCs,whichdonotprovideaCMVsafeproduct,butpreventtransfusion
associatedgraftversushostdisease.(See'Leukoreducedandirradiatedredcells'above.)

CMVseronegativePRBCsreducethetransmissionofCMVinseronegativerecipients.Wesuggestthat
CMVseronegativePRBCsbeusedforallneonates(Grade2C).WerecommendtheuseofCMV
seronegativePRBCsforimmunodeficientneonates,thosewhoareawaitingtransplantation,andpreterm
infantsofseronegativemothers(Grade1C).(See'CMVsaferedcells'above.)

Intheneonate,transfusionsgenerallyaregivenaspackedredbloodcells(PRBCs)inaliquotsof10to20
mL/kg,overtwotofourhours.Insomecircumstances,suchashemodynamicinstabilityorhypovolemiadue
tobloodloss,asmallervolume(10mL/kg)isgivenmorerapidly(overonetotwohours).Inextremelylow
birthweight(ELBW)infants(BW<1000g)smallvolumesmayrequiretheuseofspecialequipmentthat
allowsseveralaliquotstobeadministeredfromasingleunit.(See'Administration'above.)

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37.FernandesdaCunhaDH,NunesDosSantosAM,KopelmanBI,etal.TransfusionsofCPDA1redblood
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GRAPHICS

Transfusionguidelinesforthenewborninfant

OVERVIEW

Intermandpreterminfants,transfusionshouldbeconsideredifincreasedoxygendeliverytotissuesisneeded
basedupontheclinicalstatusofthepatient.
Volumeoftransfusionshouldbe20mL/kgPRBCunlessthehematocritis>29%.20mL/kgvolumemaybeused
ifsignificantphlebotomylossesareanticipatedinsmallinfantswithhematocrit>29%.
Forinfantsreceivingerythropoietin,additionalconsiderationsshouldbemaderegardingtherateofdecreasein
hemoglobinorhematocrit,theinfant'sreticulocytecount,thepostnataldayofage,theneedforsupplemental
oxygen,andtheoverallstabilityoftheinfant*.
Centralmeasurementsofhemoglobinorhematocritarepreferredwhenusinghemoglobinorhematocrittarget
levelsasindicationsfortransfusionalternatively,heelstickmeasurementsmaybeobtainedafterwarmingthe
heeladequately.

ACUTEBLOODLOSS
Acuteredbloodcelltransfusionsshouldgenerallyonlybeconsideredinthesettingofacutebloodvolumelossof
10%withsymptomsofdecreasedoxygendeliveryorwhenacutebloodvolumelossis>20%.

CHRONICBLOODLOSS
Indicationsfortransfusionforinfantswithchronicbloodlossisbasedontargethematocrit/hemoglobinlevelsthat
aredependentontheinfant'sneedforrespiratorysupportandage*.Thefollowingareguidelinesusedatthe
UniversityofNewMexicothatreflectarestrictivebloodtransfusionapproachforinfants.

Forinfantsrequiringmoderateorsignificantmechanicalventilation,definedasmeanairpressure(MAP)>8cm
H 2 OandFiO 2 >0.4onaconventionalventilator,orMAP>14andFiO 2 >0.4onhighfrequencyventilator,and
withahematocrit30%(hemoglobin10g/dL).
Forinfantsrequiringminimalmechanicalventilation,definedasMAP8cmH 2 Oand/orFiO 2 0.4ona
conventionalventilator,orMAP<14and/orFiO 2 <0.4onhighfrequency,andwithahematocrit25%
(hemoglobin8g/dL).
Forinfantsonsupplementaloxygenwhoarenotrequiringmechanicalventilation,transfusionscanbeconsidered
ifthehematocritis20%(hemoglobin7g/dL)andoneormoreofthefollowingconditionsispresent:
24hoursoftachycardia(heartrate>180beatsperminute)ortachypnea(RR>60breathsperminute)
Doublingoftheoxygenrequirementfromtheprevious48hours
Serumlactate2.5mEq/Loranacutemetabolicacidosis(pH<7.2)
Weightgain<10g/kg/dayoverthepreviousfourdayswhilereceiving120kcal/kg/day
Iftheinfantwillundergomajorsurgerywithin72hours
Forinfantswithoutanysymptoms,transfusionscanbeconsideredifthehematocritis18%(hemoglobin6
g/dL)associatedwithanabsolutereticulocytecount<100,000cells/microL(<2%).

PRBC:packedredbloodcellsFiO 2 :fractionofinspiredoxygenRR:respiratoryrate.
*RefertotheUpToDatetopiconredbloodcelltransfusioninthenewbornforfurtherdetails.

CourtesyofRobinOhls,MD.

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Diagnosticapproachtoanemiainthenewborn

HGB:hemoglobinRBC:redbloodcellDAT:directantiglobulintestMCV:meancorpuscularvolumeDIC:
disseminatedintravascularcoagulationPK:pyruvatekinaseG6PD:glucose6phosphatedehydrogenaseCMV:
cytomegalovirusHSV:herpessimplexvirus.

Reproducedfrom:GallagherPG.Theneonatalerythrocyteanditsdisorders.In:NathanandOski'sHematologyand
OncologyofInfancyandChildhood,8thEd,OrkinSH,FisherDE,LookAT,etal(Eds),WBSaunders,Philadelphia
2015.p.52.IllustrationusedwiththepermissionofElsevierInc.Allrightsreserved.

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Selectionofbloodproductsforinfantswithhemolyticdiseaseofthefetusand
newborn(HDFN)

AlloantibodycausingHDFN KeycharacteristicsforRBCs:

Rh(D) Rh(D)negative
GroupO*orABOcompatible
Crossmatchcompatible

ABOincompatibility GroupO*
Rh(D)negativeorRh(D)compatible
Crossmatchcompatible

Otherbloodgroupincompatibility(eg,antiK,antiE) Negativefortheoffendingantigen
GroupO*orABOcompatible
Rh(D)negativeorRh(D)compatible
Crossmatchcompatible

Foranexchangetransfusion,theRBCsdescribedabovearereconstitutedwithABplasma(thisplasmacontainsno
antiAorantiB),orwithABOcompatibleplasma.

Rh(D):RhesusDRBCs:redbloodcells.
*Atsomeinstitutions,groupORBCsarewashedtoremoveanytracesofantiAorantiBantibodies.Thisismostoften
usedforpretermbabiesbecausetraceamountsofantibodiesrepresentahigherproportionoftheirbloodvolume.
Atsomeinstitutions,groupORBCsareusedforallnewbornsandinfantsyoungerthanfourmonthsold,ratherthanABO
compatibleRBCs.Thissimplifiesandstandardizesthebloodbankprotocol.IfnongroupORBCsareused,thenewborn
mustalsobetestedfor"passive"antiAandantiB(ie,antiAorantiBofmaternalorigin).Theseantibodiesaredetectedby
anindirectantiglobulin(Coombs)test,whichcanbedoneontheinfant'splasma,serum,oreluateofbaby'sRBC,tested
againstAandBcellsifadirectantiglobulin(Coombs)testispositiveforimmunoglobulinG.Cordbloodcanalsobeusedfor
thispurpose.

CourtesyofJunTeruya,MD,DSc,FCAP

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Contributor Disclosures
Robin Ohls, MD Nothing to disclose Donald H Mahoney, Jr, MD Nothing to disclose Joseph A Garcia-Prats,
MD Nothing to disclose Melanie S Kim, MD Nothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform to
UpToDate standards of evidence.

Conflict of interest policy

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