NEONATAL AND PEDIATRIC TRANSFUSION MEDICINE

NEONATALANDPEDIATRICTRANSFUSIONMEDICINEDr.LaniLiebermanTransfusionCampDay1FridaySeptember17th,2021

Objectives• Highlightspecialconsiderationswhenorderingbloodproductsforneonatesandchildren

•  Cases•  PRBC•  Platelet

• Wewillnotbediscussing•  Useofplasma,cryoprecipitateorfractionatedproducts•  Intrauterinetransfusions•  Exchangetransfusions•  Bloodproductuseincardiacsurgery

Whatproportionofbloodsupplyistransfusedtochildren?

TransfusionMedicine2009;19:315–328

4.2%RBC<18yo

1.7%RBC<12mo

Evidencebasedpediatrictransfusion•  Limited• Guidelines

•  Extrapolatedfromadultdata•  Expertopinion•  Auditdata

BJH2016;175:784-828

5thingstoconsiderpriortoorderingatransfusionforaneonateorchild

1.  Bloodrecipients:similartoadult•  Oncology,hemoglobinopathy,OR,ICU

2.  Consent-shouldbeobtainedfromchild’slegalguardian(unlessthechildhascapacitytoconsent)

3.  Labreferencerangesaredifferentforchildrenandneonates

Newbornlaboratoryvalues

HEMOGLOBIN:168 (137-201 g/dl) MCV:110 fl/cell (adult levels by 9 weeks)

Transfusion2014;54,627-632Blood1987;70:165-72.Blood1988;72:1651–7.

Pediatricresources&Referenceranges

BloodyEasyCBS–ClinicalGuidehttps://professionaleducation.blood.ca/en/transfusion/guide-clinique/neonatal-and-pediatric-transfusion



2.  Consentshouldbeobtainedfromresponsibleadult(unlessthechildhascapacitytoconsent)

3.  Labreferencerangesdifferforchildren

4.  Bloodproductsshouldalwaysbeorderedbyweight

BloodProductsareorderedbyweight(ml/kg)

Product PediatricDose(ml/kg)

RBC 10-15ml/kg

Platelets 10-15ml/kg

Plasma 10-15ml/kg

Cryoprecipitate* 1-2U/10kg

BJH2016;175,784-828

BloodProductsareorderedbyweight(ml/kg)

Product PediatricDose(ml/kg) TypicalAdultDose

RBC 10-15ml/kg 1Unit≈280-300mL

Platelets 10-15ml/kg 1Unit≈250-350ml

Plasma 10-15ml/kg 3-4Units≈750-1000ml

Cryoprecipitate* 1-2U/10kg AdultPool150-200ml

Cryoprecipitate*•  Eachunit=8-15ml•  AdultPool=150-200ml•  8-10units+50ccNS

Maximumorderfornon-bleeding•  Nomorethanadultdose

BJH2016;175,784-828



2.  Consentshouldbeobtainedfromresponsibleadult(unlessthechildhascapacitytoconsent)

3.  Labreferencerangesdifferforchildren

4.  Bloodproductsshouldalwaysbeorderedbyweight

5.  Irradiationguidelines–preventTA-GVHD

IndicationsforirradiationIndicationsNeonatesExchangetransfusion PreviousIUTuntil6monthpost

deliverySmallvolumetopuptransfusion Verylowbirthweightinfants

PreviousintrauterinetransfusionCongenitalsevereTcellimmunedeficiencyComplexcongenitalcardiacabnormalities

Hematology/Oncologyindications=sameasadultrecommendations

http://www.nacblood.caNationalAdvisoryCommittee

REDBLOODCELLTRANSFUSIONS

Case:NeonatalAnemia•  25weekpremature–10daysold•  Intubated,NGfed,antibiotics,Grade2IVH• Dailybloodworksinceadmission• Hemoglobinhasbeengradually↓ •  150g/L......80g/L

NeonatalAnemia

Widnessetal.NeoReviews2008;9(11)e520

PhlebotomyBloodLossinVeryLowBirthWeight(VLBW)Infants(<1500grams)

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Cumulative phlebotomy losses typically reach 40-80 ml/kg and, in many infants, will exceed the infant’s blood volume

RBCtransfusionsinELBWinfants•  50-80%ofELBWinfantsreceiveoneormoreRBCTduringhospitalizations

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Vlalieva et at. J Pediatr 2009; 155 (3): 331-337 Keir et al. Transfusion 2015; 55:1340-6

RBCTransfusion

IncreasedO2supplytobrain

Intraventricularhemorrhage

Necrotizingenterocololitis

Bronchopulmonarydysplasia

Retinopathyofprematurity

Decreased risk of apnea ofprematurity frequency &severity

Christensenetal.JMaternFetalNeonatalMedicine.2013;26(s2):60-63MohamedA,ShahPS.Pediatrics2012;129(3):529-540GhirardelloSetal.AmJPerinatology.2017;34(1):88-95SlidsborgCetal.Ophthamology.2016;123(4):796-803.

NeonatalpediatricRBCtransfusiontrials

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PINT

Kirpalani et al. J Peds. 2006; 149:301-7 Bell et al. Pediatrics 2005; 115: 1685-1691

IOWA/ BELL

ShorttermNostatisticallysignificantdifference

indeathormorbidity

IowaTrial:SevereIVHandCystic(PeriventricularLeukomalacia)PVL

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LongTermFollowupData-Cognitive

PINT Bell(Iowa)

Ageatfollowup 18-21months 8-15years

Cognitivetesting BetterinLIBgroup BetterinRESgroup

Whyteetal.Pediatrics2009;123(1):207-213McCoyetal.ChildNeuropsychology,2011;17(4):347–367

Conflictingresults–leadstovariabilityinpractice

MethodologyETTNO

Liberalthreshold=492

1013neonates

Restrictivethreshold=521

Triggervariesby:Postnatalage&Criticalstateofhealth

DeathorNeurologicalimpairmentat24months

SecondaryoutcomesOthermeasuresofcognitivedeficitMeasuresofgrowth@D/C&FU

LengthofstayTimefrombirthtodcrespiratory

support,respstimulantgavagefeedsComplicationsofprematurity

RBC20ml/kgLeucocytereducedExclusion

1.  Major anomalies (cyanotic heart disease, chromosomal anomalies, syndromes) or malformations needing surgery

2.  Lack of viability/comfort car

3.  First neonate of multiples pregnancy

InclusionBWt400-999gGA<29wksPostnatal:

Transfusionthresholds(ETTNO)

●  Criticalhealth●  Exceptionstoguidelineswerepermitted

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MethodologyTOP

Liberalthreshold

1824neonates

Restrictivethreshold

Transfusionthresholds:

postnatalage&respiratorysupport

Death+/-Neurodevelopmentalimpairmentat22-26months

SecondaryoutcomesOthermeasuresofcognitivedeficit

MeasuresofgrowthSurvivalwithoutcomplicationsof

prematurityNumberofRBCtxns

AdministrationofRBCasperprotocolLengthofstay

RBC15ml/kg

Exclusion 1.  Cyanotic heart disease 2.  Received IUT 3.  Lack of viability 4.  Parent with hgbopathy or 5.  congenital anemia 6.  RBCtxn within 6 hours of

life 7.  Twin- twin transfusion 8.  Isoimmune hemolytic

disease 9.  Concerns re: follow up 10.  RBC txn within 6 hours of

life 11.  Congenital condition

InclusionBWt<1000g

GA22-29weeksPostnatal:<48

hours

Transfusionthresholds(TOP)

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Results:Deathorneurocognitivedeficits27

ETTNO

TOPS

NodifferenceDeath

NeurodevelopmentalImpairment

Fewertransfusions

Results28

TOPS

ETTNO

P<0.001

Weeklymedianpre-transfusionHctwas3%higherinliberalgroup

Pre-transfusionmeanHgbdifferentby1.9g/dL

Fewertransfusions

NeonatalRBCthresholdsBottomline• NodifferenceincognitiveoutcomeinneonatesreceivingRBCTinrestrictiveorliberalgroup

• Decreasedtransfusionsforneonatesinrestrictivegroup

Age of neonate

Respiratory Support

No respiratory support

Week 1 110 g/L 100 g/L

Week 2 100 g/L 85 g/L

Week 3 85 g/L 70 g/L

NICURBCTransfusionThreshold(TOPS)

RBCTRANSFUSIONSINOLDERCHILD

TRIPICU

Lowthreshold

Hemoglobin<70g/L

637PICU

Highthreshold

Hemoglobin<95g/L

Nodifferenceinprimary(multiorgandysfunction)Orsecondaryoutcomes44%fewertransfusions

NEJM2007;356:1609-19

RBCThresholdGuidelinesforChildrenPediatricPatienttype Threshold EvidencegradePICU(stable,non-cyanotic) 70g/L 1BOncology 70g/L(typicalpractice)

Insufficientliterature2C

Perioperativenon-cardiacsurgery(stable,non-bleeding)

70g/L 1C

Chronicanemia(DiamondBlackfananemia)

80g/LConsensusbased

2C

Thefollowingshouldbeconsideredforchildrenundergoingsurgerywithsignificantriskofbleeding:

Tranexamicacid(1B)Redcellsalvage(2C)

*Hemoglobinopathies

BJH2016;175:784-828

Case:Pediatricanemia•  22montholdhealthyboy•  Symptoms

•  Pale•  Eatingpaper•  Otherwiseactiveandenergetic

• Diethistory–drinks48ozofhomomilk/day;pickyeater•  PE:Patientalert,interactiveandchasingbrotherinER,VSS• Hemoglobin=52g/L;MCV=62

Whatistheetiologyofthemicrocyticanemia?

• Thalassemia• Anemiaofchronicdisease•  Irondeficiency• Leadpoisoning• Sideroblasticanemia

TAILS

Irondeficiencyanemia(IDA)Who?3.5-11%ofCanadianchildren-COMMONWhy?Multifactorial•  Increaseneedsduetorapidgrowth•  Inadequateintakeofironrichfoods• MalabsorptionOutcome•  Impairsphysicalfunctioning,infantgrowth&developmentandimmunefunction

•  ClearassociationbetweenIDAandimpairedneurocognitivedevelopment

Preventionandtreatmentareessential

Abdullah,2011,CanadianPediatricSociety

Howdowetreatit?• Oraliron

•  3-6mg/kg/dayELEMENTALiron•  Jinexpensive•  L10%absorption,poorcomplianceduetoGIsideeffects

•  IViron•  Failureoforalirontherapy•  Ironintolerance•  Needforquickrecovery•  Ironsucrose(venofer)=7mg/kg(max300mgdose)•  Safebut$$

•  PRBCTransfusion–shouldnotbeusedinstablepatient

NEJM2015;372(19):1832-43.

NEONATALPLATELETTRANSFUSIONS

Meds

Cause

AgePrematureOrterm

Bleeding

Thrombocytopenia:Factorstoconsider

Procedure

NeonatalThrombocytopeniaPrematureinfants•  Thrombocytopeniaoccursfrequently

•  73%<1000g

•  Bleedingiscommon•  30%willdevelopintraventricularhemorrhage(IVH)•  Leadingcauseofdeath&disability

•  Becauseofincreasedrisk,neonatologistshavebeenliberalwithrespecttoplatelettransfusionthresholds

Pediatrics2009;124:e826–e834

Curleyetal.NEJM2018;380(3):242-251

PLANET2:Methodology

Lowthreshold

Platelet<25x109/L

634neonates<34wkGA

Highthreshold

Platelet<50x109/L

HeadUS<6h

NoIVH

Bleedingassessmentdailyx14d

Headultrasoundweekly

BleedingorDeathat28d

Secondaryoutcomes•  Survivalafterbleedingepisode

ProportionsurvivingDChome•  Rate/timingofbleeding

•  #plateletunitsused•  Timetodischarge

•  Adverseeventstodischarge•  Neurodevelopmentupto2yrs


PLANET2:Results

Outcome N=331(%) N=329 Oddsratioorhazardratio(95%CI)

Deathtoday28(N,%) 33/330(10) 48/326(15) OR=1.57(0.95-2.55)

Newmajorbleedingepisode(N,%)

35/330(11) 45/328(14) HR1.32(1.0-1.74)

Adverseevents 92in74infants(22%)

94in81infants(25%)

OR1.1495%CI(0.78-1.67)

Atleastoneplatelettxn(N,%)

177/331(53) 296/328(90) HR2.75(2.36-3.21)

Lowthreshold

Platelet<25x109/L

634neonates<34wkGA

Highthreshold

Platelet<50x109/L


Overallconclusions

●  Moredeathsandmajorbleedingoccurredwhenahigherprophylacticplateletcountwasused

Bottomline➢  Inneonates,aprophylacticthresholdof25x109/Lshouldbe

usedpriortotransfusingplatelets

ProposedNICUPlateletTransfusionThresholds

Clinicalstatus Plateletthreshold GradeComment

Majorbleedingorrequiringmajorsurgery(e.g.neurosurgery)

<100x109/L NoRCTinprems

Bleeding,currentcoagulopathy,sx,

exchangetransfusion

<50x109/L

Nobleeding(includingNAITifnobleedingand

FHxofICH)

<30x109/L Grade2C

BJH2013;160:421–433BJH2019;185(3):549-562,

SpecialconsiderationsforNAIT–neonatalalloimmunethrombocytopenia

PLATELETTRANSFUSIONSFORCHILDREN

Pediatricplatelettransfusions• Whoreceivesplatelettransfusions?

•  CriticallyillinthePICU,Hematology/oncology,Stemcelltransplant,cardiacsurgery

•  Systematicreviewassessedeffectofplatelettransfusionsonplateletcountincrement,bleedingandmorality(only1study)•  Prospectivecohort(N=138)foundnodifferenceinmortalitybetweentransfusedandnon-transfusedcriticallyillchildren

• Oncologyandproceduralrecommendations•  Basedonadultstudies•  Expertopinion

IndianJournalofCriticalCareMedicine,2008;12:102-108NEJM1997;337:1870–1875JCO2001;19:1519-1538http://www.c17.ca

Suggestedplateletthresholdsforplatelettransfusioninchildren

Plateletthreshold(x109/L)

Clinicalsituation

<10 Irrespectiveofsignsofhemorrhage(excludingITP,TTP/HUS,HIT)

<20 SeveremucositisSepsisLaboratoryevidenceofDICintheabsenceofbleedingRiskofbleedingduetoalocaltumourinfiltration

<40 Priortolumbarpuncture

<50 Moderatehemorrhage(e.g.GIbleeding)Surgery,unlessminor(exceptatcriticalsites)

<75-100 Majorhemorrhageorsignificantpost-opbleedingSurgeryatcriticalsites:CNSincludingeyes

BJH2016;175,784-828**expertopinion

Whatistheharm?49

Adversereactions

Supply

$1158

TRIM Transfusion related immunomodulation

Iron overload

TA-NEC

Teachingpoints•  Laboratoryreferenceranges(hematologyandcoagulation)specificforneonatesandchildrenshouldbeused

•  Alwaysconsidertheetiologyoftheanemiaandthrombocytopeniapriortoorderingatransfusion

• Orderbloodproductsusingchild’sweight

Questions

Keyrecommendationsre:FreshFrozenPlasma(FFP)transfusionsinneonatesNeonatal1.  FFPshouldNOTbeusedtocorrectabnormalcoagulation

testinginnon-bleedingneonates(1C)2.  FFPmaybenefitneonateswithclinicallysignificantbleeding

orpriortoinvasiveprocedures(highriskofbleeding)iftheneonatehasanabnormalcoagulationprofile(2C)

3.  FFPshouldnotbeusedforsimplevolumereplacementorroutinelytopreventIVH(1B)

BJH2016;175,784-828

Keyrecommendationsre:FreshFrozenPlasma(FFP)transfusionsinChildren•  ProphylacticFFPshouldNOTbeadministeredtonon-bleedingchildrenwithminorcoagulationabnormalitiesincludingpriortosurgery(2B)althoughitmaybeconsideredforsurgerytocriticalsites(2C)

•  ProphylacticcryoprecipitateshouldNOTbeusedroutinelyinnonbleedingpatientswithlowfibrinogenincludingpriortosurgery(2C).

•  Prophylacticcryoprecipitatemaybeconsiderediffibrinogen<1g/Lforsurgeryatriskofsignificantbleedingortocriticalsites(2C)

BJH2016;175,784-828

NEONATAL AND PEDIATRIC TRANSFUSION MEDICINE

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