Mona MOMENI, MD, PhD Department of Acute Medicine Anesthesiology Unit Blood transfusion management BAPA refresher course
MonaMOMENI,MD,PhDDepartmentofAcuteMedicine
AnesthesiologyUnit
Bloodtransfusionmanagement
BAPArefreshercourse
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Conflictsofinterest:
Speaker’sfeesMedtronic
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PatientBloodManagementprograms
• Wellrecognized&appreciatedinadults
• Resultofevidence-basedmedicineinadults
• Neonates&children:physiologicaldifferences:higheraverageHbconcentrations
:higherO2consumptionscomparedtoadults
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• Bloodutilizationreview&auditing:comparedwithcurrentpediatric
evidencebasedtransfusionguidelines
• Perioperativeanemiamanagement
• Standardproceduresformassivetransfusion
• Maintainingahemovigilanceprogram
• Appropriatebloodproductselection(irradiated,leukoreduces,washed,..)
PatientBloodManagementprograms
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Transfusionmedicinecommunity:5rights
1. Transfusingtherightproduct2. Transfusingintherightdose3. Transfusingtotherightpatient4. Transfusiongattherighttime
5. Transfusingfortherightreason
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10,7complicationsVS2,5complicationsPer1000productstransfused
PatientBloodManagementprograms
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• PackedRBC• FFP• Plateletconcentrate
• Fibrinogen(cryoprecipitate)• Others:PPC,FVIIa
Transfusingtherightproduct&fortherightreason
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PackedRBC
Definitionofanemia????
• Children:≤7g/dL:≤5g/dL…..PediatricCriticalCareTransfusion&AnemiaExpertise• Inneonates:≤8g/dL(RCTofrestrictivevsliberaltransfusion)• Preterminfants
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RisksofAnemia
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Whatistheoutcomeyouarelookingat?
Restrictivevsliberaltransfusionstrategyinchildren
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• Largestmeta-analysis:KeirA,etal.Adverseeffectsofredbloodcelltransfusions
inneonates:asystematicreviewandmeta-analysis.
Transfusion.2016;56:2773-80
Nodifferenceinmortality
NodifferenceinNEC
NodifferenceinCLD
NodifferenceinROP
NodifferenceinIVH
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Neurodevelopmentaloutcome?????
OngoingphaseIIItransfusionstudies:
1. ETTNOtrial:EffectsofTransfusionThresholdonNeurocognitiveOutcomeofExtremelylowBirthWeightInfants2.TOPtrial:Transfusionofprematures
WhetherhigherHbvaluesleadto:
- Improvementinsurvival(=primaryoutcome)
- Ratesofneurodevelopmentalimpairmentat22-26monthsofage
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Ø Systematicreviewfrom1990–2010ofneuromonitoring&neuroprotectionstrategies
Ø Infants<1yearØ 162manuscripts
Ø Primaryoutcome:evidenceofstructuralbraininjuryin43%
Ø Mostfrequentlevelofevidence:ClassIIborLevelB(42%)
Ø TheonlypracticewithClassIIaorLevelA:avoidanceofextremehemodilution
Ø Conclusion:levelofevidenceisinsufficienttosupporteffectivenessofcurrentneuromonitoring&neuroprotectivetechniques
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Howtodetectcerebral/organhypoperfusion?
• SurrogatemarkerofO2delivery/O2consumption
• Combinedcerebral/somatic:usefulinformation
• Todatenoevidence-baseddataforitsroutineuse
CBF VO2O2supply O2consumption
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NIRS-basedtransfusionofRBC
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NIRS-basedtransfusionofRBC
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ASDclosure&PAPVR;4years;preopHb=12.7g/dL
Hb=8.1g/dL:transfusion
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When&howmuchRBCtotransfuse?
• AllowableBloodloss(ABL)ABL=EBVx(Hctstarting–Hcttarget)/Hctavg• Transfusedvolume(PRBC)=weight(kg)xdesiredHbincrease(g/dL)x5
• 10mL/kgPRBCwillincreaseHbby2g/dL
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• Ingeneraldifficulttoquantify:ventilated(maskingrespiratoryreactions)
:draping(novisualisationofurticarialreactions)
:CPB
:lackofformaluniversaldefinitionofreaction
• Transfusionassociatedcirculatoryoverload
• Transfusionrelatedacutelunginjury
Underdiagnosedinneonateswithrespiratorysymptoms
AdverseeffectsfromRBCtransfusion
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• HyperK&Ventricularfibrillation:
The«WakeupSafe»initiativefromSocietyofPediatricAnesthesia
recommendsthatRBCshouldbefresh(<1wold)orwashedifthepatient
is<1yoldorweights<10kg
• TA-GVHD:veryrarewithhighmortalityrate
:Host(immuneincompetence),donorTlymphocyte,and
environmentalfactors(inflammation)
:irradiatedcellularbloodcomponents(Japan)
• Allergicreactions:IgEmediated
AdverseeffectsfromRBCtransfusion
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• Autologousblooddonation:NO;risks>>>>benefits• rhuEPO:veryspecificcases;guidelinesagainstroutineuse
• AcuteNormovolemicHemodilution:veryspecificcases;olderchildren
• Cellsalvageexceptintumorsurgery(disseminationoftumorcells)
• Irondeficiency:exclusivebreastfeedingisariskfactor
:2–3mg/kg/doralirontopreterm/smallforgestationalage
• Reduceblooddraws
Howtooverome/treatanemia?
!Hb/Hct:samplesfromlargerveins&arteries=lowerthancapillarysamples
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• PackedRBC• FFP• Plateletconcentrate
• Fibrinogen(cryoprecipitate)• Others:PPC,FVIIa
Transfusingtherightproduct&fortherightreason
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FFP
• DecisionwhethertoadministerFFPornot:easier
• BUT……
• EvidenceguidingtransfusionofFFPfromallbloodproductsin
theneonatesistheweakest
• INDICATION:purpurafulminansduetoProteinC&ProteinSdeficiency
:congenitalthromboticthrombocytopenicpurpura
• Usually10–15mL/kgwhenclinicalbleedingandstandardcoagulation
testsare1,5xnlvalues:???Notevidencebased
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Standardcoagulationtestsgiveinadequateinformation:
- Reagentsusedtoperformcoagulationtestsaresensitivetoevenminor
reductionsincoagulationfactorlevels
- Relationshipbetweencoagulationfactorlevels&coagulationtesttimes
notlinear
-FFPoftenresultsinminimalchangesincoagulationtestresults
Point-Of-Caretests:ROTEM/TEG
FFP
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GUIDELINESBSH
• Againstroutineusetocorrectcoagulationabnormalities
• Notroutinelyperformingcoagulationtestsinallneonates
• Indicated:priortosurgeryifthereissignificantcoagulopathy:acutebleedingsecondarytocongenitalbleedingdisorders
wherespecificfactorreplacementisnotavailable(rare!)
:inthemanagementofactivebleeding&significant
coagulopathy
:NOTtobegivento«non-bleeding»childrenwithminor
coagulopathyevenbeforesurgery
FFP
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• Nodifferencebetweenbothgroupsintermsofbleedingortransfusionrequirements
• Changeindailypractice
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AdverseeffectsofFFP
• Inherenttoanyallogeneicbloodproduct
• THROMBOTICCOMPLICATIONS
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• PackedRBC• FFP• Plateletconcentrate
• Fibrinogen(cryoprecipitate)• Others:PPC,FVIIa
Transfusingtherightproduct&fortherightreason
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Plateletconcentrate
• Definition:mild=100–150x109/Lmoderate=50–99x109/Lsevere=<50x109/L• Definitioninneonateslessclear:WiedmeierSEetal.Predictableincreaseinplatelets2x109/Lperweekincreasegestationalage• Noclearrelationshipbetweenthrombocytopenia&clinicalbleeding• NoRCTavailable• GuidelinesBritishSocietyofHematology:stablechildren<4m:prophylacticif<30x109/Lstablechildren>4m:prophylacticif<10x109/L
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-Error
-Bacterial&septicinfectionsduetostorageatroomair
-Allergicreactions
-TACO&TRALIduetotheinnateplasmacomponentofplateletproducts
Adverseeffectsplateletconcentrate
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• PackedRBC• FFP• Plateletconcentrate
• Fibrinogen(cryoprecipitate)• Others:PPC,FVIIa
Transfusingtherightproduct&fortherightreason
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Fibrinogen
• Hypofibrinogenemia=majorreasonforcoagulopathicbleeding
duringcomplexpediatricsurgery
(craniosynostosis,cardiac,scoliosis)
• FFP:questionnableefficacyinrestoringfibrinogenconcentrations
• Inadults:incaseofthrombocyotopeniaand/orplateletdysfx,fibrinogen
makesastrongercontributiontoclotfirmnessthanplatelets
Langetal.AnesthAnalg2009;108:751-8
Harretal.Shock2013;39:45-9
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• Bestwaytoanalyzefibrinogenconcentrationandfibrinpolymerization:Fibtem
• Fibtem:eliminatestheplateletcontributionbyCytochalasinD
• Inadults:guidelinesEurSocietyofAnaesthesiology:cutoffFibtemMCF<8mm
Fibrinogen
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• Dose:StudybyHaas90(75–120)mg/kg
• !300mg/kg:neonateFibtemvaluesnotmeasurable
• Ruleof10inbleedingpatient:FibtemA10<10give50mg/kgFibrinogen
• €€€€
• 1LFFP:2.5-2.7gFibrinogen
• Cryoprecipitate:NotinEurope:Differentdonors:VIII+Fibrinogen+Fibronectine+XIII+vWF:2pools(±200mL):4gFibrinogen
Fibrinogen
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• PackedRBC• FFP• Plateletconcentrate
• Fibrinogen(cryoprecipitate)• Others:PCC,FVIIa
Transfusingtherightproduct&fortherightreason
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ProthrombinComplexConcentrate
• Either3factors(II,IX,X)or4(II,VII,IX,X)
• Clottingfactorconcentration25timeshigherthannormalplasma
• Indication:VitKanatgonists(1–2mL/kg)
:congenitaldeficiencyofanyofthesefactorswhenpurified
specificcoagulationfactorsarenotavailable
• Topreventactivationofthesefactors,mostcontainheparin
• MayalsocontainnaturalcoagulationinhibitorsproteinC&S
• Differenthalf–livesofthe4factors:
FII:60-72h
Others:6–24h
• Adverseeffects:HIT–allergicreactions–thromboemboliccomplications
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FactorVIIa
• Veryexpensive• Insufficientdatainpediatrics
• Aprospective,randomizedtrialinpediatriccardiacsurgeryfailed
toproveasignificantdifferenceinbloodlosswhencompared
toplacebo
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Antifibrinolytics:Tranexamicacid
• Veryeffictiveinmajorsurgery&trauma
• Optimaldosing,timingofadministration&pharmacokineticsrequirestudies
• Adverseeffects:seizures!Athighconcentrations
InhibitionofinhibitoryglycineandGABAR;theseRhavelysinebindingsites
andaremediatorsofCNSinhibition
• Newpharmacokineticstudies
10–15mg/kgover15minfollowedby5–10mg/Kg/hnon-cardiacsurgery
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Conclusions
• Transfusing¬transfusing=harmful
• MoreRCTneededtohaveevidencebaseddata
• Focusingonspecificoutcomes
• PatientBloodmanagementstrategies
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Thankyou