transfusion triggers - university of florida2. reversal of warfarin effect for emergency procedure...
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TransfusionTriggers
AnesthesiologyandCriticalCareClerkship
DepartmentofAnesthesiology
BloodBankingProcess
• 450-500ccbloodremovedfromdonor
• Preservative=CPDA– Anti-coagulatedwithCitrate– BufferedbyPhosphate– Metabolismprovidedby
Dextrose– Adenine forATPsynthesis
• Bloodgrouped:ABO&Rh• ScreenedforViruses
BloodComponentSeparation
• Wholebloodnot transfusedinUSA
• Donationseparatedbycentrifuge:– PackedRedBloodCells(PRBC)– Platelets—storedatroomtemp– FreshFrozenPlasma(FFP)
• Frozenafterseparated• Thenthawedtoprecipitateoutcryoproteins
• A2nd CentrifugationseparatestheFFPandcryoprecipitate
PackedRedBloodCells
• Storedat4°CinCPDA-AS• AS=additivesolution
– Basicallymorepreservatives– Adds7daysofpreservation
• Storedupto42days• DonorandRecipient
– TypedforABOcompatibility– Screenedfor20commonRBC
antibodies– Onlycross-matchedif“+”screen
WhentotransfusePRBC?
• ThegoalistomaintainAerobicrespiration
• CellsneedoxygentocreateATPintheKreb’s cycleandElectronTransportChainwithinmitochondria
• Transfusiontriggerisabalancetooptimizeoxygendeliverywhileminimizingtransfusionrisks
OxygenDelivery
• DO2(deliveryofoxygen)=COxCaO2
• CO(cardiacoutput)=HRxSV• CaO2(carryingcapacityofoxygen) =
(Hgb x1.34xSa02)+(PaO2x.003)
• DO2=800-1200mL/min(average70kgperson)• VO2(oxygenconsumption)=200-300mL/min(resting70kgperson)• ERO2(extractionrationofoxygen)=25%
– =VO2/DO2
AdditionalConsiderationsAffectingOxygenDelivery
• RBCcharacteristics– AffinitytoO2(O2-Hgbcurve)– AssistinO2on- /off-loading
• IntracellularO2consumption– VO2variesonmetabolicactivity
• Rheology– Flowcharacteristicsofbloodeffectbloodtransport– “viscosity”
• ValueofPaO2– Controversialimpactduetolowvalue
Oxygen-HemoglobinCurve
• SaturationofHgb basedonthepartialpressureofO2intheblood
• Right shiftindicatesthatalargerpartialpressureofoxygenisneededtomaintaina50%Hgb saturation– Hgb withlessaffinityforoxygen– MoreO2deliveredtothetissues
• Left shiftindicatesthatasmallerpartialpressureofoxygenisneededtomaintaina50%Hgb saturation– Hgb withahighaffinityforoxygen
OxygenDeliveryCompensatoryMechanisms
• IncreaseERO2– Extractmorethen25%ofoxygenfromeachHgb
• Sympatheticsurge– Redistributionofintravascularcompartments
• Augmentspreloadbyrecruitingmoreblood– Positivechronotropic andinotropiceffectonCO
• Renin-Angiotensin-Aldosterone/ADH– Redistributionofintravascularcompartments– Fluidretentionaugmentspreload
• RBCcharacteristics– 2,3-DPGdecreasingHgb affinityforoxygen
CriticalOxygenDeliveryPoint
(ReadRighttoLeft)• AsyoudeliverlessOxygen:
– ConsumesameO2– ReturntoheartlessO2– ExtractmorefromeachHgb
• CriticalDeliveryInflectionpoint:– O2consumptionbecomes
deliverydependent– Nomore“luxuryperfusion”– Anaerobicoxygenation
begins
CriticalOxygenDeliveryPoint
PRBCTriggerThreshold
• DecisiontotransfusePRBCisbasedonunderstandingtheDO2crit inflectionpoint
• Toofarfromthispointandyouareexposingthepatienttoalltherisksassociatedwithbloodtransfusionswithoutanybenefit
• Toofarintothispointyouhavebegunanaerobicrespiration
IndicationsofDO2crit
• DecreasedMixedoxygenationvaluefrompulmonaryarterycatheter
• IncreasedLacticAcid– DecreasedBicarbonatevalue(reflectinglacticacid)– DecreasedpH(reflectinglacticacid)
• Evidenceofend-organischemia– ECGchanges– RegionalWallMotionchangesonEcho– Chestpain– Confusionanddizziness
Whatabout…?
• VitalSigns– ChangesIndicatecompensatorymechanisms– Arethosechangesdetrimentaltopatient?
• Urineoutput– FluidconservationiskeytomaintainingCO– Howlong/severeisthekidneybeingunderperfused?
• HemoglobinorHematocritislow?– NeedtoconsidertheoverallCO,CaO2,andVO2,notjustonenumber.
Question#6
• Regardingthedetectionofinadequateoxygendelivery– Vitalsignsreliablyshowend-organischemia– Urineoutputrevealsend-organischemia– RegionalWallmotionabnormalitiesrevealsend-organischemia
– Alowhct reliablyshowsend-organischemia– AlowpHreliablyshowsend-organischemia
First….
• Makesurethepatientiseuvolumic
• Animalscantoleratemajorbloodlossaslongastheirintravascularstoragecompartmentisreplete
• Haveyouattemptedtoreplacetheintravascularsystemwithcrystalloids?
Alwayskeepinmind…
• Transfusiontriggersvaryingwidely acrosspatientpopulations– Considerdifferences:
• AHealthy20yo• A75yowithsevereCAD• Asingleventricleneonate• Acriticallyillmechanicallyventilatedpatient
– Needtounderstandthecomplexpathophysiologyofthesedifferentpopulationsinordertoappropriatelytransfusethem
TransfusionConsiderations
• IsthepatientEuvolumic?• Isthepatientcriticallyill/mechanicallyventilated?• Doesthepatienthavecoexistingcomorbidities?
– Cardiac– Pulmonary– Cerebralvascular
• IsthisAcuteorChronicanemia?• ThedecisiontotransfuseneverrestssolelyonaHgb
value!– Thatbeingsaid,theHgb valueisusuallybetween6-9g/dL
priortotransfusingdependingonpatientidiosyncrasies
What’stheBigDeal?Justgive2Units!
• Risks ofBloodproducttransfusion:– Incompatibilityreactions– TransfusionTransmittedInfections(TTI)– TransfusionRelatedAcuteLungInjury(TRALI)– TransfusionRelatedImmunoModulation (TRIM)– TransfusionAssociatedCardiacOverload(TACO)– Electrolytederangements– pHchanges– Temperaturedecrease– Alloimmunization– DepressedErythropoesis– ….
CoagulationOverview• Primaryhemostasis
– Injuredendotheliumexposestissuefactoranddamagedcollagen– vWF bindstocollagenandtocirculatingplatelets– Plts changefromsphericaltospindleshapedandreleasegranules– Plts aggregatetoformplateletplug
• Secondary hemostasis– Tissue Factor (TF) on damaged endothelium activates FVII– Plt surface serves as platform for coagulation “cascade”– TF-FVII activates FX, which activates FV– This complex then activates Thrombin– Thrombin cleaves fibrinogen to fibrin– Platelets receptors conform to bind to fibrin– Platelets cross-link fibrin which cross links with factor XIII
Coagulation
Mackman etal.BloodCoagulationinHemostasisandThrombosis.Arterioscel Thromb Vasc Bio2007;1692.
FreshFrozenPlasma• Traditionallyisolatedby
centrifugation• Apheresisisnowoften
used– Plasmaextractedfrom
donorwhiletheRBCsremain
– Plateletrichplasma– Frozenafterapheresis
• NeedstobeABOmatched
• RemembertypeABistheuniversalplasmadonor
FreshFrozenPlasmaFacts
• Containsallcoagulationfactors(enzymes)• 1mlhasabout1unitofeachcoagulationenzyme• 1mlhasabout1mgoffibrinogen– 1unithasabout300-400mg– 4unitshasabout1200-1500mg=1pooledcryoprecipitatebag
• UponwarmingfactorsVandVIIIdepleterapidly– Called“labile”factorsbecauseofsensitivity
IndicationsforFFP
1.Replacementofisolatedfactordeficiencies– IF isolatedrecombinantsarenotavailable
2.ReversalofWarfarineffectforemergencyprocedureorbloodloss3.MassiveBloodTransfusion
– IF >1-2BloodVolumesoverafewhours– BeststrategyistobeguidedbyThromboelastagram (TEG)
4.Antithrombin IIIdeficiency– IF recombinantisnotavailable
5.TreatmentofImmunodefiencies– IF purifiedImmunoglobulins arenotavailable
6.Treatmentofthromboticthrombocytopenicpurapura
FFPdosage
• 1mL/1kgwillgive1%ofFactors(enzymes)• Normalcoagulationcallsfor30%ofcoagulationenzymes
• Foranaverage70kgpersonwithcoagulopathy– Assume5-10%Enzymaticactivity…butcouldbeworseorbetter
– Want20%moresoneed20mL/kg=1400mL• Equals4-6unitsofFFP
– 15-20mL/kgisanaveragedosageforFFPtransfusion
Never giveFFPasVolumeReplacement!
Platelets
• Traditionallyfromcentrifugationofwholeblood• Apheresisor“singledonor”nowmorecommon– Lessriskbecausenotpooledfrommultiplesources– Willcontainsomefactorrichplasma
• Storedatroomtemperature– Increasesbacterialgrowthsusceptibility
• Freezingorwarmingwillmakethemnonviable• Storagetime=3-5days
Platelettransfusiontriggers
• Normalplateletcount150-350000• <10,000-20,000foranonbleeding patientwithoutasourceofpotentialbleeding
• <50,000formostoperations• <70,000-100,000forneurosurgicalbleedingwhereanyamountofbleedingiscatastrophic
• PlateletcountdoesNOTassessplateletfunction– Needtoconsiderquality aswellasquantity– ConsiderPlateletmappingorTEG
Cryoprecipitate
• AsFFPisthawedfromfrozen,cryo precipitatesoutfirst• Originallydevelopedforhemophiliacs– BecauseCryo isrichinFactorVIIIandvWF
• Nowmostlyusedasasourceoffibrinogen• Eachpooledunithas4majorparts– Fibrinogen:1200– 1500mg– VIII:800-1000units– vWF:800– 1000units– XIII
Cryoprecipitatetransfusiontriggers
• Fibrinogenisnecessarytomakefibrin– Fibrincross-linksonplateletstoformclot– FXIIIcross-linksfibrinpolymerstostrengthenfibrinclot
• Minimumconcentrationoffibrinogenneedediscontroversial– Traditionally,Fibrinogen<100mg/dL shouldbereplaced– Newerstudiessuggestreplacingfibrinogen<200mg/dL– OBpatientsmayneedalevelof>300mg/dL
ClotDissolution=Fibrinolysis
• BeginswithtPA,whichactivatesplasminogentoplasmin
• Plasminbindstofibrinpolymersatlysineresidue
• BreaksfibrinpolymersintotwoD-Dimers
• Anti-fibrinolytics– e-aminocaproic acid&
transexamic acid– lysineanalogs– Competitiveantagonists
Factorconcentrates
• PCC=procoagulant concentrates– 3factortypes:II,IX,X,variableamountofheparin– 4factortypes:II,VII,IX,X,variableamountofheparin– Approvedforrapidreversalofanti-vitaminKmedicationsinlifethreateningbleeding
– Comein30-40ccdosage• RecombinantfVII– Developedforhemophiliacswithreplacementinhibitors
– SetsoffTissueFactorpathway
TheEnd