Transfusion Triggers - University of Florida2. Reversal of Warfarin effect for emergency procedure or blood loss 3. Massive Blood Transfusion – IF> 1-2 Blood Volumes over a few hours

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