Download hematology review for surgical critical care

HEMATOLOGYREVIEWFORSURGICALCRITICALCARE
Overview
I.BloodandBloodComponents
II.MassiveTransfusionandResuscitationofHemorrhagicshock
III.AcuteCoagulopathyofTrauma
IV.DamageControlResuscitation
V.HemostaticAdjuncts
VI.CoagulationTesting
VII.CoagulationDisorders
VIII.AnemiaintheICU
IX.ThrombocytopeniaandHIT
X.ManagementandReversalofAnti‐coagulantsandAnti‐plateletagents
XI.Transfusion‐associatedcomplications
I.BloodandBloodComponents
A.Redbloodcells(RBC)aretheprimaryO2‐carryingcomponentofwholeblood;300
mL/unit;typicalhematocritof29%;usuallytransfusedin10‐15mL/kg“challenges;”
expectedincreaseperunittransfusedisonegram(hemoglobin)or3%(hematocrit);
typicalshelf‐lifeupto42days;groupObloodtypeisconsidereduniversaldonor(O
negativeforfemalerecipients)
B.Plasmaistheprimarysourceofcoagulationfactors;makesup55%ofbloodvolume;
200‐250mL/unit;contains400‐450mgfibrinogen/unit;otherfactorsin60‐70%range;
bufferssevereacidosis(viaitshighcitratecontent);“jumbo”plasmaunit700‐800mLfrom
singledonor(aphaeresis);FFP‐plasmafrozenwithin8hoursofreceipt;FP24‐plasma
frozenwithin24hoursorreceipt;liquidplasma‐neverfrozenplasma;FFPistobeused
within24hours,otherwise,relabeledthawedplasma‐previouslyfrozenFFPorFP24with
5dayshelflife;ABplasmaisconsidereduniversaldonor
C.Plateletsarederivedfrommegakaryocytesandplayanactiveprocessincoagulation
throughclottingfactor,fibrinandendothelialinteractions;releasedas5‐6packs(units)
(40‐50mL/unit)fromrandomdonorsorfromsingledonor(aphaeresisunit,200‐250mL)
withtypicalcountof80,000platelets;storedatroomtemperatureandonanagitator;
traditionalshelf‐lifeof5days;avoidtransfusioninpatientswithTTP(worsensneuro
symptomsandrenalfailure),HITandDIC;nouniversaldonorrequired
D.Cryoprecipitateisaconcentratedproductobtainedfromplasma;transfusedasapooled
units(4‐6unitpools),therefore,typicalbagis80‐100mL;each(10‐15mL)unittypically
contains100IUoffactorVIII,250mgoffibrinogen,andadequatestoresofvonWillebrand
factor(vWF)andfactorXIII;aswithplasma,compatibilitytestingisnotstrictlynecessary,
butABtypeistheuniversalplasmadonor;intheemergencysetting,typicallygivento
addresshypofibrinogenemia
E.Wholebloodisutilizedinausteresettingswhen(1)bloodsuppliesarestressedor
depletedand(2)whendonorscreeningiscompletedandresultsareknownpriorto
donation(militarysetting);usualvolumeofeachunitis450‐500mLwhichhasa
hematocritof>38%,plateletcount>150,000,100%clottingfactorlevelsand1000mg
fibrinogen;mustbetype‐specificproduct
II.MassiveTransfusion(MT)andHemorrhage
A.Hemorrhageaccountsforgreatestnumberofdeathswithinthefirsthourofarrivalafter
injury;exsanguinationisresponsible>80%O.R.deathsand~50%deathsinthefirst24
hoursafterinjury
B.MTtraditionallydefinedas10unitsofredbloodcells;otherdefinitionsinclude‐lossof
onebloodvolumein24hours,50%bloodvolumelosswithina3hourperiod,orlossof
bloodat150mL/min;seenin8‐10%traumapatientsinmilitarysettingand1‐3%inthe
civiliansetting
C.MTprotocolshavebeendevelopedtoaddressthis;composedofasystemwhereby
physicianactivatestheprotocolandpredeterminedbloodandbloodproductsare
deliveredinrapidandsustainedmanner;ratiosandunitsdeliveredpercycleare
institution‐specific;manycentersalsoemploytheseprotocolsfornon‐traumapatientsas
well
D.MTprotocolsratiostypicallyincluderedbloodcells,plasma,plateletsand
cryoprecipitate.Someusepharmacologicadjunctsaswell.Plasma:RBCratiosaretypically
inthe1:3‐1:1rangewithplateletsandcryoprecipitateusemorevariable.Well‐developed
protocols,irrespectiveoftheratios,havebeenassociatedwithdramaticreductionsin
mortality,reductioninmulti‐organfailureandARDS,reductioninoverallbloodandblood
componentutilizationandlowerhospitalcharges
E.ActivationofMTprotocolsmaybedirectedbyclinicalgestalt,laboratoryorphysiological
triggersoravalidatedscoringsystem;use/requestofuncross‐matchedproducthasbeen
showntoprecederecognitionofmajorbleedingandMTscenarios,assuch,transfusionof
uncross‐matchedproductsshouldactivateaninstitution’sMTprotocol;theTASHandABC
scoresarebothvalidatedscoringsystemsthathavebeenshowntopredicttheneedforMT
withAUROC0.80‐0.90;thescoreshavegoodPPVandgreatNPV;thesescoringsystems
employacombinationofhypotension,tachycardia,(+)FAST,mechanismofinjury,andbase
deficit
III.AcuteCoagulopathyofTrauma(ACoT)
A.ACoThasbeendescribedasanendogenousimpairmentofhemostasisthatoccursearly
afterinjury;coagulationabnormalitiesarecommonfollowingmajortraumaandare
presentonarrivalin25%ofpatientswithmajortrauma;mortalityamongtrauma
patientsisincreaseddramaticallywhenACoTispresent(morethan4‐foldincreasein
mortality)
B.HallmarkofACoTismicrovascular‐bleedingleadingtomassivebloodloss;purported
etiologiesincludehemodilution,majorsurgeryinducingcomplexhemostaticchanges,
consumptionofcoagulationfactors,andexcessivefibrinolysis.
C.MajorriskfactorsforACoTincludeextensivetissuedamage,shock/acidosis(basedeficit
of10orsustainedSBP<90mmHg),largeamountofprehospitalIVfluid(3000mL),and
hypothermia(temperature<35 C);ACoTisassociatedwithincreasedtransfusion
requirementsandorganfailure
IV.DamageControlResuscitation
A.Thethreetenetsinclude:permissivehypotension,limitingcrystalloidsanddelivering
higherratiosofplasmaandplatelets;toaddressthese,institutionsdevelopedand
implementedMTprotocols;however,theratioshavebeenthemoststudiedcomponent
B.Allpublishedstudiestodatehavebeennon‐randomizedandmosthavebeen
retrospectivereviewsbasedonchangesinpractice;moststudiesonratioshave
demonstratedsurvivaladvantagewithincreasingplasma:RBCandplatelet:RBCratios;at
thistime,theoptimalratioofplasma:RBCappearstobebetween1:1‐1:2
C.Survivalbiaspotentialhasbeenraisedbyseveralauthors;survivalbiassuggeststhat
patientsarenotsurvivingbecausetheyreceivedhigherratiosofproductsbuttheyare
receiving(achieving)higherratiosbecausetheyaresurvivinglongenough;thisreaffirms
thosewhostatethatthisreflectsanavailabilitybias(“youcan’tgivewhatyoudon’thave”)
asoneoftheinitialstudiespointingoutsurvivalbiasdidnotadministerplasmawithinthe
first90minutesofarrival
D.Duringtheacuteresuscitationphase,increasingvolumesofcrystalloidareassociated
withworseoutcomes;theseincludeincreasedfrequencyofandlongertimetorecovery
fromALIandARDS,increasedgastrointestinaldysmotilityandanastomoticleakrates,
morefrequentcoagulationdisturbancesandhighermortality;thesecomplicationsremain
significantevenwhencontrollingforshockandseverityofinjury;thesecomplicationsare
morecommon(andseenwithevenlessfluidadministration)intheelderlytraumapatient
E.Recentcivilian(USandUK)andmilitaryguidelinesrecommendfluidrestrictive
strategiesintheprehospitalsettings,titratingsmallfluidboluses(250mL)forpalpable
radialpulsepalpableandnormalmentalstatus;arandomizedtrialfromDuttonetal
demonstratedthattherewasnosurvivalbenefitfromresuscitatingpatientswithevidence
ofhemorrhagetoaSBP>70mmHgor>100mmHg;arecentpilotstudyfromMorrisonetal
notedthatpatientswithpenetratingtorsotraumawhowererandomizedtoanintra‐
operativeMAPof>50mmHghadlessbloodloss,receivedlesstotalfluidsandlessblood
productsthanthoserandomizedtoMAP>65mmHg
V.HemostaticAdjuncts
A.Internal‐Pharmacologic
FactorVIIa
InitiallydevelopedforuseinHemophilia,subsequentlyusedinlife‐threatening
hemorrhagefromtrauma,surgery,liverfailure.Wasalsoshowntohavearoleinreducing
strokevolumehemorrhage.Exceptionallyexpensiveduetoitsrecombinantnature.Dosing
scheduleneverwellelucidated.
Trialintraumastoppedprematurelyduetofutility.Hasbeeneffectivelyshowntoreduce
transfusionrequirementsbutNEVERtoreducemortality.Beingusedlessandlessdueto
expenseandconcernforside‐effectprofile(thromboticevents)
ProthrombinComplexconcentrates
Again,notdesignedforuseintrauma,buthavebeenusedsuccessfullyinanecdotalcasesof
patientsnotrespondingtohemostaticresuscitation.Thecorrectdosagestillneedsto
elaboratedaswellastheexactpatientpopulationthatmaybenefitfromthisdrug.
B.External
Multipleagentshavebeenusedbothonandoff‐labelwithmixedresults.Oneearlyfailure
wasWoundstat,whichwaswithdrawnduetoaconcernregardingthrombosesofnearby
vessels.
Quikclot–oneofthefirsttomarket.Initiallyingranuleform,thenrepackagedintoa
“teabag”.InitialproductHIGHLYexothermic,thenreformulated.Firstgenerationgranules
veryeffective,butatpriceoftissuedamage.Makershavemovedintothirdgeneration
dressingsnow,andareconcentratinglessonQuikclotbutstillcommerciallyavailable.
CombatGauze–Kaolinimpregnatedgauzeroll.Forexternaluseonly,butcanbe
packedintolargehemorrhagingwounds,orintothenasalcavityforexample.Trueefficacy
unclearincontrollingbleedingintraumapatientswithACoT.Nowcarriedextensivelyby
army–madebysamemanufacturersasquikclot.
C.Internal–ORadjuncts
Thrombin/Fibringlues
Usemostlyrestrictedtotheoperatingroom.Moreeffectiveinslowlyoozingbroad
surfacesthanlargevolumeorinjuredvessels.Certainlyhavearole,butoneproducthas
notbeenshowntohavesignificantsuperiorityoveranother.
Collagengauzes,granules
Surgicel/Nugauze–oxidizedcellulose.Effectiveforminorsurfacebleeding.Cheap
andnon‐toxic.Canevenbeleftinsidethepatient,andwillreabsorb.Bacteriostatic.
Othergranules,powdersavailable.Noneeffectiveformajorbleeding.
VI.CoagulationTesting
A.Rapididentificationofclottingabnormalitiesappearscriticaltoimprovingsurvival;
unfortunately,themajorityoftestsfocusonsinglepartofclottingcascade;prothrombin
time(PT)andINRreflectdefectsorintegrityoftheintrinsicpathwaywhilepartial
thromboplastintime(PTT)reflectstheextrinsicpathway;intherapidlybleedingand
unstablepatient,thesetestsareoftenrenderedworthlessduetolongintervalsinherentin
drawingblood,processingspecimen,andobtainingresults
B.PT,INR,andPTTreflectsonlystatusofplasmaproteins;thesestudiesneglectthe
contributionoftheothercomponentsofwholeblood;PT,INR,andPTTmayindicatea
certaindegreeofcoagulopathyand,whenmarkedlyelevated,correlatewithworse
outcomes;however,thesetestswereneverdevelopedorintendedforfollowingpatients
withacutecoagulopathyfromtrauma;thesetestsweredevelopedandvalidatedinpatients
beingtreatedwithoral(warfarin‐PTandINR)orintravenous(heparin‐PTT)
anticoagulants;whilePTTmayoccasionallybeprolongedwithneweranticoagulants
(dabigatran,rivaroxaban),PTandINRarenormal;othercoagulationtests(plateletand
fibrinogencount)arelimitedbytheirpurequantitativevaluesandlackoftestingof
functionorqualitativeassessment
C.Multiplepoint‐of‐carecoagulationdeviceshavebeendeveloped;unfortunately,these
haveonlybeenformallyevaluatedwithpatientsonoralanti‐coagulants;inaddition,these
PT/INRpoint‐of‐caredevicesdemonstrategoodcorrelationatlowervalues(INR<2.0)but
showconsiderablevariability(andpoorcorrelation)atvalueshigherthan2.0
D.Wholeblood‐based,viscoelastictestinghasrecentlygainedpopularity,thoughthe
technologyhasbeenaroundfor>50years;boththrombelastography(TEG)androtational
thromboelastometry(ROTEM)areavailableintheUSforevaluatingtheACoT;inboth,a
smallsampleofbloodisaddedtoacuvetteandtheclottingprocessisinitiatedbythe
additionofoneoracombinationofactivators(kaolin,tissuefactor,calciumchloride);these
testshavebeenshowntocorrelatenotonlywithpooroutcomes,but,moreimportantly,
withplasma,plateletandcryoprecipitate/fibrinogentransfusions;TEGhasalsobeen
showntopredicthypercoagulability,specificallyin‐hospitalvenousthromboembolism,
myocardialinfarction,andstroke
E.TheTEGvaluesgeneratedinclude:ACTandr‐value(representingthetimebetweenstart
oftheassayandinitialclotformation),k‐time(timetoreachspecifiedclotstrength),alpha‐
angle(slopeoftracingthatrepresentsrateofclotformation),maximalamplitude(greatest
amplitudeoftracing,reflectsabsoluteclotstrength),andtheLY30(whichrepresentsclot
stabilityandthe%amplitudereduction30minaftermaximalamplitudeachieved);
ROTEMvaluesinclude:in‐TEM(representsintrinsicpathwayactivation),hep‐TEM
(assessestheintrinsicpathway’sintegritywithheparininfluenceremoved),ex‐TEM
(representsextrinsicpathwayactivity),fib‐TEM(inhibitionofplatelets),andap‐TEM
(representingtheamountoffibrinolysis)
F.ProlongationoftheTEG’sACTandr‐valueandtheROTEM’sin‐TEMandex‐TEMfactor
reflectfactordeficiencyorseverehemodilution(usuallytreatedwithplasmaorfactor
concentrates);prolongedk‐timeordecreasedalpha‐anglecorrelatewithstatesof
hypofibrinogenemia(usuallytreatedwithcryoprecipitateorfibrinogenconcentrates);
decreasedmaximalamplitudebyTEGandfib‐TEMbyROTEMcorrespondwithplatelet
defectsordecreasedactivity(usuallytreatedwithplatelettransfusion);increasedLY30or
ap‐TEMareseenincasesofhyperfibrinolysis(treatedwithamino‐caproicacidor
tranexamicacid)
VII.CoagulationDisorders
A.HemophiliaAisasex‐linkedrecessive,factorVIIIdeficiencyassociatedwithprolonged
PTTandnormalPT(treatedwithfactorVIIIorcryoprecipitate);hemophiliaBisalsoasex‐
linkedrecessivefactorIXdeficiencyassociatedwithprolongedPTTandnormalPT
(treatmentwithfactorIXorcryoprecipitate)
B.vonWillebrand’sdiseaseisthemostcommoncongenitalbleedingdisorder;several
types,rangingfromminimalbleedingtooverthemorrhage;whiletypeIandIIare
autosomaldominant,typeIIIisrecessive;boththePT/PTTcanbenormal,checkbleeding
time(ristocetintest);typeIandIIaretreatedwithcryoprecipitateandDDAVP,whiletype
IIIistreatedwithcryoprecipitateorVIII:vWFconcentrate;insemi‐electivesettings,keyto
treatmentistheadministrationofcryoprecipitate(sixunits)approximatelysixhoursprior
tointervention
VIII.AnemiaintheICU
A.85%ofpatientswhoareintheICUforlongerthanaweekwillendupreceivingablood
transfusion.However,theTRICCtrialin1999showedthatarestrictivetransfusion
strategyofkeepingpatient’shemoglobinsbetween7‐9g/dLwasaseffectiveas10‐12g/dL
andinsomepatientswasadvantageous.Therewasimprovedsurvivalinlessinjuredand
younger(<55years)cohorts.
B.Transfusioninthenon‐bleedingICUpatientshouldconsistofasingleunitofPRBCata
time,followedbylaboratorytestingtoassesswhethertransfusionoffurtherunitsistruly
necessary.
C.Thereisadose‐dependentrelationshipbetweenthetransfusionofbloodproductsand
thedevelopmentofcomplications,particularlynosocomialinfections.The
immunosuppressiveeffectofbloodtransfusionhasbeenwellstudiedandislikelythe
causeofthisincreasedincidence.ThereforeinthestableICUpatient,eachtransfusion
shouldbecarefullyweighedastoitspotentialbenefitandrisks.
D.Thecaveatofcourseisthatpatientswhoareactivelybleedingfromwhateversourcee.g.
GIhemorrhage,trauma,etc.shouldbeaggressivelyresuscitated,preferablyusingthe
principlesofdamagecontrolresuscitationasalreadydetailed.
E.Ethryopoetinandothersimilarmedicationsshouldbelimitedonlytopatientswith
chronickidneydiseasesandanemiafromcancerorblooddyscrasias.Theirefficacyin
raisingthehemoglobinoftheaverageICUpatientislimited(10%inonestudy),andtheir
expensedoesnotjustifytheiruse.Concernregardingthromboticeventshasalsoledthe
FDAtoattachablackboxwarningtothesedrugs.
IX.ThrombocytopeniaandHIT
A.Asmanyas33%ofpatientadmittedtotheintensivecareunitwilldevelopsomedegree
of thrombocytopenia duringtheirhospitalization. However,the most feared cause due to
the associated serious thrombotic sequelae is heparin‐induced thrombocytopenia. HIT is
divided into 2 types: a benign, nonimmune mediated form (type I) and an immune‐
mediatedform(typeII).
B.TypeIthrombocytopeniamaybeobservedinupto25%ofpatients1to4daysafterthe
initiation of heparin therapy, particularly in the postoperative setting. This nonimmune
thrombocytopenia(generallyassociatedwithaplateletcountof100/Lto130/Lx109/L)is
transient,asymptomatic,andappearstobecausedbyadirectplateletagglutinatingeffect
ofheparin.Thisformisself‐limitingandgenerallyself‐resolvingwithoutanytherapeutic
adjustment.
C. type II HIT, or “true” HIT, is an antibody‐ mediated syndrome that most commonly
appearswithin5daysto14daysfromtheinitialheparinadministration.HITisaserious
prothrombotic disease caused by heparin‐dependent antibodies that trigger platelet
aggregation by binding to molecular complexes formed by platelet factor 4 (PF4) and
heparin
D.TheriskofdevelopingHeparin‐inducedThrombocytopenia(HIT)isaffectedbytypeof
heparinused(withhighestriskassociatedwithbovineUFH,followedbyporcineUFH,and
lower risk for LMWH), the duration of heparin exposure (maximal risk for treatments
lasting4daysto14days),ahistoryofrecentheparinexposure(withinthepast100days),
the patient setting (postoperative vs. medical vs. pregnancy), and the patient’s sex
(estimated 1.5 to 2 times higher relative risk in women compared with men, possibly
becauseofincreasedimmuneresponses).
E.HITcanbeconfirmedbythepresenceofanti‐PF4antibodies,whicharedetectedbyan
ELISAbloodtest.
F. When HIT is strongly suspected or confirmed, all heparins should be stopped. This
includes the removal of heparin‐coated intravascular catheters and the suspension of
heparinflushes.Ifthepatientrequiresanticoagulationforwhateverreason,Fondaparinux
canbeusedforDVTprophylaxisandArgatrobanforfullanticoagulationinstead.
X.ManagementandReversalofAnti‐coagulantsandAnti‐plateletagents
A.WarfarincanbeeffectivelyreversedbytheuseofeitherFreshFrozenPlasma(FFP)ora
ProthrombinComplexConcentrate(PCC).ThedegreeofnormalizationoftheINRbyeach
unitofFFPisdifficulttopredictandwilldependoncirculatingbloodvolume
Thisisoneofthereasonsthatitistheauthor’spreferencetoreverseWarfarinwithaPCC<
unlesstherearepressingneedstogivethepatientvolumeinaddition.
B.IndicationsforPCCtransfusioninclude:
a) Anypatientwithseriousorlife‐threateningbleeding(intracranial,gastrointestinal,
retroperitoneal,etc.)duetowarfarinmaybeconsideredfortherapyaftermeeting
anyoneofthecriteriabelow.
b) Patientisunabletotoleratethevolumeoffreshfrozenplasma(FFP)neededforINR
reversal(e.g.CHF).Patientstypicallyrequire2‐4LofFFPforadequatereversal
c) CriticalpatientsthatcannottoleratethetimerequiredforreversalwithFFP.Note
thatinfusionofFFPmaytake3‐6hoursdependingontherateofinfusionandthe
volumerequiredforreversal.CompleteINRreversalmaybedelayedinsome
circumstances
d) INRisrefractorytostandarddosesofFFP
C.Dosing
ThereareonlytwocommerciallyavailablePCCsforuseintheUSA–Profilnine,Bebulin
ReversalofINRtypicallyoccurswithin10minutesofinfusion.TheINRmaybecheckedat
30minutesanddoserepeatedifneeded.
DosingforProfilnineshownbelow(dependentonINR)
InitialINR<5:Dose=25unitsperkg
RecheckINR10to20minutesafterdrugadministration.Mayre‐dose25unitsperkgto
achieveagoalINR≤1.5.IfINR>1.5after2doses,giveFFPtoachievegoalINR
InitialINR≥5:Dose=50unitsperkg
RecheckINR10to20minutesafterdrugadministration.IfINR>1.5,giveFFPtoachieve
goalINR
AllpatientswhoreceivePCCmustbegivenVitaminK10mgIVasaninfusion.Failure
toadministerVitaminKmayresultinareboundincreaseinINRafter6hours.
C.Antiplateletdrugs
Aspirin, Clopidogrel, Ticlodipine and Prasugrel all irreversibly inhibit platelet function
thereforetheirhalf‐liveislessimportantthanthefactthatforeachdayafterinterruption
ofanyoftheseagents,∼10%to14%ofnormalplateletfunctionisrestored.
Most authorities recommend that full strength aspirin should be held for a minimum of
seven days prior to major abdominal surgery. The American College of Chest Physicians
recommends7to10daysinthelatestversionofitsguidelinespublishedin2012.
CurrentrecommendationsbythemanufacturersofPlavis(Clopidogrel)aretodiscontinue
thedrugforfivedayspriortoelectivesurgery.
There is anecdotal data to support the use of platelet transfusion to support the
irreversibleeffectsofplateletinhibitionbyPlavixorAspirin,butnorandomizedcontrolled
trials. In the circumstance described above, it would be reasonable to transfuse platelets
during the operative case to reduce the risk of intra‐operative blood loss. Other rescue
strategies have included administration of DDAVP, cryoprecipitate, and even
Methylprednisolone.
D.DabigatranandRivaroxaban
Unfortunately,todatetherearenoknownsimpleandeffectivewaystoreversethe
anticoagulanteffectsofthedirectthrombininhibitor,Dabigatran.Researchhassofar
shownthattheavailablePCCsintheUShavenotbeenabletoreliablyreversethe
anticoagulanteffect.TheyareNOTrecommendedasfirstlinetherapyinthesepatients.
Currently,2011ACCF/AHAguidelinesrecommendthatpatientswithseveredabigatran‐
associatedhemorrhagebetransfusedwithfreshfrozenplasma(FFP)and/orpackedred
bloodcells(pRBC)asnecessary.However,thisiswithoutanyclinicalorlaboratory
evidencethatFFPtransfusioniseffectiveinthesepatients.
Themanufacturersthemselvesinrecommendemergencydialysisasthemosteffective
treatmentforreversalofthisagent,with60%ofthedrugsupposedlybeingremovedin2‐3
hours.However,thisobviouslymaynotalwaysbefeasibleintheemergencysetting,and
willlikelyinvolveplacingacentralvenouscatheterfordialysisaccessinafully
anticoagulatedpatient.Thisneverthelessremainsthemostreliableoptionforreversalof
thisanticoagulant.
Rivaroxabanhasbeenshowninsomeresearchtobeatleastpartiallyreversedby
administrationofPCCandmaythereforeachievesomefavorinthefuturebecauseofthis
theoreticaladvantage.
XI.Transfusion‐associatedcomplications
Thesecanrunthegamutofanyofthefollowingconditions:
A.
B.
C.
D.
E.
F.
Hemolytictransfusionreaction
Febrilenon‐hemolytictransfusionreaction
Allergicreactions
Bacterial/Viral/Prioncontamination
Fluidoverload
TRALI
A.Thiscanbeacuteorimmediate,whenitusuallyoccurswithin24hoursoftransfusion,
andtheeffectsaregenerallyintravascular.Oritmaypresentinadelayedfashionafter1‐10
days,whentheeffectsaremostlyextravascular.Symptomscommonlyincludefeverand
chillsinbothforms,butDIC,hemodynamicinstabilityandrenalfailureismuchmore
commonwithintravascularhemolysis
Overallincidenceis1:12,000‐25,000,withamortalityof1:650,000.
B.Febrilereactionsarecommon,approx.1:100‐1:200,andarethoughttobeduetonon‐
toxicimmunecomplexes.TheeffectsareusuallyremediatedwithtreatmentusingBenadryl
/Tylenol
C.Allergicreactions(urticarial)arealsofairlycommon,withanincidenceofapproximately
1:200.Theyshouldbetreatedasaboveandthetransfusionshouldbestopped.
Bothofthesecomplicationsshouldalwaysbereportedtobloodbankincasethey
representthemoreseriousbutlesslikelyconcernforbacterialcontamination.
D.Infectiousrisksarenowverylow,theexactriskdependingonthecontaminantbeing
considered.ForexampleHIVisaslowas1in2.6million,whileHepatitisCisalsointhe
sameballparkof1in2.6million.HepatitisBissomewhathigherriskat1in600,000,while
exactfiguresforBacterialcontaminationaredifficulttocomeby,asitisveryrare.West
Nileviruscouldtheoreticallybetransmittedbuttheriskisnotyetknown,asinalsothe
casewithRabies.DespitethepolicyoftheUSbloodbankstodeferdonorsfromtheUK,
therehaveasyetbeennodescribedreportsoftransmissionofnewvariantCreutzfield‐
JakobDiseasebybloodproductadministration
E.Circulatoryoverloadisprobablyclinicallyunder‐recognized,andmayhaveanincidence
ashighas1:700.Symptomsusuallydevelopwithinhours,andthepopulationmostatrisk
istheelderlywithpoorcardiopulmonarystatus.Forunknownreasons,itismorelikely
withautologoustransfusion.Theriskcanbeminimizedbyslowingthetransfusiondownto
runover4hours,andtheadditionofpreorpostdiuresis.
F.TRALIorTransfusion‐Relatedacutelunginjuryhasbecomeaseriousproblem,withan
incidenceof1in1700‐5000.Itcanbelifethreatening,andprobablynowrepresentsthe
No.1causeoftransfusionrelateddeaths,aswellasbeingaleadingcauseofmorbidity.Itis
relatedtoPlasma‐containingbloodproducttransfusions,withFFP>Platelets>RedCells>
CRYO>IVIG.
Criteriaforitsdiagnosisinclude:
i)
ii)
iii)
iv)
v)
vi)
Anacuteonset‐duringorwithin6hrs.ofTransfusion
Hypoxemia;anO2sat<90%atroomair,oraPaO2/FiO2ratioof<300mmHg
BilateralinfiltratesonChestX‐ray
NoevidenceofLeftAtrialHypertension
NopreexistingAcuteLungInjurybeforeTransfusion
NotemporalrelationshiptoalternativeriskforALI
Treatmentissupport,withintubationasnecessaryforhypoxemia,diuresisastoleratedto
addwiththepulmonaryedema.Someauthoritieshaveadvocatedtheuseofsteroids,but
thereislittledatatosupporttheiruseinTRALI.80%ofpatientswillrecoverwithnormal
lungfunction,andfuturetransfusionsarenotnecessarilyanissue.
ItisimportantincasesofTRALItoreportthistothebloodbanksothatthedonorplasma
canbeidentified,andbothdonorandrecipienttestedforthepresenceofantibodies.This
mayleadtothedonorbeingdeferred.Plasmafrommultiparousfemaleshasamuchhigher
riskforcausingTRALI,suchthattheUnitedKingdomforexamplehasmovedtocollecting
plasmafrommalesonly.Studieshaveshownthatthisapproachcansignificantlyreducethe
incidenceofTRALIwhenadoptedbyabloodbank.