Andersons pediatric cardiology 1782
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SpecialConsiderations
ABO-IncompatibleTransplantation
Itiswellrecognizedthatinfantshavethebestoutcomesofallagegroups;their
mediansurvivalisnow20.7years(seeFig.67.10).Thissurvivaladvantageis
probablydue,atleastinpart,totheplasticityoftheinfantimmunesystem,
whichhasanotheradvantage—theabilitytosafelyundertaketransplantation
acrossbloodgroups.26Inananalysisofriskfactorsrelativetothestrategyof
listing,failuretolistforanABO-incompatiblegraftandhighclinicalstatus
emergedastheonlyfactorsassociatedwithmortality.27AnABO-incompatible
transplantcannotonlybeundertakensafelybutalsodoesnotincreasetheriskof
rejectionorcompromiseposttransplantoutcomeandsurvival.28,29
Isohemagglutininsarenotproducedagainstthedonororgan,soafurther
advantageisthat,ifretransplantationisrequired,anABO-incompatibledonor
canbeusedagain.Itisnowincreasinglyclearfromtherenalandcardiac
literaturethatsuccessfulABO-incompatibletransplantscanbeundertakenafter
infancyandevenwhensignificantisohemagglutininsarepresent.Todoso,
however,doesincreasetheriskofsignificantrejection.Ifsuchatransplantis
undertaken,strategiesincludingplasmapheresis,immunoadsorption,and
complementinhibition(eculizumab)shouldbeavailable.30
HumanLeukocyteAntigenSensitization
HLA(humanleukocyteantigen)antibodiesarenotnaturallyoccurringbut
acquiredduetoasensitizingevent.31Inthepediatricagegroup,thiseventis
usuallyamedicalintervention—especiallybloodproductsandhomografttissue
usedincongenitalheartdiseaserepairandincreasinglytheuseofaVAD.The
prevalenceofsensitizationdependsonthesensitivityofthetestingmethodology
butisprobablybetween20%and30%.Inthepastthemethodoftestingfor
theseantibodiesrequiredmixingcellsfromapanelofblooddonorswithknown
HLAtypesandplasmafromthepatientundergoingtransplantevaluationinthe
complement-dependentcytotoxicitytest.Ifthetestwaspositive,thecellswere
destroyed.BecausetheserumwastestedagainstapanelofdifferentHLA
donors,thelikelihoodoftheserumofthepotentialrecipienthavingasignificant
quantityofHLAantibodiesagainstarandomdonorcanbecalculatedasa
percentageusingthePRAtest;thehigherthePRA,themorelikelyitwouldbe
thattherecipientwouldreceiveadonortowhomheorshewassensitized.The
PHTSregistrywasevaluatedforoutcomesofsensitizedversusnonsensitized
recipients.32Itwasfoundthatby1yearafterlisting,ofthosewithaPRAof
below10%,76%weretransplantedand9%deceased,versus75%and19%for
thosewithaPRAgreaterthan50%.Forthosewhoweretransplanted,aPRA
below10%hada1-yearsurvivalof90%versus73%withaPRAgreaterthan
50%.Thus,althoughwaitingforacompatibledonorincreasedtheriskofdying
onthelist,acceptingadonortowhomtherecipientwassensitizedledtoa
poorerposttransplantoutcome.Tohelpdecidewhichisthebestapproach—take
thefirstorganofferedorwaitforthebestmatch—adecisionmodelanalysis
utilizingtheOrganProcurementandTransplantationNetworkdatabasewas
undertaken;itdemonstratedthattakingthefirstavailableorganofferedprovided
thebestoutcomesoverall.33
Inthelastdecadesolid-phaseimmunoassayhassupersededthecomplementdependentcytotoxicitytestforthedetectionandcharacterizationofHLA
antibodies.34Thisisamuchmoresensitivetechniquebuthasresultedinanew
paradigmwithrespecttotheinterpretationofdonor-specificantibodies(DSAs).
ThistestisabletodetectHLAantibodieswithexquisitesensitivity,butapplying
thisknowledgeclinicallyhasproveddifficult.InvivotheHLAepitopethatthe
HLAantibodyisdirectedagainstmaynotbeexposed;thereforealthoughthe
antibodyispresent,itmaynotbeabletoattachtoitstarget.Controversyalso
surroundstheissueofwhetheritisimportantthatHLAantibodiesbe
complement-fixing—thisisnotusuallytestedforinstandardsolid-phase
immunoassays.35Itisbeyondthescopeofthischaptertodiscussthe
managementofthesensitizedpatientindetail,butstrategiesincludeantibody
removalbyplasmapheresisorimmunoadsorption,interruptionofproductionby
utilizingB-cell(e.g.,rituximab)andplasma-cellinhibitors(e.g.,bortezomib),
andneutralizationoftheircomplement-fixingability(e.g.,eculizumab).
Evidenceofefficacy,however,issparse,withonlyafewcasereportsor
uncontrolledstudieshavingappeared.36Anotherconsequenceofourabilityto
detectHLAantibodiesistherecognitionthatrecipientsmaydevelopDSAto
theirgraftaftertransplant.Muchstillhastobelearnedaboutthesignificanceof
DSAposttransplant.37Theseproblemsmaybetransient,inwhichcase,
especiallyifearlyintheposttransplantcourse,theymaybeoflittlesignificance.
Iftheyarepersistent,however,theyareassociatedwithworsegraftsurvival.38
AlthoughstrategiestoreduceposttransplantDSAaresimilartothoseused
beforetransplantation,theirefficacyisasyetunknown.39
MechanicalSupportasaBridgeto
Transplantation
Thecurrentstateofmechanicalcirculatorysupportandavailabledevicesin
pediatricsiscoveredelsewhere.Withregardtotransplantation,theevolutionof
mechanicalsupportoptionshasprovidedmultiplepotentialcarepathsincluding
temporaryversusdurablesupportandabridgetodecision,recovery,or
transplant,alsoallowingforcrossoverbetweentheseoptions.TheuseofVADas
abridgetotransplantinthepediatricpopulationhascontinuedtoincrease
significantlyandcurrentlyaboutone-thirdofpediatricpatientsaretransplanted
fromVADsupport(Fig.67.15).Ithasallowedforreducedwaitlistmortality7
withoutcompromisingposttransplantsurvival.Thereareage-relateddifferences,
withmoreinfantsrequiringECMOsupportandresultantsuboptimaloutcomes9
(seeFigs.67.13and67.16).PatientssupportedwithaVADcanusuallybe
mobileandundergophysicalandnutritionalrehabilitationwhileawaiting
transplantation;thishaslikelycontributedtotheimprovedoutcomes.Serious
morbidity—includingstroke,bleeding,infection,anddevicemalfunction—
remaincommon.40
