Andersons pediatric cardiology 1914

includingfactorsII,V,VII,andX,andcoagulantinhibitors,suchasproteinC,
proteinS,plasminogen,andantithrombinIII.138–141Anelevatedleveloffactor
VIIIisastrongriskfactorforvenousthromboembolisminthenormaladult
population,withapredictedincidenceofrecurrentthrombosisofmorethan10%
peryearinthosewithincreasedserumlevels.142Longitudinalstudiesmonitoring
serumfactorVIIIlevelsinpatientswithafunctionallyuniventricularhearthave
demonstratedaconversionfromlowserumlevelsearlyinthecourseofstaged
reconstruction,tosignificantlyraisedlevelsafterFontancompletion.143
IncreasedfactorVIIIactivitycorrelateswithhighersuperiorvenacavapressure
intheFontancirculation.143Assuch,itishypothesizedthatincreasedpressure
transmittedtotheliversinusoidalendotheliumleadstotheupregulationoffactor
VIIIsynthesis.144Thrombocytopeniamayalsocontribute,particularlyifrelated
toheparintreatment,inwhichitmaybeassociatedwithahighriskof
thrombosis,145orwhenassociatedwithportalhypertensionandfailureofthe
Fontancirculation(seeFontanFailure).Lastly,progressiveendothelial
dysfunctiondevelopswithprolongedexposuretotheFontancirculation.Even
well-functioningadultpatientsmayhaveunderlyingendothelialdysfunction,
indicatedbyincreasedplasmaconcentrationsofendothelin-1146andabnormal
digitalpulseamplitudetonometry.147Thismultitudeoffactorsleadstothehigh
incidenceofthromboemboliceventsthatcontributetosignificantmorbidityand
mortalityearlyandlateafterFontansurgery.


FIG.73.18 Coronalplanemagneticresonanceimaginginapatientwitha
largethrombuswithintheextracardiacFontanpathway.Thereddotsshow
thelocationofthethrombus.(FromKuttyS,RathodRH,DanfordDA,
CelermajerDS.Roleofimagingintheevaluationofsingleventriclewiththe
Fontanpalliation.Heart.2016;102[3]:174–183.)

ImmunologicAbnormalities
Manychildrenwithafunctionallyuniventricularhearthaveimmunologic

anomaliesonroutinelaboratoryinvestigations,themostcommonbeing
lymphopeniathatpredominantlyinvolvesCD4Tcells.Absolutelymphocyte
countsdecreasewithtimeaftertheFontanoperation.Patientswhoaremorethan
10yearspost-Fontansurgeryhavebeenfoundtobefourtimesaslikelytohave
significantlymphopeniaascomparedwithpatientsinthefirstdecadepost
Fontan.148However,theclinicalsignificanceofthesefindingsisunclearbecause
theredoesnotappeartobeanincreaseinopportunisticinfectionseveninthe
settingofsignificantlymphopenia.Increasedlymphaticrecirculationmaybea
compensatorymechanism,allowingforpreservationofnormaltissue-levelTcellfunctioneveninthesettingoflowcellcounts.Nevertheless,thereisan
abnormallyhighincidenceofatopy(approximately60%),suggestingabnormal


skewingofthedistributionofresidualTcells.147
ThemostsignificantdeficiencieswerenotedinpatientswithPLE(seelater),
althoughlymphopeniaoccursevenintheabsenceofPLE.AllpatientswithPLE
arelymphopenic,withpreferentiallossofTcells(CD4morethanCD8)but
preservationofnormallevelsofBandnaturalkillercells.149,150
Hypogammaglobulinemiaiscommon,mainlyaffectingimmunoglobulinG
(IgG)andIgAlevels.147,148
PatientswithPLEhavehigherratesofnonresponsivenesstovaccination,
particularlytohepatitisBandmeasles,mumps,andrubella,150,151andmay
requirerepeatedvaccinationsandavoidanceoflivevaccines.Someadvocatefor
antibioticprophylaxisagainstopportunisticinfectionssuchasPneumocystis
jiroveciiandMycobacteriumavium,althoughsupportingclinicalevidenceis
lacking.150InassessingtheimmunocompromisedstateofpatientswithPLE,
confoundingfactorssuchasmalnutritionandthesideeffectsof
immunosuppressivetherapiesshouldalsobeconsidered.

RenalDysfunction
LatesurvivorsoftheFontansurgeryinvariablyexperiencemultiorgansequelae

includingprogressiveliverdysfunctionandPLE;however,thelong-term
progressionoftheirrenalfunctionispoorlyunderstood.Theearlyoccurrenceof
acutekidneyinjuryiscurrentlywellrecognizedfollowingcomplexsurgical
reconstructionintheneonate,withincreasingevidenceoflaterenaldysfunction
inthesepatients(seeChapter78).Inaddition,intheFontancirculation,thereis
reducedrenalperfusionasthechronicelevationofCVPincreasesefferent
arteriolarpressure.Glomerularfiltrationpressureisalsoincreased,leadingtoa
highincidenceofmicroalbuminuria.Inasmallretrospectivecohortstudyof21
patientsatmean11yearspost-Fontancompletion,almosthalfthegrouphadan
increasedurinemicroalbumin/creatinineratio.152Astrongcorrelationbetween
urinemicroalbumin/creatinineratioandsuperiorvenacavameanpressurewas
alsodemonstrated.
Microalbuminuriamaybeamoresensitiveindicatorofearlyrenaldisease
thantheestimatedglomerularfiltrationrate(eGFR).Inareviewof68patientsa
decadeafterFontancompletion,90%hadanormaleGFR(eGFR>90mL/min
per1.73m2)butmorethan40%hadmicroalbuminuria.153Furthermore,serum
creatininemaynotbeareliableindicatorofkidneyfunctioninthispopulation.
Fontanpatientsoftenhavealowermusclemassandarerelativelymalnourished,