17/3/2017 Therapeuticapheresis(plasmaexchangeorcytapheresis):IndicationsandtechnologyUpToDate

OfficialreprintfromUpToDate
www.uptodate.com2017UpToDate

Therapeuticapheresis(plasmaexchangeorcytapheresis):Indicationsandtechnology

Authors: JoyLFridey,MD,AndreAKaplan,MD
SectionEditor: ArthurJSilvergleid,MD
DeputyEditor: JenniferSTirnauer,MD

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Feb2017.|Thistopiclastupdated:Jan30,2017.

INTRODUCTIONTherapeuticapheresisisanextracorporealtreatmentthatremovesbloodcomponents
frompatientsitisusedforthetreatmentofconditionsinwhichapathogenicsubstanceorcomponentinthe
bloodiscausingmorbidity.

Thistopicreviewwillpresentanoverviewofthetypesofindicationsforwhichtherapeuticapheresisis
effectiveandpracticalissuesintheapheresistechnology.Complicationsoftherapeuticapheresisare
discussedseparately.(See"Therapeuticapheresis(plasmaexchangeorcytapheresis):Complications".)

Manyofthespecificindicationsfortherapeuticplasmaexchange(TPE)arepresentedinseparatetopic
reviewsonthespecificclinicalconditionsforwhichTPEisindicated.

TERMINOLOGYThefollowingterminologyisusedtodescribeproceduresrelatedtotherapeutic
apheresis:

ApheresisAnumbrellatermfor"takingaway"abloodcomponent.Apheresisincludesplasmapheresis
(takingawayplasma)andcytapheresis(takingawaybloodcells).Wedonotusetheterm"pheresis,"
whichisashortenedpronunciation(slang)forapheresis.

PlasmapheresisAgeneraltermusedtodenotetheautomated,selectiveremovalofplasma.Plasma
canbeseparatedfromthebloodusingcentrifugationorfiltration.Plasmapheresisismostlyusedto
collectplasmafromahealthyblooddonorfortransfusion(ie,plasmadonation).(See"Clinicaluseof
plasmacomponents",sectionon'Plasmaproducts'.)

TherapeuticplasmaexchangeTPE,alsocalledplasmaexchangeortherapeuticplasmapheresis,
involvesremovalofpatientplasmaandreplacementwithanotherfluid(eg,allogeneicdonorplasma,
colloid,crystalloid).Plasmaremovedduringplasmaexchangemustneverbeusedfortransfusionto
anotherindividual,accordingtoregulationsfromtheUSFoodandDrugAdministration(FDA).

Therapeuticcytapheresis(hemapheresis)Atermusedtodenoteselectiveremovalofabnormal
bloodcells(eg,sickledcells[erythrocytapheresis,redbloodcellexchange])orexcessivenumbersofcells
(eg,platelets[thrombocytapheresis],whitebloodcells[leukocytapheresis]).

DialysisAdiffusionbasedtreatmentbestsuitedfortheremovaloffluidorsmallmolecules(eg,uremic
toxins,somedrugs)fromthebloodusingafilter.Fluidisremovedbyfiltration(convection)solutesare
removedbydiffusion.

PlasmafiltrationAtechniquethatseparatesplasmafromcellularcomponentswithahighly
permeablefilter(plasmafilter)usingadialysisorhemofiltrationmachine.(See"Plasmapheresiswith
hemodialysisequipment".)

OVERVIEWOFINDICATIONS

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RationaleandbenefitsofTPEThebasicpremiseoftherapeuticplasmaexchange(TPE)isthatremoval
ofcertainpathologicsubstancesfromtheplasmawillreducefurtherdamageandmaypermitreversalofthe
pathologicprocess(table1).Thepathologicsubstancemaybeanautoantibody,immunecomplex,
cryoglobulin,myelomalightchains,endotoxin,cholesterolcontaininglipoprotein,orothersubstance.

TheTPEprocessinvolvestheremovalofaportionormostofthepatient'splasma,bypassingvenousblood
throughanextracorporealdevicethatseparatesbloodintoitscomponents(ie,redbloodcells,whiteblood
cells,andplasma),shuntssomeormostoftheplasmaintoadiscardcontainer,andreturnsmostofthe
remainingbloodtothepatient,alongwithashortactinganticoagulant(usuallycitrate).

Potentialreplacementfluidsincludethepatient'sownplasmafromwhichasubstancehasbeenremoved,
donorplasma,colloid,orcrystalloid.Insomecases,useofautologousorallogeneic(donor)plasmais
preferredbecauseitprovidesneededproteinsorotherfactorshowever,donorplasmashouldonlybeused
asreplacementfluidforspecificindications(eg,acquiredautoimmunethromboticthrombocytopenicpurpura
[TTP]).Inothercases,useofappropriatenonplasmareplacementfluideliminatesunnecessaryexposureto
donorplasma.

AtleastoneofthefollowingconditionsmustbepresentforTPEtobearationaltherapeuticchoice:

Thesubstancetoberemovedshouldbesufficientlylarge(molecularweightgreaterthan15,000)sothat
itcannotbeeasilyremovedbylessexpensivepurificationtechniquessuchashemofiltrationorhighflux
hemodialysis.

Thesubstancetoberemovedmusthaveasufficientlylonghalflifesothatextracorporealremovalis
muchmorerapidthanendogenousclearancepathways.

Thesubstancetoberemovedmustbeacutelytoxicand/orresistanttoconventionaltherapysothatthe
rapideliminationfromtheextracellularfluidbyTPEisindicated.

TPEishighlyefficaciousfortheremovalofpathogenicautoantibodies.IgGhasanaveragemolecularweight
over150,000andahalflifeofapproximately21days[1].Thus,evenifimmunosuppressivetherapycould
immediatelyhaltnewantibodyproduction,theplasmaconcentrationwouldonlyfallby50percentby21days.
Suchadelayisunacceptablewithanaggressiveautoantibody,suchasthatseeninantiglomerularbasement
membrane(antiGBM)antibodydisease.(See"TreatmentofantiGBMantibody(Goodpasture's)disease".)

TPEhasotherpotentialbenefits,whichincludeunloadingofthereticuloendothelialsystem(thereby
enhancingendogenousremovalofcirculatingtoxins)[2],stimulationoflymphocyteclonestoenhance
cytotoxictherapy[3],andthepossibilityofreinfusinglargevolumesofplasmawithouttheriskofintravascular
volumeoverload.

Theinfusionoflargevolumesofdonorplasmawithoutvolumeoverloadisparticularlyimportantinacquired
(autoimmune)thromboticthrombocytopenicpurpura(TTP),adisorderinwhichTPEusingplasmaasthe
replacementfluidislifesaving.TPEworksinthisconditionbothbyremovingveryhighmolecularweightvon
Willebrandfactor(VWF)multimersandautoantibodiestotheADAMTS13protease,whichcleavesVWF
multimers,aswellasbyprovidingadditionalADAMTS13tothepatient.(See"AcquiredTTP:Initial
treatment".)

Forsomeindications,TPEisdefinitivetherapy(eg,TTP,acuteGuillainBarrsyndrome)whereasforothers
(eg,myelomakidney),itmayneedtobecombinedwithotherdefinitivetherapysuchaschemotherapytostop
antibodyproduction.

CommonusesofTPEIntheUnitedStates,mostTPEproceduresareperformedforneurologic,
immunologic,orhematologicdiseases(table2).AcollaborativesurveybytheAABB(formerlytheAmerican
AssociationofBloodBanks)andtheAmericanSocietyforApheresis(ASFA)foundthatmorethanonehalf
ofallprocedureswereperformedforneurologicconditionssuchasGuillainBarrsyndromeormyasthenia
gravis[4,5].
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TheCanadianApheresisGrouphasreportedagrowinguseofTPEforhematologicdisorders,which
constituted55percentofalltherapeuticapheresisproceduresin2003TPEforneurologicconditionshad
decreasedfrom50percentin1988to40percentin2003[6,7].Thischangereflectsthegrowinguseof
evidencebasedpracticeandadvancesinpharmacologictreatmentsthatinsomeinstancesreplaceTPEas
standardtreatmentsforsomeconditions.

ThemorecommonindicationsforTPEarediscussedinseparatetopicreviews(table2).Examplesinclude
thefollowing:

Acquired(autoimmune)thromboticthrombocytopenicpurpura(TTP)(See"AcquiredTTP:Initial
treatment"and"RecurrentanddenovoHUSafterrenaltransplantation".)

Renaldiseases(See"Initialimmunosuppressivetherapyingranulomatosiswithpolyangiitisand
microscopicpolyangiitis"and"TreatmentofantiGBMantibody(Goodpasture's)disease".)

Hyperviscosity(See"TreatmentandprognosisofWaldenstrmmacroglobulinemia"and"Treatment
andprognosisofkidneydiseaseinmultiplemyelomaandothermonoclonalgammopathies".)

Neurologicsyndromes(See"GuillainBarrsyndromeinadults:Treatmentandprognosis"and
"Treatmentofmyastheniagravis"and"Chronicinflammatorydemyelinatingpolyneuropathy:Treatment
andprognosis".)

Multiplesclerosis,systemiclupuserythematosus,andrheumatoidarthritiswerepreviouslytreatedwithTPE,
butthispracticeoftenwasnotbasedupondatafromcontrolledstudies.Theuseofthiscomplexand
expensivetreatmentintheabsenceofsupportingdatapromptedthedevelopmentofguidelinesbasedon
betterclinicaldataratherthanonlyanecdotalreportsordatafromsmallseriesoruncontrolledtrials(table2).
(See'ASFAtherapeuticcategories'below.)

CommonusesoftherapeuticcytapheresisIncontrasttoroutineTPE,therapeuticcytapheresisisused
tolowertheleukocyteorplateletcount,ortoexchangeerythrocytes(redbloodcells[RBCs]).Appropriate
loweringoftheleukocyteorplateletcountcanbemonitoredbythecompletebloodcount(CBC).

Forhyperleukocytosis,thepostproceduretargetwhitebloodcellcount(WBC)is<100,000/microL.
Forthrombocytosis,thetargetplateletcountis<1,000,000/microL[8].

ForRBCexchange,differentparametersaremeasureddependingonthepurposeoftheprocedure.Asan
example,insicklecelldisease,exchangetransfusionisoftendoneusingautomatedcytapheresis.Thisis
monitoredusingthehemoglobinlevelandthepercenthemoglobinS.(See"Redbloodcelltransfusionin
sicklecelldisease",sectionon'Simpleversusexchangetransfusion'.)

ASFAtherapeuticcategoriesAcomprehensivereviewofindicationsfortherapeuticapheresisbasedon
extensiveliteraturereviewsispublishedeverytwotothreeyearsbytheAmericanSocietyforApheresis
(ASFA)[912].Conditionsaredividedintofourmaincategoriesbasedonevidenceofclinicalefficacyreported
inpeerreviewedliterature.TheseguidelinesarenotintendedtomandateTPEforconditionsinwhichitis
clearlynotefficacious,noraretheyintendedtodenyorexcludepatientsfromreceivingTPEwhensome
benefit,althoughsmall,mayberealized.Giventhecomplexityandexpenseoftheprocedure,however,the
guidelinesprovideaframeworkforclinicaldecisionsregardingtheuseofTPE[12]:

CategoryICategoryIincludesdisordersforwhichapheresisisacceptedasfirstlinetherapy,either
asprimarystandalonetreatmentorinconjunctionwithothermodesoftreatment.ExamplesincludeTPE
inGuillainBarrsyndromeoracquiredautoimmunethromboticthrombocytopenicpurpura(TTP),and
erythrocytapheresisinsicklecelldiseaseswithcertaincomplications(eg,stroke).(See"GuillainBarr
syndromeinadults:Treatmentandprognosis",sectionon'Plasmaexchange'and"Redbloodcell
transfusioninsicklecelldisease",sectionon'Exchangebloodtransfusion'and"AcquiredTTP:Initial
treatment",sectionon'Overviewofourapproach'.)

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CategoryIICategoryIIincludesdisordersforwhichapheresisisacceptedassecondlinetherapy,
eitherasastandalonetreatmentorinconjunctionwithothermodesoftreatment.ExamplesincludeTPE
forlifethreateninghemolyticanemiaforcoldagglutinindiseaseorLambertEatonmyasthenicsyndrome.
(See"Coldagglutinindisease",sectionon'Plasmapheresis'and"TreatmentofLambertEaton
myasthenicsyndrome",sectionon'Plasmaexchange'.)

CategoryIIICategoryIIIincludesdisordersforwhichtheoptimumroleofapheresistherapyisnot
established.Decisionmakingshouldbeindividualized.ExamplesincludeTPEforhypertriglyceridemic
pancreatitisorextracorporealphotopheresisfornephrogenicsystemicfibrosis.(See
"Hypertriglyceridemiainducedacutepancreatitis",sectionon'Apheresis'and"Nephrogenicsystemic
fibrosis/nephrogenicfibrosingdermopathyinadvancedrenalfailure",sectionon'Treatment'.).

CategoryIVCategoryIVincludesdisordersforwhichpublishedevidencedemonstratesorsuggests
apheresistobeineffectiveorharmful[13].ExamplesincludeTPEforactiverheumatoidarthritis.

Amorecomprehensivelistingofconditionsaccordingtocategoryispresentedinthetable(table2)[12].A
publicationisalsoavailablethatdescribestheefficacyofTPEinsomeconditionsandintoxicationsnot
addressedintheASFAguidelines[14].

ThevalueoftheASFAguidelinesliesnotonlyonthecomprehensivenatureoftheliteraturereviews,butalso
theconciseformatforeachlisteddiseasestate.Categoriesandrecommendationratingsaregivenforeach
condition,aswellasasuccinctliteraturesynopsis,evidencegrading,andrecommendationsforthetreatment
schedule,replacementfluids,exchangevolumes,andprocedurefrequency.Listingofconditionsbycategory
canbefoundinvariousreferences[10,15].

TECHNOLOGYTherapeuticplasmaexchange(TPE)ismostcommonlyperformedwithcentrifugation
devicesusedinbloodbankingprocedures.Thesedevicesalsooffertheadvantageofallowingselectivecell
removal(cytapheresis).

Theuseofahighlypermeablefilterwithstandardhemodialysisequipmentisdiscussedseparately.(See
"Plasmapheresiswithhemodialysisequipment".)

VenousaccessSuccessfulTPErequiresreliablevenousaccess,whichmaybeeithertwolarge,durable
peripheralveins,oracentralvenouscatheterwithaduallumenthatisrigidenoughtowithstandsignificant
flowandpressures.

Examplesofproductsthatwouldmeettheserequirementsinclude,butarenotlimitedto:theQuinton
Mahurkarcatheter,MedCompapheresiscatheters,andHickmanapheresis/dialysiscatheters.Radiographic
confirmationofcatheterplacementiscritical,especiallyforTPEprocedures,topreventperforationofvital
structuresandbecausecardiacarrhythmiasmayresultifcitrateanticoagulant(whichbindsionizedcalcium)is
infusedclosetothesinoatrialnode.

Usingperipheralveinsmayavoidcomplicationsassociatedwithacentralvenouscatheter,butisassociated
withslowerbloodflowandlongerproceduresthismayrenderperipheralveinsineffectiveoruncomfortable
forsomeTPEprocedures.

ExchangevolumesFormostconditions,ithasbecomestandardpracticetoperform1to1.5plasma
volumeexchangesperprocedure.Exchangeofthefirst1to1.5plasmavolumesremovesthehighestvolume
ofthetargetsubstance,withdiminishingamountsremovedwitheachsubsequentexchangeduringa
procedure.Asingleplasmavolumeexchangeinanaveragesizedadultusesapproximately3litersof
replacementfluid.

Ingeneral,largemolecularweightcompoundsequilibrateslowlybetweenthevascularspaceandthe
interstitium.Thus,calculationsoftherateofremovalbyTPEcanbesimplifiedtofirstorderkinetics.Asingle
plasmavolumeexchangewilllowerplasmamacromoleculelevelsby60percent,andanexchangeequalto
1.4timestheplasmavolumewilllowerplasmalevelsby75percent[16,17].
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Thefollowingformulacanbeusedtoestimatetheplasmavolumeinanadult[18]:

Estimatedplasmavolume(inliters)=0.07xweight(kg)x(1hematocrit)

Exchangingmorethanoneplasmavolumeinasingletreatmentincreasesproceduretime,challengespatient
tolerance,andincreasesthecost.Asanexample,cellseparatorscanperformonecompletevolume
exchangein1.5to2hourstwotothreeplasmaexchangeswilldoubleortriplethetimerequiredtoperform
theprocedure.

ReplacementfluidsThefluidvolumeremovedbyTPEmustbereplacedtopreventmarkedvolume
depletion.Albumin,saline,oracombinationofalbuminandsalinearethereplacementfluidsofchoicefor
mostconditions.Theoptimalchoiceoftenvarieswiththeclinicalsetting.Fivepercentalbuminisusedformost
conditionssalineforhyperviscosityandsomecombinationofalbuminandsalineifcostisaconsideration.
Weprefer5percentalbuminoracrystalloidcolloid(ie,albuminsaline)combinationasthereplacementfluid,
ratherthansalinealone.Itisgenerallyrecommendedthatplasmaonlybeusedasthereplacementfluidsfor
conditionsinwhichconstituentsofplasmaarenecessaryfortherapy(eg,TTP).

FivepercentalbuminAlbuminhastheadvantagesoflackofviraltransmission[19]andminimalrisk
ofanaphylacticreactions.However,apostapheresisdepletioncoagulopathyandanetlossof
immunoglobulinscanoccur.

AlbuminsalinecombinationWhencolloidandcrystalloidsolutionsareusedincombination,the
amountofcolloidshouldnotbelessthan50percentofthetotalinfused.Anappropriatereplacement
solutionwouldconsistof1:1ratioofalbumintowholebloodanda2:1ratioofsalinetowholeblood,or60
to80percentcolloidand20to40percentsaline[8,20].

SalinealoneSalinealoneprovidesinsufficientoncoticpressureandtendstoleadtosignificantedema
and/orhypotension.Thus,wepreferalbuminoralbuminsalineincombination.However,theremaybe
medicallycompellingreasonsfortheuseofsalineinsomecases(eg,albuminnotavailableor
complicationssuchasallergiesoccurringwithalbuminorplasma).

PlasmaPlasmacanbeprovidedintheformofFreshFrozenPlasma(FFP),PlasmaFrozenWithin24
hoursAfterPhlebotomy(PF24),ThawedPlasma,orotherproducts.(See"Clinicaluseofplasma
components",sectionon'Plasmaproducts'.)

Plasmareplacesthenormalproteinsthathavebeenremoved.Asaresult,significantdepletionof
coagulationfactorsorimmunoglobulinsdoesnotoccur.However,complicationsaremorecommonwith
plasmathanwithalbumin.(See"Therapeuticapheresis(plasmaexchangeorcytapheresis):
Complications",sectionon'Donorplasmaorredbloodcellexposure'.)

Additionalinformationaboutreplacementfluids,apheresisschedules,andothertechnicalinformationhasalso
beenpublishedbytheAmericanSocietyforApheresis(ASFA)[12].

ApheresisscheduleTheTPEscheduleshouldbedeterminedaccordingtothepathologicalsubstance
thatisbeingremovedandbythedesiredendpoint(eg,clinicalimprovementorareductioninthelevelofa
specificmeasurablepathogenicmoiety).Inimmunologicallymediated,paraproteinemic,orhyperviscosity
conditions,immunoglobulincompartmentalshifts,especiallythoseofIgGandIgM,mustbeconsidered[8].In
manyofthesecases,TPEonlyservesanadjunctiveroleasthepatientsarereceivingconcomitant
chemotherapyorimmunosuppressivetherapy.

IgMApproximately75percentofIgMisintravascular.Asaresult,onlyoneortwoproceduresare
usuallyrequiredtorapidlyreduceIgMlevels.

IgGOnly45percentofIgGisintravascular,andwithin48hoursofaproceduretheplasmaIgG
productionreturnsto40percentofthepreapheresislevel.IgGproductionisalsocharacterizedbya
"rebound"phenomenon,andcessationofTPEafterseveralprocedurescanresultinpretreatmentor

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evenhigherlevelsofIgG,especiallyifthepatientisnotonimmunosuppressivetherapy.Consequently,a
morerigorousregimeninvolvingseveralTPEproceduresandtheinstitutionofimmunosuppressive
therapyisrequiredtosignificantlyreduceIgGlevels[21].

Ifoneassumesanegligibleproductionrateofnewimmunoglobulin(dueinparttoconcurrent
immunosuppressivetherapy)andthattherateofextravasculartointravascularequilibrationisapproximately
1to2percentperhour,thenfiveseparateproceduresover7to10daysarerequiredtoremove90percentof
thetotalinitialbodyimmunoglobulinburden[22].Additionaltreatmentsmayberequiredifnewantibody
productionoccurs.

TheAABBgeneralrecommendationforconditionsrequiringTPEisthatoneexchangebeperformedevery
secondorthirdday,eachexchangeconsistingof1to1.5plasmavolumesfor,inmostcases,atotalofthree
tofiveprocedures.Exceptionsincludethefollowing:

Insomeconditions,suchasacuteGuillainBarrsyndrome,itmaybenecessaryaftertheinitial
exchangestoperformTPEonetotwotimesaweekuntilimprovementoccurs.

Inacquiredthromboticthrombocytopenicpurpura(TTP),TPEshouldbeperformeddaily.(See"Acquired
TTP:Initialtreatment".)

TreatmentforGoodpasture'ssyndrome(antiGBMmediateddisease)isgenerallyalsoperformedona
dailyoreveryotherdaybasis.(See"TreatmentofantiGBMantibody(Goodpasture's)disease".)

LaboratoryevaluationLaboratoryassessmentisbaseduponthedesiredendpointoftherapyandthe
numberofproceduresthatwillbeperformed.

ForTPEperformedwithoutaplasmaproduct,abaselinecompletebloodcount(CBC),immunoglobulinlevels,
andcoagulationandelectrolytestudiesshouldbeperformed.Ifalargenumberofcloselyspacedprocedures
areplanned,subsequentlaboratoryevaluationshouldoccurmorefrequentlythanwouldbenecessaryfora
lessaggressivecourse.

Forapatientundergoingtherapeuticcytapheresis,theappropriatecellcountdeterminestheadequacyof
response.(See'Commonusesoftherapeuticcytapheresis'above.)

SUMMARYANDRECOMMENDATIONS

Therapeuticapheresis(plasmaexchangeorcytapheresis)isanextracorporealbloodpurification
techniquefortheremovaloflargemolecularweightsubstancesorcellsfromtheplasma.(See
'Terminology'above.)

Fortherapeuticplasmaexchange(TPE)tobearationaltherapeuticchoice,thesubstancetoberemoved
shouldbesufficientlylargesothatitcannotbeeasilyremovedbyhemofiltrationorhighfluxhemodialysis,
musthaveasufficientlylonghalflife,ormustbeacutelytoxicand/orresistanttoconventionaltherapy.
Examplesincludepathogenicautoantibodies,immunecomplexes,cryoglobulins,myelomalightchains,
endotoxin,cholesterolcontaininglipoproteins.(See'RationaleandbenefitsofTPE'above.)

Therapeuticcytapheresis(ie,removalofwhitebloodcells,platelets,orredbloodcells)canbeperformed
inordertoreduceexcessivenumbersofcellsorpathologicallyabnormalcellsthismaybeusedfor
hyperleukocytosis,markedthrombocytosis,orexchangetransfusion(see'Commonusesoftherapeutic
cytapheresis'above).

TheAmericanSocietyforApheresis(ASFA)guidelinesforTPEarebasedonextensiveliteraturereviews
ofTPEformultiplediseasestates.Conditionsaredividedintofourcategoriesbasedonevidenceof
clinicalefficacyofTPEreportedinpeerreviewedliterature(table2).(See'ASFAtherapeuticcategories'
above.)

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Successfultherapeuticapheresisrequiresreliablevenousaccess,whichmaybeeithertwolarge,durable
peripheralveins,oracentralvenouscatheterwithaduallumenthatisrigidenoughtowithstand
significantflowandpressures.(See'Venousaccess'above.)

ThefluidvolumeremovedbyTPEmustbereplacedtopreventmarkedvolumedepletion.Albumin,
saline,oracombinationofalbuminandsalinearethereplacementfluidsofchoiceformostconditions.
Plasmaisappropriateinsomeconditionsthatrequireadditionofamissingplasmaprotein(eg,
ADAMTS13inacquiredautoimmunethromboticthrombocytopenicpurpura[TTP]).Formostconditions,
itisacceptabletoperform1to1.5plasmavolumeexchangesperprocedure.Asingleplasmavolume
exchangeinanaveragesizedadultusesapproximately3litersofreplacementfluid.(See'Replacement
fluids'above.)

Theapheresisscheduleshouldbedeterminedaccordingtothepathologicalsubstancethatisbeing
removed,andbythedesiredendpoint.Onlyoneortwoproceduresmayberequiredtorapidlyreduce
IgMlevelsamorerigorousregimeninvolvingseveralTPEproceduresandtheinstitutionof
immunosuppressivetherapyisrequiredtosignificantlyreduceIgGlevels.(See'Apheresisschedule'
above.)

Complicationsoftherapeuticapheresisarediscussedseparately,includinghypocalcemiadepletionof
coagulationfactors,immunoglobulins,ormedicationsangiotensinconvertingenzyme(ACE)inhibitor
relatedsymptomsandadversereactionstodonorplasmasuchasanaphylaxis,transfusionrelatedacute
lunginjury(TRALI),andexposuretoinfectiouspathogens.(See"Therapeuticapheresis(plasma
exchangeorcytapheresis):Complications"and"Approachtothepatientwithasuspectedacute
transfusionreaction".)

UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.

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22.KellerAJ,UrbaniakSJ.Intensiveplasmaexchangeonthecellseparator:effectsonserum
immunoglobulinsandcomplementcomponents.BrJHaematol197838:531.

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GRAPHICS

Pathologicsubstancesremovedbytherapeuticapheresis

Pathologicsubstance Diseases

Immunoglobulins Hyperviscositysyndrome

Waldenstrmmacroglobulinemia

Multiplemyeloma

Autoantibodies Myastheniagravis

AntiGBMantibodydisease

Systemiclupuserythematosus

Systemicvasculitis

FactorVIIIinhibitors

Thromboticthrombocytopenicpurpura

Lipoproteins Hypercholesterolemia

Leukocytes Hyperleukemicleukostasis

Platelets Severethrombocytosis

Abnormalredcells Sicklecelldisease(paincrisis,acutechestsyndrome,stroke)

Circulatingimmunecomplexes Immunecomplexglomerulonephritis

Systemiclupuserythematosus

Systemicvasculitis

Proteinboundsubstancesandtoxins Thyroidstorm

Amanitaphalloidestoxins

Hyperparasitemia Malaria,babesiosis

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AmericanSocietyforApheresis2016indicationsfortherapeuticapheresisand
cytapheresisprocedures

Indication Modality Category Evidence

Acutedisseminatedencephalomyelitis:Steroidrefractory TPE II 2C

Acuteinflammatorydemyelinatingpolyradiculoneuropathy(GuillainBarrsyndrome)

Primarytreatment TPE I 1A

Afterintravenousimmuneglobulin TPE III 2C

Acuteliverfailure TPE III 2B

TPEHV I 1A

Agerelatedmaculardegeneration,dry Rheopheresis I 1B

Amyloidosis,systemic Beta2microglobulin II 2B
column

TPE IV 2C

ANCAassociatedrapidlyprogressiveglomerulonephritis(granulomatosiswithpolyangiitis[Wegener's]
microscopicpolyangiitis)

Dialysisdependent TPE I 1A

Dialysisindependent TPE III 2C

Diffusealveolarhemorrhage TPE I 1C

Antiglomerularbasementmembranedisease(Goodpasture'ssyndrome)

Dialysisdependentandnodiffusealveolar TPE III 2B

hemorrhage

Dialysisindependent TPE I 1B

Diffusealveolarhemorrhage TPE I 1C

Aplasticanemia TPE III 2C

Atopic(neuro)dermatitis(atopiceczema),recalcitrant ECP III 2C

IA III 2C

TPE III 2C

Autoimmunehemolyticanemia

Severecoldagglutinindisease TPE II 2C

Severewarmautoimmunehemolyticanemia TPE III 2C

Babesiosis,severe RBCexchange II 2C

Burnshockresuscitation TPE III 2B

Cardiactransplantation

Cellular/recurrentrejection ECP II 1B

Desensitization TPE II 1C

Prophylaxisforrejection ECP II 2A

Treatmentofantibodymediatedrejection TPE III 2C

Cardiomyopathy,dilatedidiopathic(NYHAfunctionalclass IA II 1B
IIIV)
TPE III 2C

Catastrophicantiphospholipidsyndrome(APS) TPE II 2C

Chronicfocalencephalitis(Rasmussenencephalitis) TPE III 2C

Chronicinflammatorydemyelinatingpolyradiculoneuropathy TPE I 1B

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Coagulationfactorinhibitors

Alloantibody TPE IV 2C

IA III 2B

Autoantibody TPE III 2C

IA III 1C

Complexregionalpainsyndrome,chronic TPE III 2C

Cryoglobulinemia:Severe/symptomatic TPE II 2A

IA II 2B

CutaneousTcelllymphomamycosisfungoidesSzarysyndrome

Erythrodermic ECP I 1B

Nonerythrodermic ECP III 2C

Dermatomyositis/polymyositis TPE IV 2B

ECP IV 2C

Drugoverdoseorpoisoning TPE III 2C

EncephalitisassociatedwithNmethylDaspartatereceptor TPE I 1C
antibodies

Envenomation TPE III 2C

Erythrocytosis,secondary Erythrocytapheresis III 1C

Erythropoieticporphyria,liverdisease TPE III 2C

RBCexchange III 2C

Familialhypercholesterolemia

Heterozygotes LDLapheresis II 1A

Homozygotes LDLapheresis I 1A

Homozygoteswithsmallbloodvolume TPE II 1C

Focalsegmentalglomerulosclerosis

Recurrentintransplantedkidney TPE I 1B

Steroidresistant,innativekidney LDLapheresis III 2C

Graftversushostdisease

Acute(skinornonskin) ECP II 1C

Chronic(skinornonskin) ECP II 1B

Hashimoto'sencephalopathy:Steroidresponsive TPE II 2C
encephalopathyassociatedwithautoimmunethyroiditis

Hemolysis,elevatedliverfunctiontests,andlowplatelets(HELLP)syndrome

Antepartum TPE IV 2C

Postpartum TPE III 2C

Hematopoieticcelltransplantation,HLAdesensitization TPE III 2C

Hematopoieticcelltransplantation,majorABOincompatibility(recipienthasantiAorantiBantibodies)

Stemcellsfrombonemarrow TPE II 1B

Stemcellsfromperipheralblood TPE II 2B

Hematopoieticcelltransplantation,minorABO RBCexchange III 2C

incompatibility(donorhasantiAorantiBantibodies),stem
cellsfromperipheralblood

Hemophagocyticlymphocytosis(HLH)macrophage TPE III 2C

activatingsyndrome

HenochSchnleinpurpura:Crescenticorsevereextrarenal TPE III 2C

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HenochSchnleinpurpura:Crescenticorsevereextrarenal TPE III 2C
disease

Heparininducedthrombocytopenia(HIT):Pre TPE III 2C

cardiopulmonarybypassorwiththrombosis

Hereditaryhemochromatosis Erythrocytapheresis I 1B

Hyperleukocytosis

Prophylacticorsecondary Leukocytapheresis III 2C

Symptomatic Leukocytapheresis II 1B

Hypertriglyceridemicpancreatitis TPE III 2C

Immunethrombocytopenia(ITP):Refractory TPE III 2C

IA III 2C

ImmunoglobinAnephropathy

Chronicprogressive TPE III 2C

Crescentic TPE III 2B

Inflammatoryboweldisease

Crohndisease Adsorptive III 1B

cytapheresis

ECP III 2C

Ulcerativecolitis(UC) Adsorptive III/II 1B/2B

cytapheresis

LambertEatonmyasthenicsyndrome TPE II 2C

Lipoprotein(a)hyperlipoproteinemia LDLapheresis II 1B

Livertransplantation,ABOincompatible

Desensitization,deceaseddonororlivingdonor, TPE III 2C

antibodymediatedrejection(includesABOandHLA)

Desensitization,livingdonor TPE I 1C

Lungtransplantation

Allograftrejection(bronchiolitisobliteranssyndrome) ECP II 1C

Antibodymediatedrejectionordesensitization TPE III 2C

Malaria,severe* RBCexchange III 2B

Monoclonalgammopathieswithhyperviscosity

Prophylaxisforrituximab TPE I 1C

Treatmentofsymptoms TPE I 1B

Multiplesclerosis

Acutecentralnervoussysteminflammatory TPE II 1B
demyelinatingdisease
IA III 2C

Chronicprogressive TPE III 2B

Mushroompoisoning TPE II 2C

Myastheniagravis

Moderatesevere TPE I 1B

Prethymectomy TPE I 1C

Myelomacastnephropathy TPE II 2B

Neonatallupus,cardiac TPE III 2C

Nephrogenicsystemicfibrosis ECP III 2C

TPE III 2C

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Neuromyelitisopticaspectrumdisorders

Acute TPE II 1B

Maintenance TPE III 2C

Paraneoplasticneurologicsyndromes TPE III 2C

IA III 2C

Paraproteinemicdemyelinatingneuropathies/chronicacquireddemyelinatingpolyneuropathies

AntiMAGneuropathy TPE III 1C

IgA,IgG TPE I 1B

IgA,IgG,IgM IA III 2C

IgM TPE I 1C

Multifocalmotorneuropathy TPE IV 1C

Multiplemyeloma TPE III 2C

Pediatricautoimmuneneuropsychiatricdisordersassociated TPE II 1B
withstreptococcalinfection(PANDAS)exacerbation

Pemphigusvulgaris,severe TPE III 2B

ECP III 2C

IA III 2C

Peripheralvasculardiseases LDLapheresis II 1B

Phytanicacidstoragedisease(Refsumdisease) TPE II 2C

LDLapheresis II 2C

Polycythemiavera Erythrocytapheresis I 1B

Posttransfusionpurpura TPE III 2C

Progressivemultifocalleukoencephalopathyassociatedwith TPE I 1C
natalizumab

Pruritusduetohepatobiliarydisease,treatmentresistant TPE III 1C

Psoriasis ECP III 2B

Lymphocytapheresis III 2C

TPE IV 2C

Psoriasis,disseminatedpustular Adsorptive III 2C

cytapheresis

Pureredcellaplasia TPE III 2C

RBCalloimmunizationinpregnancy,priortointrauterine TPE III 2C

transfusionavailability

Renaltransplantation,ABOcompatible

Antibodymediatedrejectionordesensitization,living TPE I 1B
donor
IA I 1B

Deceaseddonor,desensitization TPE III 2C

IA III 2C

Renaltransplantation,ABOincompatible

Antibodymediatedrejection TPE II 1B

IA II 1B

Deceaseddonor,groupA2/A2BintogroupBrecipient TPE IV 1B

IA IV 1B

Livingdonor,desensitization TPE I 1B

IA I 1B
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IA I 1B

Rh(D)exposurefromRH(D)positiveRBCs,preventionof RBCexchange III 2C

alloimmunization

Scleroderma(systemicsclerosis) TPE III 2C

ECP III 2A

Sensorineuralhearingloss,sudden LDLapheresis III 2A

Rheopheresis III 2A

TPE III 2C

Sepsiswithmultiorganfailure TPE III 2B

Sicklecelldisease

Acutechestsyndrome,severe RBCexchange II 1C

Acutestroke RBCexchange I 1C

Multiorganfailure,pregnancy,priapism,recurrent RBCexchange III 2C

vasoocclusivepainepisodes,splenicorhepatic
sequestrationorintrahepaticcholestasis

Preoperative RBCexchange III 2A

Preventionoftransfusionalironoverloador RBCexchange I 1A
prophylaxisforprimaryorsecondarystroke

Stiffpersonsyndrome TPE III 2C

Sydenhamchorea,severe TPE III 2B

Systemiclupuserythematosus

Nephritis TPE IV 1B

Severe(eg,cerebritis,diffusealveolarhemorrhage) TPE II 2C

Thrombocytosis

Secondaryorprophylaxis Thrombocytapheresis III 2C

Symptomatic Thrombocytapheresis II 2C

Thromboticmicroangiopathy

Coagulationmediated:THBDmutation TPE III 2C

Complementmediated:Complementfactorgene TPE III 2C

mutations

Complementmediated:FactorHautoantibodies TPE I 2C

Complementmediated:Membranecofactorprotein TPE III 1C

(MCP)mutations

Drugassociated:Calcineurininhibitors TPE III 2C

Drugassociated:Clopidogrel TPE III 2B

Drugassociated:Gemcitabineorquinine TPE IV 2C

Drugassociated:Ticlopidine TPE I 2B

Hematopoieticstemcelltransplantassociated TPE III 2C

Shigatoxinmediated,absenceofsevereneurologic TPE IV 1C
symptoms

Shigatoxinmediated,withsevereneurologic TPE III 2C

symptoms
IA III 2C

Shigatoxinmediated,Streptococcuspneumonia TPE III 2C

Thromboticthrombocytopenicpurpura(TTP):Acquired, TPE I 1A
autoimmune
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autoimmune

Thyroidstorm TPE III 2C

Toxicepidermalnecrolysis,refractory TPE III 2B

Vasculitis

Behet'sdisease Adsorption II 1C
granulocytapheresis

TPE III 2C

Eosinophilicgranulomatosiswithpolyangiitis(EGPA) TPE III 1B

HepatitisBvirusassociatedpolyarteritisnodosa(HBV TPE II 2C
PAN)

Idiopathicpolyarteritisnodosa(PAN) TPE IV 1B

Voltagegatedpotassiumchannelantibodies TPE II 2C

Wilsondisease,fulminant TPE I 1C

Category
CategoryI:Disordersforwhichapheresisisacceptedasfirstlinetherapy,eitherasastandalonetreatment
orinconjunctionwithothertherapies.
CategoryII:Disordersforwhichapheresisisacceptedassecondlinetherapy,eitherasastandalone
treatmentorinconjunctionwithothertherapies.
CategoryIII:Disordersforwhichtheoptimumroleofapheresistherapyisnotestablished.
CategoryIV:Disordersforwhichpublishedevidencedemonstratesorsuggestsapheresistobeineffectiveor
harmful.
Evidence
Evidencegrade1:Strongrecommendation.
Evidencegrade2:Weakrecommendation.
EvidencequalityA:Highqualityevidence.
EvidencequalityB:Moderatequalityevidence.
EvidencequalityC:Lowqualityorverylowqualityevidence.
RefertoUpToDatetopicsonindividualconditionsforspecifictreatmentrecommendations.Dueto
UpToDatestylingandalphabetization,theorderofdiseasesinthistablemaydifferfromtheoriginalsource
publication.

ANCA:antineutrophilcytoplasmicautoantibodyECP:extracorporealphotopheresisHLA:humanleukocyteantigenIA:
immunoadsorptionLDL:lowdensitylipoproteinMAG:myelinassociatedglycoproteinNYHA:NewYorkHeart
AssociationRBC:redbloodcellTPE:therapeuticplasmaexchangeTPEHV:highvolumetherapeuticplasmaexchange.
*UpToDateauthorsdonotuseRBCexchangeforseveremalaria.
UpToDateauthorsconsiderthisentity(thromboticmicroangiopathy[TMA]inthesettingofticlopidine)tobeacquired
autoimmunethromboticthrombocytopenicpurpura(TTP)ratherthandruginducedTMAbecausethepatientshadsevere
ADAMTS13deficiency.

Adaptedfrom:SchwartzJ,PadmanabhanA,AquiN,etal.Guidelinesontheuseoftherapeuticapheresisinclinical
practiceevidencebasedapproachfromtheWritingCommitteeoftheAmericanSocietyforApheresis:Theseventh
specialissue.JClinApher201631:149.http://onlinelibrary.wiley.com/wol1/doi/10.1002/jca.21470/abstract.
Copyright2016.ReproducedwithpermissionofJohnWiley&SonsInc.Thisimagehasbeenprovidedbyoris
ownedbyWiley.FurtherpermissionisneededbeforeitcanbedownloadedtoPowerPoint,printed,sharedoremailed.
PleasecontactWiley'spermissionsdepartmenteitherviaemail:permissions@wiley.comorusetheRightsLinkserviceby
clickingontheRequestPermissionlinkaccompanyingthisarticleonWileyOnlineLibrary
(http://onlinelibrary.wiley.com).

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ContributorDisclosures
JoyLFridey,MD Nothingtodisclose AndreAKaplan,MD Grant/Research/ClinicalTrialSupport:Nipro
Corporation[Dialysis(Dialysisfilters)].Speaker'sBureau:Terumo[Plasmapheresis(Plasmapheresis
machines)].Consultant/AdvisoryBoards:VitalTherapeutics[Extracorporealliverassistdevice
(ELAD)]. ArthurJSilvergleid,MD Nothingtodisclose JenniferSTirnauer,MD Nothingtodisclose

Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseare
addressedbyvettingthroughamultilevelreviewprocess,andthroughrequirementsforreferencestobe
providedtosupportthecontent.Appropriatelyreferencedcontentisrequiredofallauthorsandmustconform
toUpToDatestandardsofevidence.

Conflictofinterestpolicy

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