Rev. Bras. Hematol. Hemoter. vol.39 número2

w w w . r b h h . o r g

Revista

Brasileira

de

Hematologia

e

Hemoterapia

Brazilian

Journal

of

Hematology

and

Hemotherapy

Original

article

Seroprevalence,

cost

per

donation

and

reduction

in

blood

supply

due

to

positive

and

indeterminate

results

for

infectious

markers

in

a

blood

bank

in

Lima,

Peru

Jeel

Moya-Salazar

,

Roberto

Ubidia-Incio

,

Maritza

Incio-Grande

,

Jorgelina

L.

Blejer

_,

_Carlos

_A.

_Gonzalez

a_{HospitalNacionalDocenteMadreNi ˜noSanBartolomé,Lima,Peru} b_{UniversidadContinental,FacultaddeCienciasdelaSalud,Huancayo,Peru} c_{UniversidadPeruanaCayetanoHeredia,FacultaddeCienciasyFilosofía,Lima,Peru} d_{HospitalCentraldePoliciaNacionaldelPeru,Lima,Peru}

e_{FundaciónHemocentroBuenosAires,BuenosAires,Argentina} f_{HospitaldeInfecciosasF.J.Mu ˜niz,BuenoAires,Argentina}

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Articlehistory:

Received21June2016 Accepted29November2016 Availableonline23January2017

Keywords:

Seroprevalence Infectiousmarker Indeterminatescreening Blooddonor

a

b

s

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Introduction:SafetyinTransfusionMedicineissubjecttoregulationsandgovernment legis-lationwithinatotalqualityframework.Theaimofthisstudywastoevaluatetheimpactof seroprevalenceandindeterminateresultsonlostunitsandcostperdonation.

Methods:Aprospectivecross-sectionalstudywasperformedintheBloodBankand Transfu-sionTherapyDepartmentoftheHospitalCentraldelaPoliciaNacionaldelPerúinLima,Peru. Allcompleteddonations(replacement/voluntary)withoutcomplicationswereincludedin thisstudy.Everydonationmettheinstitutionalrequirementsandqualitycriteriaof Pro-gramaNacionaldeHemoterapia yBancosdeSangre(PRONAHEBAS).Dataanalysiswas achievedusingtheStatisticalPackagefortheSocialSciences.

Results:Atotal of7723donationswereevaluated during2014and 2015with493being seropositive(overallprevalence5.25%)and502havingindeterminateresults(overall preva-lence5.35%).Thustotallosswas995units,437.8Lofbloodand49,750USdollars.Themost commonseropositiveinfectiousmarkerswerethecoreantibodyofhepatitisBvirus(2.82%) andsyphilis(1.02%),andthemostcommonindeterminateresultswereChagasdisease (1.27%)andthecoreantibodyofhepatitisBvirus(1.26%).Therewasnosignificantchange intheprevalenceofseropositivity(p-value=0.243)orindeterminateresults(p-value=0.227) overthetwo-yearperiodofthestudy.Astatisticalcorrelationwasfoundbetweenthecost perlostdonationandthemostprevalentmarkers(rho=0.848;p-value=<0.001).

∗ _{Correspondingauthorat:M.T.Jr.Pacifico957Urb.SanFelipe,Lima07,51001Lima,Peru.}

E-mailaddress:[email protected](J.Moya-Salazar).

http://dx.doi.org/10.1016/j.bjhh.2016.11.007

Conclusion: Seroprevalencewaslowerthantheregionalmean,buttheprevalenceof inde-terminateresultswaselevatedcausingagreatimpactonbloodsupplyandeconomiclosses tothisinstitution.

©2017Associac¸ ˜aoBrasileiradeHematologia,HemoterapiaeTerapiaCelular.Published byElsevierEditoraLtda.ThisisanopenaccessarticleundertheCCBY-NC-NDlicense (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction

SafetyinTransfusionMedicineissubjecttoregulationsand government legislation within a total quality framework. Safetyintransfusiontherapyandduringdonationisanethical issueinbloodbanksthatmusthaveprotectivemechanisms thatdetectnoxaeanddiminishrisk,makingthetransfusion practice efficient, safe and individualized for each patient withdonations beingfree ofadverse-reaction events. Nev-ertheless, new difficulties affect blood supply safety, such asstrictdonorselectionquestions,anaffordableblood sup-ply, seroconversion periods and emergent agents, among others.1,2

The relative risk from donations is considerable and changing,thereasonforwhichitsestimationandits extrap-olation to other communities are frequently hindered. In undeveloped countries, the relative risk from donations is heterogeneousduetogeographic diversity,the habitatand population groups, as well as to the socioeconomic and educationalconditions,andaccesstohealthcareresources.3

DonationsinPerurequirescreeningforatleastfiveinfectious markers:surface antigen(HBsAg)and the coreantibodyof hepatitisBvirus(HBcAb),antibodiesagainsthuman immu-nodeficiency virus (HIV) type 1 and 2 (anti-HIV 1 and/or anti-HIV2), antibodies againsthepatitis C virus (HCV)and anti-Treponema pallidum (syphilis).4 _{Additionally, antibodies}

against human lymphotropic viruses (anti-HTLV-1/2) and markers for Chagas–Mazza disease are tested in endemic zones.5,6_{Thenumberoftestsisnotthesameineachcountry}

becauseofdifferentsocio-sanitaryconditionsandbasedon sero-epidemiologicaldata. Additionaltestsareincluded for ChagasdiseaseinSouthAmerica,Canada,Mexico,andsome Western Pacific countries, for anti-human T-lymphotropic virus (HTLV)-1/2 in Portugal, France, Taiwan, Japan and Greece,butnotinTurkey,forCreutzfeldt–Jacobdisease vari-ant(vCJD)intheUnitedKingdom,Germany,Chile,Portugal and Austria, for West Nile Virus (WNV) in United States, Canada, Australia and India and for anti-plasmodium in Benin.7–13

Theeffectusuallyassociatedtoseropositiveunitsisthe lossofbloodunits(biologicalandeconomicalcosts).During thelastfifteenyears,thereducedbloodsupplytotheBlood BankingService of aHospital specialized inmaternal care atLima,Peru, and thegreateconomicimpact ofdiscarded bloodcomponentswas457.2Lofbloodand61,893USdollars, withlimitationsinthedonationchain.Thisisalsoaffected bythehigh-riskoftransfusion-transmittedinfectionsin non-healthypopulations.6_{Theprevalencesofinfectiousmarkers}

were0.23%,4.19%,0.56%,1.19%and0.5%forHIV,hepatitisB virus(HBV),HCV,syphilisandChagasdisease,respectivelyin

unitsofblood screenedinPeru;the overallprevalencewas higherthanforothercountriesintheregion.6,14–16

Thus, behavioral risk factors, donor quality and geo-graphicalendemismgeneratevariablefactorsthatcomplicate the functioning ofblood banks where screeningfor infec-tiousmarkersconstitutesaninvaluablemeasuretoeliminate unsafebloodandavoidadversetransfusionreactions.17

The aim of this study was to evaluate the impact of seroprevalence and the cost per donation in the Blood Bank and Transfusion Service of the Hospital Central de la PoliciaNacional delPerú inLima,Peru during2014 and 2015.

Methods

Ananalytical-correlationalcross-sectionalprospectivestudy wasperformedintheBloodBankandTransfusionServiceof theHospitalCentraldelaPoliciaNacionaldelPerúinLima. Thegroupofblooddonorsincludedinthisstudy was cho-senbasedonalldonationswithpositiveandindeterminate resultsforoneormoreoftheseveninfectiousmarkers:HBsAg, HBcAb,HIV1–2,HCV,Chagasdisease,syphilisandHTLV-1/2. TheoverallprevalencesoftheseinfectiousmarkersinPeru were0.23%forHIV,0.38%forHBsAg,0.56%forHCV,1.19%for syphilis,0.5%Chagasdisease,0.88%forHTLV-1/2and4.19% forHBcAb.16_{Thecutoffpointwasderivedfromtheaverageof}

threenegativecalibratorsplus afixedvalue;indeterminate resultswere definedasresultswithinthegray zone estab-lishedbythisinstitution.

All serologicaltests wereperformed induplicateduring separateroutines.Onlysamplesthathadtwopositiveresults intwodifferentrunswereclassifiedaspositive.Theseresults were notifiedtotheInstitutoNacional deSaludofPerufor confirmation using molecular methods, as defined in the epidemiologicalevaluationprogramsfordiseaseandpatient follow-up.18

Donatedbloodunitsconsideredinthisstudywereselected respectingthedonationcriteriaestablishedbythePrograma NacionaldeHemoterapiayBancodeSangre(PRONAHEBAS) andstandardoperationalprocess.6,18,19_{Theagesofalldonors}

Table1–Percentageofseropositivedonationsforseveninfectiousmarkers(n=493).

Year HIV HBsAg HCV Syphilis HBcAb HTLV Chagasdisease Total

2014 0.22 0.15 0.42 0.90 2.80 0.42 0.13 5.05

2015 0.12 0.19 0.43 1.13 2.84 0.58 0.14 5.44

Ofbothyears 0.17 0.17 0.43 1.02 2.82 0.50 0.14 5.25

2=0.96;p-value=0.243(non-significant).

Table2–Percentageofindeterminateresultsinblooddonations(n=502).

Year HIV HBsAg HCV Syphilis HBcAb HTLV Chagasdisease Total

2014 0.13 0.57 1.10 0.64 1.15 0.31 0.49 4.39

2015 0.45 0.60 0.82 0.66 1.36 0.35 2.01 6.24

Ofbothyears 0.30 0.59 0.96 0.65 1.26 0.33 1.27 5.35

2=0.07;p-value=0.227(non-significant).

Technical

data

collection

and

processing

of

the

sample

Data collection was carried out using the register book of the Donation Service where samples were discriminated by seropositivity and data were grouped in months and years.ThemethodusedforscreeningwasArchitect Chemi-luminescent Microparticle Immunoassay (Abbott Park, IL, USA). The serological screening was automated using the Architecti1000srImmunoassayAnalyzer(AbbottPark,Illinois, USA)withanincubatorandprogrammabletemperature con-trolregulatedbyArchitecti1000srSoftware.

Thedata from the Data Management System forBlood Bankse-Delphyn®registersystem(Hemasoft,Singapore)was tabulatedintothematrixinMicrosoftExcel2010forWindows (Redmond,USA)whereitwascodedandthecriteriaforthe verificationofmethodswasevaluated.Dataanalysiswas per-formedusingtheIBMStatisticalProgramforSocialSciences v21.0(Armonk,USA).KMOandBartlett’stestofsphericitywas employedto correlatevariables and Varimax Rotationwas usedforfactorialanalysis.TheChi-square testwasusedto assessdifferencesinprevalencebetweentheyearsofstudy. Seroprevalencewas calculatedasthemean,standard error and95%confidenceinterval(95%CI)andap-value<0.05was consideredstatisticallysignificant.

Results

Atotalof9388donationswereevaluatedduring2014and2015, with493havingseropositiveresults(Table1)givingan over-allprevalencewas5.25%.Theinfectiousmarkerwiththemost positiveresultswasHBcAb(n=265;2.82%),followedbysyphilis (n=96; 1.02%) and HTLV-1/2 (n=47; 0.50%; p-value <0.01 –

Table1).Fivehundredandtwounits(5.35%)hadindeterminate results(grayzone),whereChagasdisease(n=119;1.27%)and HIV(n=28;0.30%)werethemostandleastprevalent, respec-tively(p-value<0.05–Table2).Therewasnosignificantchange intheprevalenceofseropositivity(p-value=0.243)or indeter-minateresults(p-value=0.227)overthetwoyearperiodofthe

Table3–Bloodlossandcostforseropositiveand indeterminatedonations(n=995).

2014 2015 Total

Totalseropositiveunits–n 229 264 493 Totalindeterminateunits–n 199 303 502

Discardedunits–n 428 567 995

Lostblood–L 188.3 249.5 437.8

Totalcost–US$a _{21,400.00 28,350.00 49,750.00}

a _{ConsideringthepriceforTerumoquadruplebagsandbloodtests.}

Unitarycost:170.00Nuevossoles(PER)(50.00USD).

study.Figure1showstheprevalenceinthisstudycompared withtheregionalandnationalprevalences.

When seropositive and indeterminate losses were com-pared,thenumberofseropositiveunitswithalossof216.9L ofblood(493units)waslowerthantheindeterminateresults (220.9L,502units);moreover,therewasa24.5%increasein lost blood from 2014 to2015(Table3). Similarly,when the directcostofseropositiveandindeterminateunitswas ana-lyzed,therewasahighercostrelatedtoindeterminateunits (25,100USD) compared to seropositive units (24,650USD –

Table3).

Astatisticalcorrelation wasfoundbetweenthe costper lostdonationandthemostprevalentmarkers(rho=0.848;p -value=<0.001). Factorial analysisoftheseropositiveresults showedfourcomponentsthatexplainthevariance:first,the association betweenHBsAg and HBcAb; second the associ-ation betweenHTLV-1/2andHIV1–2;third,the association betweenChagasdiseaseandHCV;andthesolitarycomponent syphilis(p-value=<0.001).Fortheindeterminateresults,three componentswerefound:FirsttheassociationbetweenHBcAb, HCVandsyphilis;second,betweenChagasdisease,HTLV-1/2 andHBsAg;andfinallyHIValone(p-value>0.004).

Discussion

0.17 0.17

0.43 1.02

2.82

0.5

0.14

0.19 0.29

0.42

1.26

2.19

0.24

1.03

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5

Chagas HTLV

HBcAb SYFILIS

HCV HBsAg

HIV

Study

PAHO 2012-2013 (PER)17 HONADOMANI SB 2008-201311 PAHO 2012-2013 (Latin America)17

Figure1–PrevalencecomparingthisstudyandthelastreportofthePan-AmericanHealthOrganization(PAHO)forLatin

AmericanandPeru,andastudyaboutseroprevalenceandcostsinHospitalNacionalDocenteMadreNi ˜noSanBartolome

(HONADOMANISB),Lima,Peru.

blood.InLatinAmerican countries,theindicatorsofsafety and supply of blood showed 100% of screening units for infectiousmarkersthatdeterminedanoverallprevalenceof 1.13%.16_{Nevertheless,therearefewstudiesabout}

indetermi-nate,gray zoneresultsand theimplications totransfusion medicineandprocessesofqualityassurance.

Inthelastreport,thePan-AmericanHealthOrganization (PAHO)reported prevalencesof 0.29%,2.19%,1.26%, 0.24%, 1.03%,0.42%and0.19%forHBsAg,HBcAb,syphilis,HTLV-1/2, Chagasdisease,HCVand HIVinLatinAmerican countries, respectively.16_{InPeru,onlysyphilis(1.19%)andChagas}

dis-ease (0.5%)are below the regionalaverages; the valuesfar exceeded the averages forall the others markers, such as HBcAb (4.19%), HIV (0.23%) and dramatically for HTLV-1/2 (0.88%)(Figure 1). In this study we report low prevalences forChagasdisease,HIVandHBsAg,andhighprevalencesfor syphilisandHBcAbincomparisonwiththelastreportofthe PAHO.Itisnoteworthythattheoverallprevalenceof seroposi-tiveresultsincreasedconsiderablysincethestartofthestudy (0.39%)withvaluesundertheregionalandnationalmeans,6,16

butfarbelowtherecentreport.20_{Furthermore,oncomparing}

theprevalenceobservedinthisstudywithapreviousreport inaMotherandChildHospitalwhichbelongstothePeruvian MinistryofHealth(MINSA),alltheresultswerelow(halfofthe previousreportedvalues)similartotheevaluationperformed bythePAHOforbloodsupplyinPeru16 _(Figure1).In

princi-ple,thissuggeststhattheprevalencesofinfectiousmarkers inthisdonorgrouparecorrectforthispopulationgroupof policeofficersandtheirfamilies,allofwhomhadsimilarrisk behaviorfactorsandotherconditions.

Similarly,when the overall prevalenceofindeterminate results was assessed, most results in the gray zone were relatedtoChagasdisease,HBcAb,HCVandsyphilis(Table2). Two ofthesediseases are consideredendemicin Peruand othercountriesofLatinAmerica.TheriskforChagasdisease constitutesanimportantproblemfortransfusionmedicineas thescreeninginbloodbanksiscommonlyaffectedbydifferent

factorssuchasthehighprevalenceindonors,lackof sensi-tivityandspecificityoftheassays,lackofconfirmatorytests andcross-reactions.Allthesefactorsincreasethenumberof indeterminateresultsandrequiretheuseoftechniquesthat diagnoseinconclusiveunits.14,21,22

In a previous report, 5% of indeterminate results were found for HCV, a percentage far above the regionalmean (0.42%).14,16,23_{WithHCV,approximately7%ofindeterminate}

unitsresultedinnegativeconfirmatorytestsusingasecond sample.Thus,webelievethat itisnecessarytouse a con-firmatorytestandtofollow-uptheseindeterminatedonorsto demonstratepossibleseroconversionwhichwouldresultina significantimpactonbloodbanks.23_{Thehighproportionof}

indeterminateresultsforHBcAbandsyphilisisbecausethe majorityofdonorshavecommonriskfactorsforthese condi-tionswithasubstantialconsequenceonserologicalscreening inbloodbanks.13,16,24,25_{A10.6%overallprevalenceof}

seropos-itive and indeterminate resultswas estimated. Thispoints to a low quality of donors, high prevalence of infectious markers,thefailureofinterviews,organizationalproblemsin thebloodbankandpoorsanitary-epidemiologicalcontrolof transfusion-transmittedinfectionsinthispopulation.16,20,26

WefoundalowprevalenceforHIV,HBsAgandHTLV-1/2; thisratewassimilartoseveralpreviousreports.27_Thecurrent

study shows that the risk of HIV- or HTLV-contaminated transfusionsisanimportantdifficultyinbloodbanksdueto the characteristics ofthe lifecyclesofthese viruses.HTLV causesseriousleukemoidreactionsandchronicmyelopathy that has been poorly clarified hitherto.28,29 _{This disease is}

characterized by geographic grouping placing Peru at the top oftherankinginLatinAmerica,16_{asituation thatmay}

explain why the values in this population were less than halfthoseofotherstudies.6,16_{Furthermore,astheinfections}

bloodbanklaboratoriesinthecommunity.Itisforthisreason thatthe screeningforthis markerisbeingimprovedusing conventionaltestsinordertoobtainsafeblood.14,25,30–32_The

meanrateforHIV-positivebloodsamplesinthisstudywas coincidentwithpreviousreports.6,16,27

In addition, in Latin American countries, 29% of dis-cardedbloodisrelatedtoseropositivityorunitsreactivefor transfusion-transmittedinfections,withoutconsidering inde-terminateunits;theseresultsundoubtedly,differsignificantly tobloodbanksindevelopedcountries.33–35_{Inrespecttoblood}

lossforseroprevalenceofinfectiousmarkers,ourresultsare verylow(216.9Lperyear)comparedtoastudycarriedoutin aHospitalinLimawhere457.2Lofbloodof9560bloodunits werediscardedoverfiveyears,andreportsfromtheInstituto SuperiordeMedicinaMilitarinLaHabana.6,36_{Themajorityof}

thesediscardedunitswerefreshplasmaandredbloodcellsas mentionedinthelastreportofPAHO.Ourresults(10.6%)are alsoconsistentwiththisreportaboutdiscardedunits(11.3%) (Table3).16_{Ontheotherhand,thevaluesareverydifferent}

forindeterminateunits;inapreviousstudywereportedthat inoneyear1977indeterminate(grayzone)unitstestedusing ELISAwerediscardedintheHospitaloftheSeguroSocialde SaluddelPerú(EsSalud)generatingabloodlossof863.9L.20

Thedifferencewiththisstudyisclearasonly220.8Lofblood werediscardedinoneyear,25.4%ofthatreportedinEsSalud. Thisisduetothe50%ofgrayzoneinscreeningtheinstitution establishedforits populationofdonors(policeofficersand theirfamilies),asameasuretopreventunsafeblood transfu-sions,butpointstoaneedforstandardizationofthesizeof thegrayzoneforeachmarkerindifferentpopulationswith differentrisksandprevalentdiseases.

Theprincipal consequenceof the discardof units with positive or indeterminate (gray area) results is the quasi-immeasurableeconomicimpactandthelimitationsinchain donations,principally,inthesupplyofbloodcomponentsfor institutions.Inpreviousreportsonthecostof seropositive-eliminated donations in Peru, 61,893USD were lost in a quinquennium.6_{Here,intwoyearsofevaluation,24,650USD}

were lost bydiscardingseropositive units.6,16,36 _Thisvaries

considerablyinthecaseofindeterminateunits,whichinthe presentstudycorrespondsto25,100USDlost,arelativelylow valuecomparedtoastudybyEsSaludwhereinonlyoneyear 92,640USDwerelost,aresultthatsurpassespreviousreports aboutreactiveandpositivedonations.16,20,36,37_Theseresults

showagreateconomic,socialandsanitaryimpactforblood banksattemptingtoguaranteequalityandtransfusionsafety. We believe that guaranteeing quality in an initial step could improve processes in all stages of donation and transfusion,2,38–41_{throughamoreefficientprocessthat}

pre-ventserrors,reducescosts,andsatisfiesusers,etc.This,with theapplicationofgoodpracticesinTransfusionMedicine,the promotionofvoluntarydonations and theimplementation ofnew screeningstrategiesin the health caresystem will increasesafedonationsthatwillsavelives.

Conclusion

Toconclude,inprinciple,seropositivityisdiminishing com-paredtotheoverallprevalenceintheregionwheretestingfor

prevalentdiseasesismaintained.Forindeterminateresults, ChagasdiseaseandHbcAbinfectiousmarkersarehighwith theoverallprevalencebeinghigherthanforpositiveresults. Theseresultsdepletedthebloodsupply(discardedunits)with ahigheconomicimpact.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

Acknowledgments

WearegratefultoDr.JoséGirardClavo,RonaldTorres-Matinez, O.R.,andtoHospitalCentraldePoliciaNacionaldelPerufor alltheirsupportinthisstudy.

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s

1.GoodnoughLT,ShanderA,BrencherME.Transfusion medicine:lookingtothefuture.Lancet.2003;361(9352): 161–9.

2.CalleryMF,NevalainenDE,KirstTM.Qualitysystemsand totalprocesscontrolinbloodbanking.Transfusion(Paris). 1994;34(10):899–906.

3.CruzJR,Pérez-RosalesMD,ZickerF,SchmunisGA.Safetyof bloodsupplyintheCaribbeancountries:roleofscreening blooddonorsformarkersofhepatitisBandCviruses.JClin Virol.2005;34Suppl.2:S75–80.

4.AmericanAssociationofBloodBanks.

Transfusion-transmitteddisease.In:AABBtechnicalmanual. 14thed.Bethesda,MD:AABB;2002.p.613–23.

5.VegaMC,MontoroAJ.ManualdeMedicinaTransfusional. Espa ˜na:MosbyDoymaLibros;1994.p.11–7.

6.MoyaSJ,JulcamanyanTE.Seroprevalenceinfectiousmarkers causinglossofdonationinthebloodbankserviceinHospital NacionalDocenteMadre–Ni ˜noSanBartolomeJanuary2008 toDecember2013.HorizMed.2014;14(4):6–14.

7.SertözR,TurhanA,BozkurtH,Samlıo ˘gluP,De ˘girmenciA, AydınokY,etal.Investigationofanti-HTLV-I/II

seroprevalenceinhealthyblooddonorsinIzmirregion, Turkey.MikrobiyolBul.2010;44(4):579–84.

8.PrataA.ClinicalanepidemiologicalaspectsofChagas disease.LancetInfectDis.2001;1(2):92–100.

9.CenterofBiologicsEvaluationandResearch.Revised PrecautionaryMeasurestoreducethepossibleriskof transmissionofCreutzfeldt–JakobDisease(CJD)andnew variantCreutzfeldt–JakobDisease(nvCJD)bybloodandblood products.US:GuidanceforIndustry;1999.p.3–7.

10.GemanFederalMinistryofHealth.OverallBloodSupply StrategywithregardtovariantCreutzfeldt–JakobDisease (vCJD).ReportoftheWorkingGroupCommissionedbythe GermanFederalMinistryofHealthApril13,2006.Transfus MedHemother.2006;33Suppl.2:VII.

11.CenterforDiseaseControlandPrevention(CDC).

Transfusion-associatedtransmissionofWestNilenVirus– Arizona,2004.MorbMortalWklyRep.2004;53(36):842–4.

12.Kindel-GazardOJ,GnahouiI,MassougbodjiA.Theriskof malariatransmissionbybloodtransfusionatCotonou,Benin. Sante.2000;10(6):389–92.

14.CortésBA,GutiérrezMG.Prevalenciademarcadorespara infeccionestransmisiblesportransfusiónendonantes voluntarios.ColombMed.1996;27(1):3–10.

15.DelaCruzSR,BarreraCT,VidalEJ,RodríguezSI.Marcadores serológicosdesífilis,hepatitisByVIHendonantesdsangre enelHospitalNacionalCayetanoHeredia,Lima–Perú.Rev MedHered.1999;10(4):137–43.

16.Pan-AmericanHealthOrganization.Supplyofbloodfor transfusioninLatinAmericanandCaribbeancountries2012 and2013.Washington,DC:PAHO;2015.

17.AlleyneGA.Elpróximocuadrienio.Washington,DC:OPS; 1998.

18.MinisteriodeSalud.SistemadeGestióndelaCalidaddel PRONAHEBAS.ManualdeCalidad.NormaTécnica.No. 011-MINSA/DGSP-V.01;2004.

19.AABB.Standardsforbloodbanksandtransfusionservices. 29thed.Bethesda,MD:AmericanAssociationofBloodBanks (AABB);2014.

20.MoyaSJ,PioDL,DiazRM.Depletionofbloodsupplyandcost forindeterminatedonationsatHospitalNacionalGuillermo AlmenaraIrigoyen.HorizMed.2017;17(1):31–7.

21.BlejerJL,SaguierMC,SalamoneHJ.AntibodiestoTrypanosoma cruziamongblooddonorsinBuenosAires,Argentina.IntJ InfectDis.2001;5(2):89–93.

22.BlejerJL,SartorPA,BottassoO,SalamoneHJ,LeguizamónMS. Trans-sialidaseInhibitionAssayforthedetectionof

Trypanosomacruziinfectioninblooddonorsamplesfrom Argentina.VoxSang.2008;95(3):189–96.

23.Iborra-BendichoAM,Albert-HernándezM,

Márquez-ContrerasC,Segovia-HernándezM.ARCHITECT Chagas®:unanuevaherramientadiagnósticaenla enfermedaddeChagas.EnfermInfeccMicrobiolClin. 2012;30(8):463–5.

24.AguirreGG,MartínezAJ,ArenasEI.Resultadosenzonagris deltamizajeparaVIHyVHC,puedenindicarseroconversión inmediata.RevMexPatolClin.2005;52(1):63–8.

25.TramontE.Treponemapallidum(syphilis).In:MandellG, bennettJ,DolinR,editors.Principlesandpracticeofthe infectiousdiseases.4◦_{ed.NewYork:ChurchillLivingstone;}

1995.p.2117–33.

26.PortoFA,deAlmeida-NetoC,TeixeiraMC,StraussE. Health-relatedqualityoflifeamongblooddonorswith hepatitisBandhepatitisC:longitudinalstudybeforeand afterdiagnosis.RevBrasHematolHemoter.2015;37(6):381–7.

27.ChattorajA,BehlR,KatariaVK.Infectiousdiseasemarkersin blooddonors.MedJArmedForcesIndia.2008;64(1):33–5.

28.ZurHausenH.Thesearchforinfectiouscausesofhuman cancers:whereandwhy.Virology.2009;392(1):1–10.

29.KhabbazRF,HeneineW,GrindonA,HartleyTM,ShulmanG, KaplanJ.IndeterminateHTLVserologicresultsinU.S.blood

donors:aretheyduetoHTLV-IorHTLV-II?JAcquirImmune DeficSyndr.1992;5(4):400–4.

30.BuschMP,LeeLL,SattenGA,HenrardDR,FarzadeganH, NelsonKE,etal.Timecourseofdetectionofviraland serologicmarkersprecedinghumanimmunodeficiencyvirus type1seroconversion:implicationsforscreeningofblood andtissuedonors.Transfusion.1995;35(2):91–7.

31.BeelaertG,FransenK.Evaluationofarapidandsimple fourth-generationHIVscreeningassayforqualitative detectionofHIVp24antigenand/orantibodiestoHIV-1and HIV-2.JVirolMethods.2010;168(1–2):218–22.

32.BransonBM,OwenMS,WesolowskiLG,BennettB,WernerBG, WroblewskiKE,etal.Laboratorytestingforthediagnosisof HIVinfection.Updatedrecommendations.CenterforDisease ControlandPrevention(CDC);2014.

33.FoodandDrugAdministration(FDA).Requirementsforblood andbloodcomponentsintendedfortransfusionorforfurther manufacturinguse.FedRegist.2015;80(99):

29842–906.

34.WorldHealthOrganization(WHO).Bloodsafetyand availability.WHO;2015.FactsheetNo.279.Availablefrom:

http://www.who.int/mediacentre/factsheets/fs279/en/

[internet;cited22.02.16].

35.AlenJ,BowlerP,BurtaO,deKortW,FolléaG,HajiyevA,etal. Reportofthesurveyonbloodsupplymanagementorganised bytheTS003WorkingGroupinmemberstatesandobserver statesoftheCouncilofEurope.France:EuropeanDirectorate fortheQualityofMedicines&HealthCareoftheCouncilof Europe(EDQM);2014.

36.ViamonteRF,PérezHM,DelgadoEL,LongresManguarAL. Marcadoresserológicoscausantesdepérdidasdedonaciones. RevCubanaMedMilit.2000;29(1):41–5.

37.SánchezAS,GonzalesNP,AlvarezVJ.CostosenlaTransfusión Sanguínea.RevMexAnest.2000;23(2):66–70.

38.GrifolsEJ,MartinVC,HernándezSJ,PujolBM,GrifolsRJ, GarcíaRE.SeguridadenMedicinaTransfusional.Menarini Diagnóstics.1a_{ed.Espa ˜na:Pecalo;1998.p.73.}

39.Moya-SalazarJ,DíazRR.PlanificaciónAnalíticadelacalidad enPruebascualitativasdetamizajeserológicodeBancode Sangre.In:XVCongresoArgentinoDeMedicina

Transfusional.BuenosAires:AsociaciónArgentinade Hemoterapia,InmunohematologíayTerapiaCelular;2015.p. 215–31.

40.ISO.NormaInternacional9001:2000.Sistemasdegestiónde lacalidad-Requisitos.Ginebra:ISO;2000.