Rev. Bras. Hematol. Hemoter. vol.39 número3

revbrashematolhemoter.2017;39(3):288–289

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

Revista

Brasileira

de

Hematologia

e

Hemoterapia

Brazilian

Journal

of

Hematology

and

Hemotherapy

Letter

to

the

Editor

Assessment

of

the

Matos

&

Carvalho

index

for

distinguishing

thalassemia

from

iron

deficiency

anemia

DearEditor,

Inarecentissueofthisjournal,Matosetal.proposedanew indexfordiscriminatingbetweenirondeficiencyanemia(IDA) and thethalassemia trait.1 _{Weread theirpaperwith great}

interest,since we haveperformed similar researchin this field.2_{Recentlywecompletedastudyinwhichwecompared}

25discriminantformulasincorporatingonlybasicredblood cell(RBC)parametersusingalargedatabaseofpatientswith mildmicrocyticanemia,whoeitherhadadiagnosisofIDAor werethalassemiacarriers.3 _{Thisdatabasenowgivesusthe}

opportunitytoinvestigatethediagnosticperformanceofthe Matos&Carvalho(M&C)indexinamuchlargerpatientcohort thantheauthorsusedfortheirdevelopmentandvalidation,1

andwepresentourfindingsinthiscommunication.

Ourdatabasecomprises2664patientswithmicrocytic ane-mia,definedashemoglobin<13g/dLandmeancorpuscular volume(MCV)<80fL,irrespectiveofgender.Itwasbuiltovera periodofnineyears,duringwhichtimetheBeckmanCoulter LH780wasthemainhematologyanalyzerinuse;other hema-tologyanalyzerswereoperatedforshorterperiods.Standard biochemicalandhematologicalmethodswereusedtomake thediagnosis;thediagnosisof␣-thalassemiawasbasedon moleculartechniques.Ofourpatients,1196had“pure” tha-lassemia(319␣-thalassemiaand877␤-thalassemia),1259had simpleIDA,117 hadthalassemia withconcomitantIDA,33 hadthalassemiawithconcurrentanemiaofchronicdisease, 23hadcomplexthalassemiaand36hadotherdiseases asso-ciatedwithmicrocyticanemia.

WhenapplyingtheM&Cformulatoourdatabaseinthe receiveroperatingcharacteristic(ROC)analysis,wefoundan areaunderthecurve(AUC)of0.892(95%confidenceinterval: 0.879–0.904);asFigure1demonstratesthisAUCissignificantly (p-value<0.0001) lower than the threebest performing for-mulasinour studythat all hadAUCsaround 0.95.3 _Atthe

optimalcut-offof23.6,theM&Cindexresultedin0.854 sen-sitivity,0.795specificityand aYoudenindexof0.649.If we hadincludedtheM&Cindexinourstudy,thenitwouldhave

DOIoforiginalarticle:http://dx.doi.org/10.1016/j.bjhh.2016.05.011.

0 20 40 60 80 100

100 80 60 40 20 0

100-Specificity

S

en

si

tivi

ty

Figure1–Receiveroperatingcharacteristic(ROC)analysis

oftheMatos&Carvalho(M&C)index(black)incomparison

withtheJanel(green),Green&King(red)andJayabose

(blue)formulasfordifferentiatingirondeficiencyanemia

fromthethalassemiatrait.

ranked18outofthe26formulasinvestigated.Thisisinclear contrastwiththefindingsofMatosetal.,whoreported excel-lentdiagnosticaccuracyoftheirnewindex.However,itisnot atallunusualforauthorsofnewdiscriminantindicesto over-estimatetheperformanceoftheirinvention,asevidencedby independentvalidationstudies.3

revbrashematolhemoter.2017;39(3):288–289

289

geneticbackgrounds,sothisnumberofthalassemiapatients intheirstudymayhavebeentoolowtoproperlycharacterize thevariouscarriersubtypes;alternatively,thedisagreement maybeduetolocalcharacteristicsofthepopulationinthe area investigated. Secondly, Matoset al.excluded patients withconcomitantIDAandthethalassemiatrait;ithasbeen repeatedlydemonstratedthatthisconditioncausesmany dis-criminantformulastogiveanincorrectclassificationandby excluding this group, they may have introduced a bias in favoroftheirnewindex. If weexcludesuchpatientsfrom ouranalysis, the performanceofall discriminant formulas wouldincrease,butthiswouldnolongerrealisticallyreflect clinicalpractice,asapproximately5%ofpatientswith micro-cyticanemiasufferfromIDAassociatedwiththethalassemia trait.Thirdly, theM&C indexincludesthe mean corpuscu-larhemoglobinconcentration(MCHC),acalculatedparameter that isknown to haverelatively weak correlation between differenthematologyanalyzers.Althoughthetypeof hema-tologyanalyzerwasnotfoundtohavemuchimpactonthe performanceofdiscriminantfunctions,2_{apossiblerole}

can-notbeexcluded.Inthiscontext,itisofinterestthattheMCHC alonehasaverypoorperformancefordistinguishingIDAand thalassemia.2

In conclusion, we are unable to confirm the finding by Matosetal.thattheirnewM&Cindexhasexcellent perfor-mancefor discriminating iron deficiency anemia from the thalassemiatrait.Asamatteroffact,wedonotrecommend laboratoriesuseanynewlypublishedindexwithoutadditional validationintheirownpatientpopulation.

Conflicts

of

interest

JohannesHoffmannisascientificemployeeofAbbott Diag-nostics; Eloísa Urrechaga has no conflicts of interest to declare.

r

e

f

e

r

e

n

c

e

s

1.MatosJF,DusseLM,BorgesKB,deCastroRL,Coura-VitalW,

CarvalhoMdG.Anewindextodiscriminatebetweeniron

deficiencyanemiaandthalassemiatrait.RevBrasHematol

Hemoter.2016;38(3):214–9.

2.HoffmannJJ,UrrechagaE,AguirreU.Discriminantindicesfor

distinguishingthalassemiaandirondeficiencyinpatients

withmicrocyticanemia:ameta-analysis.ClinChemLabMed.

2015;53(12):1883–94.

3.UrrechagaE,HoffmannJJ.Criticalappraisalofdiscriminant

formulasfordistinguishingthalassemiafromirondeficiency

inpatientswithmicrocyticanemia.ClinChemLabMed.

2017;55[aheadofprint].Availablefrom:

https://www.degruyter.com/view/j/cclm.ahead-of-print/cclm-2016-0856/cclm-2016-0856.xml?format=INT.

JohannesJ.M.L.Hoffmanna_{, EloísaUrrechaga}b,∗ a_{GlobalMedicalandScientificAffairs,AbbottHematology,}

Hoofddorp,TheNetherlands

b_{HematologyLaboratory,HospitalGaldakao,Galdakao,Spain}

∗_{Corresponding author at: Hematology Laboratory, Hospital}

Galdakao-Usansolo,48960Galdakao,Vizcaya,Spain. E-mailaddress:eloisa.urrechagaigartua@osakidetza.net

(E.Urrechaga).

Received28March2017 Accepted24April2017 1516-8484/

©2017Associac¸ ˜aoBrasileiradeHematologia,Hemoterapiae TerapiaCelular.PublishedbyElsevierEditoraLtda.Thisisan openaccessarticleundertheCCBY-NC-NDlicense(http://

creativecommons.org/licenses/by-nc-nd/4.0/).

http://dx.doi.org/10.1016/j.bjhh.2017.04.003