Rev. Bras. Hematol. Hemoter. vol.37 número3

rev bras hematol hemoter. 2015;37(3):148–149

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

Revista

Brasileira

de

Hematologia

e

Hemoterapia

Brazilian

Journal

of

Hematology

and

Hemotherapy

Scientific

Comment

Fetal

hemoglobin

and

hemolysis

markers

in

sickle

cell

anemia

夽

Marina

Pereira

Colella

_,

_Fabíola

_Traina

a_{UniversidadeEstadualdeCampinas(Unicamp),Campinas,SãoPaulo,Brazil}

b_{UniversidadedeSãoPaulo(USP),RibeirãoPreto,SãoPaulo,Brazil}

Ithasbeenknown formanyyears thathigh levelsoffetal

hemoglobin (Hb F) have an important clinical benefit in

patientswithsicklecell anemia(SCA).Thisknowledgewas

initiallybasedontheobservationthatpopulationsofIndian

andArabianSCApatientswithhighHbFlevelshaveamilder

clinicalformofthedisease.1_{Lateron,epidemiological}

stud-iesdemonstrated that patientswithHb Flevelsabove20%

hadconsistentlylowerratesofrecurrentclinicaleventssuch

as vaso-occlusive crises, acute chest syndrome and

hospi-talizations, and patients with Hb F levels above 10% had

reducedoccurrenceofasepticnecrosisand strokes.2 _A

sig-nificantincreaseof1.0g/dLinhemoglobinlevelsinthehigh

HbFgroupwasalsonoted,indicatingareductionintherate

ofhemolysis.2_{Astudyoflifeexpectancyinsicklecelldisease}

(SCD)patientsdemonstratedanimprovedsurvivalofpatients

withHbFlevelsabove8.6%andanincreasedriskofearlydeath

inpatientswithlowHbFlevels.3

ThepresenceofHbFinredbloodcells(RBCs)alterscontact

betweenRBCswithhemoglobinS(HbS)andinhibitsthe

for-mationofpolymersindeoxygenatedRBCs.HbFisproduced

byafractionofRBCsdenominatedF-cells,whichcontain

vari-ableconcentrationsofHbF.4_{StudiessuggestthatwhenF-cells}

containaround10pgofHbFthereiscompleteinhibitionof

polymerformationevenwhenoxygensaturationisfrom40%

to70%.5 _{F-cellsare RBCs thathaveamuchlonger survival}

thannon-F-cells,withtheirsurvivalbeingrelatedtotheirHb

Fcontent:thehighertheHbFcontentthelongerthelifespan

ofF-cells.6_{Thesurvivalofnon-F-cellsisinverselycorrelated}

DOIoforiginalarticle:http://dx.doi.org/10.1016/j.bjhh.2015.01.008.

夽

SeepaperbyMoreiraetal.onpages167-81.

∗ _{Correspondingauthorat:UniversityofSãoPauloatRibeirãoPretoMedicalSchool,Av.Bandeirantes,3900,14049-900RibeirãoPreto,}

SP,Brazil.

E-mailaddress:[email protected](F.Traina).

tothe percentageofF-cells,possiblybecausepatientswith

higherHbFlevelshavebetterspleenfunctionandthushave

moreefficientremovalofnon-F-cellsfromthecirculation.

In the current issue of the Revista Brasileira de

Hema-tologiaeHemoterapia,thereisanarticleentitled“Patternof

hemolysisparametersandassociationwithfetalhemoglobin

in sickle cell anemia patients in steady state” by Moreira

et al.7 _{In this article the authors demonstrate the}

benefi-cial effects of elevated Hb F levels on hemolysis markers

inSCApatients. Whenpatients achievedHb Flevelsabove

10%theypresentedwithsignificantreductionsinreticulocyte

countsandlactatedehydrogenase(LDH)levels.Thisincrease

inHbFlevelswasachievedbytreatmentusinghydroxyurea

atdosesthatrangedfrom0.5to1.5g/day.Reductionofthe

rate ofhemolysisinSCApatients isofvitalimportancein

theprognosisofthesepatients. Anobservational

multicen-ter study of415 SCA patients who were followed-up fora

medianof2.4yearsreportedthatpatientswithanhemolytic

component (assessed bymeasuring LDH, aspartate

amino-transferase,totalbilirubinandreticulocytecount)intheupper

tertilepresentedoverthreetimesgreaterriskofdeath

(Haz-ard ratio of3.44).8 _{Furthermore, the hemolytic component}

waspositivelyassociatedwithhighersystemicpulsepressure,

serumN-terminalpro-brainnatriureticpeptide(NT-proBNP)

concentration, tricuspid regurgitation velocity and several

othercardiacsideeffects.8_{Therewasalsoaninverse}

correla-tionbetweentherateofhemolysisandoxygensaturationas

measuredbypulseoximetry,whichpersistedafteradjustment

http://dx.doi.org/10.1016/j.bjhh.2015.03.015

1516-8484/©2015Associac¸ãoBrasileiradeHematologia,HemoterapiaeTerapiaCelular.PublishedbyElsevierEditoraLtda.Allrights

revbrashematolhemoter.2015;37(3):148–149

149

forhemoglobinconcentration;patientsonhydroxyurea

ther-apypresentedasignificantlylowerhemolyticcomponent.8

Moreiraetal.7_{alsodemonstratedthathydroxyurea}

ther-apyandsubsequentelevationofHbFlevelswasassociated

toreductionsinarginaseIlevels.ThelowestarginaseI

lev-elswereseeninpatientstakinghydroxyureaatdosesgreater

than20mg/kg/day.ArginaseIisanenzymethatmetabolizes

l_{-arginine,theprecursorofnitricoxide(NO).Therefore,the}

increasedlevelsofarginaseIseeninSCApatientscontributeto

areductioninNOconcentration.Thefindingsofthisstudyare

inagreementwithapreviousstudyinwhichSCDpatientson

hydroxyureatherapy presentedsignificantlylower arginase

activityandhigherNOsynthaseactivity;adirectcorrelation

between Hb F levels and the decrease in arginase activity

wasalsoobserved.9 _{Theseimportantfindings indicatethat}

hydroxyureamayhaveabeneficialeffectinreducingarginase

IlevelsandintheproductionofNO.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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1.PerrineRP,PembreyME,JohnP,PerrineS,ShoupF.Natural historyofsicklecellanemiainSaudiArabs.Astudyof270 subjects.AnnInternMed.1978;88(1):1–6.

2.PowarsDR,WeissJN,ChanLS,SchroederWA.Istherea thresholdleveloffetalhemoglobinthatamelioratesmorbidity insicklecellanemia?Blood.1984;63(4):921–6.

3.PlattOS,BrambillaDJ,RosseWF,MilnerPF,CastroO,Steinberg MH,etal.Mortalityinsicklecelldisease.Lifeexpectancyand riskfactorsforearlydeath.NEnglJMed.1994;330(23): 1639–44.

4.SteinbergMH,ChuiDH,DoverGJ,SebastianiP,AlsultanA. Perspectives.Fetalhemoglobininsicklecellanemia:aglass halffull?Blood.2014;123(4):481–5.

5.Maier-RedelspergerM,NoguchiCT,deMontalembertM, RodgersGP,SchechterAN,GourbilA,etal.Variationinfetal hemoglobinparametersandpredictedhemoglobinS polymerizationinsicklecellchildreninthefirsttwoyearsof life:ParisianProspectiveStudyonSickleCellDisease.Blood. 1994;84(9):3182–8.

6.FrancoRS,YasinZ,PalascakMB,CiraoloP,JoinerCH, RucknagelDL.Theeffectoffetalhemoglobinonthesurvival characteristicssicklecells.Blood.2006;108(3):1073–6.

7.MoreiraJA,LaurentinoMR,MachadoRP,BarbosaMC,

Gonc¸alvesRP,MotaAM,etal.Patternofhemolysisparameters andassociationwithfetalhemoglobininsicklecellanemia patientsinsteadystate.RevBrasHematolHemoter. 2015;37(3):167–71.

8.NouraieM,LeeJS,ZhangY,KaniasT,ZhaoX,XiongZ,etal. Therelationshipbetweentheseverityofhemolysis,clinical manifestationsandriskofdeathin415patientswithsickle cellanemiaintheUSandEurope.Haematologica.

2013;98(3):464–72.

9.IyamuEW,CecilR,ParkinL,WoodsG,Ohene-FrempongK, AsakuraT.Modulationoferythrocytearginaseactivityinsickle celldiseasepatientsduringhydroxyureatherapy.BrJ