Rev. Bras. Hematol. Hemoter. vol.38 número3

rev bras hematol hemoter. 2016;38(3):271–273

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

Revista

Brasileira

de

Hematologia

e

Hemoterapia

Brazilian

Journal

of

Hematology

and

Hemotherapy

Case

Report

Transient

red

cell

aplasia

in

two

brothers

with

sickle

cell

anemia

and

erythrovirus

B19

infection

Marina

dos

Santos

Brito

Silva

Furtado

_,

_Marina

_Lobato

_Martins

_,

Rosângela

Maria

de

Figueiredo

_,

_Marcos

_Borato

_Viana

a_{Fundac¸ãoHemominas,BeloHorizonte,MG,Brazil} b_{HospitalInfantilJoãoPauloII,BeloHorizonte,MG,Brazil} c_{UniversidadeFederaldeMinasGerais,BeloHorizonte,MG,Brazil}

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Articlehistory:

Received26March2016 Accepted11April2016 Availableonline2May2016

Introduction

Erythrovirus B19 (B19V), a member of Parvoviridae family, genusErythrovirus,isasmallnon-envelopedDNAvirus,with approximately5000nucleotides.Therearethreedistinct geno-types(1,2and3)withgenotype1beingthemostprevalentin theworld.1

B19Vinfectionisassociatedwithmanyclinical manifes-tations,dependingontheimmunologicalandhematological statusofthepatient.Thevirushastropismforbonemarrow erythroblasts,onwhichitexertsacytotoxiceffectand deter-minestemporarysuspensionoferythropoiesis,leadingtoa transientepisodeofredcellaplasia.2

Insicklecellanemia(SCA)patients,B19Visknowntobe theetiologicagentoftransientaplasticcrises.3 _Manyother complicationsmaybeassociatedwithB19Vinfection,suchas acutesplenicsequestration4,5_{andacutechestsyndrome.}6

ThediagnosisofB19Vinfectioncanbeachievedby detec-tinganti-B19Vantibodiesorbymolecularbiologytechniques that allow the identification ofthe viral DNA using direct

∗ _{Correspondingauthorat:Al.GuilhermeHenriqueDaniel,94/206,0220-200BeloHorizonte,MG,Brazil.} E-mailaddress:[email protected](M.B.Viana).

hybridizationorpolymerasechainreaction(PCR),orevenby directidentificationofthevirusbyelectronmicroscopy.7

TheB19Vseroprevalenceincreaseswithageandcanvary from2to15%inunderfive-year-oldchildren,15to60%for individualsagedsixto19years,between30and60%inadults, andupto85%intheelderlypopulation,8_{bothindeveloped} anddevelopingcountries.9

Inastudy of278childrenwithsicklecelldisease (SSor S␤0-thalassemia,medianage5.8years;range:0.9–12.3years), ithasbeenshownthatpastorrecentviralinfectionoccurred in29.5% (95%confidenceinterval:24.1–34.9%).5 _Thisreport describestheclinicalcourseandthelaboratorytestsoftwo siblingsselectedtoparticipateinthatcohort.

Case

reports

A10-year-oldmale(LLS)withhomozygousSS,hadbeen reg-ularlyfollowedupintheoutpatientclinicoftheBloodCenter inBeloHorizontesincethediagnosisofSCAbytheNewborn ScreeningProgramofMinasGerais,Brazil.Hewasadmittedto

http://dx.doi.org/10.1016/j.bjhh.2016.04.004

272

Table1–Bloodcountsduringtransientaplasticcrisesin twosiblingswithsicklecellanemia.

Sibling1 Sibling2

Ageataplasticcrisis(years) 10 12

Gender M M

Genotype SS SS

Atadmission(Day1)

Hemoglobin(g/dL) 5.4 3.4 Hematocrit(%) 16 11.3 Leukocytes(×109/L) 3.5 9.2

Neutrophils(%) 86 54 Reticulocytes(%) Notdone* _Notdone*

Platelets(×109/L) “Normal” 301

Day2

Hemoglobin(g/dL) 6.0 4.5

Hematocrit(%) 19.9 14

Leukocytes(×109/L) 5.2 6.6

Neutrophils(%) 58 38

Reticulocytes(%) 0.3 0.1

Platelets(×109/L) 240 282

Day4

Hemoglobin(g/dL) 5.6 Notdone

Hematocrit(%) 17.4 Notdone

Leukocytes(×109/L) 7.2 Notdone

Neutrophils(%) 16 Notdone

Redcelltransfusion 10mL/kg

(Days2and5)

10mL/kg (Days1and3)

Hospitaldischarge Day6 Day4

∗ _{Reticulocytecountsarenotpartoftheroutinetestsperformedin}

thehospitallaboratory;countsontheseconddayofadmission wereperformedintheHemominaslaboratory.

theemergencyroomoftheJoãoPauloIIChildren’sHospitalin BeloHorizontewithahistoryofbackpain,headacheandfever ofupto38.7◦_{Cfortwodayspriortoadmission.Physical}

exam-inationrevealedaheartrateof90bpmandliver3cmbelow thecostalmargin,spleennotpalpableandanicteric.Onthe dayofadmission,hehadtwoepisodesofvomiting,andslurry evacuation.Respiratorysymptomswereabsent.Lowbackpain subsidedthesamedayandtheheadachebecame intermit-tent.Thevomitinganddiarrhearecededthe followingday. Ampicillinwasinitiateduponadmissionbutwasdiscontinued thenextday,sincetherewasnofeverorothersymptomsof bacterialinfection,andradiographicevaluationshowedthat chestandfacewerenormal.BloodcountsareshowninTable1. Beforethehospitaladmission,thispatienthadbeen ran-domly selected for a research study aiming to investigate B19VinfectioninchildrenwithSCA,aspreviouslymentioned. His serum sample had been drawn 16 months before the transientbonemarrowhypoplasiaevent.Inthatsampleno anti-B19Vantibodies(IgGorIgMclass–Biotrin,Ireland)had been detected, nor had viral DNA byquantitative PCR (in-housetest).Oneyearaftertheepisodeoferythroidhypoplasia anew serum sampleofthe patientwas drawn,as recom-mendedbythestudy.Thissamplewaspositiveforanti-B19V IgGantibodiesandnegativeforIgMantibodiesandviralDNA. A 12-year-old male (ALS), sibling of “Case 1”, was also regularly followed up in the outpatientclinic at Fundac¸ão HemominassincethediagnosisofSCAinthenewbornperiod.

Thepatientwasadmittedtothesamehospital13daysafter his brother. Before hospital admission, his symptoms had beenheadacheandrunnynosewithoutfeverforoneweek. They subsidedspontaneously, but afterthreedays,he pre-sentedaheadacheassociatedwithvomitingandafeverpeak of38.7◦_{C.Ibuprofenwasprescribedatagovernmenthealth}

clinicandthesymptomsreceded.Onedaypriortohospital admission,heagainhadheadachesassociatedwithpainin thecervicalspineandvomiting.Hismotherreportedthatthe degreeofherson’spallorhadclearlyincreased.Atadmission, hewas slightly dehydrated,severely paleand mildly jaun-diced.Heartandrespiratoryrateswere110bpmand26breaths per minute,respectively;blood pressurewas110/70mmHg, hisliver was7cmfrom the costalmargin, and spleenwas notpalpable.BloodcountsarealsoshowninTable1. B19V DNAwasdetectedbyrealtimePCR,andtypedasgenotype1 (Figure1).

Comments

B19Vinfectioncausessignificantmorbidityinchildrenwith SCA. Althoughstudies have been reported on the subject, therearestilllimiteddataontheepidemiologyofthis infec-tion,aswellasthecomplicationsassociatedwithit.

IntrafamilialtransmissionofB19Vinfectionisconsidered animportanteventforviralspread.Ithasbeendemonstrated thatthesingleriskfactorforB19Vseroconversioninachild wasthepresenceofsiblingswitharecentB19Vinfection(odds ratio:2.97;95%confidenceinterval:1.29–6.81).2_Therateof sec-ondaryinfectioninfamilieswithtwoormorechildrenwith sicklecelldiseasewas56.3%.

Itisknown that thevast majorityofchildrenwithSCA whohaveserologicevidenceofpreviousB19Vinfectionhad not developed symptomatic aplastic crisis,10 _{as was also} demonstratedbyourrecentcohortstudy.5_{Differentdegrees} ofbaselinehemoglobinconcentration,virusload,virus geno-typesorotherunknownfactorscouldexplainthisobservation, althoughgenotypeandvirusloadwerethesameinboth chil-drenduringanosocomialB19Voutbreak,onechildwithvery severemanifestationsandtheotherwithanasymptomatic course.11_{Itisinterestingtonotethatthediagnosisofacute} transientaplasticcrisisinchildrenwithSCAwhoarebeing treatedwithhydroxyureaisnotdifferenttothosewhoarenot beingtreatedwithhydroxyurea.Theclinicalcoursewasvery similar,relapsingorchronicB19Vinfectionwasnotobserved, and the production of B19V-specific immunoglobulins was apparentlynormal.12

Inconclusion,ourreportsuggeststhathostimmunologic background may play a significant role in the pathogene-sisand clinical courseofaplasticcrisessecondary toB19V infection, asboth brothers showed life-threatening clinical manifestations.Sinceserologicalandmoleculartestsarenot alwaysavailable,thereticulocytecountisessentialwhen tran-sientbonemarrowhypoplasiacausedbyB19Vissuspected,so thatpropersupportivecarecanbeimmediatelystarted.

Conflicts

of

interest

revbrashematolhemoter.2016;38(3):271–273

273

1.0e+001

1.0e+000 CT

Threshold

1.0e–001

Delta Rn

Delta Rn vs cycle

1.0e–002

1.0e–003

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Cycle number

17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40

Figure1–In-houserealtimepolymerasechainreactionassayusingspecifichydrolysisprobestodetecterythrovirusB19 genotypes1,2,and3.Positiveamplificationforgenotype1(blackline)wasdetectedinCase2.Thehorizontalgreenline representsthethresholdforpositivity.Intersectionofthislinewiththeblackline(arrow)indicatesthecycleamplification threshold(Ct)value.TheearlyCt=12pointsforahighvirusload.Fluorescentsignalsbelowthethresholdindicatenegative resultsforgenotypes2and3.

Ethical

approval

ThestudywasapprovedbytheHumanEthicsCommitteeon ResearchofFundac¸ãoHemominasandUniversidadeFederal de MinasGerais. Itwas conductedin accordance withthe Helsinki Declarationasrevised in2008. Childrenand their parentssignedaninformedconsentform.

Funding

Conselho Nacional de Desenvolvimento Científico e Tec-nológico,Brazil(CNPq),NúcleodeAc¸õesePesquisaemApoio Diagnóstico,Brazil(Nupad),Fundac¸ãodeAmparoàPesquisa doEstadodeMinasGerais,Brazil(Fapemig).

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