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

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rev bras hematol hemoter. 2017;39(2):95–97

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

Revista

Brasileira

de

Hematologia

e

Hemoterapia

Brazilian

Journal

of

Hematology

and

Hemotherapy

Scientific

Comment

Human

platelet

antigens

and

primary

immune

thrombocytopenia

夽

Vagner

Castro

∗

UniversidadeEstadualdeCampinas(UNICAMP),Campinas,SP,Brazil

Primary immune thrombocytopenic purpura (ITP) is an acquiredimmune-mediated disorder characterizedby tran-sient or persistent decreased platelet count (<100×109/L)

that affects children and adults in the absence of other underlying causes.1,2 _The _low _platelet _count _results _from

plateletdestructionbyantiplateletautoantibodiesassociated tocausessuchasinsufficientplateletproduction,whichisalso relatedtotheseautoantibodies,andTcellimmune dysregu-lation(Figure1).2

Thepresenceoftheautoantibodiesmaybedemonstrated intheserumofapproximately70% ofITPpatients, usually directedagainstplateletsurfaceglycoproteins(Gp),suchas Gp IIb-IIIa,Gp Ib-IX and Gp Ia-IIa.2,3 _ITP _has_an _estimated

incidenceof5.8casesin100,000youngindividualswith sim-ilar distributionbetween genders,and 1.6 casesin100,000 middleagedindividualswithhigherratesamongwomen(1.9 females:1male).Thisconditionmaybeclassifiedaccording todurationasnewlydiagnosed(lessthan3months), persis-tent(3–12months)andchronic(morethan12months).1,2_The

clinicalfeaturesareusuallydifferentinchildrenandadults. Inchildhood, ITPusuallyhas anabrupt onset,often start-ing1–2weeksafteraviralinfectionoruptosixweeksafter vaccinations (generally the measles, mumps and rubella – MMRvaccination)withrecoverybeingspontaneousinaround 70–80%ofthecaseswithinafewweeksregardlessof ther-apy.In adults,the diseasehas aninsidiousonset,withno

DOIoforiginalarticle:http://dx.doi.org/10.1016/j.bjhh.2017.01.003. 夽

SeepaperbydoCarmoetal.inRevBrasHematolHemoter.2017;39(2):122–6.

∗ _{Correspondence}_to:_Platelet_Immunology_Laboratory,_Hematology_and_Hemotherapy_Center_–_Instituto_Nacional_de_Ciência_e_Tecnologia

doSangue–INCTS,UniversidadeEstadualdeCampinas(UNICAMP),RuaCarlosChagas,480–CidadeUniversitária“Prof.ZeferinoVaz”, DistritodeBarãoGeraldo,CEP:13083-878Campinas,SP,Brazil.

E-mailaddress:[email protected]

preceding illness and frequently it has a chronic course.4

ClinicalmanifestationsofITPare usuallyaconsequenceof theseverethrombocytopenialeadingtobleedingsymptoms. Hemorrhagic events are highlyheterogeneous but patients frequently present mild mucocutaneous bleeding.5,6 _Major

bleedingriskislowinpediatricpatientsbutinadults, addi-tionalmodifierssuchasexistingcomorbidities,age,activities andmedicationsmayaffecttheriskofsignificantbleeding.6

ThemaingoalofITPtreatmentistoraisetheplateletcountto controlbleedingsymptomsandtopreventmajorhemorrhage aswellastominimizetreatmenttoxicityandmaximize qual-ityoflife.6_The_treatment_is_rarely_indicated_when_the_platelet

countisabove20×109/Lintheabsenceofotherfactorssuch

asmajorbleeding.6 _First_line_therapy _is_generally _based_on

the use of corticosteroids with an initial response rate of approximately 80%orintravenousimmunoglobulin (IgIVor anti-DinRhpositivepatients),whenarapidincreaseinthe plateletcountisneeded,withatransientresponsein approx-imately 80% of cases.6 _When _the _patient _fails _to _respond

or relapses after first-line therapy, the second-line treat-mentusedgenerallyconsistsofimmunosuppressiveagents, rituximab, splenectomy and morerecently thrombopoietin receptorantagonists(TRA).2,6_TRA_{(romiplostim,}_eltrombopag)

arenewagentsthathaveveryhighefficacyandfewsideeffects butareexpensiveandstillneedtobeevaluatedoveralonger follow-up.6,7

http://dx.doi.org/10.1016/j.bjhh.2017.02.008

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revbrashematolhemoter.2017;39(2):95–97

Environmental factors (infections, vaccines, etc)

Genetic factors

(cytokine polimorphisms, HLA, HPA, etc)

Immune system cells (APC, T cells, B cells)

Surface glycoprotein (GpIIb-IIIa, GpIb-IX)

Platelets

Immune system dysregulation

Auto-antibody formation

Antibody mediated platelet destruction

Antibody mediated megakariopoiesis impairment

Figure1–SimplifiedrepresentationofITPmechanisms.Immunedysregulationcausedbyenvironmentalfactors,suchas viralinfectionsandvaccines,associatedtogeneticfactors(cytokinepolymorphisms,HLA,HPA,etc.)resultsinautoantibody productionthatmainlyrecognizesurfaceglycoproteinssuchasGpIIb-IIIa,GpIb-IXandGpIa-IIawhicharepresentonthe surfaceofplateletsandmegakaryocytes.Theseautoantibodiesleadtoplateletdestructionanddecreasedplatelet production,resultinginthrombocytopeniaandbleedingsymptoms.

Althoughthecomprehensionofthiscomplexautoimmune disorderhasdevelopedgreatlysinceitsfirstdescriptioninthe middleoflastcentury,8_mechanisms_and_factors_leading_to_ITP

arenotyetfullyunderstood.2,6_{Environmental}_and_genetic

fac-tors,suchascytokinegenepolymorphisms,humanleukocyte antigens(HLAs)andhumanplateletantigens(HPAs)seemto playarole.9–12_HPAs_are_{polymorphisms}_of_platelet_surface_Gps

whichresultinalloantigenexpression,leadingto alloimmu-nizationmainlyaftertransfusionsandpregnancies.13_These

polymorphismshaveheterogeneousdistributionin popula-tionswithdistinctethnicbackgroundsandespeciallyHPA-2 andHPA-5havebeendescribedtobepossibleriskfactorsin thedevelopmentofITP.10,11,14,15 _In_this_issue,_Carmo_et_al.16

haveevaluatedtheassociationofHPAsandchronicITP(cITP) inasmall groupofpatientsfrom theAmazonianregionof Brazil, which has a population with a particular HPA dis-tributioncomparedtotheBrazilianpopulationingeneral.17

It isimportant to note that ITP is not a common disease andit isdifficultforasinglecenterstudy toenrolla large numberofpatients.Theauthorsfoundahigherincidenceof theHPA-1a,HPA-3bandHPA-5ballelesincITPcomparedto healthyblooddonorsfromthesameregion,buttheyfound no involvement of HPA-2 in this group of patients. These resultsdifferfrom dataobtainedinother studiesinwhich theHPA-1andHPA-3systemsseemtohavenoassociation withITP inthe populations studied, but HPA-2 and HPA-5 wereassociated.10–12,15 _The_mechanisms_that_explain_these

associationsarenotknownyet.AlthoughCarmoetal.16

eval-uatedasmallgroupofpatientsfromasinglecenter,theresults areinterestingandfurtherenhancetheconceptthatITPisa

complexautoimmunedisorder withmechanismsthatneed extensive efforttounderstand betterandprovide newand moreefficienttreatmentpossibilities.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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