Rev. Bras. Hematol. Hemoter. vol.39 número4

revbrashematolhemoter.2017;39(4):354–356

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

Revista

Brasileira

de

Hematologia

e

Hemoterapia

Brazilian

Journal

of

Hematology

and

Hemotherapy

Case

Report

Recurrent

thromboembolism

after

splenectomy

in

a

patient

with

complex

hemoglobin

disease:

a

case

report

Laura

Maria

Silva

Thiersch

_,

_André

_Rolim

_Belisario

_,

_Suely

_Meireles

_Rezende

a_{UniversidadeFederaldeMinasGerais(UFMG),BeloHorizonte,MG,Brazil}

b_{Fundac¸ãoHemominas,BeloHorizonte,MG,Brazil}

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Articlehistory:

Received27October2016 Accepted24April2017 Availableonline17May2017

Introduction

Somehematologicaldiseasescanbenefitfromsplenectomy foreitherdiagnosisortreatment.Whendealingwithpatients with thalassemia, splenectomy is a common therapeutic option,particularlyindicatedwhenthepatienthasincreased transfusiondemand,symptomaticsplenomegalyoranysigns ofpoorhealth,leucopenia,andthrombocytopenia.1_However,

splenectomycanleadtothromboembolicevents,particularly insplenectomizedpatientswiththalassemia intermedia.1,2

Thromboemboliccomplications insplenectomizedpatients withcomplexhemoglobindiseasesareseldomreporteddue totherarityoftheseconditions.Wethereforereportacaseofa womanwithhemoglobin(Hb)C/␤0-thalassemiaandrecurrent venousthromboembolismaftersplenectomy.Thepatientand allfamilymemberssignedaconsentform.

∗ _{Correspondingauthorat:DepartmentofInternalMedicine,FacultyofMedicine,UniversidadeFederaldeMinasGerais(UFMG),AvAlfredo}

Balena,190,2ndfloor,Room243,30130-100BeloHorizonte,MG,Brazil.

E-mails:srezende@medicina.ufmg.br,suely.rezende@uol.com.br(S.M.Rezende).

Case

report

Aforty-year-oldwomanwasreferredtothehematologyclinic withmild microcytichypochromic anemiaand thrombocy-tosis. Her blood film revealed anisocytosis, poikilocytosis, microcytosis,hypochromia,stomatocytes,targetcells, eryth-roblastsandmacroplatelets(Figure1).

Shereportedafamilyhistoryofthalassemiaandapersonal historyofsplenectomyin2001duetoapainfulsplenomegaly. Shedeniedtransfusion-dependency.In2002,shesuffereda pulmonaryembolism,which recurredin2003.In2004,she hadadeepvenousthrombosisofherrightlowerlimb.This hadoccurredthreedaysafteralaparoscopictubal steriliza-tionprocedure,whenwarfarinwassuspendedforfourdays before surgery.All thromboembolic eventswere objectively confirmed.

http://dx.doi.org/10.1016/j.bjhh.2017.04.006

revbrashematolhemoter.2017;39(4):354–356

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Figure1–Bloodfilmoftheproband.Bloodfilmshowing anisocytosis,poikilocytosis,microcytosis,hypocromia, stomatocytes(arrows),targetcells(smallarrows), erythroblasts(cross)andmacroplatelets.

In2005,aDopplerechocardiographyrevealedpulmonary hypertension with an estimated pulmonary pressure of 53mmHg.Finally,in2007,shewasdiagnosedwithcongestive heart failure (New York Heart Association III/IV). Throm-bophiliascreeningwasperformed,revealingabsenceofthe prothromboticmutations:factorVLeidenandprothrombin G20210A.Antiphospholipidantibodieswerealsoabsent.She isunderanticoagulationwithwarfarinindefinitelyandsince thenshehasnotpresentedanythromboembolicevent.

DNAanalysisrevealedacompoundheterozygosityforHbC (HBB:c.19G>A)/␤0-thalassemia(HBB:c.118C>T).Afamilystudy wascarriedout (Figure2).Herfatherwasheterozygousfor HBB:c.19G>A(I-1–Figure2).Hewasasymptomaticwith unre-markableblood countandfilm.Hermother (I-2– Figure2)

I

II

_∗

∗

∗

∗

III

Heterozygous Hb C Beta-thalassemia

Figure2–Pedigreeofthefamily.Moleculargenetic analyseswereperformedforsixfamilymembers.The arrowheadindicatestheproband(II-1).*Indicatesmembers inwhombloodwasnotcollected.Themutationcausing heterozygous␤0-thalassemiawasCD39(HBB:c.118C>T).

andoneofherdaughters(III-2–Figure2)wereheterozygous forHBB:c.118C>T.Liketheproband,twosistersalsocarried HbC/␤0-thalassemia (II-3andII-4 –Figure2).Theyreported transfusionsonlyduringlabor,butdeniedsplenectomyand neverhadathromboembolicevent.Theirbloodcountshowed mildmicrocytichypochromicanemia.

Discussion

Thalassemiaitself,especially␤-thalassemiaintermedia,isa well-knowncauseofahypercoagulablestatedueto abnormal-itiesinvolvingplatelets,redbloodcells(RBC),endothelialcells andthrombinactivation.3,4,5_{Otherhemostaticchangesmay}

includealterationsinthelevelsofprocoagulantor anticoagu-lantfactors,and/orchronicactivationofendothelialcells,or whitebloodcells.4_{Splenectomymayalsoincreasetheriskof}

thrombosis.1,2

Patientswith␤-thalassemiahavechronicplatelet activa-tion,increasedplateletaggregation,expressionofCD26Pand CD63and shortenedplatelet lifespan related toenhanced consumption.5 _{Moreover, there are major RBC alterations}

due to the formation and precipitation of hemichromes, presence of reactive oxygen species and an increased thrombin generationrelatedtotheexpressionof procoagu-lant negatively-chargedphospholipids onthe RBCsurface.2

Indeed,lossofthehemocathereticfunctionofthespleenleads toanincreasednumberofabnormalcirculatingRBCs,which arecapableofgeneratingthrombin.6 _{Thisexplainswhythe}

lackofregulartransfusionsincreasestheriskofthrombosis.5

The patient reported herein had three thromboembolic events, two unprovoked pulmonary embolisms and a pro-vokeddeepvenousthrombosis.Splenectomizedpatientswith thalassemia with high RBC counts, thrombocytosis, pul-monaryhypertensionandtransfusionnaivetyareathigher risk to develop thromboembolic events.1 _{This patient had}

all these risk factors. Due to the occurrence of recurrent thrombosisandtothedescribedriskfactorsforthrombosis, a long-term secondary prophylaxiswith warfarin was rec-ommendedwithatargetinternationalnormalizedratio(INR) between2and3.Thiswashighlyeffective,asshehasnothad anythromboticeventssince.

Oneimportantquestionwhileattendingpatientswith tha-lassemiaand highthrombotic riskishow tomanagethem whileinhigh-risk situationsforthrombosissuchasbefore splenectomy,immobilizationandhospitalization?Sincehigh quality evidence for recommending thromboprophylaxis is lacking,wemanagepatientswiththalassemiasimilartothe generalpopulation.Therefore,furtherstudiesonthisissueare warranted.

Conclusion

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in patients with hemoglobin diseases before they indicate splenectomy.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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2.CappelliniMD,RobbioloL,BottassoBM,CoppolaR,FiorelliG,

MannucciPM.Venousthromboembolismand

hypercoagulabilityinsplenectomizedpatientswith thalassemiaintermedia.BrJHaematol.2000;111(2):467–73.

3.TaherAT,OtrockZK,UhtmanI,CappelliniMD.Thalassemia andhypercoagulability.Blood.2008;22(5):283–92.

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Hipercoagulabilityinnon-transfusion-dependentthalassemia. BloodRev.2012;26(1):S20–3.