Rev. Bras. Hematol. Hemoter. vol.38 número2

revbrashematolhemoter.2016;38(2):163–165

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

Revista

Brasileira

de

Hematologia

e

Hemoterapia

Brazilian

Journal

of

Hematology

and

Hemotherapy

Case

Report

Immune

thrombocytopenia

associated

with

pleural

and

pericardial

tuberculosis:

case

report

João

Madaleno

,

António

Fernandes

,

Joana

Cochicho

,

Nuno

Silva

,

Armando

Carvalho

a_{CentroHospitalareUniversitáriodeCoimbra,Coimbra,Portugal}

b_{SchoolofMedicine,UniversidadedeCoimbra,Coimbra,Portugal}

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Articlehistory:

Received5January2016 Accepted7February2016 Availableonline8March2016

Background

Tuberculosis (TB) remains a major global health problem, responsiblefortheillhealthofmillionsofpeopleeachyear, and ranks as the second leading cause of death from an infectiousdiseaseworldwide.1_{Avarietyofclinical} manifes-tationsare associateddirectlyorindirectlywithTB.Among them, hematological abnormalities can be found in both the pulmonary and extrapulmonary forms of the disease, andthoughamyriadofhematological disordershavebeen described,anemia, leukocytosis, and pancytopenia are the mostfrequentlycited.2_{Thrombocytopeniaisusually} associ-atedwithdisseminatedormiliaryTBandwhenitoccurs,it doessomostcommonlyvianon-immunologicmeans, typi-callymanifestinginthecontextofpancytopeniathatdevelops secondarytogranulomatousinfiltrationofthebonemarrow.3 Acausal association between TBand immune thrombocy-topenia(ITP)is extraordinarilyrare and,toour knowledge,

∗ _{Correspondingauthorat:CentroHospitalareUniversitáriodeCoimbra,PracetaProf.MotaPinto,3000-075Coimbra,Portugal.}

E-mailaddress:[email protected](J.Madaleno).

thisisthefirstdocumentedcaseofpleuralandpericardialTB andITP.

Case

report

60-year-old,previouslyhealthy,Caucasian,malewitha his-tory of well-controlled hypertension was admitted to the EmergencyRoomwithnew-onsethematuriaandgeneralized purpuric lesions. He also described a two-week history of fever,drycough,shortnessofbreathandpleuriticchestpain. Thepatientwaswellnourished,withgeneralizednontender, nonpalpablepurpuriclesions,mostevidentinthe extremi-ties and trunk.He had anauricular temperatureof37.8◦_C andarespiratoryrateof22breaths/min.Hisbloodpressure andpulsewere,respectively,109/60mmHgand110beats/min whilesupine. Breathsounds were diminishedon the right side and the remainder of the physical examination was normal.

http://dx.doi.org/10.1016/j.bjhh.2016.02.002

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Theinitialcomplete bloodcountrevealed awhite blood cell(WBC)countof9.8×109/Lwith75.4%granulocytes,13.1% lymphocytes, 11.1%monocytes, 0.3%eosinophils,and 0.1% basophils,hemoglobinof10.8g/dLwithameancorpuscular volume(MCV)of85.6flandameancorpuscularhemoglobin (MCH)of30.0pg,andplateletcountof2.0×109/L.A periph-eral smear was remarkable for a paucityof platelets. The findings ofblood chemistries were normaland the follow-inglaboratorystudieswerenormalornegative:prothrombin time/partialthromboplastintime,fibrinogen,fibrin degrada-tionproducts(FDP),antinuclearantibodies(ANA),rheumatoid factor,hepatitisC(HCV)andhumanimmunodeficiencyvirus (HIV).Anti-plateletantibodieswerenottested.AchestX-ray demonstrated bilateral pleuraleffusions, more pronounced on the right, a large heart shadow and clear lung fields. Computed tomographyofthe chest revealed massiveright pleural effusion and a large pericardial effusion. M-mode and2Dtransthoracicechocardiogramrevealedanorganized moderate-level anterior and posterior pericardial effusion, withoutrightventricularcollapse.

ThepatientwasadmittedtotheHematologyClinicwhere he started a 5-day course of intravenous immunoglobulin (IVIg), followed by oral corticosteroid therapy with pred-nisone(1mg/kg/dayorally).Theplateletcountincreasedto 243×109/Landplatelettransfusionswerenotrequired.

Hewas then transferred toour department to evaluate the pleural and pericardial effusions. A laboratory evalua-tionrevealedanormalWBCcount,normocyticnormochromic anemia and normal platelet count. The erythrocyte sedi-mentation rate (ESR) was elevated at 88mm/h. The result oftuberculinskintestwaspositive(22mm).Athoracentesis was then performed, and the pleural fluid revealed glu-cose37mg/dL,protein4.4g/dL,lactatedehydrogenase(LDH) 890U/L, adenosine deaminase (ADA) 90.1U/L, with a WBC count of 8.0×109/L including 66% of lymphocytes and no malignant cells. Pleuralfluid acid-fast bacilli (AFB) smears werenegativebutreal-timepolymerasechainreaction(PCR) forthedetection ofMycobacterium tuberculosiscomplexwas positive, posteriorly confirmed by cultures of pleural fluid withtheidentificationofM.tuberculosis.Isoniazid,rifampin, pyrazinamide,andethambutolwerestartedimmediatelyand the patient was discharged three weeks after admission. Prednisonewastaperedovereightweeksandstopped.Four monthsafterdischarge,thepatient,whowasinstablehealth andwithaplatelet countof253×109/L,wasfoundtohave abnormalliverenzymeswithacholestaticpattern,thought tobesecondarytoanti-tuberculoustherapy (ATT).Doppler ultrasonographyofthelivershowedhepatomegaly(176mm), dilatedinferiorvenacavaandhepatic veins,withturbulent flowevidencedbycolorDopplerandapulsatilewaveformon pulsedDoppler, suggestingright-sided heartfailure. Aliver biopsy wasperformed whichrevealed sinusoidal dilatation andcongestion,withnogranulomasandnoevidenceofAFB ormalignantcells.Culturesoftheliverspecimenwerenot per-formed.Forfurtherclarification,cardiacmagneticresonance imagingwas thencarriedout whichrevealedthickening of thepericardium(6mm)withsignsofconstriction,butwithout evidenceofpericardialeffusion,andthepatientunderwent pericardiectomy.Thrombocytopeniadidnotrecurduringthe follow-up.

Discussion

ITPisanautoimmunedisordercharacterizedbyimmunologic destruction ofotherwise normal platelets mostcommonly occurring inresponse toanunknown stimulus.Classically it occurs as one oftwo forms: a childhood varietythat is acute,withoutgenderpredilection,post-viralandself-limited, and the adultform thattends tobe chronic.It may occur inisolation(primary)orinassociationwithother disorders (secondary), including autoimmune diseases (particularly antiphospholipidantibodysyndrome),viralinfections (includ-ingHCVandHIV),andcertaindrugs.ThediagnosisofITPis madebyexclusionofsecondarycausesofthrombocytopenia astherearenodiagnosticteststoconfirmITP,andingeneral, bonemarrowexaminationorassayofanti-plateletantibodies arenotneededfordiagnosisiftypicalfeaturesarepresent.In fact,anti-plateletantibodieswerelabeledasan‘unnecessary’ testfortheroutineevaluationofpatientspresentingwithITP accordingtothe2011guidelinesoftheAmericanSocietyfor Hematology,andtheinitialhistoryandphysicalexamination should aimatidentifyingevidenceofbleedingand exclud-ing other causes ofthrombocytopenia including secondary ITP.4_{TheassociationbetweenTBandITPisexceedinglyrare,} withfewcasesreportedintheworldliterature.3_Animmune basisforTB-inducedITPwassupportedbythe presenceof eitherplateletantigenspecificantibodiesorplateletsurface membraneIgGinthreereportsandbyasalutaryresponseto immunomodulating treatments,asobservedinourpatient. However,somecasesfailedtoachieveacompleteresponseto immunomodulatingtherapiesalone,whichwasonlyobtained after ATT was started, supporting the etiologic role ofTB inproducingITP.Mostauthorsusedanti-tuberculosisdrugs combined with steroids and/or IVIg. Although rifampicin hasbeenimplicatedincausingthrombocytopenia,fourdrug ATT regimens included rifampicin in all the cases with-out worsening the condition. The exact duration of the immunosuppressivetherapyisnotstandardizedandmustbe individualizedaccordingtothehematologicalresponse. How-ever,inmostofthereportedcasessteroidswerewithdrawn in1–2months.

Insummary,TB-relatedITPisararehematological man-ifestationofacommondisease.Theactualpathophysiology, clinicalsignificanceandoptimaltreatmentisnotfullyknown, but it should be recognized, especially in areas of high endemicity,thatTB-relatedITPistreatable.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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2.GlasserRM,WalkerRI,HerionJC.Thesignificanceof

hematologicabnormalitiesinpatientswithtuberculosis.Arch InternMed.1970;125(4):691–5.

3.GhobrialMW,AlbornozMA.Immunethrombocytopenia:arare presentingmanifestationoftuberculosis.AmJHematol. 2001;67(2):139–43.