Médecine Interne

Cytomegalovirus infection associated with portal vein thrombosis and thrombocytopenia: a case report

Gianfranco Di Prinzio1, Phung Nguyen Ung2, Anne-Sophie Valschaerts2, Olivier Borgniet2

CMV et Thrombose : We here present the case of portal vein thrombosis in a patient exhibiting symptoms of cytomegalovirus infection, confirmed by un binome sous-estimé serology and polymerase chain reaction (PCR) and complicated by Le Cytomegalovirus (CMV) est thrombocytopenia. The literature reveals growing evidence that responsable d’une infection virale human CMV likely plays a role in thrombotic disorders. However, commune et souvent banale chez le only 11 cases of CMV-induced visceral venous thrombosis have been sujet immunocompétent, mais qui described so far. On the other hand, thrombocytopenia is a well- n’est pas dépourvue de complications potentiellement graves. La thrombose known complication of CMV infection. The patient was successfully porte en est un exemple. Le cas que treated using high-dose immunoglobulins by intravenous route. nous décrivons concerne une patiente atteinte d’une infection à CMV, s’étant révélée par une éruption cutanée et s’étant compliquée d’une thrombose porte, en l’absence de thrombophilie connue. Une thrombopénie auto- A 36-year-old Caucasian woman was admitted to the emergency room immune est la seconde complication of our hospital, complaining since several days of sore throat, cough, survenue dans notre cas. Cet article a pour but de souligner l’enjeu d’un tel , , and rhinorrhea. She had been unsuccessfully treated diagnostic et de stimuler la réflexion sur with amoxicillin-clavulanate during the week preceding her admission. l’intérêt du dépistage échographique The medication was stopped owing to gastric intolerance. She also précoce d’une thrombose splanchnique took acetaminophen up to 6 gr a day during 3 days. No improvement associée à une infection par le CMV. was noticed. Her past medical history was unremarkable, with an appendicectomy in childhood and a tubal ligation. She worked as a Key Words nurse in a childcare center. She was taking rupatadine chronically. She Thrombose veineuse, thrombose portale, purpura, infection virale, thrombocytopénie, was not on oral contraception. She used to smoke five cigarettes a day, immunoglobulines intra-veineuses. accounting for a 3 pack-year history. On clinical examination, her blood pressure was 144/67 mmHg, her heart rate 98 bpm, her body temperature 38.3 °C, and her O2 saturation was 100 %. The clinical examination showed a cervical adenopathy, with no meningeal signs found. Neither liver nor spleen enlargements were present. A truncal skin , diagnosed a week before as rosea, was also present. Serum testing revealed a mild elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels (64 U/L, 88 U/L, and 1070 U/L, respectively). A leukocytosis was also noticed (total white blood cell count of 10910 mm3) with a mild lymphocytosis (4146/ mm3) as well as a thrombocytopenia (78.000/ microl). The C-reactive protein level was of 4 mg/l. ed 2018; 137 (4): 224-227 m ouvain l

Mots-clés  Venous thrombosis, portal vein thrombosis, purpura, viral infection, thrombocytopenia, intravenous immunoglobulins 224 225 G. Di Prinzio, P. Nguyen Ung, A.-S. Valschaerts, O. Borgniet a dose of 1 mg/kg twice aday,a doseof1mg/kgtwice witharapid initiation of was negative andthepatient was given enoxaparine at mutation, lupusanticoagulant, antibodies anti-cardiolipin C andS,factor V Leiden andG20210Aprothrombin thrombophilia screening including assays for protein by aCT-SCAN compression. withoutany extrinsic A vein (Figurethe two branches oftheportal 2),confirmed immunoglobulins, revealing anextensive thrombosis of justbeforeperformed thefirstadministration of polyclonal Meanwhile, arepeated abdomenultrasound was increased to 60.000/mm once aday for two days. After two days, theplatelet count immunoglobulins were administered at adoseof1g/kg appeared onthelower limbs(Figure 1).Polyvalent human citrate 0.109mol/lrespectively. At themeantime, apurpura hospitalization using an anticoagulant EDTA and sodium day of 18.000/ mm3and28.000/mm3/µLonthefourth progressively from 78.000 mm3/µL on admissionto the meantime,In the platelet count decreased not detected. mitochondria andanti-smooth muscleantibodies were antibodies were at detected atiter of1/320whileanti- Rickettsiosis, Leptospirosis were negative. Antinuclear Serologies for HAV, HBV, HCV, EBV, anti-Toxoplasma IgM, seroconversion. Parvovirus B19IgMwere positive aswell. admissionshowedafter aCytomegalovirus (CMV) ofserologyResults testing received three days encephalogram that were were performed bothnormal. persistent headacheaCT-SCAN ofthebrain andanelectro- normal. abdomen of ultrasound Because was strictly There was noalteration oftherenal function. The Figure 1. Purpura ofthelower limbs 3 . discontinued. vein (Figureof the portal 3), Oral anticoagulation was dischargemonths after showed acomplete recanalization An abdominalcomputed tomography repeated two range. Shehadlost3kgs. tokeepherINRinthetherapeuticbecause ofthedifficulty but shewas stillcomplaining offatigue andwas stressed count was normal, headacheshad totally disappeared At thefirst follow-up visit, onemonth later, herplatelet levels were normal. aminotransferaseAspartate andAlanine Aminotransferase from milder well controlled by Ibuprofen. When thepatient was discharged, shewas stillsuffering finally disappeared. thehospitalization therashDuring becamemilderand aiming for anINRbetween 2and3for sixmonths. oral anticoagulation withacenocumarol initially3mg/day Figure 2. Figure 3. Portal thrombosis C omplete recanalization. detection. detection. hours) probably accounting for thedecrease inviral DNA been frozen several ithadbeendrawn hoursafter (>12 low titer <1250copies/ml). (normal The serumhad 391copies ofCMV-DNA/ml,detecting whichisarelatively frozen onthepreserved serumofthepatient,performed Five months later, aPolymerase was Chain Reaction elsewhere intheliterature inSquizzato’sshown inacasereported metanalysis and because of the association between thesetwo entities, as An antiphospholipid syndrome must be ruled out, presence offactor VII/VIIa andcalcium(9). (8) aswell asfacilitate theconversion X/Xa inthe offactor express phosphatidylserine(PS)-likeprocoagulant activity (7).Moreover(ELAM-1) CMVstrain purified AD169can adhesionmolecule-1 (6) andoftheendothelialleukocyte proposed suchasCMVinduced over-expression ofCD40 CMVinfection(5).Severalafter mechanismshave been clotting timeindifferent clottingassays was observed procoagulant state invitro andinvivo. vivo, In adecreased There issomeevidence that CMVinfectioninduces a abdominal pain(4)asinourreport. contraception. Onlythree patients didnotcomplain of (3) whileanotherwas onoral oestro-progestative the latter, two patients were affected by a coagulopathy cavernoma developedportal intwo patients (3).Among recanalization was shownpartial in one case (2) and a resolution treatment after occurred in 8 cases, while 51 to 450 IU/l and ALT from 51 to 240 IU/l. A complete of transaminases withASTranging was observed, from in the literature.been reported all cases a mild elevation In 2005, 11casesofCMVrelated Portal Vein Thrombosis have According to Squizzato’s metanalysis (1) published in a role inthegeneration ofantiphospholipid antibodies canplay (CMV) that humancytomegalovirus in thefact procoagulability inCMVinfectioncanbesought aswell Références CMV INFECTION AND PORTAL THROMBOSIS 5. 4. 3. 2. 1. Haemost. 1992;68:364–70. megalovirus infected endothelialcells. Thromb VWM, MCE, AD,van Muller Dam-Mieras van Hinsbergh 287–8. thrombosis.J Gastroenterol Hepatol. 1997;12: vein tomegalovirus infection asacauseofportal C,HillaireS, Inacio Valla D, cy etal.Case report: 1270. with anenlarged tender liver. Lancet. 1995;346: J, CelisDe G,Mir Casal J, etal.31-year-old woman atr. 1995;126:586–8. associated infection.JPedi withcytomegalovirus - bosis causedby protein Candprotein Sdeficiency Arav-Boger S,Bujanover R,Reif Y. Portal vein throm- system. Thromb Haemost. 2005;93:403-10. infectiononthecoagulationman cytomegalovirus Squizzato A.,Gerdes V. A.,BüllerH.Effectsofhu-

(10) . et al. The procoagulant response ofCyto Indeed themechanismof Indeed polyvalent humanimmunoglobulins.polyvalent of theinfectiouscondition, we decidedto administer administered andbothtreatments were effective.Because preferred whereas was inanothercase (14).Ganciclovir (13)corticosteroidsby were Eisenberg andKaplan and hemolytic anemia as well. a case review In published in somecasesof Thrombotic mechanisms could beinvolved. CMVhasbeenimplicated with an immunomediated mechanism although the two dramatic response to immunoglobulinsismore consistent would rather effectwhereas suggestacytopathic the between theonsetofsymptoms andthrombocytopenia infection orimmunomediated. The temporal relationship was causedbywhether thrombocytopenia directly CMV colleagues (12)butcurrently itisimpossibleto state and CMVhasrecently beendemonstrated by Wu Z.and its mechanismisnotwell understood. The role ofEBV myelodysplasia andautoimmune abnormalities. However, asacauseof viral hasbeendescribed infections. It complication ofCMVinfectionaswell asofother CMV related isawell-known thrombocytopenia thus enhancingthrombus formation (11). andfavor adhesionto endothelialcells, leukocytes activity These antibodies canpotentially have lupusanticoagulant similar to thoseof aPL (11). properties functional sharing liver enzymes shouldbeemphasized.liver enzymes in patients presenting withCMVinfectionandelevation of underdiagnosis. The role ofultrasound asascreening test beexplained by ofsuchacondition couldthe rarity inpart mechanisms are notfullyunderstood. We supposethat thrombogenicity have buttheunderlying beendescribed complication ofCMVinfection(15).Several patterns of Portal Vein Thrombosis canbearare butdangerous CMV INDUCED THROMBOCYTOPENIACMV CONCLUSION - - 9. 8. 7. 6. 13514, December 1997 ruses Proc. Natl. Acad. USA Sci. Vol. 94,pp. 13510– E.Pryzdial L.G.Coagulation initiated- onherpesvi H, CM,Leenknegt MR,Raynor Sutherland Wright F, lipids. Blood. 1994;84:3749–57. contains procoagulantalovirussurface phospho on anenveloped- :evidence that thecytomeg ELG,Pryzdial Wright FJ. Prothrombinase assembly Suppl 2:S97–109. in human cytomegalovirus. J Clin Virol. 2002; 25 genetic determinants ofendothelialcell tropism Bolovan-Fritts CA, Wiedeman theviral JA.Mapping 12. human cytomegalovirus. J Virol. 2002; 76: 12803– CD40 expression onendothelial cells infected with Maisch T, Kropff B, SinzgerC,etal.Upregulation of -

226 Cytomegalovirus infection associated with portal vein thrombosis and thrombocytopenia: a case report 227 G. Di Prinzio, P. Nguyen Ung, A.-S. Valschaerts, O. Borgniet 2 1 Centre HospitalierUniversitaire DinantRueSaint Jacques Dinant, -Mont-Godinne, 501,B-5500 Belgique Références affiliations Division ofGastro-Enterology, CHUNamursite Dinant, rueSaint Jacques Dinant, 501,B-5500 Belgium Division ofHematology, Cliniques universitaires Saint-Luc, Av. HippocrateBruxelles, 10,B-1200 Belgium

10. 12. 11. , Smith KJ rus (CMV) in immune thrombocytopenia. rus (CMV) - andcytomegalovi role ofEpstein-Barr virus (EBV) ogy. 2013Sep;18(5):295-9. Z Wu . 2002;46:545–52 Rheum ofendothelialcellsand activation invivo. tomegalovirus-derived peptidecausethrombosis bodies induced inmice by immunization withacy en-Stanfield M, Gharavi AE, mia. Arch Dermatol. 1995;131:357–8. 1-positivetype patients vire and cytomegalovirus virus ous thrombosis inhumanimmunodeficiency , Zhou J Skelton HG, Pierangeli SS, , Wei X, Harris EN. Harris Wang X, Yeager J, , Espinola RG Antiphospholipid anti - Li Y Wagner KF. , Peng B Liu X, , Niu T Niu Hematol- Arthritis Arthritis Cutane Cold- . The - - - 15. 14. 13. Acta Clin.Belg.Acta 2016Aug; 71(4):231-4. tion: epidemiologyandpredisposing conditions. lism associated withacute infec cytomegalovirus Yldiz H, Zech F, Hainaut P, Venous thromboembo Jan;92(1):218-20. immunocompetent adult. BrJHaematol. 1996 duced andhaemolysis thrombocytopenia inan van Spronsen DJ, Breed WP. Cytomegalovirus-in- tent adult. West 158(5):525–526. JMed. 1993May; induced inanimmunocompe thrombocytopenia Cytomegalovirus-M JEisenberg andBKaplan D r. Gianfranco Cliniques universitaires Saint-Luc C B-1200 Bruxelles –Belgium orrespondance Avenue 10 Hippocrate Service d'hématologie Service Di Prinzio , MD - - - MEDICAL MEDICAL MEDICAL EDITING TRANSLATION WRITING

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