Case
Report
Non-traumatic
splenic
rupture
on
dual
antiplatelet
therapy
with
aspirin
and
ticagrelor
after
stenting
for
acute
coronary
syndrome
Elisa
Grifoni
(MD)
a,*
,
Rita
Paniccia
(BSc)
a,
Betti
Giusti
(BSc)
a,
Elena
Sticchi
(BSc)
a,
Luigi
Padeletti
(MD)
a,
Claudio
Cavallini
(MD)
b,
Rossella
Marcucci
(MD,
PhD)
a aDepartmentandExperimentalandClinicalMedicine,UniversityofFlorence,Florence,Italy
b
DivisionofCardiology,S.MariadellaMisericordiaHospital,Perugia,Italy
Introduction
Ruptureofthespleenisrelativelycommon,bothimmediately and delayed, after abdominal trauma,whereas non-traumatic splenic ruptureisarareevent,andismoreoftenassociatedwithpathological pre-existingsplenicabnormalities.Amongthese,infarctiondueto cardiacthromboembolism,infectious(i.e.malaria,mononucleosis), inflammatory (i.e. immuno-rheumatologic), and infiltrative
(i.e.amyloidosis,hematologiclymphoproliferative,and myelopro-liferativeneoplasms)diseaseshavebeenreportedintheliteratureas themostfrequentcauses.However,casesofsplenicruptureinthe absenceoftraumaorpathologicalpre-existingconditions,evenless frequent,havealsobeenreported.Arecentreviewoftheliterature showedanassociationwithmedicalprocedures,suchas colonosco-py, and ongoingmedical treatmentwith antithromboticagents, mainlyanticoagulantsandthrombolyticdrugs,butalsotwocases duringantiplatelettherapywithticlopidine[1–3].
Here,wereportacaseofnon-traumaticruptureofthespleenin a57-year-oldmanondualantiplatelettherapy(DAPT)withaspirin andticagrelorafterpercutaneouscoronaryintervention(PCI)and newgenerationdrug-elutingstent(DES)implantationfornon-ST elevationmyocardialinfarction.
JournalofCardiologyCases12(2015)65–67
ARTICLE INFO
Articlehistory:
Received25March2015
Receivedinrevisedform26April2015
Accepted10May2015 Keywords: Splenicrupture Antiplatelets Aspirin Ticagrelor
Acutecoronarysyndrome
Stenting
ABSTRACT
Wereportacaseofnon-traumaticsplenicruptureina57-year-oldmanondualantiplatelettherapy (DAPT)withaspirinandticagrelor,sevenmonthsafterpercutaneouscoronaryinterventionand drug-elutingstentimplantationfornon-STelevationmyocardialinfarction.Nosplenicabnormalitieswere foundathistopathologicalanalysisaftersplenectomy,andnohistoryofrecenttraumawasreported. Once restarted, DAPT after splenectomy, assessment of platelet function was performedby light transmittance aggregometry, showing a profound inhibition of platelet function by adenosine diphosphate,arachidonicacid,andcollagen.Takingintoaccountthebleedingriskassociated with lowon-treatmentplateletreactivity,andtoswitchthepatientfromticagrelortoalesspotentP2Y12 inhibitor suchasclopidogrel,cytochromeP450, geneticpolymorphismsaccountingforclopidogrel responsevariabilitywereanalyzed.Thepolymorphismsassociatedwithlowerresponse(CYP2C19*2, CYP2C19*3)wereabsent.Therefore,ticagrelorwaswithdrawn,andDAPTwascontinuedwithaspirin andclopidogrel.Ruptureofthespleenmayoccurintheabsenceofmajortraumaorprevioussplenic diseases, and could be a complication of antithrombotic treatments.Moreover,low on-treatment plateletreactivityduringDAPTis emergingasapossiblerisk factorforbleeding complications,so underliningtheusefulnessofassessingplateletfunctioninspecialconditionstoensurethatthepatient receivesthebesttailoredantiplatelettherapy.
<Learningobjective:Non-traumaticsplenicruptureisarareevent,andismoreoftenassociatedwith pre-existing splenicabnormalities. However,itmaybe alsoa complicationofmedicaltreatments, especiallywithantithromboticdrugs.Lowon-treatmentplateletreactivityisemergingasapossiblerisk factorforbleedingcomplications;therefore,assessingplateletfunctioninspecialconditionscouldbe usefultoensurethepatientreceivesthebest-tailoredantiplatelettherapy.>
ß2015JapaneseCollegeofCardiology.PublishedbyElsevierLtd.Allrightsreserved.
* Correspondingauthorat:CenterforAtherothromboticDiseases–AOUCareggi,
DepartmentandExperimentalandClinicalMedicine,UniversityofFlorence,Largo
Brambilla,3–50134Florence,Italy.Tel.:+390557949420;fax:+390557949418.
E-mailaddress:elisa.grifoni@unifi.it(E.Grifoni).
ContentslistsavailableatScienceDirect
Journal
of
Cardiology
Cases
j our na l h ome p a ge : w ww . e l se v i e r. co m/ l oc a te / j c ca se
http://dx.doi.org/10.1016/j.jccase.2015.05.001
Casereport
A 57-year-old manunderwent PCI and newgeneration DES implantation for non-ST elevation myocardial infarction with angiographic demonstration of two-vessel coronary disease (March2014).DAPTwithaspirin100mgoncedailyandticagrelor 90mg twice daily had been started soon after myocardial revascularization,and initially plannedtobe continuedforone year.Sevenmonthsaftertheevent,thepatientcametomedical attentionforsuddenonsetofabdominalpainandhypotension.An abdomencomputedtomographyshowedhemoperitoneumdueto splenicrupture.Urgentsplenectomywasperformed.Nosignsof splenic infarctionor otherabnormalities (i.e. micro-aneurysms, inflammatoryorinfiltrativedisorders)werefoundat histopatho-logical analysis of surgical specimen. No history of recent abdominaltraumahadbeenreported;neither clinicalor biohu-moralsignssuggestinginfectiousorauto-immunediseaseswere detected.Laboratoryexaminationshowednosignificantdropin hemoglobin values, and also showedan increasedwhite blood cell and platelet count (17.3109L–1 and 1.222109L–1,
respectively),asexpectedaftersplenectomy.Antiplatelettherapy, withaspirinsoonafterdischarge,togetherwithticagrelor15days later, was restarted. After 10 days, an assessment of platelet function was performed by light transmittance aggregometry (LTA)onplatelet-richplasma(PRP)withanAPACT4004 aggreg-ometer (Axiom, Bursta¨dt, Germany) [4]. This test showed a profoundinhibitionofplateletfunctionbyadenosinediphosphate (ADP)10
m
M,arachidonicacid1mM,andcollagen2m
g/mL(LTA 14%, 11%, and 4%, respectively) (Fig. 1). To avoid confounding results due to high platelet count (as normal response after splenectomy),LTA test wasrepeatedwithdifferentdilutionsof PRPsamples,obtainingsimilarresults.Plateletcountatthetimeof thefirstanalysiswas1.247109L–1.Plateletaggregationontheundiluted, and diluted samples with a platelet count of 800109L–1and 600
109L–1 (whichis the maximal platelet
count recommended for the APACT 4004 light transmittance aggregometer),respectively,arereported inFig.2[5–7].Taking intoaccountthebleedingriskassociatedwithlowon-treatment plateletreactivityandinordertoswitchthepatientfromticagrelor to a less potent P2Y12 inhibitor such as clopidogrel, genetic polymorphisms accounting for clopidogrel response variability wereanalyzed.CytochromeP450polymorphismsassociatedwith alowerresponsetoclopidogreladministration(CYP2C19*2 and CYP2C19*3 alleles) were absent, whereas homozygous CYP2C19*17polymorphism,whichisonthecontraryassociated withahigherresponse,wasdetected[8].Moreover,noacquired
clinical determinants oflower response toclopidogrel, such as older age, diabetes, renal impairment, or heart failure, were present in ourpatient. Therefore, takinginto account both the spontaneousnatureofbleedingand laboratorytest results,and time elapsed from PCI and stent implantation (more than 6 months) together with the use of less thrombogenic new generationDES,adecisionwasmadetostopticagrelortreatment and continue DAPTwithaspirin 100mgand clopidogrel 75mg oncedaily.Fifteendaysafterstartingclopidogrel,thepercentageof plateletaggregationonLTA,withaplateletcountof608109L–1,
was35%,12%,and12%byADP10
m
M,arachidonicacid1mM,and collagen 2m
g/mL, respectively. No clinical, instrumental, or laboratorysignsraisingsuspicionofrestenosisorstentthrombosis after ticagrelor withdrawal were present. After two months of DAPTwithaspirinandclopidogrel,thepatientremained asymp-tomatic,hemoglobinvalueswerestable,andabdomencomputed tomographydidnotshowanypathologicalfinding.Discussion
Non-traumaticsplenic rupture is a rare and life-threatening causeofintraperitonealhemorrhage,andismoreoftenassociated with pre-existing splenic abnormalities. Among rare cases of splenic rupture in the absence of trauma or pathological pre-existing conditions, anassociation withongoing medical treat-mentwithantithromboticagentshasalsobeenreported[1–3].To the best of our knowledge,our case is the first description of splenicruptureduringDAPTwithaspirinandticagrelor.Neither recent traumaticabdominal injuryhad occurred, norhistory of infectious or auto-immune diseases had been reported in our patient.Moreover,noinflammatoryorinfiltrativeabnormalitiesof the spleen were documented. DAPT was the only risk factor associated withpotentialbleeding complications.The profound inhibitionofplateletfunctiondocumentedbyLTAafterrestarting treatment with aspirin and ticagrelor might have contributed tothedevelopmentofasplenichematomaandconsequentrupture ofthespleen.Indeed,thereisagrowingbodyofevidencethatlow on-treatment platelet reactivity, induced by ADP and collagen, duringantiplatelettreatmentwithP2Y12inhibitorsisassociated withahigherriskofbleeding[9,10].Ithasbeenpostulatedthat thereisatherapeuticwindowforP2Y12receptorblockers,thus indicatingthathighon-treatmentplateletreactivityisassociated with thrombotic events, whereas low on-treatment platelet reactivityisassociatedwithbleedingcomplications[10].
Inconclusion, ourcase reportunderlinesthatruptureofthe spleen may occur even in the absence of major trauma or
Fig.1.
Plateletaggregationonlighttransmittanceaggregometryinduced byadenosinediphosphate(ADP)10mM,arachidonicacid(AA)1mM, andcollagen2mg/mLafterrestartingdualantiplatelettherapywith aspirinandticagrelor.
Fig.2.
Effect of dilution of platelet-rich plasma samples on light transmittance aggregometry induced by adenosine diphosphate (ADP)10mM,arachidonicacid(AA)1mM,andcollagen2mg/mL.
E.Grifonietal./JournalofCardiologyCases12(2015)65–67
previouslydiagnosedsplenicdiseases,andcouldbeacomplication of medical treatments, especially with antithrombotic drugs. Moreover, low on-treatment platelet reactivity during DAPT is emergingasa possibleriskfactorforbleeding complicationsin thesepatients,sounderliningtheusefulnessofassessingplatelet function in special conditions, in order to ensure the patient receivesthebesttailoredantiplatelettherapy.
Conflictofinterest
Dr Marcucci reported receiving honoraria for lectures from AstraZeneca,Bayer,EliLilly,MerckSharpDohme,andPfizer.No otherdisclosureswerereported.
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