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Myocardial infarction and thrombophilia: Do not miss
the right diagnosis!
Arnaud Hubert, Pierre Guéret, Guillaume Leurent, Raphael P. Martins,
Vincent Auffret, Marc Bedossa
To cite this version:
Arnaud Hubert, Pierre Guéret, Guillaume Leurent, Raphael P. Martins, Vincent Auffret, et al..
My-ocardial infarction and thrombophilia: Do not miss the right diagnosis!. Revista Portuguesa de
Cardi-ología, Elsevier España (Elsevier Doyma), 2018, 37 (1), pp.89.e1-89.e4. �10.1016/j.repc.2016.12.018�.
�hal-01718027�
www.revportcardiol.org
Revista
Portuguesa
de
Cardiologia
Portuguese
Journal
of
Cardiology
CASE
REPORT
Myocardial
infarction
and
thrombophilia:
Do
not
miss
the
right
diagnosis!
Arnaud
Hubert
a,b,c,∗,
Pierre
Guéret
d,
Guillaume
Leurent
a,b,c,
Raphael
P.
Martins
a,b,c,
Vincent
Auffret
a,b,c,
Marc
Bedossa
a,b,caCentreHospitalierUniversitaire(CHU)deRennes,ServicedeCardiologieetMaladiesVasculaires,Rennes,France bUniversitédeRennes1,LaboratoireTraitementduSignaletdel’Image(LTSI),Rennes,France
cInstitutNationaldelaSantéetdelaRechercheMédicale(Inserm),Rennes,France
dCentreHospitalierUniversitaire(CHU)deRennes,Laboratoired’Hématologie-Hémostase,Rennes,France
Received14July2016;accepted14December2016 Availableonline15December2017
KEYWORDS Myocardialinfarction; Coronarythrombosis; Thrombophilia; Intravascular ultrasound; Atherosclerosis; Plateletaggregation inhibitors
Abstract Protein C deficiencyis a coagulation cascade disorder often resulting invenous thromboemboliceventsbutisalsoapossiblecontributortoarterialthrombosis.Todate, approx-imatelytencasesofmyocardialinfarction(MI)duetoproteinCdeficiencyhavebeenreportedin theliterature.However,affirmingthismechanismrequiresrulingoutthemostcommoncauses ofMI,i.e.theruptureorerosionofanatheroscleroticplaque.Intravascularimagingofcoronary arteriescanbeofhelptoidentifyangiographicallyundetectedatherosclerosis.Wereportacase ofanST-segmentelevationmyocardialinfarction(STEMI)inayoungmanwithapparent evi-denceofarterialthrombosisresultingfromproteinCdeficiencyandheterozygousfactorLeiden mutationwhichwascontradictedbyintravascularimagingdemonstratingatherosclerosis. © 2017SociedadePortuguesade Cardiologia.Publishedby ElsevierEspa˜na,S.L.U.Allrights reserved. PALAVRAS-CHAVE Enfartedomiocárdio; Trombosecoronária; Trombofilia; Ultrassonografia intravascular; Aterosclerose; Inibidoresde agregac¸ão plaquetária
Enfartedomiocárdioetrombofilia:nãofalheodiagnósticocorreto!
Resumo AdeficiênciadeproteínaCconstituiumaalterac¸ãoemcascatadacoagulac¸ão,dá origem muitasvezes aoseventostromboembólicosvenosos eétambémum contributo pos-síveldetrombosearterial.Aproximadamentedezcasosdeenfartedomiocárdio(EM)devidos à deficiência da proteína C foram referenciados na literatura. No entanto, a confirmac¸ão desse mecanismo requer a exclusão das etiologiasmais comuns de EM, i.e. arotura ou a erosãodaplacaaterosclerótica.Aavaliac¸ãoimagiológicaintravasculardasartériascoronárias poderiaserumaajudaparaidentificaraaterosclerosenãodetetadaporangiografia. Apresen-tamosocasodeumenfartedomiocárdio comelevac¸ãodosegmento-ST(STEMI)querevela ∗Correspondingauthor.
E-mailaddress:arnaud.hubert@chu-rennes.fr(A.Hubert).
https://doi.org/10.1016/j.repc.2016.12.018
89.e2 A.Hubertetal.
evidênciaaparente detrombosearterialdevidaàdeficiênciadaproteínaCeàmutac¸ãodo fatorheterozigóticoLeidenquefoicontestadaatravésdeavaliac¸ãoimagiológicaintravascular edemonstrouaterosclerosenumhomemnovo.
©2017SociedadePortuguesadeCardiologia.PublicadoporElsevierEspa˜na,S.L.U.Todosos direitosreservados.
Introduction
Combined thrombophilia can be a cause of myocardial infarction,butpatientswiththrombophiliashouldbe thor-oughly investigated for atherosclerosis in the event of coronarythrombosis.Intravascularimagingcan help iden-tify atherosclerosis which has remained undetected by angiogram.Thishasanimpactonpatientmanagement,as antiplatelettherapybecomesmandatoryifatherosclerosis isdetected.Therearenorecommendationsat presentfor thetreatmentofacutecoronarysyndromeinpatientswith thrombophiliaandatherosclerosis.
Case
report
A 40-year-old Caucasian man with an asymptomatic het-erozygousProtein Cdeficiencyandahistoryof pulmonary embolism in first-degree relatives was admitted with a three-day history of repeated episodes of chest pain at restlasting15to30minutes.Hehadnocardiovascularrisk factors(obesity,dyslipidemia,smoking,diabetes, hyperten-sion,familialhistory).
At admission, the patient was asymptomatic. He was hemodynamically stable with a blood pressure of 125/83mmHgandaheartrateof90bpm.Physical exami-nationwasunremarkable.TheinitialECGrevealedanterior sequelae of ischemia withanterior ST-segmentelevation. Initial troponin T concentration was1538 pg/mL (normal <14 pg/mL) and renal function was normal (creatinine 65 mol/L, normal 59-104 mol/L). Further labora-tory investigations found that complete blood count, blood chemistry and lipid profile were all within normal ranges.Troponinconcentrationwasintheascendingphase (2156pg/mLonday1,2869pg/mLonday2).Thescreening for antiphospholipid antibodies was negative. Antithrom-binwas97%(normal80-120%).ProteinCconcentrationwas abnormal, with a level of 61% (normal 70-120%) checked bychronometricandchromogenicmethods.Aheterozygous FactorVLeidenmutationwasalsofoundinadditiontohis proteinCdeficiency.Therefore,thispatienthadacombined thrombophilia.
Transthoracic echocardiogram showeda depressed left ventricularejectionfractionof34%withapicalakinesia,no valvediseases,andnovisiblethrombi.Coronary angiogra-phy showedproximal andmedial leftanteriordescending occlusionscausedbyamassivethrombus(Figure1,panelA; movingangiogramsinsupplementarymaterials).Circumflex and right coronary arteries were normal. In view of the
historyofthrombophilia,coronaryangioplastywasnot ini-tially performed and antithrombotic treatment combining anticoagulation with unfractionated heparin (monitored by anti-Xa activity, targeting 0.3 to 0.7 IU/mL) and dual antiplatelet therapy was initiated. A second coronary angiogramwasperformedafterfivedaysofantithrombotic treatmentandshowedcompleteregressionofthethrombus withan underlying normalleftanteriordescending artery
(Figure 1, panel B). However, an intravascular ultrasound
study (IVUS)revealed an atheromatousplaque (Figure2). Thus, we hypothesized that two mechanisms were in play: therupture of an atheromatousplaqueinitiating an anterior myocardial infarction aggravated by his mixed coagulopathy (ProteinC deficiency associatedwithFactor VLeidenmutation).
Discussion
ProteinCisavitaminK-dependentglycoproteinthatplays an important role in the regulation of blood clotting as a natural anticoagulant.1 Protein C deficiency is a known
risk factor forvenous thromboembolicevents,2 but alsoa
riskfactorforarterialthrombosis,inparticularmyocardial infarction.Indeed, abouttwenty case reports andalarge study3havebeenpublishedinthepastfewyearsregarding
patientswithheterozygousProteinCdeficiencyresponsible for ischemic cerebralstroke or myocardialinfarction. Iso-lated heterozygousFactorVLeidenmutationusuallydoes not induce myocardial infraction4 but there have been a
few case reports on myocardial infarction provoked by a combinedthrombophilia.5
This case could be included in a larger entity called ‘‘Myocardialinfarctionwithnon-obstructivecoronary arter-ies (MINOCA)’’. As Pasupathy et al. said in their review paper,6 ‘‘this diagnosis is made in a patient presenting
withdiagnosticfeaturesofanacutemyocardialinfarction, in whom angiographydoes not show obstructivecoronary arterydisease,andthereisnoimmediatelyapparentcause forthepresentation.’’Itcouldbeconsideredasa‘‘working diagnosis’’.Infact,itdoesnotconsistofadefinitive diag-nosisbutitdoesallowustoclassifyaclinicalentityinorder to better manage investigation of the ‘‘real diagnosis’’. A recent meta-analysis7 showed an association between
MINOCAandthrombophilia.Indeed,ProteinCdeficiencyhas aprevalenceof0.1%to1%inthegeneralpopulation, reach-ing2.6%inpatientswithMINOCA,6whereasfactorVLeiden
mutationhasaprevalenceof3%to7%inWesterncountries, butaffects12%ofMINOCApatients.
Figure1 PanelA:Thrombusoftheleft anteriordescendingartery; PanelB:Totalregressionofthethrombuswithoutvisible stenosis.
Figure2 Intravascularultrasoundconfirmsthediagnosisofplaquerupturewithpersistenceofalesionofthemediaofthe artery.
Atherosclerosis is the most common cause of myocar-dial infarction. As recommended in European guidelines, whencoronaryangiographyisnormal,intravascularimaging canbeusedtodetect smallatherosclerosis plaques(class IIbB recommendation).8 In our patient, to improve
diag-nosticaccuracy,we performedan IVUSwhich revealedan atheroscleroticplaqueinanangiographicallynormalartery. Wethenhypothesized,eventhoughalackofscientific evi-dencemeansthatthisentityremainsunderdebate,thatthe patienthadaSTEMIforthefollowingreasons:ruptureofan atherosclerotic plaqueinitiating thrombusgenesis, ampli-fiedbythethrombophilia.
This case demonstrates:(i) thatIVUS is of greatvalue to more accurately rule in/out atherosclerosis when a coronarythrombosisis suspectedin patientswithclotting
disorders;and(ii)thenecessityofestablishing recommen-dationstomanagethissituationandproperlyassessthisrare diagnosis, as there is a lack of consensus in the current literatureregardingthemanagementofsuchpatients.
Authorship
ArnaudHubert,RaphaelMartinsandVincentAuffret: Writ-ingofthecasereport,clinicalcare.
Guillaume LeurentandMarc Bedossa:Performingand interpretationofangiography/intravascularultrasounds.
89.e4 A.Hubertetal.
Conflicts
of
interest
Theauthorshavenoconflictsofinteresttodeclare.
Appendix
A.
Supplementary
material
Supplementary material associated with this article can be found in the online version at doi:10.1016/
j.repc.2016.12.018.
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