Case report
Myocardial infarction and thrombophilia: Do not miss the right diagnosis!
Enfarte do miocárdio e trombofilia: não falhe o diagnóstico correto!
Arnaud Huberta,b,c,
, Pierre Guéretd, Guillaume Leurenta,b,c, Raphael P. Martinsa,b,c, Vincent Auffreta,b,c, Marc Bedossaa,b,c
Corresponding author
a Centre Hospitalier Universitaire (CHU) de Rennes, Service de Cardiologie et Maladies Vasculaires, Rennes, France
b Université de Rennes 1, Laboratoire Traitement du Signal et de l’Image (LTSI), Rennes, France
c Institut National de la Santé et de la Recherche Médicale (Inserm), Rennes, France
d Centre Hospitalier Universitaire (CHU) de Rennes, Laboratoire d’Hématologie-Hémostase, Rennes, France
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"apellidos" => "Martins" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 4 => array:3 [ "nombre" => "Vincent" "apellidos" => "Auffret" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 5 => array:3 [ "nombre" => "Marc" "apellidos" => "Bedossa" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Centre Hospitalier Universitaire (CHU) de Rennes, Service de Cardiologie et Maladies Vasculaires, Rennes, France" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Université de Rennes 1, Laboratoire Traitement du Signal et de l’Image (LTSI), Rennes, France" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Institut National de la Santé et de la Recherche Médicale (Inserm), Rennes, France" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Centre Hospitalier Universitaire (CHU) de Rennes, Laboratoire d’Hématologie-Hémostase, Rennes, France" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Enfarte do miocárdio e trombofilia: não falhe o diagnóstico correto!" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 661 "Ancho" => 1500 "Tamanyo" => 132509 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Panel A: Thrombus of the left anterior descending artery; Panel B: Total regression of the thrombus without visible stenosis.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Combined thrombophilia can be a cause of myocardial infarction, but patients with thrombophilia should be thoroughly investigated for atherosclerosis in the event of coronary thrombosis. Intravascular imaging can help identify atherosclerosis which has remained undetected by angiogram. This has an impact on patient management, as antiplatelet therapy becomes mandatory if atherosclerosis is detected. There are no recommendations at present for the treatment of acute coronary syndrome in patients with thrombophilia and atherosclerosis.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case report</span><p id="par0010" class="elsevierStylePara elsevierViewall">A 40-year-old Caucasian man with an asymptomatic heterozygous Protein C deficiency and a history of pulmonary embolism in first-degree relatives was admitted with a three-day history of repeated episodes of chest pain at rest lasting 15 to 30 minutes. He had no cardiovascular risk factors (obesity, dyslipidemia, smoking, diabetes, hypertension, familial history).</p><p id="par0015" class="elsevierStylePara elsevierViewall">At admission, the patient was asymptomatic. He was hemodynamically stable with a blood pressure of 125/83 mmHg and a heart rate of 90 bpm. Physical examination was unremarkable. The initial ECG revealed anterior sequelae of ischemia with anterior ST-segment elevation. Initial troponin T concentration was 1538 pg/mL (normal <14 pg/mL) and renal function was normal (creatinine 65 μmol/L, normal 59-104 μmol/L). Further laboratory investigations found that complete blood count, blood chemistry and lipid profile were all within normal ranges. Troponin concentration was in the ascending phase (2156 pg/mL on day 1, 2869 pg/mL on day 2). The screening for antiphospholipid antibodies was negative. Antithrombin was 97% (normal 80-120%). Protein C concentration was abnormal, with a level of 61% (normal 70-120%) checked by chronometric and chromogenic methods. A heterozygous Factor V Leiden mutation was also found in addition to his protein C deficiency. Therefore, this patient had a combined thrombophilia.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Transthoracic echocardiogram showed a depressed left ventricular ejection fraction of 34% with apical akinesia, no valve diseases, and no visible thrombi. Coronary angiography showed proximal and medial left anterior descending occlusions caused by a massive thrombus (<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>, panel A; moving angiograms in supplementary materials). Circumflex and right coronary arteries were normal. In view of the history of thrombophilia, coronary angioplasty was not initially 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 angiogram was performed after five days of antithrombotic treatment and showed complete regression of the thrombus with an underlying normal left anterior descending artery (<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>, panel B). However, an intravascular ultrasound study (IVUS) revealed an atheromatous plaque (<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>). Thus, we hypothesized that two mechanisms were in play: the rupture of an atheromatous plaque initiating an anterior myocardial infarction aggravated by his mixed coagulopathy (Protein C deficiency associated with Factor V Leiden mutation).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0025" class="elsevierStylePara elsevierViewall">Protein C is a vitamin K-dependent glycoprotein that plays an important role in the regulation of blood clotting as a natural anticoagulant.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a> Protein C deficiency is a known risk factor for venous thromboembolic events,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">2</span></a> but also a risk factor for arterial thrombosis, in particular myocardial infarction. Indeed, about twenty case reports and a large study<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">3</span></a> have been published in the past few years regarding patients with heterozygous Protein C deficiency responsible for ischemic cerebral stroke or myocardial infarction. Isolated heterozygous Factor V Leiden mutation usually does not induce myocardial infraction<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">4</span></a> but there have been a few case reports on myocardial infarction provoked by a combined thrombophilia.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">This case could be included in a larger entity called “Myocardial infarction with non-obstructive coronary arteries (MINOCA)”. As Pasupathy et al. said in their review paper,<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">6</span></a> “this diagnosis is made in a patient presenting with diagnostic features of an acute myocardial infarction, in whom angiography does not show obstructive coronary artery disease, and there is no immediately apparent cause for the presentation.” It could be considered as a “working diagnosis”. In fact, it does not consist of a definitive diagnosis but it does allow us to classify a clinical entity in order to better manage investigation of the “real diagnosis”. A recent meta-analysis<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">7</span></a> showed an association between MINOCA and thrombophilia. Indeed, Protein C deficiency has a prevalence of 0.1% to 1% in the general population, reaching 2.6% in patients with MINOCA,<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">6</span></a> whereas factor V Leiden mutation has a prevalence of 3% to 7% in Western countries, but affects 12% of MINOCA patients.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Atherosclerosis is the most common cause of myocardial infarction. As recommended in European guidelines, when coronary angiography is normal, intravascular imaging can be used to detect small atherosclerosis plaques (class IIbB recommendation).<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">8</span></a> In our patient, to improve diagnostic accuracy, we performed an IVUS which revealed an atherosclerotic plaque in an angiographically normal artery. We then hypothesized, even though a lack of scientific evidence means that this entity remains under debate, that the patient had a STEMI for the following reasons: rupture of an atherosclerotic plaque initiating thrombus genesis, amplified by the thrombophilia.</p><p id="par0040" class="elsevierStylePara elsevierViewall">This case demonstrates: (i) that IVUS is of great value to more accurately rule in/out atherosclerosis when a coronary thrombosis is suspected in patients with clotting disorders; and (ii) the necessity of establishing recommendations to manage this situation and properly assess this rare diagnosis, as there is a lack of consensus in the current literature regarding the management of such patients.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Authorship</span><p id="par0045" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Arnaud Hubert</span>, <span class="elsevierStyleBold">Raphael Martins</span> and <span class="elsevierStyleBold">Vincent Auffret</span>: Writing of the case report, clinical care.</p><p id="par0050" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Guillaume Leurent</span> and <span class="elsevierStyleBold">Marc Bedossa</span>: Performing and interpretation of angiography/intravascular ultrasounds.</p><p id="par0055" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Pierre Guéret</span>: Interpretation of coagulation disorders.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conflicts of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres987397" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec954793" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres987396" "titulo" => "Resumo" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec954792" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Case report" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Authorship" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflicts of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-07-14" "fechaAceptado" => "2016-12-14" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec954793" "palabras" => array:6 [ 0 => "Myocardial infarction" 1 => "Coronary thrombosis" 2 => "Thrombophilia" 3 => "Intravascular ultrasound" 4 => "Atherosclerosis" 5 => "Platelet aggregation inhibitors" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec954792" "palabras" => array:6 [ 0 => "Enfarte do miocárdio" 1 => "Trombose coronária" 2 => "Trombofilia" 3 => "Ultrassonografia intravascular" 4 => "Aterosclerose" 5 => "Inibidores de agregação plaquetária" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Protein C deficiency is a coagulation cascade disorder often resulting in venous thromboembolic events but is also a possible contributor to arterial thrombosis. To date, approximately ten cases of myocardial infarction (MI) due to protein C deficiency have been reported in the literature. However, affirming this mechanism requires ruling out the most common causes of MI, i.e. the rupture or erosion of an atherosclerotic plaque. Intravascular imaging of coronary arteries can be of help to identify angiographically undetected atherosclerosis. We report a case of an ST-segment elevation myocardial infarction (STEMI) in a young man with apparent evidence of arterial thrombosis resulting from protein C deficiency and heterozygous factor Leiden mutation which was contradicted by intravascular imaging demonstrating atherosclerosis.</p></span>" ] "pt" => array:2 [ "titulo" => "Resumo" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A deficiência de proteína C constitui uma alteração em cascata da coagulação, dá origem muitas vezes aos eventos tromboembólicos venosos e é também um contributo possível de trombose arterial. Aproximadamente dez casos de enfarte do miocárdio (EM) devidos à deficiência da proteína C foram referenciados na literatura. No entanto, a confirmação desse mecanismo requer a exclusão das etiologias mais comuns de EM, <span class="elsevierStyleItalic">i.e.</span> a rotura ou a erosão da placa aterosclerótica. A avaliação imagiológica intravascular das artérias coronárias poderia ser uma ajuda para identificar a aterosclerose não detetada por angiografia. Apresentamos o caso de um enfarte do miocárdio com elevação do segmento-ST (STEMI) que revela evidência aparente de trombose arterial devida à deficiência da proteína C e à mutação do fator heterozigótico Leiden que foi contestada através de avaliação imagiológica intravascular e demonstrou aterosclerose num homem novo.</p></span>" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0070" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>" "etiqueta" => "Appendix A" "titulo" => "Supplementary material" "identificador" => "sec0035" ] ] ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 661 "Ancho" => 1500 "Tamanyo" => 132509 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Panel A: Thrombus of the left anterior descending artery; Panel B: Total regression of the thrombus without visible stenosis.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1680 "Ancho" => 2500 "Tamanyo" => 351215 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Intravascular ultrasound confirms the diagnosis of plaque rupture with persistence of a lesion of the media of the artery.</p>" ] ] 2 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:3 [ "fichero" => "mmc1.mp4" "ficheroTamanyo" => 1010779 "Video" => array:2 [ "mp4" => array:5 [ "fichero" => "mmc1.m4v" "poster" => "mmc1.jpg" "tiempo" => 0 "alto" => 0 "ancho" => 0 ] "flv" => array:5 [ "fichero" => "mmc1.flv" "poster" => "mmc1.jpg" "tiempo" => 0 "alto" => 0 "ancho" => 0 ] ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:8 [ 0 => array:3 [ "identificador" => "bib0045" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Advances in understanding pathogenic mechanisms of thrombophilic disorders" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "B. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 6 | 6 | 12 |
| 2024 October | 44 | 29 | 73 |
| 2024 September | 54 | 22 | 76 |
| 2024 August | 47 | 25 | 72 |
| 2024 July | 33 | 35 | 68 |
| 2024 June | 37 | 28 | 65 |
| 2024 May | 33 | 23 | 56 |
| 2024 April | 34 | 23 | 57 |
| 2024 March | 44 | 32 | 76 |
| 2024 February | 37 | 23 | 60 |
| 2024 January | 22 | 20 | 42 |
| 2023 December | 29 | 24 | 53 |
| 2023 November | 27 | 34 | 61 |
| 2023 October | 31 | 17 | 48 |
| 2023 September | 23 | 15 | 38 |
| 2023 August | 31 | 15 | 46 |
| 2023 July | 39 | 12 | 51 |
| 2023 June | 47 | 14 | 61 |
| 2023 May | 61 | 23 | 84 |
| 2023 April | 40 | 7 | 47 |
| 2023 March | 64 | 24 | 88 |
| 2023 February | 48 | 22 | 70 |
| 2023 January | 29 | 11 | 40 |
| 2022 December | 49 | 33 | 82 |
| 2022 November | 76 | 29 | 105 |
| 2022 October | 66 | 32 | 98 |
| 2022 September | 46 | 33 | 79 |
| 2022 August | 44 | 38 | 82 |
| 2022 July | 37 | 47 | 84 |
| 2022 June | 45 | 27 | 72 |
| 2022 May | 39 | 33 | 72 |
| 2022 April | 48 | 37 | 85 |
| 2022 March | 39 | 46 | 85 |
| 2022 February | 37 | 38 | 75 |
| 2022 January | 65 | 27 | 92 |
| 2021 December | 20 | 27 | 47 |
| 2021 November | 38 | 32 | 70 |
| 2021 October | 34 | 38 | 72 |
| 2021 September | 25 | 25 | 50 |
| 2021 August | 32 | 36 | 68 |
| 2021 July | 55 | 26 | 81 |
| 2021 June | 24 | 21 | 45 |
| 2021 May | 26 | 39 | 65 |
| 2021 April | 55 | 72 | 127 |
| 2021 March | 27 | 21 | 48 |
| 2021 February | 37 | 18 | 55 |
| 2021 January | 25 | 17 | 42 |
| 2020 December | 36 | 9 | 45 |
| 2020 November | 19 | 16 | 35 |
| 2020 October | 24 | 11 | 35 |
| 2020 September | 33 | 18 | 51 |
| 2020 August | 24 | 7 | 31 |
| 2020 July | 40 | 13 | 53 |
| 2020 June | 37 | 10 | 47 |
| 2020 May | 36 | 9 | 45 |
| 2020 April | 45 | 10 | 55 |
| 2020 March | 34 | 5 | 39 |
| 2020 February | 42 | 23 | 65 |
| 2020 January | 27 | 6 | 33 |
| 2019 December | 29 | 5 | 34 |
| 2019 November | 23 | 6 | 29 |
| 2019 October | 34 | 8 | 42 |
| 2019 September | 20 | 10 | 30 |
| 2019 August | 22 | 6 | 28 |
| 2019 July | 26 | 10 | 36 |
| 2019 June | 23 | 11 | 34 |
| 2019 May | 18 | 8 | 26 |
| 2019 April | 24 | 15 | 39 |
| 2019 March | 22 | 14 | 36 |
| 2019 February | 32 | 7 | 39 |
| 2019 January | 17 | 11 | 28 |
| 2018 December | 28 | 11 | 39 |
| 2018 November | 53 | 16 | 69 |
| 2018 October | 71 | 9 | 80 |
| 2018 September | 18 | 11 | 29 |
| 2018 August | 24 | 4 | 28 |
| 2018 July | 9 | 1 | 10 |
| 2018 June | 18 | 5 | 23 |
| 2018 May | 22 | 5 | 27 |
| 2018 April | 29 | 1 | 30 |
| 2018 March | 103 | 22 | 125 |
| 2018 February | 12 | 4 | 16 |
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