Myocardial Infarction With Intracardiac Thrombosis as the Presentation of Acute Promyelocytic Leukemia
2011; Lippincott Williams & Wilkins; Volume: 123; Issue: 10 Linguagem: Inglês
10.1161/circulationaha.110.986208
ISSN1524-4539
AutoresThomas J. Cahill, Oni Chowdhury, Saul Myerson, Oliver Ormerod, Neil Herring, David Grimwade, Tim Littlewood, Andy Peniket,
Tópico(s)Antioxidant Activity and Oxidative Stress
ResumoHomeCirculationVol. 123, No. 10Myocardial Infarction With Intracardiac Thrombosis as the Presentation of Acute Promyelocytic Leukemia Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplementary MaterialsFree AccessResearch ArticlePDF/EPUBMyocardial Infarction With Intracardiac Thrombosis as the Presentation of Acute Promyelocytic LeukemiaDiagnosis and Follow-Up by Cardiac Magnetic Resonance Imaging Thomas J. Cahill, MA, MBBS, MRCP, Oni Chowdhury, MBBCh, MRCP, Saul G. Myerson, MBChB, MD, MRCP, FESC, Oliver Ormerod, DM, FRCP, Neil Herring, MA, DPhil, MRCP, David Grimwade, PhD, MRCP, FRCPath, Tim Littlewood, MBBCh, MD, FRCP, FRCPath and Andy Peniket, MBBCh, MRCP, FRCPath Thomas J. CahillThomas J. Cahill From the Department of Haematology (T.J.C., O.C., T.L., A.P.), Churchill Hospital, Oxford; Department of Cardiology (S.G.M., O.O., N.H.), John Radcliffe Hospital, Oxford, United Kingdom; and Department of Medical and Molecular Genetics (D.G.), King's College London School of Medicine, Guy's Hospital, London, United Kingdom. , Oni ChowdhuryOni Chowdhury From the Department of Haematology (T.J.C., O.C., T.L., A.P.), Churchill Hospital, Oxford; Department of Cardiology (S.G.M., O.O., N.H.), John Radcliffe Hospital, Oxford, United Kingdom; and Department of Medical and Molecular Genetics (D.G.), King's College London School of Medicine, Guy's Hospital, London, United Kingdom. , Saul G. MyersonSaul G. Myerson From the Department of Haematology (T.J.C., O.C., T.L., A.P.), Churchill Hospital, Oxford; Department of Cardiology (S.G.M., O.O., N.H.), John Radcliffe Hospital, Oxford, United Kingdom; and Department of Medical and Molecular Genetics (D.G.), King's College London School of Medicine, Guy's Hospital, London, United Kingdom. , Oliver OrmerodOliver Ormerod From the Department of Haematology (T.J.C., O.C., T.L., A.P.), Churchill Hospital, Oxford; Department of Cardiology (S.G.M., O.O., N.H.), John Radcliffe Hospital, Oxford, United Kingdom; and Department of Medical and Molecular Genetics (D.G.), King's College London School of Medicine, Guy's Hospital, London, United Kingdom. , Neil HerringNeil Herring From the Department of Haematology (T.J.C., O.C., T.L., A.P.), Churchill Hospital, Oxford; Department of Cardiology (S.G.M., O.O., N.H.), John Radcliffe Hospital, Oxford, United Kingdom; and Department of Medical and Molecular Genetics (D.G.), King's College London School of Medicine, Guy's Hospital, London, United Kingdom. , David GrimwadeDavid Grimwade From the Department of Haematology (T.J.C., O.C., T.L., A.P.), Churchill Hospital, Oxford; Department of Cardiology (S.G.M., O.O., N.H.), John Radcliffe Hospital, Oxford, United Kingdom; and Department of Medical and Molecular Genetics (D.G.), King's College London School of Medicine, Guy's Hospital, London, United Kingdom. , Tim LittlewoodTim Littlewood From the Department of Haematology (T.J.C., O.C., T.L., A.P.), Churchill Hospital, Oxford; Department of Cardiology (S.G.M., O.O., N.H.), John Radcliffe Hospital, Oxford, United Kingdom; and Department of Medical and Molecular Genetics (D.G.), King's College London School of Medicine, Guy's Hospital, London, United Kingdom. and Andy PeniketAndy Peniket From the Department of Haematology (T.J.C., O.C., T.L., A.P.), Churchill Hospital, Oxford; Department of Cardiology (S.G.M., O.O., N.H.), John Radcliffe Hospital, Oxford, United Kingdom; and Department of Medical and Molecular Genetics (D.G.), King's College London School of Medicine, Guy's Hospital, London, United Kingdom. Originally published15 Mar 2011https://doi.org/10.1161/CIRCULATIONAHA.110.986208Circulation. 2011;123:e370–e372A 29-year-old woman presented in February 2010 with acute-onset severe chest pain. This radiated to the left shoulder and was associated with breathlessness. She was afebrile, her saturations were 100% on air, and her clinical examination was entirely normal. An electrocardiogram showed diffuse 2- to 3-mm ST-segment elevation. At presentation, troponin I was elevated at 2.4 ng/mL (normal 160 mg/L (normal 20 000 μg/L (normal 0 to 500 μg/L). Her electrocardiogram showed further widespread ST elevation, and repeat bedside echocardiogram demonstrated a mass at the left ventricular apex, with apical hypokinesis (Figure 1 and online-only Data Supplement Movie I). A cardiac magnetic resonance scan revealed apical scarring consistent with a small myocardial infarct, with adherent apical thrombus in both the left and right ventricles (Figures 2 and 3 and online-only Data Supplement Movies II and III).Download figureDownload PowerPointFigure 1. A, Electrocardiogram showing diffuse ST-segment elevation. B, Transthoracic echocardiogram: apical 4-chamber view in systole showing mass (§) at the apex of the left ventricle (LV).Download figureDownload PowerPointFigure 2. A through C, Steady-state free-precession white blood images show the signal from the mass to be almost iso-intense to the myocardium. The right ventricle thrombus is poorly seen. D through F, Early gadolinium images show clear differentiation of the thrombus (black) from the myocardium.Download figureDownload PowerPointFigure 3. Late gadolinium images in the horizontal (A) and vertical (B) long axes, and an apical short axis plane (C) show thrombus at the left (§) and right (*) ventricular apices and enhancement in the myocardium of both apices, consistent with infarction (arrows).Coronary angiography showed no evidence of coronary artery disease. To exclude paradoxical embolism, a bubble echocardiogram was performed, which was normal. In view of her intracardiac thrombus, therapeutic dose low–molecular-weight heparin was commenced.Over the 3 days after admission, she developed an isolated neutropenia, with her neutrophil count dropping to 0.92× 109/L (2.0 to 7.0×109/L). In addition to her elevated D-dimer at presentation, she developed further evidence of a coagulopathy, with a prolonged prothrombin time (17.0 seconds, NR 12.0 to 15.5 seconds), activated partial thromboplastin time (39.1 seconds, NR 24 to 34 seconds) and low fibrinogen (1.4 g/L, NR 1.5 to 4.0). These results were consistent with disseminated intravascular coagulation.Examination of her peripheral blood film showed abnormal, granular, bilobed promyelocytes. A bone marrow aspirate was performed and demonstrated a diffuse infiltration of these abnormal promyelocytes, consistent with a diagnosis of acute promyelocytic leukemia (APL). She was started on all-trans retinoic acid (ATRA) and idarubicin chemotherapy according to an established protocol for management of APL. Her coagulopathy was corrected with fresh frozen plasma and cryoprecipitate.The diagnosis of APL was confirmed by molecular analysis, which showed a rare molecular variant (Signal Transducer and Activator of Transcription 5 beta - Retinoic Acid Receptor Alpha) rather than the typical ProMyelocytic Leukemia - Retinoic Acid Receptor Alpha fusion that occurs in ≈95% of cases. After completing 1 cycle of ATRA and idarubicin chemotherapy, the patient was in clinical, morphological, and cytogenetic remission.Signal Transducer and Activator of Transcription 5 beta - Retinoic Acid Receptor Alpha APL was first described in 1998, with only a handful of cases reported since.1 Clinical characterization remains poor, but it has previously been shown to be unresponsive to ATRA. On this basis, the patient was subsequently changed to standard chemotherapy for acute myeloid leukemia.A follow-up cardiac magnetic resonance imaging scan at 2 months showed dramatic reduction (although not complete resolution) in the thrombus size (Figure 4 and online-only Data Supplement Movie IV). The follow-up cardiac magnetic resonance imaging scan also showed a drop in ejection fraction from 71% to 45%, probably because of anthracycline chemotherapy. The patient has since had further chemotherapy and remains in remission to date.Download figureDownload PowerPointFigure 4. Follow-up study after 2 months of low–molecular-weight heparin and chemotherapy. Early (A) and late (B and C) gadolinium images show almost complete resolution of thrombus.DiscussionAPL accounts for 10% to 15% of cases of acute myeloid leukemia; patients characteristically present with pancytopenia and a coagulopathy, which may manifest as hemorrhage or thrombosis. Although bleeding is more common, accounting for the majority of the early mortality, ≈10% of patients with APL have evidence of thrombosis at presentation.2We hypothesize that our patient's myocardial infarct occurred because of in situ coronary artery thrombosis, previously reported as a rare presenting feature of APL.3,4 To our knowledge, this is the first report of intracardiac thrombus complicating acute myocardial infarction in APL. Other types of arterial thrombosis have been reported, including ischemic stroke and acute limb ischemia.Complex pathophysiology underlies the paradox of bleeding and thrombosis in APL. There is disseminated activation of the coagulation cascade, with release of potent procoagulant factors from leukemia cells, including tissue factor, cancer procoagulant, and prothrombotic cytokines. Tissue factor binds with factor VII whereas cancer procoagulant activates factor X, both acting to promote thrombosis.A critical component of the initial management of APL is blood product support, to correct the coagulopathy, and initiation of ATRA. Management of thrombosis in APL is without strong evidence base, but in the absence of bleeding, low–molecular-weight heparin may be of benefit by offsetting pathological activation of factor Xa by leukemia cells.In this case, myocardial ischemia resolved after initiation of low–molecular-weight heparin, but percutaneous coronary intervention has previously been described for coronary artery thrombosis in APL.3 Low–molecular-weight heparin was continued beyond the acute phase to reduce the risk of extension or embolization of the intracardiac thrombus.APL should be considered as a rare cause of myocardial infarction. Management of thrombosis in APL is complicated by the risk of life-threatening hemorrhage. For patients presenting with a thrombotic episode, prompt recognition of the underlying leukemia and initiation of appropriate therapy are key to reducing overall morbidity and mortality. In this case, cardiac magnetic resonance imaging aided both diagnosis and assessment of response to treatment of the intracardiac thrombus.AcknowledgmentsThe authors acknowledge the contributions of Jelena Jovanovic (Department of Medical and Molecular Genetics, King's College London, UK), Dr Paresh Vyas, Dr Anna Schuh, and the Cytogenetics Team (Churchill Hospital, Oxford, UK).Sources of FundingDr Peniket and Dr Myerson are supported by the Oxford NIHR Biomedical Research Centre. Professor Grimwade is funded by Leukaemia and Lymphoma Research. Dr Herring is a Clinical Lecturer in Cardiovascular Medicine at Oxford University and is supported by the British Heart Foundation.DisclosuresNone.FootnotesThe online-only Data Supplement is available with this article at http://circ.ahajournals.org/cgi/content/full/123/10/e370/DC1.Correspondence to Thomas J. Cahill, MA, MBBS, MRCP, Academic Clinical Fellow, Department of Cardiovascular Medicine, University of Oxford, Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford, OX3 7BN, UK. E-mail thomas.[email protected]ox.ac.ukReferences1. Arnould C, Philippe C, Bourdon V, Gregoire MJ, Berger R, Jonveaux P. The signal transducer and activator of transcription STAT5b gene is a new partner of retinoic acid receptor alpha in acute promyelocytic-like leukaemia. Human Mol Genet. 1999; 8:1741–1749CrossrefMedlineGoogle Scholar2. De Stefano V, Sorà F, Rossi E, Chiusolo P, Laurenti L, Fianchi L, Zini G, Pagano L, Sica S, Leone G. The risk of thrombosis in patients with acute leukemia: occurrence of thrombosis at diagnosis and during treatment. J Thromb Haemost. 2005; 3:1985–1992CrossrefMedlineGoogle Scholar3. Altwegg SC, Altwegg LA, Maier W. Intracoronary thrombus with tissue factor expression heralding acute promyelocytic leukaemia. Eur Heart J. 2007; 28:2731CrossrefMedlineGoogle Scholar4. Lou Y, Mai W, Jin J. Simultaneous presentation of acute myocardial infarction and acute promyelocytic leukemia. Ann Hematol. 2006; 85:409–410CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By MacDougall K, Chukkalore D, Rehan M, Kashi M and Bershadskiy A (2021) Acute promyelocytic leukemia presenting as recurrent venous and arterial thrombotic events: a case report and review of the literature, Journal of Community Hospital Internal Medicine Perspectives, 10.1080/20009666.2021.1973657, 11:6, (832-838), Online publication date: 2-Nov-2021. Feher A, Kampaktsis P, Parameswaran R, Stein E, Steingart R and Gupta D (2017) Aspirin Is Associated with Improved Survival in Severely Thrombocytopenic Cancer Patients with Acute Myocardial Infarction, The Oncologist, 10.1634/theoncologist.2016-0110, 22:2, (213-221), Online publication date: 1-Feb-2017. Liu L and Yuan X (2016) Transient ischemic attack as an unusual initial manifestation of acute promyelocytic leukemia, International Journal of Hematology, 10.1007/s12185-016-1982-6, 104:1, (134-138), Online publication date: 1-Jul-2016. Iliescu C, Grines C, Herrmann J, Yang E, Cilingiroglu M, Charitakis K, Hakeem A, Toutouzas K, Leesar M and Marmagkiolis K (2016) SCAI Expert consensus statement: Evaluation, management, and special considerations of cardio-oncology patients in the cardiac catheterization laboratory (endorsed by the cardiological society of india, and sociedad Latino Americana de Cardiologıa interve, Catheterization and Cardiovascular Interventions, 10.1002/ccd.26379, 87:5, (E202-E223), Online publication date: 1-Apr-2016. Kharwar R, Sharma K and Jain S (2016) Acute Myeloid Leukemia with Intracardiac Thrombus Presenting as Acute Limb Ischemia, Journal of Cardiovascular Ultrasound, 10.4250/jcu.2016.24.2.174, 24:2, (174), . Benedek I, Lázár E, Sándor-Kéri J, Bíró S, Jakab S and Benedek I (2016) Acute Coronary Syndromes in Patients with Hematological Disorders, Journal Of Cardiovascular Emergencies, 10.1515/jce-2016-0024, 2:4, (159-168), Online publication date: 1-Dec-2016. Munoz E, Iliescu G, Marmadgkiolis K and Iliescu C (2016) Miscellaneous Syndromes (Takotsubo's, Orthostasis, and Differentiation Syndrome) Clinical Cardio-Oncology, 10.1016/B978-0-323-44227-5.00015-6, (291-312), . Özkurt Z, Aypar E, Sarifakiogullari S, Taçoy G, Özdag M, Kahraman S and Çengel A (2015) Acute myocardial infarction as a finding of acute promyelocytic leukemia–related coagulation disorder, Blood Coagulation & Fibrinolysis, 10.1097/MBC.0000000000000331, 26:8, (949-952), Online publication date: 1-Dec-2015. Iland H, Seymour J and Wei A (2014) Optimal approach for high-risk acute promyelocytic leukemia, Current Opinion in Hematology, 10.1097/MOH.0000000000000025, 21:2, (102-113), Online publication date: 1-Mar-2014. Rashidi A, Silverberg M, Conkling P and Fisher S (2013) Thrombosis in acute promyelocytic leukemia, Thrombosis Research, 10.1016/j.thromres.2012.11.024, 131:4, (281-289), Online publication date: 1-Apr-2013. Chang H, Kuo M, Shih L, Wu J, Lin T, Dunn P, Tang T, Hung Y and Wang P (2013) Acute Promyelocytic Leukemia-Associated Thrombosis, Acta Haematologica, 10.1159/000345833, 130:1, (1-6), . Breen K, Grimwade D and Hunt B (2011) The pathogenesis and management of the coagulopathy of acute promyelocytic leukaemia, British Journal of Haematology, 10.1111/j.1365-2141.2011.08922.x, 156:1, (24-36), Online publication date: 1-Jan-2012. Sobas M, Talarn-Forcadell M, Martínez-Cuadrón D, Escoda L, García-Pérez M, Mariz J, Mela-Osorio M, Fernández I, Alonso-Domínguez J, Cornago-Navascués J, Rodríguez-Macias G, Amutio M, Rodríguez-Medina C, Esteve J, Sokół A, Murciano-Carrillo T, Calasanz M, Barrios M, Barragán E, Sanz M and Montesinos P (2020) PLZF-RARα, NPM1-RARα, and Other Acute Promyelocytic Leukemia Variants: The PETHEMA Registry Experience and Systematic Literature Review, Cancers, 10.3390/cancers12051313, 12:5, (1313) Guarnera L, Ottone T, Fabiani E, Divona M, Savi A, Travaglini S, Falconi G, Panetta P, Rapanotti M and Voso M (2022) Atypical Rearrangements in APL-Like Acute Myeloid Leukemias: Molecular Characterization and Prognosis, Frontiers in Oncology, 10.3389/fonc.2022.871590, 12 March 15, 2011Vol 123, Issue 10 Advertisement Article InformationMetrics © 2011 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.110.986208PMID: 21403118 Originally publishedMarch 15, 2011 PDF download Advertisement SubjectsComputerized Tomography (CT)Thrombosis
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