Rendimiento de redes neuronales artificiales para la predicción de sangrado en pacientes asistentes a una Clínica de Anticoagulación Fase I descriptiva

La anticoagulación demostró reducción de hasta 70% de tromboembolia, las intervenciones de una clínica de anticoagulación promueven la adherencia y uso seguro de las terapias. Se incluyeron 307 pacientes; con una mediana para la edad de 69 años, 58% fueron mujeres. Las comorbilidades asociadas fuero...

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Autores:
Romero Almanza, July Paola
Palomino Ariza, Gustavo Alejandro
Tipo de recurso:
Trabajo de grado de pregrado
Fecha de publicación:
2019
Institución:
Universidad Militar Nueva Granada
Repositorio:
Repositorio UMNG
Idioma:
spa
OAI Identifier:
oai:repository.unimilitar.edu.co:10654/36468
Acceso en línea:
http://hdl.handle.net/10654/36468
Palabra clave:
Anticoagulation clinic
HASBLED
Atrial Fibrillation
Anticoagulation
Risk of bleeding
MEDICINA INTERNA
REDES NEURALES (COMPUTADORES)
TROMBOSIS
HEMORRAGIA
ANTICOAGULANTES (MEDICINA)
Clínica de Anticoagulación
HASBLED
Fibrilación Auricular
Riesgo de sangrado
Anticoagulación
Rights
openAccess
License
http://creativecommons.org/licenses/by-nc-nd/4.0/
id UNIMILTAR2_ab0aacc6bfdba4a8b9a241cfc5689cd8
oai_identifier_str oai:repository.unimilitar.edu.co:10654/36468
network_acronym_str UNIMILTAR2
network_name_str Repositorio UMNG
repository_id_str
dc.title.spa.fl_str_mv Rendimiento de redes neuronales artificiales para la predicción de sangrado en pacientes asistentes a una Clínica de Anticoagulación Fase I descriptiva
dc.title.translated.spa.fl_str_mv Characterization of patients attending an anticoagulation clinic and factors associated with bleeding Phase I Descriptive
title Rendimiento de redes neuronales artificiales para la predicción de sangrado en pacientes asistentes a una Clínica de Anticoagulación Fase I descriptiva
spellingShingle Rendimiento de redes neuronales artificiales para la predicción de sangrado en pacientes asistentes a una Clínica de Anticoagulación Fase I descriptiva
Anticoagulation clinic
HASBLED
Atrial Fibrillation
Anticoagulation
Risk of bleeding
MEDICINA INTERNA
REDES NEURALES (COMPUTADORES)
TROMBOSIS
HEMORRAGIA
ANTICOAGULANTES (MEDICINA)
Clínica de Anticoagulación
HASBLED
Fibrilación Auricular
Riesgo de sangrado
Anticoagulación
title_short Rendimiento de redes neuronales artificiales para la predicción de sangrado en pacientes asistentes a una Clínica de Anticoagulación Fase I descriptiva
title_full Rendimiento de redes neuronales artificiales para la predicción de sangrado en pacientes asistentes a una Clínica de Anticoagulación Fase I descriptiva
title_fullStr Rendimiento de redes neuronales artificiales para la predicción de sangrado en pacientes asistentes a una Clínica de Anticoagulación Fase I descriptiva
title_full_unstemmed Rendimiento de redes neuronales artificiales para la predicción de sangrado en pacientes asistentes a una Clínica de Anticoagulación Fase I descriptiva
title_sort Rendimiento de redes neuronales artificiales para la predicción de sangrado en pacientes asistentes a una Clínica de Anticoagulación Fase I descriptiva
dc.creator.fl_str_mv Romero Almanza, July Paola
Palomino Ariza, Gustavo Alejandro
dc.contributor.advisor.none.fl_str_mv Palomino Ariza, Gustavo Alejandro
dc.contributor.author.none.fl_str_mv Romero Almanza, July Paola
Palomino Ariza, Gustavo Alejandro
dc.contributor.corporatename.spa.fl_str_mv Universidad Militar Nueva Granada
dc.subject.keywords.spa.fl_str_mv Anticoagulation clinic
HASBLED
Atrial Fibrillation
Anticoagulation
Risk of bleeding
topic Anticoagulation clinic
HASBLED
Atrial Fibrillation
Anticoagulation
Risk of bleeding
MEDICINA INTERNA
REDES NEURALES (COMPUTADORES)
TROMBOSIS
HEMORRAGIA
ANTICOAGULANTES (MEDICINA)
Clínica de Anticoagulación
HASBLED
Fibrilación Auricular
Riesgo de sangrado
Anticoagulación
dc.subject.decs.spa.fl_str_mv MEDICINA INTERNA
REDES NEURALES (COMPUTADORES)
TROMBOSIS
HEMORRAGIA
ANTICOAGULANTES (MEDICINA)
dc.subject.proposal.spa.fl_str_mv Clínica de Anticoagulación
HASBLED
Fibrilación Auricular
Riesgo de sangrado
Anticoagulación
description La anticoagulación demostró reducción de hasta 70% de tromboembolia, las intervenciones de una clínica de anticoagulación promueven la adherencia y uso seguro de las terapias. Se incluyeron 307 pacientes; con una mediana para la edad de 69 años, 58% fueron mujeres. Las comorbilidades asociadas fueron; 58.9% hipertensión arterial, 32,2% fibrilación auricular 23,8%, insuficiencia cardiaca congestiva, 20,2% diabetes mellitus tipo 2. Las principales indicaciones para anticoagulación fueron tromboembolismo venoso, fibrilación auricular no valvular y portador de válvula cardiaca. Los desenlaces significativos en pacientes con sangrado fueron sobreanticoagulación de importancia clínica, hospitalización y mortalidad. Este estudio permitió identificar diferencias entre pacientes que presentaron sangrado y permitió validar algunos de los principales factores relacionados con el sangrado y desenlaces adversos.
publishDate 2019
dc.date.issued.none.fl_str_mv 2019-12-12
dc.date.accessioned.none.fl_str_mv 2020-10-03T12:25:29Z
dc.date.available.none.fl_str_mv 2020-10-03T12:25:29Z
dc.type.local.spa.fl_str_mv Tesis/Trabajo de grado - Monografía - Especialización
dc.type.driver.spa.fl_str_mv info:eu-repo/semantics/bachelorThesis
dc.type.coar.*.fl_str_mv http://purl.org/coar/resource_type/c_7a1f
format http://purl.org/coar/resource_type/c_7a1f
dc.identifier.uri.none.fl_str_mv http://hdl.handle.net/10654/36468
dc.identifier.instname.spa.fl_str_mv instname:Universidad Militar Nueva Granada
dc.identifier.reponame.spa.fl_str_mv reponame:Repositorio Institucional Universidad Militar Nueva Granada
dc.identifier.repourl.spa.fl_str_mv repourl:https://repository.unimilitar.edu.co
url http://hdl.handle.net/10654/36468
identifier_str_mv instname:Universidad Militar Nueva Granada
reponame:Repositorio Institucional Universidad Militar Nueva Granada
repourl:https://repository.unimilitar.edu.co
dc.language.iso.spa.fl_str_mv spa
language spa
dc.relation.references.spa.fl_str_mv 1. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37(38):2893–962.
2. Comité SEC-Sociedad Española de Cardiología. Fibrilación Auricular Estándar de Calidad SEC. Sociedad Española de Cardiología. 2015. 1–73 p.
3. MacFarlane RG. An Enzyme Cascade in the Blood Clotting Mechanism, and its Function as a Biochemical Amplifier. Nature. 1964;202(4931):498–9.
4. Jerjes-sánchez C, Cantú-brito C, Arauz A, Martínez-sánchez C, Eid-lidt G, Elizalde-gonzález JJ, et al. Guías para Anticoagulación y Trombolisis del Tromboembolismo Venoso, Infarto con Elevación del ST, Cardioembolismo Cerebral y del Infarto Cerebral Agudo. Arch Cardiol Mex. 2017;87(supl 1):1–66.
5. Morrison SA, Jesty J. Tissue factor-dependent activation of tritium-labeled factor IX and factor X in human plasma. Blood. 1984;63(6):1338–47.
6. Vidaillet H, Granada JF, Chyou P.-H, Maassen K, Ortiz M, Pulido JN, et al. A population-based study of mortality among patients with atrial fibrillation or flutter. Am J Med. 2002;113(5):365–70.
7. Kannel WB, Abbott RD, Savage DD, McNamara PM. Epidemiologic Features of Chronic Atrial Fibrillation. N Engl J Med. 1982;306(17):1018–22. .
8. Wolf PA, D’Agostino RB, Belanger AJ, Kannel WB. Probability of stroke: a risk profile from the Framingham Study. Stroke. 1991;22(3):312–8.
9. Wolf PA, Dawber TR, Thomas HE, Kannel WB. Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: The fiamingham Study. Neurology. 1978;28(10):973
0. Stollberger C. Transesophageal Echocardiography To Assess Embolic Risk in Patients with Atrial Fibrillation. Ann Intern Med. 1998;128(8):630.
11. Chimowitz MI, DeGeorgia MA, Poole RM, Hepner A, Armstrong WM. Left atrial spontaneous echo contrast is highly associated with previous stroke in patients with atrial fibrillation or mitral stenosis. Stroke. 1993;24(7):1015–9.
12. Ntaios G, Lip GYH, Makaritsis K, Papavasileiou V, Vemmou A, Koroboki E, et al. CHADS2, CHA2DS2-VASc, and long-term stroke outcome in patients without atrial fibrillation. Neurology. 2013;80(11):1009–17.
13. Ostrander LD, Brandt RL, Kjelsberg MO, Epstein FH. Electrocardiographic Findings Among the Adult Population of a Total Natural Community, Tecumseh, Michigan. Circulation. 1965;31(6):888–98.
14. Lijfering WM, Rosendaal FR, Cannegieter SC. Risk factors for venous thrombosis - current understanding from an epidemiological point of view. Br J Haematol. 2010;149(6):824–33.
15. Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G. Oral Anticoagulant Therapy. Chest. 2012;141(2):e44S-e88S
16. Barnes GD, Ageno W, Ansell J, Kaatz S. Recommendation on the nomenclature for oral anticoagulants: communication from the SSC of the ISTH. J Thromb Haemost. 2015;13(6):1154–6.
17. Seligsohn U, Lubetsky A. Genetic Susceptibility to Venous Thrombosis. N Engl J Med. 2001;344(16):1222–31.
18. Anderson FA. A Population-Based Perspective of the Hospital Incidence and Case-Fatality Rates of Deep Vein Thrombosis and Pulmonary Embolism. Arch Intern Med. 1991;151(5):933.
19. Subar M. Clinical evaluation of hypercoagulable states. Clin Geriatr Med. 2001;17(1):57–70.
20. Silverstein MD, Heit JA, Mohr DN, Petterson TM, O’Fallon WM, Melton LJ. Trends in the Incidence of Deep Vein Thrombosis and Pulmonary Embolism. Arch Intern Med. 1998;158(6):585.
21. Pengo V, Lensing AWA, Prins MH, Marchiori A, Davidson BL, Tiozzo F, et al. Incidence of Chronic Thromboembolic Pulmonary Hypertension after Pulmonary Embolism. N Engl J Med. 2004;350(22):2257–64.
22. Cannegieter SC, Rosendaal FR, Briët E. Thromboembolic and bleeding complications in patients with mechanical heart valve prostheses. Circulation. 1994;89(2):635–41.
23. Mok CK, Boey J, Wang R, Chan TK, Cheung KL, Lee PK, et al. Warfarin versus dipyridamole-aspirin and pentoxifylline-aspirin for the prevention of prosthetic heart valve thromboembolism: a prospective randomized clinical trial. Circulation. 1985 Nov;72(5):1059–63.
24. Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. EP Eur. 2013;15(5):625–51.
25. Heneghan C, Ward A, Perera R, Bankhead C, Fuller A, Stevens R, et al. Self-monitoring of oral anticoagulation: systematic review and meta-analysis of individual patient data. Lancet. 2012;379(9813):322–34.
26. Fiedler KA, Maeng M, Mehilli J, Schulz-Schüpke S, Byrne RA, Sibbing D, et al. Duration of Triple Therapy in Patients Requiring Oral Anticoagulation After Drug-Eluting Stent Implantation. J Am Coll Cardiol. 2015;65(16):1619–29.
27. Gibson CM, Mehran R, Bode C, Halperin J, Verheugt FW, Wildgoose P, et al. Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI. N Engl J Med. 2016;375(25):2423–34.
28. Gelfand E V, Piazza G, Goldhaber SZ. Venous Thromboembolism Guidebook. Crit Pathways Cardiol A J Evidence-Based Med. 2002;1(1):26–43.
29. Goldhaber SZ, Morrison RB. Pulmonary Embolism and Deep Vein Thrombosis. Circulation. 2002;106(12):1436–8.
30. Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. J Am Coll Cardiol. 1988 Dec;12(6):A3–13
31. Ornato JP, Hand MM. Warning Signs of a Heart Attack. Circulation. 2001;104(11):1212–3.
32. Weitz JI. Low-Molecular-Weight Heparins. N Engl J Med. 1997;337(10):688–99.
33. Hirsh J, Levine MN. Low molecular weight heparin. Blood. 1992;79(1):1–17.
34. Prandoni P. Heparins and Venous Thromboembolism: Current Practice and Future Directions. Thromb Haemost. 2001;86(07):488–98.
35. White RH, Ginsberg JS. Low-Molecular-Weight Heparins: Are they all the Same? Br J Haematol. 2003;121(1):12–20.
36. Choay J, Petitou M, Lormeau JC, Sinaÿ P, Casu B, Gatti G. Structure-activity relationship in heparin: A synthetic pentasaccharide with high affinity for antithrombin III and eliciting high anti-factor Xa activity. Biochem Biophys Res Commun. 1983;116(2):492–9.
37. Marcum JA, McKenney JB, Rosenberg RD. Acceleration of thrombin-antithrombin complex formation in rat hindquarters via heparinlike molecules bound to the endothelium. J Clin Invest. 1984;74(2):341–50.
38. Rojas L, Aizman A, Ernst D, Acuña MP, Moya P, Mellado R, et al. Anti-Xa Activity After Enoxaparin Prophylaxis In Hospitalized Patients Weighing Less Than Fifty-Five Kilograms. Thromb Res. 2013;132(6):761–4.
39. Harrison L. Comparison of 5-mg and 10-mg Loading Doses in Initiation of Warfarin Therapy. Ann Intern Med. 1997;126(2):133.
40. Crowther MA, Ginsberg JB, Kearon C, Harrison L, Johnson J, Massicotte MP, et al. A Randomized Trial Comparing 5-mg and 10-mg Warfarin Loading Doses. Arch Intern Med. 1999;159(1):46.
41. Poller L, Keown M, Ibragim S, Lowe G, Moia M, Turpie AG, et al. An international multicenter randomized study of computer-assisted oral anticoagulant dosage vs. medical staff dosage. J Thromb Haemost. 2008;6(6):935–43.
42. Gage BF, Eby C, Johnson JA, Deych E, Rieder MJ, Ridker PM, et al. Use of Pharmacogenetic and Clinical Factors to Predict the Therapeutic Dose of Warfarin. Clin Pharmacol Ther. 2008;84(3):326–31.
43. Kovacs MJ, Rodger M, Anderson DR, Morrow B, Kells G, Kovacs J, et al. Comparison of 10-mg and 5-mg Warfarin Initiation Nomograms Together with Low-Molecular-Weight Heparin for Outpatient Treatment of Acute Venous Thromboembolism. Ann Intern Med. 2003;138(9):714.
44. Lubetsky A, Dekel-Stern E, Chetrit A, Lubin F, Halkin H. Vitamin K Intake and Sensitivity to Warfarin in Patients Consuming Regular Diets. Thromb Haemost. 1999;81(03):396–9.
45. Masuko S, Linhardt RJ. Chemoenzymatic synthesis of the next generation of ultralow MW heparin therapeutics. Future Med Chem. 2012;4(3):289–96.
46. Samama MM. The mechanism of action of rivaroxaban – an oral, direct Factor Xa inhibitor – compared with other anticoagulants. Thromb Res. 2011;127(6):497–504
47. Stangier J, Rathgen K, Stähle H, Mazur D. Influence of Renal Impairment on the Pharmacokinetics and Pharmacodynamics of Oral Dabigatran Etexilate. Clin Pharmacokinet. 2010;49(4):259–68.
48. Bristol-Myers Squibb. eliquis (apixaban) prescribing information. 2019. p. 1–16.
49. Belley-Cote E, Hanif H, D’Aragon F, Eikelboom J, Anderson J, Borgman M, et al. Genotype-guided versus standard vitamin K antagonist dosing algorithms in patients initiating anticoagulation. Thromb Haemost. 2015;114(10):768–77.
50. Benedetti G, Neccia M, Agati L. Direct oral anticoagulants use in elderly patients with non valvular atrial fibrillation: state of evidence. Minerva Cardioangiol. 2018;66(3):301–13.
51. Huhtakangas J, Tetri S, Juvela S, Saloheimo P, Bode MK, Hillbom M. Effect of Increased Warfarin Use on Warfarin-Related Cerebral Hemorrhage. Stroke. 2011;42(9):2431–5.
52. Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJGM, Lip GYH. A Novel User-Friendly Score (HAS-BLED) To Assess 1-Year Risk of Major Bleeding in Patients With Atrial Fibrillation. Chest. 2010;138(5):1093–100.
53. Beyth RJ, Quinn LM, Landefeld CS. Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin. Am J Med. 1998;105(2):91–9.
54. Gage BF, Yan Y, Milligan PE, Waterman AD, Culverhouse R, Rich MW, et al. Clinical classification schemes for predicting hemorrhage: Results from the National Registry of Atrial Fibrillation (NRAF). Am Heart J. 2006;151(3):713–9.
55. Singh S, Kaur S, Goel N. A Review of Computational Intelligence Methods for Eukaryotic Promoter Prediction. Nucleosides, Nucleotides and Nucleic Acids. 2015;34(7):449–62.
56. Xie J, Ding W, Chen L, Guo Q, Zhang W. Advances in Protein Contact Map Prediction Based on Machine Learning. Med Chem (Los Angeles). 2015;11(3):265–70.
57. Lima AN, Philot EA, Trossini GHG, Scott LPB, Maltarollo VG, Honorio KM. Use of machine learning approaches for novel drug discovery. Expert Opin Drug Discov. 2016;11(3):225–39.
58. Lugo-Reyes SO, Maldonado-Colín G, Murata C. Artificial intelligence to assist clinical diagnosis in medicine. Rev Alerg Mex. 2014;61(2):110–20.
59. Roldán V, Marín F, Muiña B, Torregrosa JM, Hernández-Romero D, Valdés M, et al. Plasma von Willebrand Factor Levels Are an Independent Risk Factor for Adverse Events Including Mortality and Major Bleeding in Anticoagulated Atrial Fibrillation Patients. J Am Coll Cardiol. 2011;57(25):2496–504.
60. Nutescu EA, Macik BG, Nutescu EA. The Future of Anticoagulation Clinics. J Thromb Thrombolysis. 2003;16(1/2):61–3.
62. Chiquette E, Amato MG, Bussey HI. Comparison of an Anticoagulation Clinic With Usual Medical Care. Arch Intern Med. 1998;158(15):1641.
64. Hirsh J, Dalen JE, Anderson DR, Poller L, Bussey H, Ansell J, et al. Oral Anticoagulants: Mechanism of Action, Clinical Effectiveness, and Optimal Therapeutic Range. Chest. 2001;119(1):8S-21S.
65. Sociedad Colombiana de Cardiología y Cirugía Cardiovascular. Clínica de Anticoagulación. Primera Ed. 2005.
66. Franchini M, Mannucci PM. New anticoagulants for treatment of venous thromboembolism. Eur J Intern Med. 2012;23(8):692–5.
67. Agewall S, Camm J, Barón Esquivias G, Budts W, Carerj S, Casselman F, et al. Guía ESC 2016 sobre el diagnóstico y tratamiento de la fibrilación auricular, desarrollada en colaboración con la EACTS. Rev Española Cardiol. 2017;70(1):50.e1-50.e84.
68. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J Chronic Dis. 1987 Jan;40(5):373–83.
69. Quan H, Li B, Couris CM, Fushimi K, Graham P, Hider P, et al. Updating and Validating the Charlson Comorbidity Index and Score for Risk Adjustment in Hospital Discharge Abstracts Using Data From 6 Countries. Am J Epidemiol. 2011 Mar 15;173(6):676–82.
70. Lip GYH, Frison L, Halperin JL, Lane DA. Comparative Validation of a Novel Risk Score for Predicting Bleeding Risk in Anticoagulated Patients With Atrial Fibrillation. J Am Coll Cardiol. 2011;57(2):173–80.
71. Lip GYH, Nieuwlaat R, Pisters R, Lane DA, Crijns HJGM. Refining Clinical Risk Stratification for Predicting Stroke and Thromboembolism in Atrial Fibrillation Using a Novel Risk Factor-Based Approach. Chest. 2010;137(2):263–72.
72. Olesen JB, Lip GYH, Hansen PR, Lindhardesen J, Ahlehoff O, Andersson C, et al. Bleeding risk in ‘real world’ patients with atrial fibrillation: comparison of two established bleeding prediction schemes in a nationwide cohort. J Thromb Haemost. 2011;9(8):1460–7.
73. Senoo K, Lau YC, Lip GYH. Updated NICE guideline: management of atrial fibrillation (2014). Expert Rev Cardiovasc Ther. 2014;12(9):1037–40.
74. Pugh RNH, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973 Aug;60(8):646–9.
75. Cockcroft DW, Gault H. Prediction of Creatinine Clearance from Serum Creatinine. Nephron. 1976;16(1):31–41.
76. Levey AS, Stevens LA, Schmid CH, Zhang Y (Lucy), Castro AF, Feldman HI, et al. A New Equation to Estimate Glomerular Filtration Rate. Ann Intern Med. 2009 May 5;150(9):604.
77. Inker LA, Schmid CH, Tighiouart H, Eckfeldt JH, Feldman HI, Greene T, et al. Estimating Glomerular Filtration Rate from Serum Creatinine and Cystatin C. N Engl J Med. 2012 Jul 5;367(1):20–9.
78. Laverde LP, Gómez SE, Montenegro AC, Lineros A, Wills B, Buitrago AF. Experiencia de una clínica de anticoagulación. Rev Colomb Cardiol. 2015 Sep;22(5):224–30.
79. Miranda H, Osório S, Giraldo DP, Duque J, Ubeimar-Cataño J, Tobón LI. Tiempo en rango terapéutico (TRT) en clínica de anticoagulación: Reportes de eventos adversos y factores asociados a bajo TRT. Acta Médica Colomb. 2016;41(1):42–8.
80. Ocampo Kohn C, Hernández Ortiz O, Velásquez Franco CJ, Tobón Acosta LI, Mejía Restrepo FA. La clínica de anticoagulación del Hospital Universitario San Vicente de Paúl: demografía, efectividad y complicaciones. Iatreia. 2004;17(2):105–14.
81. Fanikos J, Grasso-Correnti N, Shah R, Kucher N, Goldhaber SZ. Major Bleeding Complications in a Specialized Anticoagulation Service. Am J Cardiol. 2005 Aug;96(4):595–8.
82. Jover E, Roldán V, Gallego P, Hernández-Romero D, Valdés M, Vicente V, et al. Valor predictivo de la escala CHA 2DS 2-VASc en pacientes con fibrilación auricular de alto riesgo embólico en tratamiento anticoagulante. Rev Esp Cardiol. 2012;65(7):627–33.
83. Lip GY, Golding DJ, Nazir M, Beevers DG, Child DL, Fletcher RI. A survey of atrial fibrillation in general practice: the West Birmingham Atrial Fibrillation Project. Br J Gen Pract. 1997 May;47(418):285–9.
84. Pinto DA, Sánchez-Vallejo CA, López Pedraza A, Vergara EP, Sáenz ÓA, González F, et al. Descripción de los pacientes con fibrilación auricular no valvular que ingresan al servicio de urgencias. Rev Colomb Cardiol. 2016;23(4):270–6.
84. Pinto DA, Sánchez-Vallejo CA, López Pedraza A, Vergara EP, Sáenz ÓA, González F, et al. Descripción de los pacientes con fibrilación auricular no valvular que ingresan al servicio de urgencias. Rev Colomb Cardiol. 2016;23(4):270–6.
85. Enríquez A, Baranchuk A, Corbalán R. Manejo de hemorragia asociada a anticoagulantes orales directos: estado actual de las estrategias de reversión. Rev Med Chil. 2019;147(1):73–82.
86. Ntaios G, Papavasileiou V, Makaritsis K, Vemmos K, Michel P, Lip GYH. Real-World Setting Comparison of Nonvitamin-K Antagonist Oral Anticoagulants Versus Vitamin-K Antagonists for Stroke Prevention in Atrial Fibrillation. Stroke. 2017 Sep;48(9):2494–503.
87. Wilkins T, Wheeler B, Carpenter M. Upper Gastrointestinal Bleeding in Adults: Evaluation and Management. Am Fam Physician. 2020;101(5):294–300.
88. Mantilla-Villabona LY, Ospina-Galeano DC, Gutiérrez-Ortiz AJ, Camacho PA. Pacientes con fibrilación auricular atendidos en consulta de atención primaria de una institución de alta complejidad. Rev Colomb Cardiol. 2018;25(2):124–30.
88. Mantilla-Villabona LY, Ospina-Galeano DC, Gutiérrez-Ortiz AJ, Camacho PA. Pacientes con fibrilación auricular atendidos en consulta de atención primaria de una institución de alta complejidad. Rev Colomb Cardiol. 2018;25(2):124–30.
89. Brenner PF. Differential diagnosis of abnormal uterine bleeding. Am J Obstet Gynecol. 1996 Sep;175(3):766–9.
90. Wilansky DL, Greisman B. Early hypothyroidism in patients with menorrhagia. Am J Obstet Gynecol. 1989 Mar;160(3):673–7.
91. Pincus D, Gomes T, Hellings C, Zheng H, Paterson JM, Mamdani MM, et al. A Population-Based Assessment of the Drug Interaction Between Levothyroxine and Warfarin. Clin Pharmacol Ther. 2012 Dec 24;92(6):766–70.
91. Pincus D, Gomes T, Hellings C, Zheng H, Paterson JM, Mamdani MM, et al. A Population-Based Assessment of the Drug Interaction Between Levothyroxine and Warfarin. Clin Pharmacol Ther. 2012 Dec 24;92(6):766–70.
92. Kamthornthanakarn I, Krittayaphong R. Optimal INR level for warfarin therapy after mechanical mitral valve replacement. BMC Cardiovasc Disord. 2019 Dec 25;19(1):97.
93. Aimo A, Giugliano RP, De Caterina R. Non–Vitamin K Antagonist Oral Anticoagulants for Mechanical Heart Valves. Circulation. 2018 Sep 25;138(13):1356–65.
94. Wojakowski E, Cheruvil C, Hassan A, Holsen MR, Chen L, Rossi M, et al. Albumin and bleed risk in rivaroxaban treated patients. J Thromb Thrombolysis. 2020 Apr 11;
95. Fender AC, Dobrev D. Bound to bleed: How altered albumin binding may dictate warfarin treatment outcome. IJC Hear Vasc. 2019 Mar;22:214–5.
96. Kawai M, Harada M, Motoike Y, Koshikawa M, Ichikawa T, Watanabe E, et al. Impact of serum albumin levels on supratherapeutic PT-INR control and bleeding risk in atrial fibrillation patients on warfarin: A prospective cohort study. IJC Hear Vasc. 2019 Mar;22:111–6.
97. Zeng J, Yu P, Cui W, Wang X, Ma J, Zeng C. Comparison of HAS-BLED with other risk models for predicting the bleeding risk in anticoagulated patients with atrial fibrillation. Medicine (Baltimore). 2020 Jun 19;99(25):e20782.
98. Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014 Mar;383(9921):955–62.
99. Murphy A, Banerjee A, Breithardt G, Camm AJ, Commerford P, Freedman B, et al. The World Heart Federation Roadmap for Nonvalvular Atrial Fibrillation. Glob Heart. 2017;12(4):273–84.
100. Lee V, Jairam V, Yu JB, Park HS. Nationwide patterns of hemorrhagic stroke among patients hospitalized with brain metastases: influence of primary cancer diagnosis and anticoagulation. Sci Rep. 2020 Dec 22;10(1):10084.
101. Dahal K, Kunwar S, Rijal J, Schulman P, Lee J. Stroke, Major Bleeding, and Mortality Outcomes in Warfarin Users With Atrial Fibrillation and Chronic Kidney Disease. Chest. 2016 Apr;149(4):951–9
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spelling Palomino Ariza, Gustavo AlejandroRomero Almanza, July PaolaPalomino Ariza, Gustavo AlejandroEspecialista en Medicina InternaUniversidad Militar Nueva GranadaHospital Militar Central Bogotá D.CEnero a Agosto de 2020Medicina2020-10-03T12:25:29Z2020-10-03T12:25:29Z2019-12-12http://hdl.handle.net/10654/36468instname:Universidad Militar Nueva Granadareponame:Repositorio Institucional Universidad Militar Nueva Granadarepourl:https://repository.unimilitar.edu.coLa anticoagulación demostró reducción de hasta 70% de tromboembolia, las intervenciones de una clínica de anticoagulación promueven la adherencia y uso seguro de las terapias. Se incluyeron 307 pacientes; con una mediana para la edad de 69 años, 58% fueron mujeres. Las comorbilidades asociadas fueron; 58.9% hipertensión arterial, 32,2% fibrilación auricular 23,8%, insuficiencia cardiaca congestiva, 20,2% diabetes mellitus tipo 2. Las principales indicaciones para anticoagulación fueron tromboembolismo venoso, fibrilación auricular no valvular y portador de válvula cardiaca. Los desenlaces significativos en pacientes con sangrado fueron sobreanticoagulación de importancia clínica, hospitalización y mortalidad. Este estudio permitió identificar diferencias entre pacientes que presentaron sangrado y permitió validar algunos de los principales factores relacionados con el sangrado y desenlaces adversos.TABLA DE CONTENIDO 1. RESUMEN 5 2. INTRODUCCIÓN 7 3. MARCO TEÓRICO 9 4. IDENTIFICACIÓN Y FORMULACIÓN DEL PROBLEMA 21 4.1. PREGUNTA DE INVESTIGACIÓN 22 5. OBJETIVOS E HIPÓTESIS 23 5.1. GENERAL 23 5.2. ESPECÍFICOS 23 5.3. HIPÓTESIS 23 6. METODOLOGÍA 25 6.1 TIPO Y DISEÑO GENERAL DEL ESTUDIO 25 6.2 LUGAR DE LA INVESTIGACIÓN 25 6.3 POBLACIÓN 25 6.3.1. Población Blanco 25 6.3.2. Población Referencia 25 6.3.3. Población estudio 25 6.4 CRITERIOS DE INCLUSIÓN Y EXCLUSIÓN 26 6.4.1 Criterios de inclusión 26 6.4.2 Criterios de exclusión 26 6.5 SELECCIÓN Y TAMAÑO DE MUESTRA 26 6.5.1. Muestreo 26 6.5.2. Tamaño de la muestra 27 6.6 DEFINICIÓN DE LAS VARIABLES 28 6.7. ESTUDIOS DE INTERVENCIÓN 34 6.8. ESTRATEGIAS PARA SUPRIMIR AMENAZAS A LA VALIDEZ DE RESULTADOS 34 6.9. INSTRUMENTOS UTILIZADOS 35 6.10. PLAN DE RECOLECCIÓN DE DATOS 37 6.11. PLAN DE ANÁLISIS 39 7. ASPECTOS ÉTICOS 40 8. RESULTADOS 42 9. DISCUSIÓN 50 10. CONCLUSIONES 60 11. REFERENCIAS BIBLIOGRÁFICAS 62Anticoagulation demonstrated up to 70% reduction of thromboembolis, the interventions of an anticoagulation clinic promote adherence and a safe use of these therapies.307 patients were included; with a median for age of 69 years, 58% were women. The associated comorbidities were 58.9% arterial hypertension, 32.2% atrial fibrillation 23.8%, congestive heart failure, 20.2% type 2 diabetes mellitus. The main indications for anticoagulation were venous thromboembolism, nonvalvular atrial fibrillation and heart valve carrier. The significant outcomes in patients with bleeding compared to those who did not bleed were clinically important overanticoagulation (30.9% vs 3.8%, p = 0.00001), hospitalization (45.2% vs 4.5%, p = 0 , 00001) and mortality (7.1% vs 0.7%, p = 0.002). This study made it possible to identify differences between patients who presented bleeding and allowed to validate some of the main factors related to bleeding and adverse outcomes.Especializaciónapplicaction/pdfspahttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 InternationalAcceso abiertoRendimiento de redes neuronales artificiales para la predicción de sangrado en pacientes asistentes a una Clínica de Anticoagulación Fase I descriptivaCharacterization of patients attending an anticoagulation clinic and factors associated with bleeding Phase I DescriptiveTesis/Trabajo de grado - Monografía - Especializacióninfo:eu-repo/semantics/bachelorThesishttp://purl.org/coar/resource_type/c_7a1fAnticoagulation clinicHASBLEDAtrial FibrillationAnticoagulationRisk of bleedingMEDICINA INTERNAREDES NEURALES (COMPUTADORES)TROMBOSISHEMORRAGIAANTICOAGULANTES (MEDICINA)Clínica de AnticoagulaciónHASBLEDFibrilación AuricularRiesgo de sangradoAnticoagulaciónMedicina InternaFacultad de MedicinaUniversidad Militar Nueva Granada1. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37(38):2893–962.2. Comité SEC-Sociedad Española de Cardiología. Fibrilación Auricular Estándar de Calidad SEC. Sociedad Española de Cardiología. 2015. 1–73 p.3. MacFarlane RG. An Enzyme Cascade in the Blood Clotting Mechanism, and its Function as a Biochemical Amplifier. Nature. 1964;202(4931):498–9.4. Jerjes-sánchez C, Cantú-brito C, Arauz A, Martínez-sánchez C, Eid-lidt G, Elizalde-gonzález JJ, et al. Guías para Anticoagulación y Trombolisis del Tromboembolismo Venoso, Infarto con Elevación del ST, Cardioembolismo Cerebral y del Infarto Cerebral Agudo. Arch Cardiol Mex. 2017;87(supl 1):1–66.5. Morrison SA, Jesty J. Tissue factor-dependent activation of tritium-labeled factor IX and factor X in human plasma. Blood. 1984;63(6):1338–47.6. Vidaillet H, Granada JF, Chyou P.-H, Maassen K, Ortiz M, Pulido JN, et al. A population-based study of mortality among patients with atrial fibrillation or flutter. Am J Med. 2002;113(5):365–70.7. Kannel WB, Abbott RD, Savage DD, McNamara PM. Epidemiologic Features of Chronic Atrial Fibrillation. N Engl J Med. 1982;306(17):1018–22. .8. Wolf PA, D’Agostino RB, Belanger AJ, Kannel WB. Probability of stroke: a risk profile from the Framingham Study. Stroke. 1991;22(3):312–8.9. Wolf PA, Dawber TR, Thomas HE, Kannel WB. Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: The fiamingham Study. Neurology. 1978;28(10):9730. Stollberger C. Transesophageal Echocardiography To Assess Embolic Risk in Patients with Atrial Fibrillation. Ann Intern Med. 1998;128(8):630.11. Chimowitz MI, DeGeorgia MA, Poole RM, Hepner A, Armstrong WM. Left atrial spontaneous echo contrast is highly associated with previous stroke in patients with atrial fibrillation or mitral stenosis. Stroke. 1993;24(7):1015–9.12. Ntaios G, Lip GYH, Makaritsis K, Papavasileiou V, Vemmou A, Koroboki E, et al. CHADS2, CHA2DS2-VASc, and long-term stroke outcome in patients without atrial fibrillation. Neurology. 2013;80(11):1009–17.13. Ostrander LD, Brandt RL, Kjelsberg MO, Epstein FH. Electrocardiographic Findings Among the Adult Population of a Total Natural Community, Tecumseh, Michigan. Circulation. 1965;31(6):888–98.14. Lijfering WM, Rosendaal FR, Cannegieter SC. Risk factors for venous thrombosis - current understanding from an epidemiological point of view. Br J Haematol. 2010;149(6):824–33.15. Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G. Oral Anticoagulant Therapy. Chest. 2012;141(2):e44S-e88S16. Barnes GD, Ageno W, Ansell J, Kaatz S. Recommendation on the nomenclature for oral anticoagulants: communication from the SSC of the ISTH. J Thromb Haemost. 2015;13(6):1154–6.17. Seligsohn U, Lubetsky A. Genetic Susceptibility to Venous Thrombosis. N Engl J Med. 2001;344(16):1222–31.18. Anderson FA. A Population-Based Perspective of the Hospital Incidence and Case-Fatality Rates of Deep Vein Thrombosis and Pulmonary Embolism. Arch Intern Med. 1991;151(5):933.19. Subar M. Clinical evaluation of hypercoagulable states. Clin Geriatr Med. 2001;17(1):57–70.20. Silverstein MD, Heit JA, Mohr DN, Petterson TM, O’Fallon WM, Melton LJ. Trends in the Incidence of Deep Vein Thrombosis and Pulmonary Embolism. Arch Intern Med. 1998;158(6):585.21. Pengo V, Lensing AWA, Prins MH, Marchiori A, Davidson BL, Tiozzo F, et al. Incidence of Chronic Thromboembolic Pulmonary Hypertension after Pulmonary Embolism. N Engl J Med. 2004;350(22):2257–64.22. Cannegieter SC, Rosendaal FR, Briët E. Thromboembolic and bleeding complications in patients with mechanical heart valve prostheses. Circulation. 1994;89(2):635–41.23. Mok CK, Boey J, Wang R, Chan TK, Cheung KL, Lee PK, et al. Warfarin versus dipyridamole-aspirin and pentoxifylline-aspirin for the prevention of prosthetic heart valve thromboembolism: a prospective randomized clinical trial. Circulation. 1985 Nov;72(5):1059–63.24. Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. EP Eur. 2013;15(5):625–51.25. Heneghan C, Ward A, Perera R, Bankhead C, Fuller A, Stevens R, et al. Self-monitoring of oral anticoagulation: systematic review and meta-analysis of individual patient data. Lancet. 2012;379(9813):322–34.26. Fiedler KA, Maeng M, Mehilli J, Schulz-Schüpke S, Byrne RA, Sibbing D, et al. Duration of Triple Therapy in Patients Requiring Oral Anticoagulation After Drug-Eluting Stent Implantation. J Am Coll Cardiol. 2015;65(16):1619–29.27. Gibson CM, Mehran R, Bode C, Halperin J, Verheugt FW, Wildgoose P, et al. Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI. N Engl J Med. 2016;375(25):2423–34.28. Gelfand E V, Piazza G, Goldhaber SZ. Venous Thromboembolism Guidebook. Crit Pathways Cardiol A J Evidence-Based Med. 2002;1(1):26–43.29. Goldhaber SZ, Morrison RB. Pulmonary Embolism and Deep Vein Thrombosis. Circulation. 2002;106(12):1436–8.30. Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. J Am Coll Cardiol. 1988 Dec;12(6):A3–1331. Ornato JP, Hand MM. Warning Signs of a Heart Attack. Circulation. 2001;104(11):1212–3.32. Weitz JI. Low-Molecular-Weight Heparins. N Engl J Med. 1997;337(10):688–99.33. Hirsh J, Levine MN. Low molecular weight heparin. Blood. 1992;79(1):1–17.34. Prandoni P. Heparins and Venous Thromboembolism: Current Practice and Future Directions. Thromb Haemost. 2001;86(07):488–98.35. White RH, Ginsberg JS. Low-Molecular-Weight Heparins: Are they all the Same? Br J Haematol. 2003;121(1):12–20.36. Choay J, Petitou M, Lormeau JC, Sinaÿ P, Casu B, Gatti G. Structure-activity relationship in heparin: A synthetic pentasaccharide with high affinity for antithrombin III and eliciting high anti-factor Xa activity. Biochem Biophys Res Commun. 1983;116(2):492–9.37. Marcum JA, McKenney JB, Rosenberg RD. Acceleration of thrombin-antithrombin complex formation in rat hindquarters via heparinlike molecules bound to the endothelium. J Clin Invest. 1984;74(2):341–50.38. Rojas L, Aizman A, Ernst D, Acuña MP, Moya P, Mellado R, et al. Anti-Xa Activity After Enoxaparin Prophylaxis In Hospitalized Patients Weighing Less Than Fifty-Five Kilograms. Thromb Res. 2013;132(6):761–4.39. Harrison L. Comparison of 5-mg and 10-mg Loading Doses in Initiation of Warfarin Therapy. Ann Intern Med. 1997;126(2):133.40. Crowther MA, Ginsberg JB, Kearon C, Harrison L, Johnson J, Massicotte MP, et al. A Randomized Trial Comparing 5-mg and 10-mg Warfarin Loading Doses. Arch Intern Med. 1999;159(1):46.41. Poller L, Keown M, Ibragim S, Lowe G, Moia M, Turpie AG, et al. An international multicenter randomized study of computer-assisted oral anticoagulant dosage vs. medical staff dosage. J Thromb Haemost. 2008;6(6):935–43.42. Gage BF, Eby C, Johnson JA, Deych E, Rieder MJ, Ridker PM, et al. Use of Pharmacogenetic and Clinical Factors to Predict the Therapeutic Dose of Warfarin. Clin Pharmacol Ther. 2008;84(3):326–31.43. Kovacs MJ, Rodger M, Anderson DR, Morrow B, Kells G, Kovacs J, et al. Comparison of 10-mg and 5-mg Warfarin Initiation Nomograms Together with Low-Molecular-Weight Heparin for Outpatient Treatment of Acute Venous Thromboembolism. Ann Intern Med. 2003;138(9):714.44. Lubetsky A, Dekel-Stern E, Chetrit A, Lubin F, Halkin H. Vitamin K Intake and Sensitivity to Warfarin in Patients Consuming Regular Diets. Thromb Haemost. 1999;81(03):396–9.45. Masuko S, Linhardt RJ. Chemoenzymatic synthesis of the next generation of ultralow MW heparin therapeutics. Future Med Chem. 2012;4(3):289–96.46. Samama MM. The mechanism of action of rivaroxaban – an oral, direct Factor Xa inhibitor – compared with other anticoagulants. Thromb Res. 2011;127(6):497–50447. Stangier J, Rathgen K, Stähle H, Mazur D. Influence of Renal Impairment on the Pharmacokinetics and Pharmacodynamics of Oral Dabigatran Etexilate. Clin Pharmacokinet. 2010;49(4):259–68.48. Bristol-Myers Squibb. eliquis (apixaban) prescribing information. 2019. p. 1–16.49. Belley-Cote E, Hanif H, D’Aragon F, Eikelboom J, Anderson J, Borgman M, et al. Genotype-guided versus standard vitamin K antagonist dosing algorithms in patients initiating anticoagulation. Thromb Haemost. 2015;114(10):768–77.50. Benedetti G, Neccia M, Agati L. Direct oral anticoagulants use in elderly patients with non valvular atrial fibrillation: state of evidence. Minerva Cardioangiol. 2018;66(3):301–13.51. Huhtakangas J, Tetri S, Juvela S, Saloheimo P, Bode MK, Hillbom M. Effect of Increased Warfarin Use on Warfarin-Related Cerebral Hemorrhage. Stroke. 2011;42(9):2431–5.52. Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJGM, Lip GYH. A Novel User-Friendly Score (HAS-BLED) To Assess 1-Year Risk of Major Bleeding in Patients With Atrial Fibrillation. Chest. 2010;138(5):1093–100.53. Beyth RJ, Quinn LM, Landefeld CS. Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin. Am J Med. 1998;105(2):91–9.54. Gage BF, Yan Y, Milligan PE, Waterman AD, Culverhouse R, Rich MW, et al. Clinical classification schemes for predicting hemorrhage: Results from the National Registry of Atrial Fibrillation (NRAF). Am Heart J. 2006;151(3):713–9.55. Singh S, Kaur S, Goel N. A Review of Computational Intelligence Methods for Eukaryotic Promoter Prediction. Nucleosides, Nucleotides and Nucleic Acids. 2015;34(7):449–62.56. Xie J, Ding W, Chen L, Guo Q, Zhang W. Advances in Protein Contact Map Prediction Based on Machine Learning. Med Chem (Los Angeles). 2015;11(3):265–70.57. Lima AN, Philot EA, Trossini GHG, Scott LPB, Maltarollo VG, Honorio KM. Use of machine learning approaches for novel drug discovery. Expert Opin Drug Discov. 2016;11(3):225–39.58. Lugo-Reyes SO, Maldonado-Colín G, Murata C. Artificial intelligence to assist clinical diagnosis in medicine. Rev Alerg Mex. 2014;61(2):110–20.59. Roldán V, Marín F, Muiña B, Torregrosa JM, Hernández-Romero D, Valdés M, et al. Plasma von Willebrand Factor Levels Are an Independent Risk Factor for Adverse Events Including Mortality and Major Bleeding in Anticoagulated Atrial Fibrillation Patients. J Am Coll Cardiol. 2011;57(25):2496–504.60. Nutescu EA, Macik BG, Nutescu EA. The Future of Anticoagulation Clinics. J Thromb Thrombolysis. 2003;16(1/2):61–3.62. Chiquette E, Amato MG, Bussey HI. Comparison of an Anticoagulation Clinic With Usual Medical Care. Arch Intern Med. 1998;158(15):1641.64. Hirsh J, Dalen JE, Anderson DR, Poller L, Bussey H, Ansell J, et al. Oral Anticoagulants: Mechanism of Action, Clinical Effectiveness, and Optimal Therapeutic Range. Chest. 2001;119(1):8S-21S.65. Sociedad Colombiana de Cardiología y Cirugía Cardiovascular. Clínica de Anticoagulación. Primera Ed. 2005.66. Franchini M, Mannucci PM. New anticoagulants for treatment of venous thromboembolism. Eur J Intern Med. 2012;23(8):692–5.67. Agewall S, Camm J, Barón Esquivias G, Budts W, Carerj S, Casselman F, et al. Guía ESC 2016 sobre el diagnóstico y tratamiento de la fibrilación auricular, desarrollada en colaboración con la EACTS. Rev Española Cardiol. 2017;70(1):50.e1-50.e84.68. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J Chronic Dis. 1987 Jan;40(5):373–83.69. Quan H, Li B, Couris CM, Fushimi K, Graham P, Hider P, et al. Updating and Validating the Charlson Comorbidity Index and Score for Risk Adjustment in Hospital Discharge Abstracts Using Data From 6 Countries. Am J Epidemiol. 2011 Mar 15;173(6):676–82.70. Lip GYH, Frison L, Halperin JL, Lane DA. Comparative Validation of a Novel Risk Score for Predicting Bleeding Risk in Anticoagulated Patients With Atrial Fibrillation. J Am Coll Cardiol. 2011;57(2):173–80.71. Lip GYH, Nieuwlaat R, Pisters R, Lane DA, Crijns HJGM. Refining Clinical Risk Stratification for Predicting Stroke and Thromboembolism in Atrial Fibrillation Using a Novel Risk Factor-Based Approach. Chest. 2010;137(2):263–72.72. Olesen JB, Lip GYH, Hansen PR, Lindhardesen J, Ahlehoff O, Andersson C, et al. Bleeding risk in ‘real world’ patients with atrial fibrillation: comparison of two established bleeding prediction schemes in a nationwide cohort. J Thromb Haemost. 2011;9(8):1460–7.73. Senoo K, Lau YC, Lip GYH. Updated NICE guideline: management of atrial fibrillation (2014). Expert Rev Cardiovasc Ther. 2014;12(9):1037–40.74. Pugh RNH, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973 Aug;60(8):646–9.75. Cockcroft DW, Gault H. Prediction of Creatinine Clearance from Serum Creatinine. Nephron. 1976;16(1):31–41.76. Levey AS, Stevens LA, Schmid CH, Zhang Y (Lucy), Castro AF, Feldman HI, et al. A New Equation to Estimate Glomerular Filtration Rate. Ann Intern Med. 2009 May 5;150(9):604.77. Inker LA, Schmid CH, Tighiouart H, Eckfeldt JH, Feldman HI, Greene T, et al. Estimating Glomerular Filtration Rate from Serum Creatinine and Cystatin C. N Engl J Med. 2012 Jul 5;367(1):20–9.78. Laverde LP, Gómez SE, Montenegro AC, Lineros A, Wills B, Buitrago AF. Experiencia de una clínica de anticoagulación. Rev Colomb Cardiol. 2015 Sep;22(5):224–30.79. Miranda H, Osório S, Giraldo DP, Duque J, Ubeimar-Cataño J, Tobón LI. Tiempo en rango terapéutico (TRT) en clínica de anticoagulación: Reportes de eventos adversos y factores asociados a bajo TRT. Acta Médica Colomb. 2016;41(1):42–8.80. Ocampo Kohn C, Hernández Ortiz O, Velásquez Franco CJ, Tobón Acosta LI, Mejía Restrepo FA. La clínica de anticoagulación del Hospital Universitario San Vicente de Paúl: demografía, efectividad y complicaciones. Iatreia. 2004;17(2):105–14.81. Fanikos J, Grasso-Correnti N, Shah R, Kucher N, Goldhaber SZ. Major Bleeding Complications in a Specialized Anticoagulation Service. Am J Cardiol. 2005 Aug;96(4):595–8.82. Jover E, Roldán V, Gallego P, Hernández-Romero D, Valdés M, Vicente V, et al. Valor predictivo de la escala CHA 2DS 2-VASc en pacientes con fibrilación auricular de alto riesgo embólico en tratamiento anticoagulante. Rev Esp Cardiol. 2012;65(7):627–33.83. Lip GY, Golding DJ, Nazir M, Beevers DG, Child DL, Fletcher RI. A survey of atrial fibrillation in general practice: the West Birmingham Atrial Fibrillation Project. Br J Gen Pract. 1997 May;47(418):285–9.84. Pinto DA, Sánchez-Vallejo CA, López Pedraza A, Vergara EP, Sáenz ÓA, González F, et al. Descripción de los pacientes con fibrilación auricular no valvular que ingresan al servicio de urgencias. Rev Colomb Cardiol. 2016;23(4):270–6.84. Pinto DA, Sánchez-Vallejo CA, López Pedraza A, Vergara EP, Sáenz ÓA, González F, et al. Descripción de los pacientes con fibrilación auricular no valvular que ingresan al servicio de urgencias. Rev Colomb Cardiol. 2016;23(4):270–6.85. Enríquez A, Baranchuk A, Corbalán R. Manejo de hemorragia asociada a anticoagulantes orales directos: estado actual de las estrategias de reversión. Rev Med Chil. 2019;147(1):73–82.86. Ntaios G, Papavasileiou V, Makaritsis K, Vemmos K, Michel P, Lip GYH. Real-World Setting Comparison of Nonvitamin-K Antagonist Oral Anticoagulants Versus Vitamin-K Antagonists for Stroke Prevention in Atrial Fibrillation. Stroke. 2017 Sep;48(9):2494–503.87. Wilkins T, Wheeler B, Carpenter M. Upper Gastrointestinal Bleeding in Adults: Evaluation and Management. Am Fam Physician. 2020;101(5):294–300.88. Mantilla-Villabona LY, Ospina-Galeano DC, Gutiérrez-Ortiz AJ, Camacho PA. Pacientes con fibrilación auricular atendidos en consulta de atención primaria de una institución de alta complejidad. Rev Colomb Cardiol. 2018;25(2):124–30.88. Mantilla-Villabona LY, Ospina-Galeano DC, Gutiérrez-Ortiz AJ, Camacho PA. Pacientes con fibrilación auricular atendidos en consulta de atención primaria de una institución de alta complejidad. Rev Colomb Cardiol. 2018;25(2):124–30.89. Brenner PF. Differential diagnosis of abnormal uterine bleeding. Am J Obstet Gynecol. 1996 Sep;175(3):766–9.90. Wilansky DL, Greisman B. Early hypothyroidism in patients with menorrhagia. Am J Obstet Gynecol. 1989 Mar;160(3):673–7.91. Pincus D, Gomes T, Hellings C, Zheng H, Paterson JM, Mamdani MM, et al. A Population-Based Assessment of the Drug Interaction Between Levothyroxine and Warfarin. Clin Pharmacol Ther. 2012 Dec 24;92(6):766–70.91. Pincus D, Gomes T, Hellings C, Zheng H, Paterson JM, Mamdani MM, et al. A Population-Based Assessment of the Drug Interaction Between Levothyroxine and Warfarin. Clin Pharmacol Ther. 2012 Dec 24;92(6):766–70.92. Kamthornthanakarn I, Krittayaphong R. Optimal INR level for warfarin therapy after mechanical mitral valve replacement. BMC Cardiovasc Disord. 2019 Dec 25;19(1):97.93. Aimo A, Giugliano RP, De Caterina R. Non–Vitamin K Antagonist Oral Anticoagulants for Mechanical Heart Valves. Circulation. 2018 Sep 25;138(13):1356–65.94. Wojakowski E, Cheruvil C, Hassan A, Holsen MR, Chen L, Rossi M, et al. Albumin and bleed risk in rivaroxaban treated patients. J Thromb Thrombolysis. 2020 Apr 11;95. Fender AC, Dobrev D. Bound to bleed: How altered albumin binding may dictate warfarin treatment outcome. IJC Hear Vasc. 2019 Mar;22:214–5.96. Kawai M, Harada M, Motoike Y, Koshikawa M, Ichikawa T, Watanabe E, et al. Impact of serum albumin levels on supratherapeutic PT-INR control and bleeding risk in atrial fibrillation patients on warfarin: A prospective cohort study. IJC Hear Vasc. 2019 Mar;22:111–6.97. Zeng J, Yu P, Cui W, Wang X, Ma J, Zeng C. Comparison of HAS-BLED with other risk models for predicting the bleeding risk in anticoagulated patients with atrial fibrillation. Medicine (Baltimore). 2020 Jun 19;99(25):e20782.98. Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014 Mar;383(9921):955–62.99. Murphy A, Banerjee A, Breithardt G, Camm AJ, Commerford P, Freedman B, et al. The World Heart Federation Roadmap for Nonvalvular Atrial Fibrillation. Glob Heart. 2017;12(4):273–84.100. Lee V, Jairam V, Yu JB, Park HS. Nationwide patterns of hemorrhagic stroke among patients hospitalized with brain metastases: influence of primary cancer diagnosis and anticoagulation. Sci Rep. 2020 Dec 22;10(1):10084.101. Dahal K, Kunwar S, Rijal J, Schulman P, Lee J. Stroke, Major Bleeding, and Mortality Outcomes in Warfarin Users With Atrial Fibrillation and Chronic Kidney Disease. 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