Frecuencia de eventos trombóticos y sangrado en pacientes usuarios de la clínica anticoagulación del Hospital Militar Central 2019-2020
Los anticoagulantes son un grupo farmacológico, con amplio uso alrededor del mundo para la prevención y tratamiento de las enfermedades trombóticas. Las clínicas de anticoagulación son un equipo de atención integral del paciente usuario de anticoagulantes, que entre algunas de sus funciones está el...
- Autores:
-
Largo Gil, Jorge Mario
- Tipo de recurso:
- Trabajo de grado de pregrado
- Fecha de publicación:
- 2022
- Institución:
- Universidad Militar Nueva Granada
- Repositorio:
- Repositorio UMNG
- Idioma:
- spa
- OAI Identifier:
- oai:repository.unimilitar.edu.co:10654/39989
- Acceso en línea:
- http://hdl.handle.net/10654/39989
- Palabra clave:
- warfarin
direct anticoagulants
bleeding
thromboembolism
anticoagulation clinic
TROMBOSIS
MEDICINA INTERNA
ANTICOAGULANTES
EMBOLIA
Warfarina
Anticoagulantes directos
Clinica anticoagulacion
tromboembolismo
sangrado
- Rights
- openAccess
- License
- http://creativecommons.org/licenses/by-nc-nd/4.0/
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oai:repository.unimilitar.edu.co:10654/39989 |
network_acronym_str |
UNIMILTAR2 |
network_name_str |
Repositorio UMNG |
repository_id_str |
|
dc.title.spa.fl_str_mv |
Frecuencia de eventos trombóticos y sangrado en pacientes usuarios de la clínica anticoagulación del Hospital Militar Central 2019-2020 |
dc.title.translated.spa.fl_str_mv |
Frequency of thrombotic events and bleeding in patients using the anticoagulation clinic of the Hospital Militar Central -2019-2020 Autores |
title |
Frecuencia de eventos trombóticos y sangrado en pacientes usuarios de la clínica anticoagulación del Hospital Militar Central 2019-2020 |
spellingShingle |
Frecuencia de eventos trombóticos y sangrado en pacientes usuarios de la clínica anticoagulación del Hospital Militar Central 2019-2020 warfarin direct anticoagulants bleeding thromboembolism anticoagulation clinic TROMBOSIS MEDICINA INTERNA ANTICOAGULANTES EMBOLIA Warfarina Anticoagulantes directos Clinica anticoagulacion tromboembolismo sangrado |
title_short |
Frecuencia de eventos trombóticos y sangrado en pacientes usuarios de la clínica anticoagulación del Hospital Militar Central 2019-2020 |
title_full |
Frecuencia de eventos trombóticos y sangrado en pacientes usuarios de la clínica anticoagulación del Hospital Militar Central 2019-2020 |
title_fullStr |
Frecuencia de eventos trombóticos y sangrado en pacientes usuarios de la clínica anticoagulación del Hospital Militar Central 2019-2020 |
title_full_unstemmed |
Frecuencia de eventos trombóticos y sangrado en pacientes usuarios de la clínica anticoagulación del Hospital Militar Central 2019-2020 |
title_sort |
Frecuencia de eventos trombóticos y sangrado en pacientes usuarios de la clínica anticoagulación del Hospital Militar Central 2019-2020 |
dc.creator.fl_str_mv |
Largo Gil, Jorge Mario |
dc.contributor.advisor.none.fl_str_mv |
Largo Gil, Jorge Mario |
dc.contributor.author.none.fl_str_mv |
Largo Gil, Jorge Mario |
dc.contributor.other.none.fl_str_mv |
Palomino Ariza, Gustavo Alejandro |
dc.subject.keywords.spa.fl_str_mv |
warfarin direct anticoagulants bleeding thromboembolism anticoagulation clinic |
topic |
warfarin direct anticoagulants bleeding thromboembolism anticoagulation clinic TROMBOSIS MEDICINA INTERNA ANTICOAGULANTES EMBOLIA Warfarina Anticoagulantes directos Clinica anticoagulacion tromboembolismo sangrado |
dc.subject.decs.spa.fl_str_mv |
TROMBOSIS MEDICINA INTERNA ANTICOAGULANTES EMBOLIA |
dc.subject.proposal.spa.fl_str_mv |
Warfarina Anticoagulantes directos Clinica anticoagulacion tromboembolismo sangrado |
description |
Los anticoagulantes son un grupo farmacológico, con amplio uso alrededor del mundo para la prevención y tratamiento de las enfermedades trombóticas. Las clínicas de anticoagulación son un equipo de atención integral del paciente usuario de anticoagulantes, que entre algunas de sus funciones está el de estandarizar el tratamiento, seguimiento, educación y vigilancia de los pacientes para impactar en desenlaces como prevención de complicaciones asociadas. |
publishDate |
2022 |
dc.date.accessioned.none.fl_str_mv |
2022-02-08T16:53:26Z |
dc.date.available.none.fl_str_mv |
2022-02-08T16:53:26Z |
dc.date.issued.none.fl_str_mv |
2022-01-31 |
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/10654/39989 |
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/10654/39989 |
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. Nutescu EA. The future of anticoagulation clinics. J Thrombosis and Thrombolysis 2003; 16 (1/2): 61-63 2. Anseel JE, Hughes RM. Involving models of warfarin management: anticoagulation clinics, patient selfmonitoring and patients self-management. Am Heart J 1996; 1095-1100 3. Chiquette E, Amanto MG, Bussey HI. Comparison of an anticoagulation clinics with usual medical care anticoagulation control, patient outcomes and health care cost. Arch Intern Med 1998; 158: 1641-1647 4. Gadisseur AP, Kaptein AA, Breukink-Engbers WG, van der Meer FJ, Rosendaal FR. Patient self-management of oral anticoagulant care vs. management by specialized anticoagulation clinics: positive effects on quality of life. J Thromb Haemost 2004; 2 (4): 584-91 5. Cromheecke ME, Colly LP, et al. Oral anticoagulation selfmanagement and management by a specialist anticoagulation clinics: a randomized cross-over comparison. Lancet 2000; 353 (8). 6. Macik BG. The future of anticoagulation clinics. J Thrombosis and Thrombolysis 2003; 16 (1/2): 55-59. 7. Hirsh J, Dalen JE, Anderson DR, et al. Oral anticoagulants: mechanism of action, clinical effectiveness and optimal therapeutic range. Sixth ACCP. Consensus Conference on Antithrombotic Therapy. Chest 2001; 119 (1) (suppl): 8S- 21S 8. Hernandez DA, Palomino GA, Caracterizacion de la clinica de anticoagulacion del hospital militar central. Recuperado el 10 de agosto de 2021, URL :http://hdl.handle.net/10654/34920. Universidad Militar Nueva Granada 9. Franchini M, Mannucci PM. New anticoagulants for treatment of venous thromboembolism. Eur J Intern Med. 2012;23(8):692---5 10. Connolly SJ, Eikelboom J, Joyner C, Diener HC, Hart R, GolitsynS, et al. Apixaban in patients with auricular auricular fibrillation.N Engl J Med. 2011;364(9):806---17. 11. Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM,Hanna M, et al. Apixaban versus warfarin in patients wit-hauricular auricular fibrillation. N Engl J Med. 2011;365(11):981---92.5. 12. Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P; European Heart Rhythm Association. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013;15:625–651 13. Heidbuchel H, Verhamme P, Alings M, Antz M, Diener HC, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 2015;17:1467–1507. 14. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener HC, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Popescu BA, Schotten U, Van Putte B, Vardas P, Agewall S, Camm J, Baron Esquivias G, Budts W, Carerj S, Casselman F, Coca A, De Caterina R Deftereos S, Dobrev D, Ferro JM, Filippatos G, Fitzsimons D, Gorenek 15. B, Guenoun M, Hohnloser SH, Kolh P, Lip GY, Manolis A, McMurray J, Ponikowski P, Rosenhek R, Ruschitzka F, Savelieva I, Sharma S, Suwalski P, Tamargo JL, Taylor CJ, Van Gelder IC, Voors AA, Windecker S, Zamorano JL, Zeppenfeld K. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016;37:2893–2962. 16. Sáenz M O, Sanabria F, Rubio AM, González A F, Gamba N. Clínica de anticoagulación de la Subred Centro Oriente, en Bogotá. rev. colomb. neumol. [Internet]. 6 de julio de 2021 [citado 20 de enero de 2022];32(2):37-45. Disponible en: https://revistas.asoneumocito.org/index.php/rcneumologia/article/view/531 17. J. Steffel et al. 2018 EHRA Practical Guide on NOACs in AF. European Heart Journal (2018) 39, 1330–1393 18. Ocampo C, Hernández O, Velásquez C, Tobón I, Mejía F. La clínica de anticoagulación del Hospital Universitario San Vicentede Paúl: demografía, efectividad y complicaciones. Iatreia.2004;17(2):105---14. 19. Taboada LB, Silva LE, Montenegro AC. Beneficios de la clínica de anticoagulación. Acta Med Colomb. 2013;38:239---43 20. Ligia P. Laverde, Sonia E. Gómez, Ana C. Montenegro, Alberto Lineros, Beatriz Wills y Andrés F. Buitrago. Experiencia de una clínica de anticoagulación. Rev Colomb Cardiol. 2015;22(5):224---230 21. Corey S. Miller, BA, Sonia M Grandi, MSc, Avi Shimony, MD, Kristian B Filion, PhD, and Mark J. Eisenberg, MD, MPH. Meta-Analysis of Efficacy and Safety of New Oral Anticoagulants (Dabigatran, Rivaroxaban, Apixaban) Versis Warfarin in Patients With Atrial Fibrillation. Am J Cardiol 2012;110:453-460) 22. Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G, et al. Oral anticoagulant therapy: Antithrombo-tic Therapy and Prevention of Thrombosis, 9th. ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141 2 Suppl:e44S---88S. 23. Bruce Furie, M.D., and Barbara C. Furie, Ph.D. Mechanisms of Thrombus Formation. New England Journal of Medicine 2008;359:938-49. 24. Kojima H, Newton-Nash D, Weiss HJ, et al. Production and characterization of transformed B-lymphocytes expressing the membrane defect of Scott syndrome. J Clin Invest 1994; 94:2237. 25. Hansson K, Stenflo J. Post-translational modifications in proteins involved in blood coagulation. J Thromb Haemost 2005; 3:2633. 26. Mann KG, Brummel-Ziedins K, Orfeo T, Butenas S. Models of blood coagulation. Blood Cells Mol Dis 2006; 36:108. 27. Morrison SA, Jesty J. Tissue factor-dependent activation of tritium-labeled factor IX and factor X in human plasma. Blood 1984; 63:1338. 28. Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns Hj. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest 2010; Feb 137(2):263 - 72 29. Ntauis G, et al. CHADS2, CHA2DS2-VASc, and long term stroke outcome in patientes without atrial fibrillation. Neurology, March 12; 80(11): 1009-17 30. Ostranderld JR, Brandt RL, Kjelsberg M, Eppstein FH. Electrocardiographic findings among the adult population of a total natural community, Te cumshed, Michigan. Circulation 1965; 31: 888-98. 31. Kannel W, Abbott RD, Savage AD, McNamara PM. Epidemiologic features of chronic atrial fibrillation: The Framingham study. N Eng J Med 1982; 306: 1018-22. 32. Vidaillet H, Granada JF, Chyou et al. A population-based study of mortality among patients with atrial fibrillation or flutter. Am J Med 2002; 113: 365-70. 33. Wolf P, D’Agostino R, Belanger A et al. Probality of stroke: a risk profile from the Framingham study. Stroke 1991; 22: 312-8. 34. Wolf P, Dawber T, Thomas H et al. Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: the Framingham study. Neurology 1978; 28: 973-7. 35. Stöllberger C, Chnupa P, Kronik G et al. Transesophageal echocardiography to assess embolic risk in patients with atrial fibrillation. Ann Intern Med 1998; 128: 630-8. 36. Chimowitz M, DeGeorgia M, Poole R et al. Left atrial spontaneous echo contrast is highly associated with previous stroke in patients with atrial fibrillation or mitral stenosis. Stroke 1993; 24: 1015-9. 37. Heppell RM, Berkin K, McLenachan et al. Haemostatic and haemodinamic abnormalities associated with left atrial thrombosis in non-rheumatic atrial fibrillation. Heart 1997; 77: 407-11. 38. Friberg L, Rosenquist M, Lip GY. Evaluation of risk stratificationschemes for ischaemic stroke and bleeding in 182678 patientes with atrial fibrillation: the Swedish Atrial Fibrillation cohort Study. Eur Heart . 2012 Jun 33(12): 1500-10. 39. Lijfering WM, Rosendaal FR, Cannegieter SC. Risk factors for venous thrombosis-current understanding from an epidemiologic point of view. Br J Haematol. 2010; 149(6): 824. 40. Dickson BC. Venous thrombosis: on the history of Virchow´s triad. Univ Toronto Med J. 2004; 81:166. 41. Bauer KA, The thrombophilias: Well-defined risk factors with uncertain thrapeutic implications, vol. 135, p. 367. Annals of Internal Medicine. 2001 42. den Exter PL, van Es J, Erkens PM, van Roosmalen MJ, et al. Impact of delay in clinical presentation on the diagnostic managment and prognosis of patientts with suspected pulmnary embolism. Am J Respir Crit Care Med. 2013 Jun; 187(12):1369-73 43. Browse NL, homas ML. Source of non-lethal pulmonary emboli. Lancet. 1974; 1(7851):258. 44. Nishimura RAm Otto CM, Bonow RO, Carabello BA, et al. 2014 AHA/ACC guideline for the management of patientes with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014; 63(22): e57. Epub 2014 Mar 3 45. Hirsh J, Weitz JI. New antithrombotic agents. Lancet. 1999;353(9162):1431. 46. Laux V, Perzborn E, Heitmeier S, von Degenfeld G, Dittrich-Wengenroth E, Buchmüller A, Gerdes C, Misselwitz F. Direct inhibitors of coagulation proteins - the end of the heparin and low-molecular-weight heparin era for anticoagulant therapy?. Thromb Haemost. 2009;102(5):892. 47. Samama MM. The mechanism of action of rivaroxaban--an oral, direct Factor Xa inhibitor--compared with other anticoagulants. Thromb Res. 2011 Jun;127(6):497-504. Epub 2010 Oct 2. 48. HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use PRADAXA Capsules safely and effectively . Disponible en: https://docs.boehringeringelheim.com/Prescribing%20Information/PIs/Pradaxa/Pradaxa.pdf 49. van Ryn J, Stangier J, Haertter S, Liesenfeld KH, Wienen W, Feuring M, Clemens A. Dabigatran etexilate--a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost. 2010;103(6):1116. Epub 2010 Mar 29. 50. Stangier J, Rathgen K, Stähle H, Mazur D. Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate: an open-label, parallel-group, single-centre study. Clin Pharmacokinet. 2010;49(4):259. 51. Gosselin RC, Adcock DM, Bates SM, et al. International Council for Standardization in Haematology (ICSH) Recommendations for Laboratory Measurement of Direct Oral Anticoagulants. Thromb Haemost 2018; 118:437. 52. Douros A, Azoulay L, Yin H, et al. Non-Vitamin K Antagonist Oral Anticoagulants and Risk of Serious Liver Injury. J Am Coll Cardiol 2018; 71:1105.1.37). 53. Martin K, Beyer-Westendorf J, Davidson BL, et al. Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. J Thromb Haemost 2016; 14:1308. 54. Moore KT, Kröll D. Influences of Obesity and Bariatric Surgery on the Clinical and Pharmacologic Profile of Rivaroxaban. Am J Med 2017; 130:1024. 55. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022406s004lbl.pdf 56. Beyer-Westendorf J, Siegert G. Of men and meals. J Thromb Haemost 2015; 13:943. 57. Poulsen BK, Grove EL, Husted SE. New oral anticoagulants: a review of the literature with particular emphasis on patients with impaired renal function. Drugs 2012; 72:1739. 58. Nutescu E, Chuatrisorn I, Hellenbart E. Drug and dietary interactions of warfarin and novel oral anticoagulants: an update. J Thromb Thrombolysis 2011; 31:326. 59. http://packageinserts.bms.com/pi/pi_eliquis.pdf 60. Stergiopoulos K, Brown DL. Genotype-guided vs clinical dosing of warfarin and its analogues: meta-analysis of randomized clinical trials. JAMA Intern Med 2014; 174:1330. 61. Belley-Cote EP, Hanif H, D'Aragon F, et al. Genotype-guided versus standard vitamin K antagonist dosing algorithms in patients initiating anticoagulation. A systematic review and meta-analysis. Thromb Haemost 2015; 114:768. 62. Harrison L, Johnston M, Massicotte MP, et al. Comparison of 5-mg and 10-mg loading doses in initiation of warfarin therapy. Ann Intern Med 1997; 126:133 63. Crowther MA, Ginsberg JB, Kearon C, et al. A randomized trial comparing 5-mg and 10-mg warfarin loading doses. Arch Intern Med 1999; 159:46. 64. Farahmand S, Saeedi M, Seyed Javadi HH, Khashayar P. High doses of warfarin are more beneficial than its low doses in patients with deep vein thrombosis. Am J Emerg Med 2011; 29:1222. 65. Kovacs MJ, Rodger M, Anderson DR, 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. A randomized, double-blind, controlled trial. Ann Intern Med 2003; 138:714. 66. Cushman M, Booth SL, Possidente CJ, et al. The association of vitamin K status with warfarin sensitivity at the onset of treatment. Br J Haematol 2001; 112:572. 67. Lubetsky A, Dekel-Stern E, Chetrit A, et al. Vitamin K intake and sensitivity to warfarin in patients consuming regular diets. Thromb Haemost 1999; 81:396. 68. Khan T, Wynne H, Wood P, et al. Dietary vitamin K influences intra-individual variability in anticoagulant response to warfarin. Br J Haematol 2004; 124:348. 69. Franco V, Polanczyk CA, Clausell N, Rohde LE. Role of dietary vitamin K intake in chronic oral anticoagulation: prospective evidence from observational and randomized protocols. Am J Med 2004; 116:651. 70. Limdi NA, Beasley TM, Baird MF, et al. Kidney function influences warfarin responsiveness and hemorrhagic complications. J Am Soc Nephrol 2009; 20:912. 71. Keeling D, Baglin T, Tait C, et al. Guidelines on oral anticoagulation with warfarin - fourth edition. Br J Haematol 2011; 154:311. 72. Garcia P, Ruiz W, Loza Munárriz C. Warfarin initiation nomograms for venous thromboembolism. Cochrane Database Syst Rev 2016; :CD007699. 73. Poller L, Keown M, Ibrahim S, et al. An international multicenter randomized study of computer-assisted oral anticoagulant dosage vs. medical staff dosage. J Thromb Haemost 2008; 6:935. 74. Gage BF, Eby C, Johnson JA, et al. Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin. Clin Pharmacol Ther 2008; 84:326. 75. Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e152S. 76. Ansell J, Hirsh J, Hylek E, et al. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:160S. 77. Barnes GD, Froehlich JB. Anticoagulation: a pathway to clinical effectiveness. Am J Med 2009; 122:126 78. Kim YK, Nieuwlaat R, Connolly SJ, et al. Effect of a simple two-step warfarin dosing algorithm on anticoagulant control as measured by time in therapeutic range: a pilot study. J Thromb Haemost 2010; 8:101 79. Le Gal G, Carrier M, Tierney S, et al. Prediction of the warfarin maintenance dose after completion of the 10 mg initiation nomogram: do we really need genotyping? J Thromb Haemost 2010; 8:90. 80. Borgman MP, Pendleton RC, McMillin GA, et al. Prospective pilot trial of PerMIT versus standard anticoagulation service management of patients initiating oral anticoagulation. Thromb Haemost 2012; 108:561. 81. Van Spall HG, Wallentin L, Yusuf S, et al. Variation in warfarin dose adjustment practice is responsible for differences in the quality of anticoagulation control between centers and countries: an analysis of patients receiving warfarin in the randomized evaluation of long-term anticoagulation therapy (RE-LY) trial. Circulation 2012; 126:2309. 82. Jones M, McEwan P, Morgan CL, et al. Evaluation of the pattern of treatment, level of anticoagulation control, and outcome of treatment with warfarin in patients with non-valvar atrial fibrillation: a record linkage study in a large British population. Heart 2005; 91:472. 83. Wallentin L, Yusuf S, Ezekowitz MD, et al. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet 2010; 376:975 84. Rose AJ, Ozonoff A, Berlowitz DR, et al. Warfarin dose management affects INR control. J Thromb Haemost 2009; 7:94. 85. Witt DM, Nieuwlaat R, Clark NP, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy. Blood Adv 2018; 2:3257. 86. Metlay JP, Hennessy S, Localio AR, et al. Patient reported receipt of medication instructions for warfarin is associated with reduced risk of serious bleeding events. J Gen Intern Med 2008; 23:1589. 87. Kaatz S. Determinants and measures of quality in oral anticoagulation therapy. J Thromb Thrombolysis 2008; 25:61. 88. Phillips KW, Ansell J. Outpatient management of oral vitamin K antagonist therapy: defining and suring high-quality management. Expert Rev Cardiovasc Ther 2008; 6:57. 89. van Walraven C, Jennings A, Oake N, et al. Effect of study setting on anticoagulation control: a systematic review and metaregression. Chest 2006; 129:1155. 90. Muñoz EM, Linhardt RJ. Heparin-binding domains in vascular biology. Arterioscler Thromb Vasc Biol 2004; 24:1549. 91. Masuko S, Linhardt RJ. Chemoenzymatic synthesis of the next generation of ultralow MW heparin therapeutics. Future Med Chem 2012; 4:289. 92. Grigas D, Hodous T, Welton W, Pearson D. Medical grand rounds from the West Virginia University Hospital. Sarcoidosis. W V Med J 1978; 74:242. 93. Ceri H, Hwang WS, Cheung H. Endogenous heparin-binding lectin activity in human placenta: purification and developmental expression. Biochem Cell Biol 1990; 68:790. 94. Tessler S, Rockwell P, Hicklin D, et al. Heparin modulates the interaction of VEGF165 with soluble and cell associated flk-1 receptors. J Biol Chem 1994; 269:12456. 95. Fatma N, Singh DP, Shinohara T, Chylack LT Jr. Heparin's roles in stabilizing, potentiating, and transporting LEDGF into the nucleus. Invest Ophthalmol Vis Sci 2000; 41:2648. 96. Wijelath E, Namekata M, Murray J, et al. Multiple mechanisms for exogenous heparin modulation of vascular endothelial growth factor activity. J Cell Biochem 2010; 111:461. 97. Baglin T, Barrowcliffe TW, Cohen A, et al. Guidelines on the use and monitoring of heparin. Br J Haematol 2006; 133:19. 98. Hirsh J, Bauer KA, Donati MB, et al. Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:141S 99. Weitz JI. Low-molecular-weight heparins. N Engl J Med 1997; 337:688. 100. Hirsh J, Levine MN. Low molecular weight heparin. Blood 1992; 79:1. 101. Prandoni P. Heparins and venous thromboembolism: current practice and future directions. Thromb Haemost 2001; 86:488. 102. White RH, Ginsberg JS. Low-molecular-weight heparins: are they all the same? Br J Haematol 2003; 121:12. 103. Choay J, Petitou M, Lormeau JC, et al. 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; 116:492. 104. Perry DJ. Antithrombin and its inherited deficiencies. Blood Rev 1994; 8:37. 105. 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; 74:341. 106. Danielsson A, Raub E, Lindahl U, Björk I. Role of ternary complexes, in which heparin binds both antithrombin and proteinase, in the acceleration of the reactions between antithrombin and thrombin or factor Xa. J Biol Chem 1986; 261:15467. 107. http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020164s083lbl.pdf. 108. Rojas L, Aizman A, Ernst D, et al. Anti-Xa activity after enoxaparin prophylaxis in hospitalized patients weighing less than fifty-five kilograms. Thromb Res 2013; 132:761. 109. Garcia DA, Baglin TP, Weitz JI, et al. Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e24S. 110. W, Dentali F, Eikelboom JW, Crowther MA. Meta-analysis: low-molecular-weight heparin and bleeding in patients with severe renal insufficiency. Ann Intern Med 2006; 144:673. 111. Crowther M, Lim W. Low molecular weight heparin and bleeding in patients with chronic renal failure. Curr Opin Pulm Med 2007; 13:409. 112. Nagge J, Crowther M, Hirsh J. Is impaired renal function a contraindication to the use of low-molecular-weight heparin? Arch Intern Med 2002; 162:2605. 113. Chai-Adisaksopha C, Crowther M, Isayama T, Lim W. The impact of bleeding complications in patients receiving target-specific oral anticoagulants: a systematic review and meta-analysis. Blood 2014; 124:2450. 114. Ruff CT, Giugliano RP, Braunwald E, 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; 383:955. 115. Garcia DA, Lopes RD, Hylek EM. New-onset atrial fibrillation and warfarin initiation: high risk periods and implications for new antithrombotic drugs. Thromb Haemost 2010; 104:1099 116. Jiang R, Shi Y, Zhang R, et al. Comparative efficacy and safety of low-intensity warfarin therapy in preventing unprovoked recurrent venous thromboembolism: A systematic review and meta-analysis. Clin Respir J 2018; 12:2170. 117. Robert-Ebadi H, Le Gal G, Righini M. Use of anticoagulants in elderly patients: practical recommendations. Clin Interv Aging 2009; 4:165. 118. Benedetti G, Neccia M, Agati L. Direct oral anticoagulants use in elderly patients with non valvular atrial fibrillation: state of evidence. Minerva Cardioangiol 2018; 66:301. 119. Huhtakangas J, Tetri S, Juvela S, et al. Effect of increased warfarin use on warfarin-related cerebral hemorrhage: a longitudinal population-based study. Stroke 2011; 42:2431 120. Carmeliet P, Jain RK. Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases. Nat Rev Drug Discov 2011; 10:417. 121. Pisters R, Lane DA, Nieuwlaat R, et al. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 2010; 138:1093. 122. Lip GY, Frison L, Halperin JL, Lane DA. Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score. J Am Coll Cardiol 2011; 57:173. 123. Olesen JB, Lip GY, Hansen PR, 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; 9:1460. 124. Apostolakis S, Lane DA, Guo Y, et al. Performance of the HEMORR(2)HAGES, ATRIA, and HAS-BLED bleeding risk-prediction scores in patients with atrial fibrillation undergoing anticoagulation: the AMADEUS (evaluating the use of SR34006 compared to warfarin or acenocoumarol in patients with atrial fibrillation) study. J Am Coll Cardiol 2012; 60:861 125. Cairns JA, Connolly S, McMurtry S, et al. Canadian Cardiovascular Society atrial fibrillation guidelines 2010: prevention of stroke and systemic thromboembolism in atrial fibrillation and flutter. Can J Cardiol 2011; 27:74. 126. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016; 37:2893. 127. Asunción Esteve-Pastor M, Miguel Rivera-Caravaca J, Roldán V, et al. Long-term bleeding risk prediction in 'real world' patients with atrial fibrillation: Comparison of the HAS-BLED and ABC-Bleeding risk scores. Thromb Haemost 2017; 117:1848. 128. Fang MC, Go AS, Chang Y, et al. A new risk scheme to predict warfarin-associated hemorrhage: The ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) Study. J Am Coll Cardiol 2011; 58:395. 129. 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; 105:91. 130. Gage BF, Yan Y, Milligan PE, et al. Clinical classification schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF). Am Heart J 2006; 151:713. 131. Pengo V, Pegoraro C, Cucchini U, Iliceto S. Worldwide ma-nagement of oral anticoagulant therapy: the ISAM study.J Thromb Thrombolysis. 2006;21(1):73-7. doi: 10.1007/s11239-006-5580-y |
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Largo Gil, Jorge MarioLargo Gil, Jorge MarioEspecialista en Medicina InternaPalomino Ariza, Gustavo AlejandroHospital militar centralBogotá2019- 2020Medicina2022-02-08T16:53:26Z2022-02-08T16:53:26Z2022-01-31http://hdl.handle.net/10654/39989instname:Universidad Militar Nueva Granadareponame:Repositorio Institucional Universidad Militar Nueva Granadarepourl:https://repository.unimilitar.edu.coLos anticoagulantes son un grupo farmacológico, con amplio uso alrededor del mundo para la prevención y tratamiento de las enfermedades trombóticas. Las clínicas de anticoagulación son un equipo de atención integral del paciente usuario de anticoagulantes, que entre algunas de sus funciones está el de estandarizar el tratamiento, seguimiento, educación y vigilancia de los pacientes para impactar en desenlaces como prevención de complicaciones asociadas.1. RESUMEN 7 2. MARCO TEÓRICO 11 2.1. HEMOSTASIA 13 2.2. EVENTOS TROMBÓTICOS RELEVANTES EN LA CLÍNICA 21 2.2.1. Fibrilación auricular 21 2.2.2. Enfermedad tromboembólica venosa 22 2.2.3. Prótesis valvulares cardiacas mecánicas 24 2.3. ESTRATEGIAS ANTICOAGULANTES 25 2.3.1. Anticoagulantes antagonistas de la Vitamina K 25 2.3.2. Anticoagulantes directos no dependientes de Vitamina K 29 2.3.3. Heparinas de bajo peso molecular 29 2.4. COMPLICACIONES DE LA TERAPIA ANTICOAGULANTE 36 2.4.1. Sangrado 36 3. IDENTIFICACIÓN Y FORMULACIÓN DEL PROBLEMA 39 3.1. PREGUNTA DE INVESTIGACIÓN 42 4. JUSTIFICACIÓN 43 5. OBJETIVOS E HIPÓTESIS 47 5.1. OBJETIVO PRINCIPAL 47 5.2. OBJETIVOS SECUNDARIOS 47 6. METODOLOGÍA 48 6.1. TIPO Y DISEÑO GENERAL 48 6.2. LUGAR DONDE SE REALIZARÁ LA INVESTIGACIÓN 48 6.3. POBLACION 48 6.4. SELECCIÓN Y TAMAÑO DE MUESTRA 48 6.5. CRITERIOS DE INCLUSIÓN Y EXCLUSIÓN 48 6.6. DEFINICIÓN DE LAS VARIABLES 48 6.7. ESTRATEGIAS PARA SUPRIMIR AMENAZAS A LA VALIDEZ DE RESULTADOS 63 6.8. MEDICIONES E INSTRUMENTOS 63 7. PLAN DE ANÁLISIS 65 8. ASPECTOS ÉTICOS 65 9. RESULTADOS 67 10. DISCUSION 69 11.ANEXOS 74 12. CONCLUSIONES 78 13.REFERENCIAS BIBLIOGRÁFICAS 83Anticoagulants are a pharmacological group, widely used around the world for the prevention and treatment of thrombotic diseases. The anticoagulation clinics are a comprehensive care team for patients who use anticoagulants, which among some of its functions is to standardize the treatment, follow-up, education and surveillance of patients to impact outcomes such as prevention of associated complications.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 abiertoFrecuencia de eventos trombóticos y sangrado en pacientes usuarios de la clínica anticoagulación del Hospital Militar Central 2019-2020Frequency of thrombotic events and bleeding in patients using the anticoagulation clinic of the Hospital Militar Central -2019-2020 AutoresTesis/Trabajo de grado - Monografía - Especializacióninfo:eu-repo/semantics/bachelorThesishttp://purl.org/coar/resource_type/c_7a1fwarfarindirect anticoagulantsbleedingthromboembolismanticoagulation clinicTROMBOSISMEDICINA INTERNAANTICOAGULANTESEMBOLIAWarfarinaAnticoagulantes directosClinica anticoagulaciontromboembolismosangradoMedicina InternaFacultad de MedicinaUniversidad Militar Nueva Granada1. Nutescu EA. The future of anticoagulation clinics. J Thrombosis and Thrombolysis 2003; 16 (1/2): 61-632. Anseel JE, Hughes RM. Involving models of warfarin management: anticoagulation clinics, patient selfmonitoring and patients self-management. Am Heart J 1996; 1095-11003. Chiquette E, Amanto MG, Bussey HI. Comparison of an anticoagulation clinics with usual medical care anticoagulation control, patient outcomes and health care cost. Arch Intern Med 1998; 158: 1641-16474. Gadisseur AP, Kaptein AA, Breukink-Engbers WG, van der Meer FJ, Rosendaal FR. Patient self-management of oral anticoagulant care vs. management by specialized anticoagulation clinics: positive effects on quality of life. J Thromb Haemost 2004; 2 (4): 584-915. Cromheecke ME, Colly LP, et al. Oral anticoagulation selfmanagement and management by a specialist anticoagulation clinics: a randomized cross-over comparison. Lancet 2000; 353 (8).6. Macik BG. The future of anticoagulation clinics. J Thrombosis and Thrombolysis 2003; 16 (1/2): 55-59.7. Hirsh J, Dalen JE, Anderson DR, et al. Oral anticoagulants: mechanism of action, clinical effectiveness and optimal therapeutic range. Sixth ACCP. Consensus Conference on Antithrombotic Therapy. Chest 2001; 119 (1) (suppl): 8S- 21S8. Hernandez DA, Palomino GA, Caracterizacion de la clinica de anticoagulacion del hospital militar central. Recuperado el 10 de agosto de 2021, URL :http://hdl.handle.net/10654/34920. Universidad Militar Nueva Granada9. Franchini M, Mannucci PM. New anticoagulants for treatment of venous thromboembolism. Eur J Intern Med. 2012;23(8):692---510. Connolly SJ, Eikelboom J, Joyner C, Diener HC, Hart R, GolitsynS, et al. Apixaban in patients with auricular auricular fibrillation.N Engl J Med. 2011;364(9):806---17.11. Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM,Hanna M, et al. Apixaban versus warfarin in patients wit-hauricular auricular fibrillation. N Engl J Med. 2011;365(11):981---92.5.12. Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P; European Heart Rhythm Association. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013;15:625–65113. Heidbuchel H, Verhamme P, Alings M, Antz M, Diener HC, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 2015;17:1467–1507.14. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener HC, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Popescu BA, Schotten U, Van Putte B, Vardas P, Agewall S, Camm J, Baron Esquivias G, Budts W, Carerj S, Casselman F, Coca A, De Caterina R Deftereos S, Dobrev D, Ferro JM, Filippatos G, Fitzsimons D, Gorenek15. B, Guenoun M, Hohnloser SH, Kolh P, Lip GY, Manolis A, McMurray J, Ponikowski P, Rosenhek R, Ruschitzka F, Savelieva I, Sharma S, Suwalski P, Tamargo JL, Taylor CJ, Van Gelder IC, Voors AA, Windecker S, Zamorano JL, Zeppenfeld K. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016;37:2893–2962.16. Sáenz M O, Sanabria F, Rubio AM, González A F, Gamba N. Clínica de anticoagulación de la Subred Centro Oriente, en Bogotá. rev. colomb. neumol. [Internet]. 6 de julio de 2021 [citado 20 de enero de 2022];32(2):37-45. Disponible en: https://revistas.asoneumocito.org/index.php/rcneumologia/article/view/53117. J. Steffel et al. 2018 EHRA Practical Guide on NOACs in AF. European Heart Journal (2018) 39, 1330–139318. Ocampo C, Hernández O, Velásquez C, Tobón I, Mejía F. La clínica de anticoagulación del Hospital Universitario San Vicentede Paúl: demografía, efectividad y complicaciones. Iatreia.2004;17(2):105---14.19. Taboada LB, Silva LE, Montenegro AC. Beneficios de la clínica de anticoagulación. Acta Med Colomb. 2013;38:239---4320. Ligia P. Laverde, Sonia E. Gómez, Ana C. Montenegro, Alberto Lineros, Beatriz Wills y Andrés F. Buitrago. Experiencia de una clínica de anticoagulación. Rev Colomb Cardiol. 2015;22(5):224---23021. Corey S. Miller, BA, Sonia M Grandi, MSc, Avi Shimony, MD, Kristian B Filion, PhD, and Mark J. Eisenberg, MD, MPH. Meta-Analysis of Efficacy and Safety of New Oral Anticoagulants (Dabigatran, Rivaroxaban, Apixaban) Versis Warfarin in Patients With Atrial Fibrillation. Am J Cardiol 2012;110:453-460)22. Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G, et al. Oral anticoagulant therapy: Antithrombo-tic Therapy and Prevention of Thrombosis, 9th. ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141 2 Suppl:e44S---88S.23. Bruce Furie, M.D., and Barbara C. Furie, Ph.D. Mechanisms of Thrombus Formation. New England Journal of Medicine 2008;359:938-49.24. Kojima H, Newton-Nash D, Weiss HJ, et al. Production and characterization of transformed B-lymphocytes expressing the membrane defect of Scott syndrome. J Clin Invest 1994; 94:2237.25. Hansson K, Stenflo J. Post-translational modifications in proteins involved in blood coagulation. J Thromb Haemost 2005; 3:2633.26. Mann KG, Brummel-Ziedins K, Orfeo T, Butenas S. Models of blood coagulation. Blood Cells Mol Dis 2006; 36:108.27. Morrison SA, Jesty J. Tissue factor-dependent activation of tritium-labeled factor IX and factor X in human plasma. Blood 1984; 63:1338.28. Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns Hj. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest 2010; Feb 137(2):263 - 7229. Ntauis G, et al. CHADS2, CHA2DS2-VASc, and long term stroke outcome in patientes without atrial fibrillation. Neurology, March 12; 80(11): 1009-1730. Ostranderld JR, Brandt RL, Kjelsberg M, Eppstein FH. Electrocardiographic findings among the adult population of a total natural community, Te cumshed, Michigan. Circulation 1965; 31: 888-98.31. Kannel W, Abbott RD, Savage AD, McNamara PM. Epidemiologic features of chronic atrial fibrillation: The Framingham study. N Eng J Med 1982; 306: 1018-22.32. Vidaillet H, Granada JF, Chyou et al. A population-based study of mortality among patients with atrial fibrillation or flutter. Am J Med 2002; 113: 365-70.33. Wolf P, D’Agostino R, Belanger A et al. Probality of stroke: a risk profile from the Framingham study. Stroke 1991; 22: 312-8.34. Wolf P, Dawber T, Thomas H et al. Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: the Framingham study. Neurology 1978; 28: 973-7.35. Stöllberger C, Chnupa P, Kronik G et al. Transesophageal echocardiography to assess embolic risk in patients with atrial fibrillation. Ann Intern Med 1998; 128: 630-8.36. Chimowitz M, DeGeorgia M, Poole R et al. Left atrial spontaneous echo contrast is highly associated with previous stroke in patients with atrial fibrillation or mitral stenosis. Stroke 1993; 24: 1015-9.37. Heppell RM, Berkin K, McLenachan et al. Haemostatic and haemodinamic abnormalities associated with left atrial thrombosis in non-rheumatic atrial fibrillation. Heart 1997; 77: 407-11.38. Friberg L, Rosenquist M, Lip GY. Evaluation of risk stratificationschemes for ischaemic stroke and bleeding in 182678 patientes with atrial fibrillation: the Swedish Atrial Fibrillation cohort Study. Eur Heart . 2012 Jun 33(12): 1500-10.39. Lijfering WM, Rosendaal FR, Cannegieter SC. Risk factors for venous thrombosis-current understanding from an epidemiologic point of view. Br J Haematol. 2010; 149(6): 824.40. Dickson BC. Venous thrombosis: on the history of Virchow´s triad. Univ Toronto Med J. 2004; 81:166.41. Bauer KA, The thrombophilias: Well-defined risk factors with uncertain thrapeutic implications, vol. 135, p. 367. Annals of Internal Medicine. 200142. den Exter PL, van Es J, Erkens PM, van Roosmalen MJ, et al. Impact of delay in clinical presentation on the diagnostic managment and prognosis of patientts with suspected pulmnary embolism. Am J Respir Crit Care Med. 2013 Jun; 187(12):1369-7343. Browse NL, homas ML. Source of non-lethal pulmonary emboli. Lancet. 1974; 1(7851):258.44. Nishimura RAm Otto CM, Bonow RO, Carabello BA, et al. 2014 AHA/ACC guideline for the management of patientes with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014; 63(22): e57. Epub 2014 Mar 345. Hirsh J, Weitz JI. New antithrombotic agents. Lancet. 1999;353(9162):1431.46. Laux V, Perzborn E, Heitmeier S, von Degenfeld G, Dittrich-Wengenroth E, Buchmüller A, Gerdes C, Misselwitz F. Direct inhibitors of coagulation proteins - the end of the heparin and low-molecular-weight heparin era for anticoagulant therapy?. Thromb Haemost. 2009;102(5):892.47. Samama MM. The mechanism of action of rivaroxaban--an oral, direct Factor Xa inhibitor--compared with other anticoagulants. Thromb Res. 2011 Jun;127(6):497-504. Epub 2010 Oct 2.48. HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use PRADAXA Capsules safely and effectively . Disponible en: https://docs.boehringeringelheim.com/Prescribing%20Information/PIs/Pradaxa/Pradaxa.pdf49. van Ryn J, Stangier J, Haertter S, Liesenfeld KH, Wienen W, Feuring M, Clemens A. Dabigatran etexilate--a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost. 2010;103(6):1116. Epub 2010 Mar 29.50. Stangier J, Rathgen K, Stähle H, Mazur D. Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate: an open-label, parallel-group, single-centre study. Clin Pharmacokinet. 2010;49(4):259.51. Gosselin RC, Adcock DM, Bates SM, et al. International Council for Standardization in Haematology (ICSH) Recommendations for Laboratory Measurement of Direct Oral Anticoagulants. Thromb Haemost 2018; 118:437.52. Douros A, Azoulay L, Yin H, et al. Non-Vitamin K Antagonist Oral Anticoagulants and Risk of Serious Liver Injury. J Am Coll Cardiol 2018; 71:1105.1.37).53. Martin K, Beyer-Westendorf J, Davidson BL, et al. Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. J Thromb Haemost 2016; 14:1308.54. Moore KT, Kröll D. Influences of Obesity and Bariatric Surgery on the Clinical and Pharmacologic Profile of Rivaroxaban. Am J Med 2017; 130:1024.55. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022406s004lbl.pdf56. Beyer-Westendorf J, Siegert G. Of men and meals. J Thromb Haemost 2015; 13:943.57. Poulsen BK, Grove EL, Husted SE. New oral anticoagulants: a review of the literature with particular emphasis on patients with impaired renal function. Drugs 2012; 72:1739.58. Nutescu E, Chuatrisorn I, Hellenbart E. Drug and dietary interactions of warfarin and novel oral anticoagulants: an update. J Thromb Thrombolysis 2011; 31:326.59. http://packageinserts.bms.com/pi/pi_eliquis.pdf60. Stergiopoulos K, Brown DL. Genotype-guided vs clinical dosing of warfarin and its analogues: meta-analysis of randomized clinical trials. JAMA Intern Med 2014; 174:1330.61. Belley-Cote EP, Hanif H, D'Aragon F, et al. Genotype-guided versus standard vitamin K antagonist dosing algorithms in patients initiating anticoagulation. A systematic review and meta-analysis. Thromb Haemost 2015; 114:768.62. Harrison L, Johnston M, Massicotte MP, et al. Comparison of 5-mg and 10-mg loading doses in initiation of warfarin therapy. Ann Intern Med 1997; 126:13363. Crowther MA, Ginsberg JB, Kearon C, et al. A randomized trial comparing 5-mg and 10-mg warfarin loading doses. Arch Intern Med 1999; 159:46.64. Farahmand S, Saeedi M, Seyed Javadi HH, Khashayar P. High doses of warfarin are more beneficial than its low doses in patients with deep vein thrombosis. Am J Emerg Med 2011; 29:1222.65. Kovacs MJ, Rodger M, Anderson DR, 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. A randomized, double-blind, controlled trial. Ann Intern Med 2003; 138:714.66. Cushman M, Booth SL, Possidente CJ, et al. The association of vitamin K status with warfarin sensitivity at the onset of treatment. Br J Haematol 2001; 112:572.67. Lubetsky A, Dekel-Stern E, Chetrit A, et al. Vitamin K intake and sensitivity to warfarin in patients consuming regular diets. Thromb Haemost 1999; 81:396.68. Khan T, Wynne H, Wood P, et al. Dietary vitamin K influences intra-individual variability in anticoagulant response to warfarin. Br J Haematol 2004; 124:348.69. Franco V, Polanczyk CA, Clausell N, Rohde LE. Role of dietary vitamin K intake in chronic oral anticoagulation: prospective evidence from observational and randomized protocols. Am J Med 2004; 116:651.70. Limdi NA, Beasley TM, Baird MF, et al. Kidney function influences warfarin responsiveness and hemorrhagic complications. J Am Soc Nephrol 2009; 20:912.71. Keeling D, Baglin T, Tait C, et al. Guidelines on oral anticoagulation with warfarin - fourth edition. Br J Haematol 2011; 154:311.72. Garcia P, Ruiz W, Loza Munárriz C. Warfarin initiation nomograms for venous thromboembolism. Cochrane Database Syst Rev 2016; :CD007699.73. Poller L, Keown M, Ibrahim S, et al. An international multicenter randomized study of computer-assisted oral anticoagulant dosage vs. medical staff dosage. J Thromb Haemost 2008; 6:935.74. Gage BF, Eby C, Johnson JA, et al. Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin. Clin Pharmacol Ther 2008; 84:326.75. Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e152S.76. Ansell J, Hirsh J, Hylek E, et al. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:160S.77. Barnes GD, Froehlich JB. Anticoagulation: a pathway to clinical effectiveness. Am J Med 2009; 122:12678. Kim YK, Nieuwlaat R, Connolly SJ, et al. Effect of a simple two-step warfarin dosing algorithm on anticoagulant control as measured by time in therapeutic range: a pilot study. J Thromb Haemost 2010; 8:10179. Le Gal G, Carrier M, Tierney S, et al. Prediction of the warfarin maintenance dose after completion of the 10 mg initiation nomogram: do we really need genotyping? J Thromb Haemost 2010; 8:90.80. Borgman MP, Pendleton RC, McMillin GA, et al. Prospective pilot trial of PerMIT versus standard anticoagulation service management of patients initiating oral anticoagulation. Thromb Haemost 2012; 108:561.81. Van Spall HG, Wallentin L, Yusuf S, et al. Variation in warfarin dose adjustment practice is responsible for differences in the quality of anticoagulation control between centers and countries: an analysis of patients receiving warfarin in the randomized evaluation of long-term anticoagulation therapy (RE-LY) trial. Circulation 2012; 126:2309.82. Jones M, McEwan P, Morgan CL, et al. Evaluation of the pattern of treatment, level of anticoagulation control, and outcome of treatment with warfarin in patients with non-valvar atrial fibrillation: a record linkage study in a large British population. Heart 2005; 91:472.83. Wallentin L, Yusuf S, Ezekowitz MD, et al. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet 2010; 376:97584. Rose AJ, Ozonoff A, Berlowitz DR, et al. Warfarin dose management affects INR control. J Thromb Haemost 2009; 7:94.85. Witt DM, Nieuwlaat R, Clark NP, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy. Blood Adv 2018; 2:3257.86. Metlay JP, Hennessy S, Localio AR, et al. Patient reported receipt of medication instructions for warfarin is associated with reduced risk of serious bleeding events. J Gen Intern Med 2008; 23:1589.87. Kaatz S. Determinants and measures of quality in oral anticoagulation therapy. J Thromb Thrombolysis 2008; 25:61.88. Phillips KW, Ansell J. Outpatient management of oral vitamin K antagonist therapy: defining and suring high-quality management. Expert Rev Cardiovasc Ther 2008; 6:57.89. van Walraven C, Jennings A, Oake N, et al. Effect of study setting on anticoagulation control: a systematic review and metaregression. Chest 2006; 129:1155.90. Muñoz EM, Linhardt RJ. Heparin-binding domains in vascular biology. Arterioscler Thromb Vasc Biol 2004; 24:1549.91. Masuko S, Linhardt RJ. Chemoenzymatic synthesis of the next generation of ultralow MW heparin therapeutics. Future Med Chem 2012; 4:289.92. Grigas D, Hodous T, Welton W, Pearson D. Medical grand rounds from the West Virginia University Hospital. Sarcoidosis. W V Med J 1978; 74:242.93. Ceri H, Hwang WS, Cheung H. Endogenous heparin-binding lectin activity in human placenta: purification and developmental expression. Biochem Cell Biol 1990; 68:790.94. Tessler S, Rockwell P, Hicklin D, et al. Heparin modulates the interaction of VEGF165 with soluble and cell associated flk-1 receptors. J Biol Chem 1994; 269:12456.95. Fatma N, Singh DP, Shinohara T, Chylack LT Jr. Heparin's roles in stabilizing, potentiating, and transporting LEDGF into the nucleus. Invest Ophthalmol Vis Sci 2000; 41:2648.96. Wijelath E, Namekata M, Murray J, et al. Multiple mechanisms for exogenous heparin modulation of vascular endothelial growth factor activity. J Cell Biochem 2010; 111:461.97. Baglin T, Barrowcliffe TW, Cohen A, et al. Guidelines on the use and monitoring of heparin. Br J Haematol 2006; 133:19.98. Hirsh J, Bauer KA, Donati MB, et al. Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:141S99. Weitz JI. Low-molecular-weight heparins. N Engl J Med 1997; 337:688.100. Hirsh J, Levine MN. Low molecular weight heparin. Blood 1992; 79:1.101. Prandoni P. Heparins and venous thromboembolism: current practice and future directions. Thromb Haemost 2001; 86:488.102. White RH, Ginsberg JS. Low-molecular-weight heparins: are they all the same? Br J Haematol 2003; 121:12.103. Choay J, Petitou M, Lormeau JC, et al. 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; 116:492.104. Perry DJ. Antithrombin and its inherited deficiencies. Blood Rev 1994; 8:37.105. 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; 74:341.106. Danielsson A, Raub E, Lindahl U, Björk I. Role of ternary complexes, in which heparin binds both antithrombin and proteinase, in the acceleration of the reactions between antithrombin and thrombin or factor Xa. J Biol Chem 1986; 261:15467.107. http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020164s083lbl.pdf.108. Rojas L, Aizman A, Ernst D, et al. Anti-Xa activity after enoxaparin prophylaxis in hospitalized patients weighing less than fifty-five kilograms. Thromb Res 2013; 132:761.109. Garcia DA, Baglin TP, Weitz JI, et al. Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e24S.110. W, Dentali F, Eikelboom JW, Crowther MA. Meta-analysis: low-molecular-weight heparin and bleeding in patients with severe renal insufficiency. Ann Intern Med 2006; 144:673.111. Crowther M, Lim W. Low molecular weight heparin and bleeding in patients with chronic renal failure. Curr Opin Pulm Med 2007; 13:409.112. Nagge J, Crowther M, Hirsh J. Is impaired renal function a contraindication to the use of low-molecular-weight heparin? Arch Intern Med 2002; 162:2605.113. Chai-Adisaksopha C, Crowther M, Isayama T, Lim W. The impact of bleeding complications in patients receiving target-specific oral anticoagulants: a systematic review and meta-analysis. Blood 2014; 124:2450.114. Ruff CT, Giugliano RP, Braunwald E, 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; 383:955.115. Garcia DA, Lopes RD, Hylek EM. New-onset atrial fibrillation and warfarin initiation: high risk periods and implications for new antithrombotic drugs. Thromb Haemost 2010; 104:1099116. Jiang R, Shi Y, Zhang R, et al. Comparative efficacy and safety of low-intensity warfarin therapy in preventing unprovoked recurrent venous thromboembolism: A systematic review and meta-analysis. Clin Respir J 2018; 12:2170.117. Robert-Ebadi H, Le Gal G, Righini M. Use of anticoagulants in elderly patients: practical recommendations. Clin Interv Aging 2009; 4:165.118. Benedetti G, Neccia M, Agati L. Direct oral anticoagulants use in elderly patients with non valvular atrial fibrillation: state of evidence. Minerva Cardioangiol 2018; 66:301.119. Huhtakangas J, Tetri S, Juvela S, et al. Effect of increased warfarin use on warfarin-related cerebral hemorrhage: a longitudinal population-based study. Stroke 2011; 42:2431120. Carmeliet P, Jain RK. Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases. Nat Rev Drug Discov 2011; 10:417.121. Pisters R, Lane DA, Nieuwlaat R, et al. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 2010; 138:1093.122. Lip GY, Frison L, Halperin JL, Lane DA. Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score. J Am Coll Cardiol 2011; 57:173.123. Olesen JB, Lip GY, Hansen PR, 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; 9:1460.124. Apostolakis S, Lane DA, Guo Y, et al. Performance of the HEMORR(2)HAGES, ATRIA, and HAS-BLED bleeding risk-prediction scores in patients with atrial fibrillation undergoing anticoagulation: the AMADEUS (evaluating the use of SR34006 compared to warfarin or acenocoumarol in patients with atrial fibrillation) study. J Am Coll Cardiol 2012; 60:861125. Cairns JA, Connolly S, McMurtry S, et al. Canadian Cardiovascular Society atrial fibrillation guidelines 2010: prevention of stroke and systemic thromboembolism in atrial fibrillation and flutter. Can J Cardiol 2011; 27:74.126. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016; 37:2893.127. Asunción Esteve-Pastor M, Miguel Rivera-Caravaca J, Roldán V, et al. Long-term bleeding risk prediction in 'real world' patients with atrial fibrillation: Comparison of the HAS-BLED and ABC-Bleeding risk scores. Thromb Haemost 2017; 117:1848.128. Fang MC, Go AS, Chang Y, et al. A new risk scheme to predict warfarin-associated hemorrhage: The ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) Study. J Am Coll Cardiol 2011; 58:395.129. 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; 105:91.130. Gage BF, Yan Y, Milligan PE, et al. Clinical classification schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF). Am Heart J 2006; 151:713.131. Pengo V, Pegoraro C, Cucchini U, Iliceto S. 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