Spontaneous Intracranial Hemorrhage and Oral Anticoagulation A Retrospective Study
Main Article Content
Keywords
Intracranial hemorrhage, cerebral hemorrhage, Warfarin, antithrombins factor Xa inhibitors
Abstract
Background: Canadian data on intracranial hemorrhage (ICH) associated with oral anticoagulation is limited. Objectives: Primary study outcomes were baseline hematoma volumes and in-hospital mortality in patients with ICH associated with direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs). Second-ary outcomes included the use of four-factor prothrombin complex concentrate (4f-PCC).
Methods: Retrospective cohort study of patients with ICH associated with oral anticoagulation in three ter-tiary care hospitals in Montreal, Canada, between 2011 and 2018.
Results: Twenty-nine patients were receiving DOACs and 114 patients were under VKAs. Median baseline hematoma volumes were similar, 14.8 ml [5.7–42.8] in the DOAC group and 15.6 ml [5.9–38.1] in the VKA group (p = 0.91). In-hospital mortality rate was 34.5% in the DOAC group and 48.2% in the VKA group (p = 0.26). Only 17 patients (58.6%) in the DOAC group received 4f-PCC.
Conclusion: Our study did not demonstrate significant differences in outcomes of ICH associated with DOACs versus VKAs. Management approaches were variable.
Résumé
Contexte: Il existe peu de données canadiennes sur l’hémorragie intracrânienne (HIC) associée à la prise d’anticoagulants par voie orale.
Objectifs: Les critères d’évaluation principaux de l’étude sont le volume initial de l’hématome et la mortalité à l’hôpital chez des patients présentant une HIC associée à la prise d’anticoagulants oraux directs (AOD) par rapport à la prise d’antagonistes de la vitamine K (AVK). Les critères d’évaluation secondaires comprennent l’utilisation d’un concentré de complexe prothrombique à quatre facteurs (4f-PCC pour four-factor prothrombin complex concentrate).
Méthodologie: Étude de cohorte rétrospective portant sur des patients présentant une HIC associée à la prise d’anticoagulants oraux dans trois hôpitaux de soins tertiaires de Montréal (Canada) entre 2011 et 2018. Résultats: Au total, 29 patients prenaient des AOD et 114 des AVK. Les volumes médians des hématomes au départ sont semblables, soit de 14,8 ml (de 5,7 à 42,8) dans le groupe des AOD et de 15,6 ml (de 5,9 à 38,1) dans le groupe des AVK (p = 0,91). Le taux de mortalité à l’hôpital est de 34,5 % pour le groupe des AOD et de 48,2 % pour celui des AVK (p = 0,26). Seuls 17 patients (58,6 %) du groupe des AOD ont reçu le 4f-PCC.
Conclusion: Notre étude ne montre aucune différence importante dans les résultats concernant l’HIC associée à la prise d’AOD par rapport à la prise d’AVK. Les méthodes de prise en charge sont variables.
References
2. Ortel TL, Neumann I, Ageno W, et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism. Blood Adv 2020;4:4693-738. doi: 10.1182/bloodadvances.2020001830.
3. Andrade JG, Aguilar M, Atzema C, et al. The 2020 Canadian Cardiovascular Society/Canadian Heart Rhythm Society Comprehensive Guidelines for the management of atrial fibrillation. Can J Cardiol 2020;36:1847-948. doi: 10.1016/j.cjca.2020.09.001.
4. Gomez-Outes A, Terleira-Fernandez AI, Lecumberri R, Suarez-Gea ML, Vargas-Castrillon E. Direct oral anticoagulants in the treatment of acute venous thromboembolism: a systematic review and meta-analysis. Thromb Res 2014;134:774-82. doi: 10.1016/j.thromres.2014.06.020.
5. 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 randomized trials. Lancet 2014;383:955-62. doi: 10.1016/S0140-6736(13)62343-0.
6. Foerch C, Lo EH, van Leyen K, Lauer A, Schaefer JH. Intracerebral hemorrhage formation under direct oral anticoagulants. Stroke 2019;50:1034-42. doi: 10.1161/STROKEAHA.118.023722.
7. Ahmed A, Ahmed R, Ali SS, et al. Intracerebral hemorrhage outcomes in patients using direct oral anticoagulants versus vitamin K antagonists: a meta-analysis. Clin Neurol Neurosurg 2020;198:106146. doi: 10.1016/j.clineuro.2020.106146.
8. DiRisio AC, Harary M, Muskens IS, et al. Outcomes of intraparenchymal hemorrhage after direct oral anticoagulant or vitamin K antagonist therapy: A systematic review and meta-analysis. J Clin Neurosci 2019;62:188-94. doi: 10.1016/j.jocn.2018.11.032.
9. Inohara T, Xian Y, Liang L, et al. Association of intracerebral hemorrhage among patients taking non-vitamin K antagonists vs vitamin K antagonist oral anticoagulants with in-hospital mortality. JAMA 2018;319:463-73. doi: 10.1001/jama.2017.21917.
10. Xian Y, Zhang S, Inohara T, et al. Clinical characteristics and outcomes associated with oral anticoagulant use among patients hospitalized with intracerebral hemorrhage. JAMA Netw Open 2021;4:e2037438. doi: 10.1001/jamanetworkopen.2020.37438.
11. Frontera JA, Lewin JJ, Rabinstein AA, et al. Guidelines for reversal of antithrombotics in intracranial hemorrhage. A statement for healthcare professionals from the Neurocritical Care Society and Society of Critical Care Medicine. Neurocrit Care 2016;24:6-46 doi: 10.1007/s12028-015-0222-x.
12. Pollack CV, Reilly PA, van Ryn J, et al. Idarucizumab for dabigatran reversal - Full cohort analysis. N Engl J Med 2017;377:431-41. doi: 10.1056/NEJMoa1707278.
13. Connolly SJ, Crowther M, Eikelboom JW, et al. Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors. N Engl J Med 2019;380:1326-35. doi: 10.1056/NEJMoa1814051.
14. Tomaselli GF, Mahaffey KW, Cuker A, et al. 2020 ACC expert consensus decision pathway on management of bleeding in patients on oral anticoagulants: a report from the American College of Cardiology solution set oversight committee. J Am Coll Cardiol 2020;76:594-622. doi: 10.1016/j.jacc.2020.04.053.
15. Shoamanesh A, Lindsay MP, Castellucci et al. Canadian stroke best practice recommendations: Management of spontaneous intracerebral hemorrhage 7th Edition update 2020. Int J Stroke 2021;16:321-41. doi: 10.1177/1747493020968424.
16. Kamal N, Lindsay MP, Côté R, Fang J, Kapral MK, Hill MD. Ten-year trends in stroke admissions and outcomes in Canada. Can J Neurol Sci 2015;42:168-75. doi: 10.1017/cjn.2015.20
17. Pham TM, Thanh NX, Wasylak T, et al. Average lifespan shortened due to stroke in Canada A nationwide descriptive study from 1990 to 2015. Stroke 2021;52:573-81. doi: 10.1161/STROKEAHA.120.032028.
18. Yu AYX, Fang J, Porter J, Austin PC, Smith EE, Kapral MK. Hospital-based cohort study to determine the association between home-time and disability after stroke by age, sex, stroke type and study year in Canada. BMJ Open 2019;9:e031379. doi: 10.1136/bmjopen-2019-031379
19. Fernando SM, Qureshi D, Talarico R, et al. Intracerebral hemorrhage incidence, mortality, and association with anticoagulant use. Stroke 2021;52:1673-81. doi: 10.1161/STROKEAHA.120.032550
20. Weitz JI, Semchuk W, Turpie AGG, et al. Trends in prescribing oral anticoagulants in Canada 2008-2014. Clin Ther 2015;37:2506-14. doi: 10.1016/j.clinthera.2015.09.008.
21. Piran S, Schulman S, Salib M, Delaney J, Panju M, Pai M. Direct Oral Anticoagulants in the Real World: Insights into Canadian Health Care Providers’ Understanding of Medication Dosing and Use. Can Journ Gen Int Med 2017;12:23-7.
22. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap) – A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009;42:377-81. doi: 10.1016/j.jbi.2008.08.010.
23. Harris PA, Taylor R, Minor BL, et al. The REDCap consortium: Building an international community of software partners. J Biomed Inform 2019;95:103208. doi: 10.1016/j.jbi.2019.103208
24. World Health Organization. (2004). ICD-10 : international statistical classification of diseases and related health problems : tenth revision, 2nd ed. World Health Organization. https://apps.who.int/iris/handle/10665/42980
25. Morotti, A., Boulouis G, Dowlatshahi D, et al. Standards for detecting, interpreting, and reporting noncontrast computed tomographic markers of intracerebral hemorrhage expansion. Ann Neurol 2019; 86: 480-92. doi: 10.1002/ana.25563.
26. Yogendrakumar V., Ramsay T, Fergusson DA, et al. Redefining hematoma expansion with the inclusion of intraventricular hemorrhage growth. Stroke 2020; 51:1120-7. doi: 10.1161/STROKEAHA.119.027451.
27. Fedorov A., Beichel R., Kalpathy-Cramer J., et al. 3D Slicer as an image computing platform for the quantitative imaging network. Magn Reson Imaging. 2012;30:1323-41. doi: 10.1016/j.mri.2012.05.001.
28. Wilson D, Seiffge DJ, Traenka C, et al. Outcome of intracerebral hemorrhage associated with different oral anticoagulants. Neurology 2017;88:1693-700. doi: 10.1212/WNL.0000000000003886.
29. Tsivgoulis G, Lioutas VA, Varelas P, et al. Direct oral anticoagulant vs vitamin K antagonist-related nontraumatic intracerebral hemorrhage. Neurology 2017;89:1142-51. doi: 10.1212/WNL.0000000000004362.
30. Tsivgoulis G, Wilson D, Katsanos AH, et al. Neuroimaging and clinical outcomes of oral anticoagulant-associated intracerebral hemorrhage. Ann Neurol 2018;84:694-704. doi: 10.1002/ana.25342.
31. Melmed KR, Lyden P, Gellada N, Moheet A. Intracerebral hemorrhagic expansion occurs in patients using non-vitamin K antagonist oral anticoagulants comparable with patients using warfarin. J Stroke Cerebrovasc Dis 2017;26:1874-82. doi: 10.1016/j.jstrokecerebrovasdis.2017.04.025.
32. Al-Shahi Salman R, Frantzias J, Lee RJ, et al. Absolute risk and predictors of the growth of acute spontaneous intracerebral hemorrhage: a systematic review and meta-analysis of individual patient data. Lancet Neurol 2018;17:885-94. doi: 10.1016/S1474-4422(18)30253-9.
33. Kuramatsu JB, Gerner ST, Schellinger PD, et al. Anticoagulation reversal, blood pressure levels, and anticoagulation resumption in patients with anticoagulation-related intracerebral hemorrhage. JAMA 2015;313:824-36. doi: 10.1001/jama.2015.0846.
34. Baharoglu MI, Cordonnier C, Al-Shahi Salman R, et al. Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral hemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial. Lancet 2016;387:2605-13. doi: 10.1016/S0140-6736(16)30392-0.
35. Tsai CT, Liao JN, Chiang CE, et al. Association of ischemic stroke, major bleeding, and other adverse events with warfarin use vs non-vitamin K antagonist oral anticoagulant use in patients with atrial fibrillation with a history of intracranial hemorrhage. JAMA Netw Open 2020;3:e206424. doi: 10.1001/jamanetworkopen.2020.6424.
36. Huttner HB, Steiner T, Hartmann M, et al. Comparison of ABC/2 estimation technique to computer-assisted planimetric analysis in warfarin-related intracerebral parenchymal hemorrhage. Stroke 2006;37:404-8. doi: 10.1161/01.STR.0000198806.67472.5c.
37. Concha M, Cohen AT. Recommendations for research assessing outcomes for patients with anticoagulant-related intracerebral bleeds. Stroke 2021;52:1520-6. doi: 10.1161/STROKEAHA.120.031730.
38. National Library of Medicine (U.S.) (2018 Sept 7 -). Trial of andexanet in ICH patients receiving an oral FXa inhibitor. Identifier NCT03661528, https://clinicaltrials.gov/ct2/show/NCT03661528.
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Marie Duquet-Armand, Université de Montréal, Montréal, Québec, Canada
Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada
Faculté de médecine, Université de Montréal, Montréal, Québec, Canada
Amine Bouziane, Université de Montréal, Montréal, Québec, Canada
Pharmacy Department, Centre Hospitalier de de Montréal, Montréal, Québec, Canada;
Faculté de pharmacie, Université de Montréal, Montréal, Québec, Canada
Health Innovation and Evaluation Hub Axis, Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Québec, Canada
Alexandra Arruda, Université de Montréal, Montréal, Québec, Canada; Hôpital Rivière-des-Prairies, CIUSSS du Nord-de-l’Île-de-Montréal, Montréal, Québec, Canada
Faculté de pharmacie, Université de Montréal, Montréal, Québec, Canada
Pharmacy Department, Hôpital Rivière-des-Prairies, CIUSSS du Nord-de-l’Île-de-Montréal, Montréal, Québec, Canada
Jean-Simon Denault, Université de Montréal, Montréal, Québec, Canada
Pharmacy Department, Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada
Faculté de pharmacie, Université de Montréal, Montréal, Québec, Canada
Annie Routhier, Université de Montréal, Montréal, Québec, Canada
Pharmacy Department, Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada
Faculté de pharmacie, Université de Montréal, Montréal, Québec, Canada
Tasha Cusson, Université de Montréal, Montréal, Québec, Canada
Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada
Faculté de médecine, Université de Montréal, Montréal, Québec, Canada
Antoine Halwagi, Université de Montréal, Montréal, Québec, Canada
Department of Anesthesiology and Division of Critical Care, Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada
Neuroscience Axis, Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada
David Williamson, Université de Montréal, Montréal, Québec, Canada; CIUSSS-du-Nord-de-l’Île-de-Montréal, Montréal, Québec, Canada
Faculté de pharmacie, Université de Montréal, Montréal, Québec, Canada
Pharmacy Department, Hôpital du Sacré-Cœur, CIUSSS-du-Nord-de-l’Île-de-Montréal, Montréal, Québec, Canada
Research center CIUSSS-du-Nord-de-l’île-de-Montréal, Québec, Canada
Marc Perreault, Université de Montréal, Montréal, Québec, Canada; McGill University Health Center, Montréal, Québec, Canada
Faculté de pharmacie, Université de Montréal, Montréal, Québec, Canada
Pharmacy Department, McGill University Health Center, Montréal, Québec, Canada
Marie Lordkipanidze, Université de Montréal, Montréal, Québec, Canada; Centre de recherche de l’Institut de cardiologie de Montréal, Montréal, Québec, Canada
Faculté de pharmacie, Université de Montréal, Montréal, Québec, Canada
Centre de recherche de l’Institut de cardiologie de Montréal, Montréal, Québec, Canada
Laurent Létourneau-Guillon, Université de Montréal, Montréal, Québec, Canada;
Faculté de médecine, Université de Montréal, Montréal, Québec, Canada
Department of Radiology, Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada
Imaging and Engineering Axis, Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada
Zoé Thiboutot, Université de Montréal, Montréal, Québec, Canada
Pharmacy Department, Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada
Faculté de pharmacie, Université de Montréal, Montréal, Québec, Canada
Health Innovation and Evaluation Hub Axis, Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Québec, Canada