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Intracranial hemorrhage in patients taking oral anticoagulants. Current possibilities for therapy

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The paper reviews an update on the possibilities of providing care for patients with spontaneous non-traumatic intracranial hemorrhage (ICH) developing in patients with atrial fibrillation who use oral anticoagulants. The incidence of ICH is shown to be considerably lower when nonvitamin K-dependent anticoagulants (NOACs) are used, but the hematoma evolution scenarios do not differ between the groups of patients receiving vitamin K antagonists or NOACs. The results of studies assessing hypertension therapy in patients with ICH are compared. The possibilities of using various reversal agents for various oral anticoagulants are also discussed. Since one of the main problems associated with increased mortality and severe disabilities is the progression rate of ICH, the possibility of using a specific antagonist can determine the choice of an anticoagulant for the primary prevention of ischemic stroke in a patient with atrial fibrillation.

About the Author

S. N. Yanishevsky
S.M. Kirov Military Medical Academy
Russian Federation

M.I. Astvatsaturov Department of Nervous Diseases, 

6, Academician Lebedev St., Saint Petersburg 195027


1. Qureshi AI, Mohammed YM, Yahia AM, et al. A prospective multi-center study to evaluate the feasibility and safety of aggressive antihypertensive treatment in patients with acute intracerebral hemorrhage. J Intensive Care Med. 2005;20:34-42. doi: 10.1177/0885066604271619

2. Sutherland GR, Auer RN. Primary intracerebal hemorrhage. J Clin Neuroscience. 2006; 13:511-7. doi: 10.1016/j.jocn.2004.12.012

3. Purrucker JC, Haas K, Rizos T, et al. Early clinical and radiological course, management, and outcome of intracerebral hemorrhage related to new oral anticoagulants. JAMA Neurol. 2016;73:169-77. doi: 10.1001/jamaneurol.2015.3682

4. Roquer J, Vivanco-Hidalgo RM, Capellades J, et al. Ultra-early hematoma growth in antithrombotic pretreated patients with intracerebral hemorrhage. Eur J Neurol. 2018;25: 83-9. doi: 10.1111/ene.13458

5. 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

6. Hankey GJ, Stevens SR, Piccini JP, et al. Intracranial hemorrhage among patients with atrial fibrillation anticoagulated with warfarin or rivaroxaban: The rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation. Stroke. 2014;45:1304-12. doi: 10.1161/STROKEAHA.113.004506

7. Hart RG, Diener HC, Yang S, et al. Intracranial hemorrhage in atrial fibrillation patients during anticoagulation with warfarin or dabigatran: The rely trial. Stroke. 2012;43:1511-7. doi: 10.1161/STROKEAHA.112.650614

8. Steiner T, Rosand J, Diringer M. Intracerebral hemorrhage associated with oral anticoagulant therapy: current practices and unresolved questions. Stroke. 2006;37(1):256-62. doi: 10.1161/01.STR.0000196989.09900.f8

9. Hansen ML, Sorensen R, Clausen MT, et al. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med. 2010;170:1433-41. doi: 10.1001/archinternmed. 2010.271

10. Ray B, Keyrouz SG. Management of anticoagulant-related intracranial hemorrhage: an evidence-based review. Crit Care. 2014;18(3): 223-3. doi: 10.1186/cc13889

11. Sturgeon JD, Folsom AR, Longstreth WT Jr, et al. Risk factors for intracerebral hemorrhage in a pooled prospective study. Stroke. 2007 Oct; 38(10):2718-25. doi: 10.1161/STROKEAHA.107.487090

12. 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;383:955-62. doi: 10.1016/S0140-6736(13)62343-0

13. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883-91. doi: 10.1056/NEJMoa1009638

14. Granger CB, Alexander JH, McMurray J, et al. Apixaban versus warfarin in patients with atrial fibrillation. New Engl J Med. 2011;365:981-92. doi: 10.1056/NEJMoa1107039

15. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. New Engl J Med. 2009;361: 1139-51. doi: 10.1056/NEJMoa0905561

16. Wilson D, Seiffge DJ, Traenka C, et al; and the CROMIS-2 Collaborators. Outcome of intracerebral hemorrhage associated with different oral anticoagulants. Neurology. 2017;88: 1693-700. doi: 10.1212/WNL.000000000 0003886

17. Boulouis G, Morotti A, Pasi M, et al. Outcome of intracerebral haemorrhage related to non-vitamin K antagonists oral anticoagulants versus vitamin K antagonists: A comprehensive systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2018;89:263-70. doi: 10.1136/jnnp-2017-316631

18. Saji N, Kimura K, Aoki J, et al. Intracranial hemorrhage caused by non-vitamin K antagonist oral anticoagulants (NOACs) – multicenter retrospective cohort study in Japan. Circ J. 2015; 79:1018-23. doi: 10.1253/circj.CJ-14-1209

19. Hagii J, Tomita H, Metoki N, et al. Characteristics of intracerebral hemorrhage during rivaroxaban treatment. Stroke. 2014; 45:2805-7. doi: 10.1161/STROKEAHA. 114.006661

20. Kawabori M, Niiya Y, Iwasaki M, et al. Characteristics of symptomatic intracerebral hemorrhage in patient receiving direct oral anticoagulants: Comparison with warfarin. J Stroke Cerebrovasc Dis. 2018;27(5):1338-42. doi: 10.1016/j.jstrokecerebrovasdis.2017.12.020

21. Kurogi R, Nishimura K, Nakai M, et al. Comparing intracerebral hemorrhages associated with direct oral anticoagulants or warfarin. Neurology. 2018;90(13):e1143-9. doi: 10.1212/ WNL.0000000000005207

22. Komori M, Yasaka M, Kokuba K, et al. Intracranial hemorrhage during dabigatran treatment; case series of eight patients. Circ J. 2014;78:1335-41. doi: 10.1253/circj.CJ-13-1534

23. Adachi T, Hoshino H, Takagi M, Fujioka S. Volume and characteristics of intracerebral hemorrhage with direct oral anticoagulants in comparison with warfarin. Cerebrovasc Dis Extra. 2017;7:62-71. doi: 10.1159/000462985

24. Wilson D, Charidimou A, Shakeshaft C, et al. Volume and functional outcome of intracerebral hemorrhage according to oral anticoagulant type. Neurology. 2016; 86:360-6. doi: 10.1212/WNL.0000000000002310

25. Apostolaki-Hansson T, Ullberg T, Norrving B, Petersson J. Prognosis for intracerebral hemorrhage during ongoing oral anticoagulant treatment. Acta Neurol Scand. 2019;00:1-7. doi: 10.1111/ane.13068

26. Lioutas V-A, Goyal N, Katsanos AH, et al. Clinical outcomes and neuroimaging profiles in nondisabled patients with anticoagulant-related intracerebral hemorrhage. Stroke. 2018;49:2309-16. doi: 10.1161/STROKEAHA.118.021979

27. Hemphill JC 3rd, Bonovich DC, Besmertis L, Manley GT, Johnston SC. The ICH score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke. 2001 Apr; 32(4):891-7. doi: 10.1161/01.STR.32.4.891

28. Kate MP, Hansen MB, Mouridsen K, et al. Blood pressure reduction does not reduce perihematoma oxygenation: a CT perfusion study. J Cereb Blood Flow Metab. 2014 Jan;34(1):81-6. doi: 10.1038/jcbfm.2013.164

29. Anderson CS, Huang Y, Wang JG, et al. Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial. Lancet Neurol. 2008 May;7(5):391-9. doi: 10.1016/S1474-4422(08)70069-3

30. Anderson CS, Heeley E, Huang Y. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med. 2013 Jun 20;368(25):2355-65. doi: 10.1056/NEJMoa1214609

31. Qureshi AI, Palesch YY, Barsan WG, et al. Intensive blood-pressure lowering in patients with acute cerebral hemorrhage. N Engl J Med. 2016 Sep 15;375(11):1033-43. doi: 10.1056/NEJMoa1603460

32. Hemphill JC 3rd, Greenberg SM, Anderson CS, et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2015 Jul;46(7):2032-60. doi: 10.1161/STR.0000000000000069

33. Hickey M, Gatien M, Taljaard M, et al. Outcomes of urgent warfarin reversal with frozen plasma versus prothrombin complex concentrate in the emergency department. Circulation. 2013;128(4):360-4. doi: 10.1161/CIRCULATIONAHA.113.001875

34. Sarode R, Milling TJ, Refaai MA, et al. Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma-controlled, phase IIIb study. Circulation. 2013;128(11):1234-43. doi: 10.1161/CIRCULATIONAHA.113.002283

35. Crowther MA, Kittl E, Lorenz T, et al. A phase 2 ran- domized, double-blind, placebocontrolled trial of PRT064445, a novel, universal antidote for direct and indirect factor Xa inhibitors. J Thromb Haemost. 2013;11(Suppl 2): OC20.1.

36. Becker RC. The biochemistry, enzymology and pharmacology of non-vitamin K anticoagulant drug reversal agents and antidotes. J Thromb Thrombolysis. 2016;41:273-8. doi: 10.1007/s11239-015-1286-3

37. Pollack CV Jr, Reilly PA, Eikelboom J, et al. Idarucizumab for dabigatran reversal. N Engl J Med. 2015;373:511-20. doi: 10.1056/NEJMoa 1502000

38. Kermer P, Eschenfelder CC, Diener H-C, et al. Antagonizing dabigatran by idarucizumab in cases of ischemic stroke or intracranial hemorrhage in Germany – A national case collection. Int J Stroke. 2017;12(4):383-91. doi: 10.1177/1747493017701944

39. Purrucker JC, Haas K, Rizos T, et al. Early clinical and radiological course, management, and outcome of intra-cerebral hemorrhage related to new oral anticoagulants. JAMA Neurol. 2016;73:169-77. doi: 10.1001/jamaneurol.2015. 3682


For citations:

Yanishevsky S.N. Intracranial hemorrhage in patients taking oral anticoagulants. Current possibilities for therapy. Neurology, Neuropsychiatry, Psychosomatics. 2019;11(3S):82-88. (In Russ.)

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