nnpNeurology, Neuropsychiatry, PsychosomaticsНеврология, нейропсихиатрия, психосоматика2074-27112310-1342"IMA-Press", LLC10.14412/2074-2711-2019-3S-82-88nnp-1138Research ArticleREVIEWSОБЗОРЫIntracranial hemorrhage in patients taking oral anticoagulants. Current possibilities for therapyВнутричерепные кровотечения у пациентов, принимающих оральные антикоагулянты. Современные возможности терапииЯнишевскийС. Н.YanishevskyS. N.

кафедра нервных болезней им. М.И. Аствацатурова,

195027, Санкт-Петербург, ул. Академика Лебедева, 6

M.I. Astvatsaturov Department of Nervous Diseases, 

6, Academician Lebedev St., Saint Petersburg 195027

stasya71@yandex.ruФГБВОУ ВО «Военно-медицинская академия им. С.М. Кирова»РоссияS.M. Kirov Military Medical AcademyRussian Federation201924062019113SСпецвыпуск: когнитивные нарушения, цереброваскулярные заболевания8288Copyright © Yanishevsky S.N., 20192019Янишевский С.Н.Yanishevsky S.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://nnp.ima-press.net/nnp/article/view/1138

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.

Представлен обзор современных данных, касающихся возможностей оказания помощи пациентам со спонтанными нетравматическими внутричерепными кровотечениями (ВЧК), развивающимися у пациентов с фибрилляцией предсердий на фоне использования оральных антикоагулянтов. Показано, что частота ВЧК существенно ниже при использовании не-витамин-К-зависимых антикоагулянтов (НОАК), но сценарии эволюции гематомы не различаются между группами пациентов, получающих антагонисты витамина К или НОАК. Сравниваются результаты исследований, посвященных терапии артериальной гипертензии у пациентов с ВЧК. Также обсуждаются возможности использования различных реверсивных агентов для различных пероральных антикоагулянтов. Так как одной из основных проблем, ассоциированных с повышенной смертностью и выраженной инвалидизацией, является темп нарастания ВЧК, возможность применения специфического антагониста может определять выбор антикоагулянта при первичном назначении для профилактики ишемического инсульта у пациента с фибрилляцией предсердий.

фибрилляция предсердийпрофилактика инсультавнутричерепное кровотечениеоральные антикоагулянтыновые оральные антикоагулянтыпрямые оральные антикоагулянтыантагонисты витамина Кспецифический антагонистдабигатранидаруцизумабatrial fibrillationstroke preventionintracranial hemorrhageoral anticoagulantsnew oral anticoagulantsdirect oral anticoagulantsvitamin K antagonistsspecific antagonistdabigatranidarucizumabReferencesQureshi 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: 10.1177/0885066604271619Qureshi 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: 10.1177/0885066604271619Sutherland GR, Auer RN. Primary intracerebal hemorrhage. J Clin Neuroscience. 2006; 13:511-7. doi: 10.1016/j.jocn.2004.12.012Sutherland GR, Auer RN. Primary intracerebal hemorrhage. J Clin Neuroscience. 2006; 13:511-7. doi: 10.1016/j.jocn.2004.12.012Purrucker 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.2015.3682Purrucker 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.2015.3682Roquer 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.13458Roquer 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.13458Melmed 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.2017.04.025Melmed 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.2017.04.025Hankey 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.113.004506Hankey 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.113.004506Hart 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.112.650614Hart 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.112.650614Steiner 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.f8Steiner 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.f8Hansen 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. 2010.271Hansen 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. 2010.271Ray B, Keyrouz SG. Management of anticoagulant-related intracranial hemorrhage: an evidence-based review. Crit Care. 2014;18(3): 223-3. doi: 10.1186/cc13889Ray B, Keyrouz SG. Management of anticoagulant-related intracranial hemorrhage: an evidence-based review. Crit Care. 2014;18(3): 223-3. doi: 10.1186/cc13889Sturgeon 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.107.487090Sturgeon 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.107.487090Ruff 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)62343-0Ruff 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)62343-0Patel 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/NEJMoa1009638Patel 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/NEJMoa1009638Granger 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/NEJMoa1107039Granger 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/NEJMoa1107039Connolly 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/NEJMoa0905561Connolly 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/NEJMoa0905561Wilson 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 0003886Wilson 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 0003886Boulouis 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-2017-316631Boulouis 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-2017-316631Saji 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-14-1209Saji 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-14-1209Hagii J, Tomita H, Metoki N, et al. Characteristics of intracerebral hemorrhage during rivaroxaban treatment. Stroke. 2014; 45:2805-7. doi: 10.1161/STROKEAHA. 114.006661Hagii J, Tomita H, Metoki N, et al. Characteristics of intracerebral hemorrhage during rivaroxaban treatment. Stroke. 2014; 45:2805-7. doi: 10.1161/STROKEAHA. 114.006661Kawabori 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.2017.12.020Kawabori 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.2017.12.020Kurogi 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.0000000000005207Kurogi 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.0000000000005207Komori 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-13-1534Komori 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-13-1534Adachi 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: 10.1159/000462985Adachi 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: 10.1159/000462985Wilson 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.0000000000002310Wilson 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.0000000000002310Apostolaki-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.13068Apostolaki-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.13068Lioutas 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.118.021979Lioutas 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.118.021979Hemphill 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.32.4.891Hemphill 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.32.4.891Kate 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.2013.164Kate 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.2013.164Anderson 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)70069-3Anderson 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)70069-3Anderson 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/NEJMoa1214609Anderson 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/NEJMoa1214609Qureshi 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/NEJMoa1603460Qureshi 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/NEJMoa1603460Hemphill 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.0000000000000069Hemphill 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.0000000000000069Hickey 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.113.001875Hickey 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.113.001875Sarode 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.113.002283Sarode 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.113.002283Crowther 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.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.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/s11239-015-1286-3Becker 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/s11239-015-1286-3Pollack CV Jr, Reilly PA, Eikelboom J, et al. Idarucizumab for dabigatran reversal. N Engl J Med. 2015;373:511-20. doi: 10.1056/NEJMoa 1502000Pollack CV Jr, Reilly PA, Eikelboom J, et al. Idarucizumab for dabigatran reversal. N Engl J Med. 2015;373:511-20. doi: 10.1056/NEJMoa 1502000Kermer 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: 10.1177/1747493017701944Kermer 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: 10.1177/1747493017701944Purrucker 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. 3682Purrucker 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

The authors declare that there are no conflicts of interest present.