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Risk of intracerebral bleeding in patients treated with anticoagulants

W David Freeman, MD
Maria I Aguilar, MD
Jeffrey Weitz, MD
Section Editors
Lawrence LK Leung, MD
Jose Biller, MD, FACP, FAAN, FAHA
Deputy Editors
Janet L Wilterdink, MD
Jennifer S Tirnauer, MD


Antithrombotic therapies (eg, antiplatelet agents, heparins, vitamin K antagonists, direct thrombin inhibitors, direct factor Xa inhibitors) are widely used in clinical medicine based upon well-designed randomized clinical trials that have rigorously defined their benefits relative to associated bleeding risks. In most of these trials, patients presumed to be at especially high risk for intracerebral hemorrhage (ICH) were excluded from participation, in large part because the antithrombotic benefits were yet to be fully defined while the bleeding risks appeared unduly high.

Because of under-representation in clinical trials, determining the relative efficacy and safety of antithrombotic agents in patients at varying increased risks for ICH is problematic. Nevertheless, clinicians are regularly faced with risk/benefit decisions regarding antithrombotic therapy for such patients. (See "Atrial fibrillation: Anticoagulant therapy to prevent embolization" and "Anticoagulation in older adults", section on 'Considerations about treatment choices'.)

The risk of intracerebral hemorrhage in patients treated with warfarin and other vitamin K antagonists will be reviewed here. Other related topic reviews include the following:

Risk of intracerebral bleeding associated with antiplatelet therapy (see "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis", section on 'Antithrombotic therapy')

Risk of subdural hematoma in patients on anticoagulants are presented separately (see "Subdural hematoma in adults: Etiology, clinical features, and diagnosis")


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Literature review current through: Sep 2016. | This topic last updated: Oct 29, 2013.
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  1. Fang MC, Go AS, Chang Y, et al. Death and disability from warfarin-associated intracranial and extracranial hemorrhages. Am J Med 2007; 120:700.
  2. Rosand J, Eckman MH, Knudsen KA, et al. The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage. Arch Intern Med 2004; 164:880.
  3. Hart RG, Tonarelli SB, Pearce LA. Avoiding central nervous system bleeding during antithrombotic therapy: recent data and ideas. Stroke 2005; 36:1588.
  4. García-Rodríguez LA, Gaist D, Morton J, et al. Antithrombotic drugs and risk of hemorrhagic stroke in the general population. Neurology 2013; 81:566.
  5. Woo D, Sauerbeck LR, Kissela BM, et al. Genetic and environmental risk factors for intracerebral hemorrhage: preliminary results of a population-based study. Stroke 2002; 33:1190.
  6. Flaherty ML, Kissela B, Woo D, et al. The increasing incidence of anticoagulant-associated intracerebral hemorrhage. Neurology 2007; 68:116.
  7. He J, Whelton PK, Vu B, Klag MJ. Aspirin and risk of hemorrhagic stroke: a meta-analysis of randomized controlled trials. JAMA 1998; 280:1930.
  8. Hart RG, Halperin JL, McBride R, et al. Aspirin for the primary prevention of stroke and other major vascular events: meta-analysis and hypotheses. Arch Neurol 2000; 57:326.
  9. Hart RG, Benavente O, Pearce LA. Increased risk of intracranial hemorrhage when aspirin is combined with warfarin: A meta-analysis and hypothesis. Cerebrovasc Dis 1999; 9:215.
  10. Shireman TI, Howard PA, Kresowik TF, Ellerbeck EF. Combined anticoagulant-antiplatelet use and major bleeding events in elderly atrial fibrillation patients. Stroke 2004; 35:2362.
  11. Eikelboom JW, Connolly SJ, Brueckmann M, et al. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med 2013; 369:1206.
  12. Mega JL, Braunwald E, Wiviott SD, et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med 2012; 366:9.
  13. Sjöblom L, Hårdemark HG, Lindgren A, et al. Management and prognostic features of intracerebral hemorrhage during anticoagulant therapy: a Swedish multicenter study. Stroke 2001; 32:2567.
  14. Saloheimo P, Ahonen M, Juvela S, et al. Regular aspirin-use preceding the onset of primary intracerebral hemorrhage is an independent predictor for death. Stroke 2006; 37:129.
  15. Foerch C, Sitzer M, Steinmetz H, Neumann-Haefelin T. Pretreatment with antiplatelet agents is not independently associated with unfavorable outcome in intracerebral hemorrhage. Stroke 2006; 37:2165.
  16. Cucchiara B, Messe S, Sansing L, et al. Hematoma growth in oral anticoagulant related intracerebral hemorrhage. Stroke 2008; 39:2993.
  17. Zubkov AY, Mandrekar JN, Claassen DO, et al. Predictors of outcome in warfarin-related intracerebral hemorrhage. Arch Neurol 2008; 65:1320.
  18. 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.
  19. Flaherty ML, Tao H, Haverbusch M, et al. Warfarin use leads to larger intracerebral hematomas. Neurology 2008; 71:1084.
  20. Wong KS, Mok V, Lam WW, et al. Aspirin-associated intracerebral hemorrhage: clinical and radiologic features. Neurology 2000; 54:2298.
  21. Toyoda K, Okada Y, Minematsu K, et al. Antiplatelet therapy contributes to acute deterioration of intracerebral hemorrhage. Neurology 2005; 65:1000.
  22. Shen AY, Yao JF, Brar SS, et al. Racial/ethnic differences in the risk of intracranial hemorrhage among patients with atrial fibrillation. J Am Coll Cardiol 2007; 50:309.
  23. Walsh, S. FDA approves Pradaxa to prevent stroke in people with atrial fibrillation. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm230241.htm (Accessed on December 03, 2010).
  24. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361:1139.
  25. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365:883.
  26. Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365:981.
  27. Koennecke HC. Cerebral microbleeds on MRI: prevalence, associations, and potential clinical implications. Neurology 2006; 66:165.
  28. Viswanathan A, Chabriat H. Cerebral microhemorrhage. Stroke 2006; 37:550.
  29. Orken DN, Kenangil G, Uysal E, Forta H. Cerebral microbleeds in ischemic stroke patients on warfarin treatment. Stroke 2009; 40:3638.
  30. Fang MC, Go AS, Hylek EM, et al. Age and the risk of warfarin-associated hemorrhage: the anticoagulation and risk factors in atrial fibrillation study. J Am Geriatr Soc 2006; 54:1231.
  31. Hylek EM, Go AS, Chang Y, et al. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N Engl J Med 2003; 349:1019.
  32. Eckman MH, Wong LK, Soo YO, et al. Patient-specific decision-making for warfarin therapy in nonvalvular atrial fibrillation: how will screening with genetics and imaging help? Stroke 2008; 39:3308.
  33. Rosand J, Hylek EM, O'Donnell HC, Greenberg SM. Warfarin-associated hemorrhage and cerebral amyloid angiopathy: a genetic and pathologic study. Neurology 2000; 55:947.
  34. Fang MC, Chang Y, Hylek EM, et al. Advanced age, anticoagulation intensity, and risk for intracranial hemorrhage among patients taking warfarin for atrial fibrillation. Ann Intern Med 2004; 141:745.
  35. Gorter JW. Major bleeding during anticoagulation after cerebral ischemia: patterns and risk factors. Stroke Prevention In Reversible Ischemia Trial (SPIRIT). European Atrial Fibrillation Trial (EAFT) study groups. Neurology 1999; 53:1319.
  36. PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358:1033.
  37. Mant J, Hobbs FD, Fletcher K, et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007; 370:493.
  38. Hylek EM, Evans-Molina C, Shea C, et al. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007; 115:2689.
  39. Gage BF, Birman-Deych E, Kerzner R, et al. Incidence of intracranial hemorrhage in patients with atrial fibrillation who are prone to fall. Am J Med 2005; 118:612.
  40. Pugh D, Pugh J, Mead GE. Attitudes of physicians regarding anticoagulation for atrial fibrillation: a systematic review. Age Ageing 2011; 40:675.
  41. Donzé J, Clair C, Hug B, et al. Risk of falls and major bleeds in patients on oral anticoagulation therapy. Am J Med 2012; 125:773.
  42. Man-Son-Hing M, Laupacis A. Anticoagulant-related bleeding in older persons with atrial fibrillation: physicians' fears often unfounded. Arch Intern Med 2003; 163:1580.
  43. Man-Son-Hing M, Nichol G, Lau A, Laupacis A. Choosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls. Arch Intern Med 1999; 159:677.
  44. Sellers MB, Newby LK. Atrial fibrillation, anticoagulation, fall risk, and outcomes in elderly patients. Am Heart J 2011; 161:241.
  45. Guidelines for minor head injured patients' management in adult age. The Study Group on Head Injury of the Italian Society for Neurosurgery. J Neurosurg Sci 1996; 40:11.
  46. Garra G, Nashed AH, Capobianco L. Minor head trauma in anticoagulated patients. Acad Emerg Med 1999; 6:121.
  47. Cohen DB, Rinker C, Wilberger JE. Traumatic brain injury in anticoagulated patients. J Trauma 2006; 60:553.
  48. Itshayek E, Rosenthal G, Fraifeld S, et al. Delayed posttraumatic acute subdural hematoma in elderly patients on anticoagulation. Neurosurgery 2006; 58:E851.
  49. Kaen A, Jimenez-Roldan L, Arrese I, et al. The value of sequential computed tomography scanning in anticoagulated patients suffering from minor head injury. J Trauma 2010; 68:895.
  50. Buresly K, Eisenberg MJ, Zhang X, Pilote L. Bleeding complications associated with combinations of aspirin, thienopyridine derivatives, and warfarin in elderly patients following acute myocardial infarction. Arch Intern Med 2005; 165:784.
  51. Smith EE, Rosand J, Knudsen KA, et al. Leukoaraiosis is associated with warfarin-related hemorrhage following ischemic stroke. Neurology 2002; 59:193.
  52. Greenberg SM, Vernooij MW, Cordonnier C, et al. Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol 2009; 8:165.
  53. Cordonnier C, Potter GM, Jackson CA, et al. improving interrater agreement about brain microbleeds: development of the Brain Observer MicroBleed Scale (BOMBS). Stroke 2009; 40:94.
  54. Lee SH, Ryu WS, Roh JK. Cerebral microbleeds are a risk factor for warfarin-related intracerebral hemorrhage. Neurology 2009; 72:171.
  55. Wong KS, Chan YL, Liu JY, et al. Asymptomatic microbleeds as a risk factor for aspirin-associated intracerebral hemorrhages. Neurology 2003; 60:511.
  56. Saloheimo P, Juvela S, Hillbom M. Use of aspirin, epistaxis, and untreated hypertension as risk factors for primary intracerebral hemorrhage in middle-aged and elderly people. Stroke 2001; 32:399.