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Thromb Haemost 2014; 111(01): 14-18
DOI: 10.1160/TH13-08-0667
Clinical Focus
Schattauer GmbH

Should oral anticoagulants be restarted after warfarin-associated cerebral haemorrhage in patients with atrial fibrillation?

Maurizio Paciaroni
1   Stroke Unit and Division of Internal and Cardiovascular Medicine, University of Perugia, Santa Maria della Misericordia Hospital, Perugia, Italy
,
Giancarlo Agnelli
1   Stroke Unit and Division of Internal and Cardiovascular Medicine, University of Perugia, Santa Maria della Misericordia Hospital, Perugia, Italy
› Author Affiliations
Further Information

Publication History

Received: 15 August 2013

Accepted after major revision: 05 November 2013

Publication Date:
21 November 2017 (online)

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Summary

Intracranial haemorrhage (ICH), which affects up to 1% of patients on oral anticoagulation per year, is the most feared and devastating complication of this treatment. After such an event, it is unclear whether anticoagulant therapy should be resumed. Such a decision hinges upon the assessment of the competing risks of haematoma growth or recurrent ICH and thromboembolic events. ICH location and the risk for ischaemic cerebrovascular event seem to be the key factors that lead to risk/benefit balance of restarting anticoagulation after ICH. Patients with lobar haemorrhage or cerebral amyloid angiopathy remain at higher risk for anticoagulant-related ICH recurrence than thromboembolic events and, therefore would be best managed without anticoagulants. Patients with deep hemispheric ICH and a baseline risk of ischemic stroke >6.5% per year, that corresponds to CHADS2 ≥ 4 or CHA2DS2-VASc ≥ 5, may receive net benefit from restarting anticoagulation. To date, a reasonable recommendation regarding time to resumption of anticoagulation therapy would be after 10 weeks. Available data regarding the role of magnetic resonance imaging in assessing the risks of both ICH and warfarin-related ICH do not support the use of this test for excluding anticoagulation in patients with atrial fibrillation.

Keywords

Cerebral haemorrhage - warfarin - anticoagulants - atrial fibrillation
 

  • References

  • 1 Lansberg MG, O’Donnell MJ, Khatri P. et al. Antithrombotic and thrombolytic therapy for ischaemic stroke: Antithrombotic therapy and prevention of thrombosis. American College of Chest Physician Evidence-Based Clinical Practice Guidelines (9th Edition). Chest 2012; 141: 601S-636S.
    CrossrefPubMedSearch in Google Scholar
  • 2 Dowlatshahi D, Butcher KS, Asdaghi N. et al. Poor Prognosis in Warfarin-Associated Intracranial Haemorrhage Despite Anticoagulation Reversal. Stroke 2012; 43: 1812-1817.
    CrossrefPubMedSearch in Google Scholar
  • 3 Friberg L, Rosenqvist M, Lip GYH. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J 2012; 33: 1500-1510.
    CrossrefPubMedSearch in Google Scholar
  • 4 Steiner T. Resumption of oral anticoagulants after warfarin associated intracer-ebral haemorrhage: Yes. Stroke 2011; 42: 3661-3662.
    CrossrefPubMedSearch in Google Scholar
  • 5 Schulman S. Resumption of oral anticoagulants after warfarin associated intra-cerebral haemorrhage: No. Stroke 2011; 42: 3663-3664.
    CrossrefPubMedSearch in Google Scholar
  • 6 Molina CA, Selim MH. The dilemma of resuming anticoagulation after intra-cranial haemorrhage. Little evidence facing big fear. Stroke 2011; 42: 3665-3666.
    CrossrefPubMedSearch in Google Scholar
  • 7 Eckman MH, Rosand J, Knudsen KA, Singer DE, Greenberg SM. Can patients be anticoagulated after intracerebral haemorrhage? A decision analysis. Stroke 2003; 34: 1710-1716.
    CrossrefPubMedSearch in Google Scholar
  • 8 Singer DE, Chang Y, Fan MC. et al. The net clinical benefit of warfarin antico- agulation in atrial fibrillation. Ann Intern Med 2009; 151: 297-305.
    CrossrefPubMedSearch in Google Scholar
  • 9 Paciaroni M, Agnelli G. Solutions to Reduce Cardiovascular Events in Patients with Atrial Fibrillation. J A Fib 2012; 5: 45-53.
    PubMedSearch in Google Scholar
  • 10 Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. J Am Med Assoc 2001; 285: 2864-2870.
    CrossrefPubMedSearch in Google Scholar
  • 11 Gage BF, van Walraven C, Pearce L. et al. Selecting patients with atrial fibrillation for anticoagulation: stroke risk stratification in patients taking aspirin. Circulation 2004; 110: 2287-2292.
    CrossrefPubMedSearch in Google Scholar
  • 12 Lip GY, Nieuwlaat R, Pisters R. et al. 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; 137: 263-272.
    CrossrefPubMedSearch in Google Scholar
  • 13 Camm AJ, Lip GYH, De Caterina R. et al. 2012 focused update of the ESC guidelines for the management of atrial fibrillation. Eur Heart J 2012; 33: 2719-2747.
    CrossrefPubMedSearch in Google Scholar
  • 14 Ogawa S, Aonuma K, Tse HF. et al. The APHRS’s 2013 statement on antithrombotic therapy of patients with nonvalvular atrial fibrillation. J Arrhythmia 2013; 29: 190-200.
    CrossrefPubMedSearch in Google Scholar
  • 15 Olesen JB, Torp-Pedersen C, Hansen ML. et al. The value of the CHA2DS2-VASc score for refining stroke risk stratification in patients with at-rial fibrillation with CHADS2 score 0-1: a nationwide cohort study. Thromb Haemost 2012; 107: 1172-1179.
    Thieme ConnectPubMedSearch in Google Scholar
  • 16 Lip GYH, Andreotti F, Fauchier L. et al. Bleeding risk assessment and management in atrial fibrillation patients. Thromb Haemost 2011; 106: 997-1011.
    Thieme ConnectPubMedSearch in Google Scholar
  • 17 Gage BE, Yan Y, Milligan PE. et al. Clinical classification schemes for predicting haemorrhage: Results from the National Registry of Atrial Fibrillation (NRAF). Am Heart J 2006; 151: 713-719.
    CrossrefPubMedSearch in Google Scholar
  • 18 Pisters R, Lane DA, Nieuwlaat R. et al. A novel user-friendly score (HAS-BLED) to assess one year risk of major bleeding in atrial fibrillation patients: The Euro Heart Survey. Chest 2010; 138: 1103-1100.
    CrossrefPubMedSearch in Google Scholar
  • 19 Apostolakis S, Lane D, Guo Y. et al. Performance of the HAEMORR 2 HAGES, ATRIA, and HAS-BLED bleeding risk-prediction scores in nonwarfarin antico-agulated atrial fibrillation patients. J Am Coll Cardiol 2013; 61: 386-387.
    CrossrefPubMedSearch in Google Scholar
  • 20 Olesen B, Lip GYH, Lindhardsen J. et al. Risks of thromboembolism and bleeding with thromboprophylaxis in patients with atrial fibrillation: A net clinical benefit analysis using a “real world” nationwide cohort study. Thromb Haemost 2011; 106: 739-749.
    Thieme ConnectPubMedSearch in Google Scholar
  • 21 Katramados A, Varelas P. Haemorrhagic stroke. In: The Stroke Book. Torbey MT, Selim MH. Eds. Cambridge University Press; New York: 2007: 60-70.
    Search in Google Scholar
  • 22 O’Donnell HC, Rosand J, Knudsen KA. et al. Apolipoprotein E genotype and the risk of recurrent lobar intracerebral haemorrhage. N Engl J Med 2000; 342: 240-245.
    CrossrefPubMedSearch in Google Scholar
  • 23 Viswanathan A, Rakich SM, Engel C. et al. Antiplatelet use after intracerebral haemorrhage. Neurology 2006; 66: 206-209.
    CrossrefPubMedSearch in Google Scholar
  • 24 Yung D, Kapral MK, Asllani E. et al. Reinitiation of anticoagulation after warfarin-associated intracerebral haemorrhage and mortality risk: the best practice for reinitiating anticoagulation therapy after intracranial bleeding (BRAIN) study. Can J Cardiol 2012; 28: 33-39.
    CrossrefPubMedSearch in Google Scholar
  • 25 Majeed A, Kim YK, Roberts RS. et al. Optimal timing of resumption of warfarin after intracerebral haemorrhage. Stroke 2010; 41: 2860-2866.
    CrossrefPubMedSearch in Google Scholar
  • 26 Genes for Cerebral Haemorrhage on Anticoagulation (GOCHA) Collaborative Group. Exploiting common genetic variation to make anticoagulation safer. Stroke 2009; 40 (Suppl. 03) 564-566.
    CrossrefPubMedSearch in Google Scholar
  • 27 Tzourio C, Arima H, Harmap S. et al. ApoE genotype, ethnicity, and the risk of cerebral haemorrhage. Neurology 2008; 70: 1322-1328.
    CrossrefPubMedSearch in Google Scholar
  • 28 Bailey RD, Hart RG, Benavente O. et al. Recurrent brain haemorrhage is more frequent than ischaemic stroke after intracranial haemorrhage. Neurology 2001; 56: 773-777.
    CrossrefPubMedSearch in Google Scholar
  • 29 De Vleeschouwer S, Van Calenbergh F, van Loon J. et al. Risk analysis of throm-boembolic and recurrent bleeding events in the management of intracranial haemorrhage due to oral anticoagulation. Arch Chir Belg 2005; 105: 268-274.
    PubMedSearch in Google Scholar
  • 30 Claassen DO, Kazemi N, Zubkov AY. et al. Restarting anticoagulation therapy after warfarin-associated intracranial haemorrhage. Arch Neurol 2008; 65: 1313-1318.
    CrossrefPubMedSearch in Google Scholar
  • 31 Greenberg SM, Vernooij MW, Cordonnier C. et al. Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol 2009; 8: 165-174.
    CrossrefPubMedSearch in Google Scholar
  • 32 Greenberg SM, Eng JA, Ning M. et al. Haemorrhage burden predicts recurrent intracerebral haemorrhage after lobar haemorrhage. Stroke 2004; 35: 1415-1420.
    CrossrefPubMedSearch in Google Scholar
  • 33 Thijs V, Lemmens R, Schoofs C. et al. Microbleeds and the Risk of Recurrent Stroke. Stroke 2010; 41: 2005-2009.
    CrossrefPubMedSearch in Google Scholar
  • 34 Ueno H, Naka H, Ohshita T. et al. Association between Cerebral Microbleeds on T2*-Weighted MR Images and Recurrent Haemorrhagic Stroke in Patients Treated with Warfarin following Ischaemic Stroke. Am J Neuroradiol 2008; 29: 1483-1486.
    CrossrefPubMedSearch in Google Scholar
  • 35 Janaway BM, Simpson JE, Hoggard N. et al. on behalf of the MRC Cognitive Function and Ageing Neuropathology Study. . Brain haemosiderin in older people: pathological evidence for an ischaemic origin of MRI microbleeds. Neuropathol Appl Neurobiol. 2013 Epub ahead of print.
    PubMedSearch in Google Scholar
  • 36 Rasmussen LH, Larsen TB, Graungaard T. et al. Primary and secondary prevention with new oral anticoagulant drugs for stroke prevention in atrial fibrillation: indirect comparison analysis. Br Med J 2012; 345: e7097
    CrossrefPubMedSearch in Google Scholar
  • 37 Banerjee A, Lane DA, Torp-Pedersen C. et al. Net clinical benefit of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus no treatment in a “real world” atrial fibrillation population: A modelling analysis based on a nationwide cohort study. Thromb Haemost 2012; 107: 584-589.
    Thieme ConnectPubMedSearch in Google Scholar