Skip to main content
SpringerLink
Log in

Management of Antithrombotic-Related Intracerebral Hemorrhage

  • Chapter
  • First Online:
Stroke Revisited: Hemorrhagic Stroke

Part of the book series: Stroke Revisited ((STROREV))

  • 1749 Accesses

Abstract

Even though hemorrhagic stroke is less common than ischemic stroke, the former is generally associated with worse clinical outcomes. Intracerebral hemorrhage (ICH) is a key type of hemorrhagic stroke, with a variety of important causes including antithrombotic-related ICH. Antithrombotic-related ICH accounts for about 8–14% of all ICH and is linked to much poorer prognosis than ICH without antithrombotic use. Indeed, iatrogenic coagulopathy poses a unique challenge to emergency medicine physicians, vascular neurologists, neurointensivists, and neurosurgeons. This is because premorbid use of an anticoagulant or antiplatelet agent can quickly and significantly foster hematoma growth within the first 24 h of ictus thereby leading to poor ICH outcomes. However, timely and appropriate administration of reversal agents can mitigate the extent of hematoma growth and lower the risk of a devastating outcome. In this chapter, we review the epidemiology of commonly used outpatient antiplatelet- and anticoagulant-related ICH, discuss the pharmacology of these antithrombotic drugs and their reversal agents, outline the general and specific management of antithrombotic-related ICH, and highlight areas for future research.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Ikram MA, Wieberdink RG, Koudstaal PJ. International epidemiology of intracerebral hemorrhage. Curr Atheroscler Rep. 2012;14:300–6.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Flaherty ML, Woo D, Haverbusch M, et al. Racial variations in location and risk of intracerebral hemorrhage. Stroke. 2005;36:934–7.

    Article  PubMed  Google Scholar 

  3. Labovitz DL, Halim A, Boden-Albala B, et al. The incidence of deep and lobar intracerebral hemorrhage in whites, blacks, and Hispanics. Neurology. 2005;65:518–22.

    Article  CAS  PubMed  Google Scholar 

  4. Tsai C-F, Thomas B, Sudlow CLM. Epidemiology of stroke and its subtypes in Chinese vs white populations: a systematic review. Neurology. 2013;81:264–72.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Van Asch CJ, Luitse MJ, Rinkel GJ, et al. Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurol. 2010;9:167–76.

    Article  PubMed  Google Scholar 

  6. Mcquaid KR, Laine L. Systematic review and meta-analysis of adverse events of low-dose aspirin and clopidogrel in randomized controlled trials. Am J Med. 2006;119:624–38.

    Article  CAS  PubMed  Google Scholar 

  7. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51.

    Article  CAS  PubMed  Google Scholar 

  8. Granger CB, Alexander JH, Mcmurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981–92.

    Article  CAS  PubMed  Google Scholar 

  9. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883–91.

    Article  CAS  PubMed  Google Scholar 

  10. Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369:2093–104.

    Article  CAS  PubMed  Google Scholar 

  11. Gomez-Outes A, Terleira-Fernandez AI, Calvo-Rojas G, et al. Dabigatran, rivaroxaban, or apixaban versus warfarin in patients with nonvalvular atrial fibrillation: a systematic review and meta-analysis of subgroups. Thrombosis. 2013;2013:640723.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  13. Villines Todd CT. Safety of direct oral anticoagulants: insights from postmarketing studies. Am J Med. 2016;129:S41.

    Article  CAS  PubMed  Google Scholar 

  14. 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;50:309–15.

    Article  PubMed  Google Scholar 

  15. Wang K-L, Lip GYH, Lin S-J, et al. Non-vitamin K antagonist oral anticoagulants for stroke prevention in Asian patients with nonvalvular atrial fibrillation: meta-analysis. Stroke. 2015;46:2555–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Shinohara Y, Katayama Y, Uchiyama S, et al. Cilostazol for prevention of secondary stroke (CSPS 2): an aspirin-controlled, double-blind, randomised non-inferiority trial. Lancet Neurol. 2010;9:959–68.

    Article  CAS  PubMed  Google Scholar 

  17. Shi L, Pu J, Xu L, et al. The efficacy and safety of cilostazol for the secondary prevention of ischemic stroke in acute and chronic phases in Asian population—an updated meta-analysis. BMC Neurol. 2014;14:251.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Sudlow CL, Mason G, Maurice JB, et al. Thienopyridine derivatives versus aspirin for preventing stroke and other serious vascular events in high vascular risk patients. Cochrane Database Syst Rev. 2009;4:CD001246.

    Google Scholar 

  19. Li-Wan-Po A, Girard T, Farndon P, et al. Pharmacogenetics of CYP2C19: functional and clinical implications of a new variant CYP2C19*17. Br J Clin Pharmacol. 2010;69:222–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Zabalza M, Subirana I, Sala J, et al. Meta-analyses of the association between cytochrome CYP2C19 loss- and gain-of-function polymorphisms and cardiovascular outcomes in patients with coronary artery disease treated with clopidogrel. Heart. 2012;98:100–8.

    Article  CAS  PubMed  Google Scholar 

  21. Ruff CT, Giugliano RP, Antman EM. Management of bleeding with non-vitamin K antagonist oral anticoagulants in the era of specific reversal agents. Circulation. 2016;134:248–61.

    Article  CAS  PubMed  Google Scholar 

  22. Sansing LH, Messe SR, Cucchiara BL, et al. Prior antiplatelet use does not affect hemorrhage growth or outcome after ICH. Neurology. 2009;72:1397–402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Naidech AM, Jovanovic B, Liebling S, et al. Reduced platelet activity is associated with early clot growth and worse 3-month outcome after intracerebral hemorrhage. Stroke. 2009;40:2398–401.

    Article  PubMed  Google Scholar 

  24. Naidech AM, Bernstein RA, Levasseur K, et al. Platelet activity and outcome after intracerebral hemorrhage. Ann Neurol. 2009;65:352–6.

    Article  PubMed  Google Scholar 

  25. Baharoglu MI, Cordonnier C, Al-Shahi Salman R, et al. Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial. Lancet. 2016;387:2605–13.

    Article  PubMed  Google Scholar 

  26. Steiner T, Poli S, Griebe M, et al. Fresh frozen plasma versus prothrombin complex concentrate in patients with intracranial haemorrhage related to vitamin K antagonists (INCH): a randomised trial. Lancet Neurol. 2016;15:566–73.

    Article  CAS  PubMed  Google Scholar 

  27. Sorensen B, Johansen P, Nielsen GL, et al. Reversal of the International Normalized Ratio with recombinant activated factor VII in central nervous system bleeding during warfarin thromboprophylaxis: clinical and biochemical aspects. Blood Coagul Fibrinolysis. 2003;14:469–77.

    Article  CAS  Google Scholar 

  28. Mayer SA, Brun NC, Begtrup K, et al. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med. 2008;358:2127–37.

    Article  CAS  PubMed  Google Scholar 

  29. Wilson D, Seiffge DJ, Traenka C, et al. Outcome of intracerebral hemorrhage associated with different oral anticoagulants. Neurology. 2017;88:1693–700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Eerenberg ES, Kamphuisen PW, Sijpkens MK, et al. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation. 2011;124:1573–9.

    Article  CAS  PubMed  Google Scholar 

  31. Levi M, Moore KT, Castillejos CF, et al. Comparison of three-factor and four-factor prothrombin complex concentrates regarding reversal of the anticoagulant effects of rivaroxaban in healthy volunteers. J Thromb Haemost. 2014;12:1428–36.

    Article  CAS  PubMed  Google Scholar 

  32. Zahir H, Brown KS, Vandell AG, et al. Edoxaban effects on bleeding following punch biopsy and reversal by a 4-factor prothrombin complex concentrate. Circulation. 2015;131:82–90.

    Article  CAS  PubMed  Google Scholar 

  33. Perzborn E, Heitmeier S, Laux V, et al. Reversal of rivaroxaban-induced anticoagulation with prothrombin complex concentrate, activated prothrombin complex concentrate and recombinant activated factor VII in vitro. Thromb Res. 2014;133:671–81.

    Article  CAS  PubMed  Google Scholar 

  34. Marlu R, Hodaj E, Paris A, et al. Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban: a randomised crossover ex vivo study in healthy volunteers. Thromb Haemost. 2012;108:217–24.

    Article  CAS  PubMed  Google Scholar 

  35. Escolar G, Fernandez-Gallego V, Arellano-Rodrigo E, et al. Reversal of apixaban induced alterations in hemostasis by different coagulation factor concentrates: significance of studies in vitro with circulating human blood. PLoS One. 2013;8:e78696.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Dibu JR, Weimer JM, Ahrens C, et al. The role of FEIBA in reversing novel oral anticoagulants in intracerebral hemorrhage. Neurocrit Care. 2016;24:413–9.

    Article  CAS  PubMed  Google Scholar 

  37. Raval AN, Cigarroa JE, Chung MK, et al. Management of patients on non-vitamin K antagonist oral anticoagulants in the acute care and periprocedural setting: a scientific statement from the American Heart Association. Circulation. 2017;135:e604–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Pollack CVJ, Reilly PA, Van Ryn J, et al. Idarucizumab for dabigatran reversal—full cohort analysis. N Engl J Med. 2017;377:431–41.

    Article  CAS  PubMed  Google Scholar 

  39. Steiner T, Weitz JI, Veltkamp R. Anticoagulant-associated intracranial hemorrhage in the era of reversal agents. Stroke. 2017;48:1432–7.

    Article  PubMed  Google Scholar 

  40. Tireli D, He J, Nordling MM, et al. Systemic thrombolysis in acute ischemic stroke after dabigatran etexilate reversal with idarucizumab—a case report. J Stroke Cerebrovasc Dis. 2017;26:e123–5.

    Article  PubMed  Google Scholar 

  41. Vosko MR, Bocksrucker C, Drwiła R, et al. Real-life experience with the specific reversal agent idarucizumab for the management of emergency situations in dabigatran-treated patients: a series of 11 cases. J Thromb Thrombolysis. 2017;43:306–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Siegal DM, Curnutte JT, Connolly SJ, et al. Andexanet alfa for the reversal of factor Xa inhibitor activity. N Engl J Med. 2015;373:2413–24.

    Article  CAS  PubMed  Google Scholar 

  43. Connolly SJ, Milling TJJ, Eikelboom JW, et al. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med. 2016;375:1131–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Ansell JE, Bakhru SH, Laulicht BE, et al. Use of PER977 to reverse the anticoagulant effect of edoxaban. N Engl J Med. 2014;371:2141–2.

    Article  PubMed  Google Scholar 

  45. Goldstein JN, Fazen LE, Wendell L, et al. Risk of thromboembolism following acute intracerebral hemorrhage. Neurocrit Care. 2009;10:28–34.

    Article  CAS  PubMed  Google Scholar 

  46. Paciaroni M, Agnelli G, Venti M, et al. Efficacy and safety of anticoagulants in the prevention of venous thromboembolism in patients with acute cerebral hemorrhage: a meta-analysis of controlled studies. J Thromb Haemost. 2011;9:893–8.

    Article  CAS  PubMed  Google Scholar 

  47. Eckman MH, Rosand J, Knudsen KA, et al. Can patients be anticoagulated after intracerebral hemorrhage? A decision analysis. Stroke. 2003;34:1710–6.

    Article  PubMed  Google Scholar 

  48. Nielsen PB, Larsen TB, Skjoth F, et al. Restarting anticoagulant treatment after intracranial hemorrhage in patients with atrial fibrillation and the impact on recurrent stroke, mortality, and bleeding: a nationwide cohort study. Circulation. 2015;132:517–25.

    Article  CAS  PubMed  Google Scholar 

  49. Murthy SB, Gupta A, Merkler AE, et al. Restarting anticoagulant therapy after intracranial hemorrhage. A systematic review and meta-analysis. Stroke. 2017;48:1594–600.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Majeed A, Kim YK, Roberts RS, et al. Optimal timing of resumption of warfarin after intracranial hemorrhage. Stroke. 2010;41:2860–6.

    Article  CAS  PubMed  Google Scholar 

  51. Chong BH, Chan KH, Pong V, et al. Use of aspirin in Chinese after recovery from primary intracranial haemorrhage. Thromb Haemost. 2012;107:241–7.

    Article  CAS  PubMed  Google Scholar 

  52. Flynn RW, Macdonald TM, Murray GD, et al. Prescribing antiplatelet medicine and subsequent events after intracerebral hemorrhage. Stroke. 2010;41:2606–11.

    Article  PubMed  Google Scholar 

  53. Viswanathan A, Rakich SM, Engel C, et al. Antiplatelet use after intracerebral hemorrhage. Neurology. 2006;66:206–9.

    Article  CAS  PubMed  Google Scholar 

  54. Biffi A, Halpin A, Towfighi A, et al. Aspirin and recurrent intracerebral hemorrhage in cerebral amyloid angiopathy. Neurology. 2010;75:693–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Wang DN, Hou XW, Yang BW, et al. Quantity of cerebral microbleeds, antiplatelet therapy, and intracerebral hemorrhage outcomes: a systematic review and meta-analysis. J Stroke Cerebrovasc Dis. 2015;24:2728–37.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical University of South Carolina, Charleston, SC, USA

    Tarun Girotra & Wuwei Feng

  2. Department of Neurology, Medical University of South Carolina, Charleston, SC, USA

    Bruce Ovbiagele

Authors
  1. Tarun Girotra
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wuwei Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bruce Ovbiagele
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bruce Ovbiagele .

Editor information

Editors and Affiliations

  1. Department of Neurology, Seoul National University Hospital Department of Neurology, Seoul, Korea (Republic of)

    Seung-Hoon Lee

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Science+Business Media Singapore

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Girotra, T., Feng, W., Ovbiagele, B. (2018). Management of Antithrombotic-Related Intracerebral Hemorrhage. In: Lee, SH. (eds) Stroke Revisited: Hemorrhagic Stroke. Stroke Revisited. Springer, Singapore. https://doi.org/10.1007/978-981-10-1427-7_14

Download citation

  • DOI: https://doi.org/10.1007/978-981-10-1427-7_14

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-10-1426-0

  • Online ISBN: 978-981-10-1427-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation