Skip to main content
SpringerLink
Log in

Bleeding on Anti-Xa Drugs: “Does All Bleeding Really Stop?”

  • Chapter
  • First Online:
Case Studies in Emergency Medicine

  • 1502 Accesses

Abstract

Anticoagulation for many different indications is common. Atrial fibrillation, valvular heart disease, congestive heart failure, pulmonary embolism, and deep venous thrombosis top the list. While traditionally warfarin played a significant role in anticoagulation, newer agents that require little to no monitoring and are easier to manage are beginning to take over the scene. While some agents target factor II, the largest degree of growth in the world of anticoagulation is represented by anti-Xa inhibitors. Reversal of this class of drugs has been limited to replenishing of additional coagulation factors in a nonspecific attempt to overwhelm the circulating anti-Xa agent. While this strategy has been largely adopted in the face of no specific antidotes, its effectiveness has been questioned. Now a novel antidote is available, which is very effective in restoring coagulation and reducing anti-Xa levels to almost normal. Despite this, we are still faced with the question of reversal agents improving survival in patients anticoagulated on anti-Xa agents who suffer a bleeding event. The benefits must be weighed along with the high cost of andexanet. Further, the high degree of thrombosis after reversal with this agent needs to be understood in terms of the general reversal of hypercoagulable patients versus some here-to-for unknown prothrombotic properties of andexanet.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 69.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 89.99
Price excludes VAT (USA)
  • Compact, lightweight 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. Patel MR, Mahaffey KW, Garg J, et al; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883–91.

    Article  CAS  Google Scholar 

  2. Granger CB, Alexander JH, McMurray JJ, et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981–92.

    Google Scholar 

  3. Piccini JP, Garg J, Patel MR, et al; ROCKET AF Investigators. Management of major bleeding events in patients treated with rivaroxaban vs. warfarin: results from the ROCKET AF trial. Eur Heart J. 2014;35(28):1873–80.

    Google Scholar 

  4. Sangkuhla K, Shuldinerc AR, Kleina TE, Altmana RB. Platelet aggregation pathway. Pharmacogenet Genomics. 2011;21(8):516–21.

    Article  Google Scholar 

  5. Furie B, Furie BC. Thrombus formation in vivo. J Clin Invest. 2005;115(12):3355–62.

    Article  CAS  Google Scholar 

  6. Roehrig S, Straub A, Pohlmann J, et al. Discovery of the novel antithrombotic agent 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide (BAY 59-7939): an oral, direct factor Xa inhibitor. J Med Chem. 2005;48(19):5900–8.

    Article  CAS  Google Scholar 

  7. Blommel ML, Blommel AL. Dabigatran etexilate: a novel oral direct thrombin inhibitor. Am J Health Syst Pharm. 2011;68(16):1506–19.

    Article  CAS  Google Scholar 

  8. Frumkin K. Rapid reversal of warfarin-associated hemorrhage in the emergency department by prothrombin complex concentrates. Ann Emerg Med. 2013;62(6):616–26. e8

    Article  Google Scholar 

  9. Hirsh J, Raschke R. Heparin and low-molecular-weight heparin: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3. Suppl):188S–203S.

    Article  CAS  Google Scholar 

  10. Weitz JI. Low-molecular-weight heparins. N Engl J Med. 1997;337(10):688–98.

    Article  CAS  Google Scholar 

  11. Weitz JI, Hirsh J. New anticoagulant drugs. Chest. 2001;119(1 Suppl):95S–107S.

    Article  CAS  Google Scholar 

  12. Cuker A, Siegal DM, Crowther MA, Garcia DA. Laboratory measurement of the anticoagulant activity of the nonvitamin K oral anticoagulants. J Am Coll Cardiol. 2014;64(11):1128–39.

    Article  CAS  Google Scholar 

  13. Cuker A, Husseinzadeh H. Laboratory measurement of the anticoagulant activity of edoxaban: a systemic review. J Thromb Thrombolysis. 2015;39(3):288–94.

    Article  CAS  Google Scholar 

  14. van Ryn J, Stangier J, Haertter S, et al. Dabigatran etexilate – a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost. 2010;103(6):1116–27.

    Article  Google Scholar 

  15. Nowak G. The ecarin clotting time, a universal method to quantify direct thrombin inhibitors. Pathophysiol Haemost Thromb. 2003;33(4):173–18.

    Article  CAS  Google Scholar 

  16. da Luz LT, Nascimento B, Rizoli S. Thrombelastography (TEG®): practical considerations on its clinical use in trauma resuscitation. Scand J Trauma Resusc Emerg Med. 2013;21:29.

    Article  Google Scholar 

  17. 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(9):1428–36.

    Article  CAS  Google Scholar 

  18. Mao G, King L, Young S, et al. Factor Eight Inhibitor Bypassing Agent (FEIBA) for reversal of target-specific oral anticoagulants in life-threatening intracranial bleeding. J Emerg Med. 2017;52(5):731–7.

    Article  Google Scholar 

  19. 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(14):1573–9.

    Article  CAS  Google Scholar 

  20. Song Y, Wang Z, Perlstein I, et al. Reversal of apixaban anticoagulation by four-factor prothrombin complex concentrates in healthy subjects: a randomized three-period crossover study. J Thromb Haemost. 2017;15(11):2125–37.

    Article  CAS  Google Scholar 

  21. Brown KS, Wickremasingha P, Parasrampuria DA, et al. The impact of a three-factor prothrombin complex concentrate on the anticoagulatory effects of the factor Xa inhibitor edoxaban. Thromb Res. 2015;136(4):825–31.

    Article  CAS  Google Scholar 

  22. 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(1):82–90.

    Article  CAS  Google Scholar 

  23. Gerner ST, Kuramatsu JB, Sembill JA, et al. Association of prothrombin complex concentrate administration and hematoma enlargement in non-vitamin K antagonist oral anticoagulant-related intracerebral hemorrhage. Ann Neurol. 2018;83(1):186–96.

    Article  CAS  Google Scholar 

  24. Kaatz S, Kouides PA, Garcia DA, et al. Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors. Am J Hematol. 2012;87(Suppl 1):S141–5.

    Article  CAS  Google Scholar 

  25. Tomaselli GF, Mahaffey KW, Cuker A, et al. 2017 ACC expert consensus decision pathway on management of bleeding in patients on oral anticoagulants: a report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol. 2017;70(24):3042–67.

    Article  Google Scholar 

  26. Connolly SJ, Crowther M, Eikelboom JW, et al; ANNEXA-4 Investigators. Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors. N Engl J Med. 2019. https://doi.org/10.1056/NEJMoa1814051.

    Article  CAS  Google Scholar 

  27. Andexanet alfa (Andexxa) [package insert]. South San Francisco: Portola Pharmaceuticals, Inc; 2018.

    Google Scholar 

  28. Siegal DM, Curnutte JT, Connolly SJ, et al. Andexanet alfa for the reversal of factor Xa inhibitor activity. N Engl J Med. 2015;373(25):2413–24.

    Article  CAS  Google Scholar 

Download references

Disclosure Statement

Kelsey Kauffman has no disclosures to report.

Colin Kaide reports affiliation with Callibra inc. No relevance to this chapter.

Also Colin Kaide provides Lecturing for Portola pharmaceuticals. All possible biases were explored by both authors and every attempt to provide unbiased information was made, including final editing by Kelsey Kauffman who has no Portola connections.

Author information

Authors and Affiliations

  1. Department of Emergency Medicine, Wexner Medical Center at The Ohio State University, Columbus, OH, USA

    Colin G. Kaide & Kelsey Kauffman

Authors
  1. Colin G. Kaide
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kelsey Kauffman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Colin G. Kaide .

Editor information

Editors and Affiliations

  1. Wexner Medical Center, Ohio State University, Columbus, OH, USA

    Colin G. Kaide

  2. Wexner Medical Center, Ohio State University, Columbus, OH, USA

    Christopher E. San Miguel

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kaide, C.G., Kauffman, K. (2020). Bleeding on Anti-Xa Drugs: “Does All Bleeding Really Stop?”. In: Kaide, C., San Miguel, C. (eds) Case Studies in Emergency Medicine. Springer, Cham. https://doi.org/10.1007/978-3-030-22445-5_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-22445-5_1

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-22444-8

  • Online ISBN: 978-3-030-22445-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation