Bleeding with anticoagulation

The purpose of this page will be to focus on toxicity of anticoagulation, i.e., bleeding. It will be further organized over time.

Apixaban (Eliquis) reversal

To be completed

Andexanet alfa (Andexxa)

• Andexanet alfa (Andexxa) as follows:
  • Apixaban dose up to 5 mg: 400 mg IV bolus at a target rate of 30 mg/min then 480 mg IV infusion at a rate of 4 mg/min for 2 hours
  • Apixaban dose greater than 5mg or unknown but at least 8 hours since last administration: 400 mg IV bolus at a target rate of 30 mg/min then 480 mg IV infusion at a rate of 4 mg/min for 2 hours
  • Apixaban dose greater than 5mg or unknown and less than 8 hours since last administration: 800 mg IV bolus at a target rate of 30 mg/min then 960 mg IV infusion at a rate of 8 mg/min for 2 hours

References

1. ANNEXA-A: Siegal DM, Curnutte JT, Connolly SJ, Lu G, Conley PB, Wiens BL, Mathur VS, Castillo J, Bronson MD, Leeds JM, Mar FA, Gold A, Crowther MA. Andexanet alfa for the reversal of factor Xa inhibitor activity. N Engl J Med. 2015 Dec 17;373(25):2413-24. Epub 2015 Nov 11. link to original article PubMed NCT02207725
2. ANNEXA-R: Siegal DM, Curnutte JT, Connolly SJ, Lu G, Conley PB, Wiens BL, Mathur VS, Castillo J, Bronson MD, Leeds JM, Mar FA, Gold A, Crowther MA. Andexanet alfa for the reversal of factor Xa inhibitor activity. N Engl J Med. 2015 Dec 17;373(25):2413-24. Epub 2015 Nov 11. link to original article PubMed NCT02220725
3. ANNEXA-4: Connolly SJ, Milling TJ Jr, Eikelboom JW, Gibson CM, Curnutte JT, Gold A, Bronson MD, Lu G, Conley PB, Verhamme P, Schmidt J, Middeldorp S, Cohen AT, Beyer-Westendorf J, Albaladejo P, Lopez-Sendon J, Goodman S, Leeds J, Wiens BL, Siegal DM, Zotova E, Meeks B, Nakamya J, Lim WT, Crowther M; ANNEXA-4 Investigators. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med. 2016 Sep 22;375(12):1131-41. Epub 2016 Aug 30. link to original article link to PMC article PubMed NCT02329327
   1. Update: Connolly SJ, Crowther M, Eikelboom JW, Gibson CM, Curnutte JT, Lawrence JH, Yue P, Bornson MD, Lu G, Conley PB, Verhamme P, Schmidt J; ANNEXA-4 Investigators. Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors. N Engl J Med. 2019 Apr 4;380(14):1326-1335. Epub 2019 Feb 07. link to original article link to PMC article PubMed

Dabigatran (Pradaxa) reversal

Idarucizumab (Praxbind)

• To be completed

References

1. RE-VERSE AD: Pollack CV Jr, Reilly PA, Eikelboom J, Glund S, Verhamme P, Bernstein RA, Dubiel R, Huisman MV, Hylek EM, Kamphuisen PW, Kreuzer J, Levy JH, Sellke FW, Stangier J, Steiner T, Wang B, Kam CW, Weitz JI. Idarucizumab for dabigatran reversal. N Engl J Med. 2015 Aug 6;373(6):511-520. Epub 2015 Jun 22. link to original article PubMed NCT02104947
   1. Update: Pollack CV Jr, Reilly PA, van Ryn J, Eikelboom JW, Glund S, Bernstein RA, Dubiel R, Huisman MV, Hylek EM, Kam CW, Kamphuisen PW, Kreuzer J, Levy JH, Royle G, Sellke FW, Stangier J, Steiner T, Verhamme P, Wang B, Young L, Weitz JI. Idarucizumab for dabigatran reversal - full cohort analysis. N Engl J Med. 2017 Aug 3;377(5):431-441. Epub 2017 Jul 11. link to original article PubMed

Dalteparin (Fragmin) reversal

Protamine sulfate (USP)

• To be completed

Enoxaparin (Lovenox) reversal

Protamine sulfate (USP)

• To be completed

Unfractionated heparin (UFH) reversal

Protamine sulfate (USP)

• To be completed

Rivaroxaban (Xarelto) reversal

Andexanet alfa (Andexxa)

• Andexanet alfa (Andexxa) as follows:
  • Rivaroxaban dose up to 10 mg: 400 mg IV bolus at a target rate of 30 mg/min then 480 mg IV infusion at a rate of 4 mg/min for 2 hours
  • Rivaroxaban dose greater than 10 mg or unknown but at least 8 hours since last administration: 400 mg IV bolus at a target rate of 30 mg/min then 480 mg IV infusion at a rate of 4 mg/min for 2 hours
  • Rivaroxaban dose greater than 10 mg or unknown and less than 8 hours since last administration: 800 mg IV bolus at a target rate of 30 mg/min then 960 mg IV infusion at a rate of 8 mg/min for 2 hours

References

1. ANNEXA-A: Siegal DM, Curnutte JT, Connolly SJ, Lu G, Conley PB, Wiens BL, Mathur VS, Castillo J, Bronson MD, Leeds JM, Mar FA, Gold A, Crowther MA. Andexanet alfa for the reversal of factor Xa inhibitor activity. N Engl J Med. 2015 Dec 17;373(25):2413-24. Epub 2015 Nov 11. link to original article PubMed NCT02207725
2. ANNEXA-R: Siegal DM, Curnutte JT, Connolly SJ, Lu G, Conley PB, Wiens BL, Mathur VS, Castillo J, Bronson MD, Leeds JM, Mar FA, Gold A, Crowther MA. Andexanet alfa for the reversal of factor Xa inhibitor activity. N Engl J Med. 2015 Dec 17;373(25):2413-24. Epub 2015 Nov 11. link to original article PubMed NCT02220725
3. ANNEXA-4: Connolly SJ, Milling TJ Jr, Eikelboom JW, Gibson CM, Curnutte JT, Gold A, Bronson MD, Lu G, Conley PB, Verhamme P, Schmidt J, Middeldorp S, Cohen AT, Beyer-Westendorf J, Albaladejo P, Lopez-Sendon J, Goodman S, Leeds J, Wiens BL, Siegal DM, Zotova E, Meeks B, Nakamya J, Lim WT, Crowther M; ANNEXA-4 Investigators. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med. 2016 Sep 22;375(12):1131-41. Epub 2016 Aug 30. link to original article link to PMC article PubMed NCT02329327
   1. Update: Connolly SJ, Crowther M, Eikelboom JW, Gibson CM, Curnutte JT, Lawrence JH, Yue P, Bornson MD, Lu G, Conley PB, Verhamme P, Schmidt J; ANNEXA-4 Investigators. Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors. N Engl J Med. 2019 Apr 4;380(14):1326-1335. Epub 2019 Feb 07. link to original article link to PMC article PubMed

Bleeding risk calculators

• Bleeding risk on anticoagulation: HAS-BLED; HEMORR2HAGES