Difference between revisions of "Bleeding with anticoagulation"

From HemOnc.org - A Hematology Oncology Wiki
Jump to navigation Jump to search
m (Text replacement - "'''Use of this site is subject to you reading and agreeing with the terms set forth in the disclaimer.'''" to "'''Use of this site is subject to you reading and agreeing with the terms set forth in the disclaimer. If this is your first time visiting, we suggest you read the tutorial.'''")
m
 
(33 intermediate revisions by 5 users not shown)
Line 1: Line 1:
−
'''Use of this site is subject to you reading and agreeing with the terms set forth in the [[HemOnc.org_-_A_Hematology_Oncology_Wiki:General_disclaimer|disclaimer]]. If this is your first time visiting, we suggest you read the [[tutorial]].'''
+
''The purpose of this page will be to focus on toxicity of anticoagulation, i.e., bleeding. It will be further organized over time.''
  
−
The purpose of this page will be to focus on toxicity of anticoagulation, i.e., bleeding. It will be further organized in the near future.
+
=[[Apixaban (Eliquis)]] reversal=
 +
To be completed
  
−
==[[Apixaban (Eliquis)]]==
+
==[[Andexanet alfa (Andexxa)]]==
−
# '''APPRAISE-2:''' Alexander JH, Lopes RD, James S, Kilaru R, He Y, Mohan P, Bhatt DL, Goodman S, Verheugt FW, Flather M, Huber K, Liaw D, Husted SE, Lopez-Sendon J, De Caterina R, Jansky P, Darius H, Vinereanu D, Cornel JH, Cools F, Atar D, Leiva-Pons JL, Keltai M, Ogawa H, Pais P, Parkhomenko A, Ruzyllo W, Diaz R, White H, Ruda M, Geraldes M, Lawrence J, Harrington RA, Wallentin L; APPRAISE-2 Investigators. Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med. 2011 Aug 25;365(8):699-708. Epub 2011 Jul 24. [http://www.nejm.org/doi/full/10.1056/NEJMoa1105819 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21780946 PubMed]
+
*[[Andexanet alfa (Andexxa)]] as follows:
−
# '''ARISTOTLE:''' Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011 Sep 15;365(11):981-92. Epub 2011 Aug 27. [http://www.nejm.org/doi/full/10.1056/NEJMoa1107039 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21870978 PubMed]
+
**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
−
# '''PLIFY-EXT:''' Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Porcari A, Raskob GE, Weitz JI; PLIFY-EXT Investigators. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013 Feb 21;368(8):699-708. Epub 2012 Dec 8. [http://www.nejm.org/doi/full/10.1056/NEJMoa1207541 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23216615 PubMed]
+
**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
−
# '''AMPLIFY:''' Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Masiukiewicz U, Pak R, Thompson J, Raskob GE, Weitz JI; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013 Aug 29;369(9):799-808. Epub 2013 Jul 1. [http://www.nejm.org/doi/full/10.1056/NEJMoa1302507 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23808982 PubMed]
+
**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
−
==[[Argatroban (Acova)]]==
+
===References===
−
==[[Aspirin]]==
+
# '''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. [https://doi.org/10.1056/NEJMoa1510991 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26559317/ PubMed] [https://clinicaltrials.gov/study/NCT02207725 NCT02207725]
−
# '''APPRAISE-2:''' Alexander JH, Lopes RD, James S, Kilaru R, He Y, Mohan P, Bhatt DL, Goodman S, Verheugt FW, Flather M, Huber K, Liaw D, Husted SE, Lopez-Sendon J, De Caterina R, Jansky P, Darius H, Vinereanu D, Cornel JH, Cools F, Atar D, Leiva-Pons JL, Keltai M, Ogawa H, Pais P, Parkhomenko A, Ruzyllo W, Diaz R, White H, Ruda M, Geraldes M, Lawrence J, Harrington RA, Wallentin L; APPRAISE-2 Investigators. Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med. 2011 Aug 25;365(8):699-708. Epub 2011 Jul 24. [http://www.nejm.org/doi/full/10.1056/NEJMoa1105819 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21780946 PubMed]
+
# '''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. [https://doi.org/10.1056/NEJMoa1510991 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26559317/ PubMed] [https://clinicaltrials.gov/study/NCT02220725 NCT02220725]
−
# Larocca A, Cavallo F, Bringhen S, Di Raimondo F, Falanga A, Evangelista A, Cavalli M, Stanevsky A, Corradini P, Pezzatti S, Patriarca F, Cavo M, Peccatori J, Catalano L, Carella AM, Cafro AM, Siniscalchi A, Crippa C, Petrucci MT, Yehuda DB, Beggiato E, Di Toritto TC, Boccadoro M, Nagler A, Palumbo A. Aspirin or enoxaparin thromboprophylaxis for patients with newly diagnosed multiple myeloma treated with lenalidomide. Blood. 2012 Jan 26;119(4):933-9. Epub 2011 Aug 11. [http://www.bloodjournal.org/content/119/4/933.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21835953 PubMed]
+
# '''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. [https://doi.org/10.1056/NEJMoa1607887 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568772/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27573206/ PubMed] [https://clinicaltrials.gov/study/NCT02329327 NCT02329327]
−
# '''WARFASA:''' Becattini C, Agnelli G, Schenone A, Eichinger S, Bucherini E, Silingardi M, Bianchi M, Moia M, Ageno W, Vandelli MR, Grandone E, Prandoni P; WARFASA Investigators. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med. 2012 May 24;366(21):1959-67. Erratum in: N Engl J Med. 2012 Oct 18;367(16):1573. [http://www.nejm.org/doi/full/10.1056/NEJMoa1114238 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22621626 PubMed]
+
## '''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. [https://doi.org/10.1056/NEJMoa1814051 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6699827/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30730782/ PubMed]
−
# '''EINSTEIN CHOICE:''' Weitz JI, Lensing AWA, Prins MH, Bauersachs R, Beyer-Westendorf J, Bounameaux H, Brighton TA, Cohen AT, Davidson BL, Decousus H, Freitas MCS, Holberg G, Kakkar AK, Haskell L, van Bellen B, Pap AF, Berkowitz SD, Verhamme P, Wells PS, Prandoni P; EINSTEIN CHOICE Investigators. Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med. 2017 Mar 30;376(13):1211-1222. Epub 2017 Mar 18. [http://www.nejm.org/doi/full/10.1056/NEJMoa1700518 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28316279 PubMed]
 
−
==[[Bivalirudin (Angiomax)]]==
 
−
==[[Betrixaban (Bevyxxa)]]==
 
−
# '''APEX:''' Cohen AT, Harrington RA, Goldhaber SZ, Hull RD, Wiens BL, Gold A, Hernandez AF, Gibson CM; APEX Investigators. Extended thromboprophylaxis with betrixaban in acutely ill medical patients. N Engl J Med. 2016 Aug 11;375(6):534-44. Epub 2016 May 27. [http://www.nejm.org/doi/full/10.1056/NEJMoa1601747 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27232649 PubMed]
 
−
==[[Dabigatran (Pradaxa)]]==
 
−
# '''RE-LY:''' Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009 Sep 17;361(12):1139-51. Epub 2009 Aug 30. Erratum in: N Engl J Med. 2010 Nov 4;363(19):1877. [http://www.nejm.org/doi/full/10.1056/NEJMoa0905561 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19717844 PubMed]
 
−
# '''RE-COVER:''' Schulman S, Kearon C, Kakkar AK, Mismetti P, Schellong S, Eriksson H, Baanstra D, Schnee J, Goldhaber SZ; RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009 Dec 10;361(24):2342-52. [http://www.nejm.org/doi/full/10.1056/NEJMoa0906598 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19966341 PubMed]
 
−
# '''RE-MEDY:''' Schulman S, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D, Kvamme AM, Friedman J, Mismetti P, Goldhaber SZ; RE-MEDY Trial Investigators; RE-SONATE Trial Investigators. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013 Feb 21;368(8):709-18. [http://www.nejm.org/doi/full/10.1056/NEJMoa1113697 link to original article] [[https://www.ncbi.nlm.nih.gov/pubmed/23425163 PubMed]
 
−
# '''RE-ALIGN:''' Eikelboom JW, Connolly SJ, Brueckmann M, Granger CB, Kappetein AP, Mack MJ, Blatchford J, Devenny K, Friedman J, Guiver K, Harper R, Khder Y, Lobmeyer MT, Maas H, Voigt JU, Simoons ML, Van de Werf F; RE-ALIGN Investigators. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med. 2013 Sep 26;369(13):1206-14. Epub 2013 Aug 31. [http://www.nejm.org/doi/full/10.1056/NEJMoa1300615 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23991661 PubMed]
 
−
# '''RE-COVER II:''' Schulman S, Kakkar AK, Goldhaber SZ, Schellong S, Eriksson H, Mismetti P, Christiansen AV, Friedman J, Le Maulf F, Peter N, Kearon C; RE-COVER II Trial Investigators. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014 Feb 18;129(7):764-72. Epub 2013 Dec 16. [http://circ.ahajournals.org/content/129/7/764.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24344086 PubMed]
 
−
==[[Dalteparin (Fragmin)]]==
 
−
# '''CLOT:''' Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M; Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003 Jul 10;349(2):146-53. [http://www.nejm.org/doi/full/10.1056/NEJMoa025313 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12853587 PubMed]
 
−
==[[Edoxaban (Savaysa)]]==
 
−
# '''HOKUSAI-VTE:''' Hokusai-VTE Investigators, Büller HR, Décousus H, Grosso MA, Mercuri M, Middeldorp S, Prins MH, Raskob GE, Schellong SM, Schwocho L, Segers A, Shi M, Verhamme P, Wells P. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013 Oct 10;369(15):1406-15. Epub 2013 Aug 31. Erratum in: N Engl J Med. 2014 Jan 23;370(4):390. [http://www.nejm.org/doi/full/10.1056/NEJMoa1306638 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23991658 PubMed]
 
−
## '''Subset analysis:''' Raskob GE, van Es N, Segers A, Angchaisuksiri P, Oh D, Boda Z, Lyons RM, Meijer K, Gudz I, Weitz JI, Zhang G, Lanz H, Mercuri MF, Büller HR; Hokusai-VTE investigators. Edoxaban for venous thromboembolism in patients with cancer: results from a non-inferiority subgroup analysis of the Hokusai-VTE randomised, double-blind, double-dummy trial. Lancet Haematol. 2016 Aug;3(8):e379-87. Epub 2016 Jul 1. [http://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(16)30057-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27476789 PubMed]
 
−
# '''ENGAGE AF-TIMI-48:''' Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Špinar J, Ruzyllo W, Ruda M, Koretsune Y, Betcher J, Shi M, Grip LT, Patel SP, Patel I, Hanyok JJ, Mercuri M, Antman EM; ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013 Nov 28;369(22):2093-104. Epub 2013 Nov 19. [http://www.nejm.org/doi/full/10.1056/NEJMoa1310907 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24251359 PubMed]
 
−
==[[Enoxaparin (Lovenox)]]==
 
−
# Meyer G, Marjanovic Z, Valcke J, Lorcerie B, Gruel Y, Solal-Celigny P, Le Maignan C, Extra JM, Cottu P, Farge D. Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study. Arch Intern Med. 2002 Aug 12-26;162(15):1729-35. [http://archinte.jamanetwork.com/article.aspx?articleid=754085 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12153376 PubMed]
 
−
# Larocca A, Cavallo F, Bringhen S, Di Raimondo F, Falanga A, Evangelista A, Cavalli M, Stanevsky A, Corradini P, Pezzatti S, Patriarca F, Cavo M, Peccatori J, Catalano L, Carella AM, Cafro AM, Siniscalchi A, Crippa C, Petrucci MT, Yehuda DB, Beggiato E, Di Toritto TC, Boccadoro M, Nagler A, Palumbo A. Aspirin or enoxaparin thromboprophylaxis for patients with newly diagnosed multiple myeloma treated with lenalidomide. Blood. 2012 Jan 26;119(4):933-9. Epub 2011 Aug 11. [http://www.bloodjournal.org/content/119/4/933.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21835953 PubMed]
 
−
# '''APEX:''' Cohen AT, Harrington RA, Goldhaber SZ, Hull RD, Wiens BL, Gold A, Hernandez AF, Gibson CM; APEX Investigators. Extended thromboprophylaxis with betrixaban in acutely ill medical patients. N Engl J Med. 2016 Aug 11;375(6):534-44. Epub 2016 May 27. [http://www.nejm.org/doi/full/10.1056/NEJMoa1601747 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27232649 PubMed]
 
−
==[[Fondaparinux (Arixtra)]]==
 
−
==[[Heparin]]==
 
−
==[[Lepirudin (Refludan)]]==
 
−
==[[Rivaroxaban (Xarelto)]]==
 
−
# '''EINSTEIN-DVT:''' EINSTEIN Investigators, Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, Gallus AS, Lensing AW, Misselwitz F, Prins MH, Raskob GE, Segers A, Verhamme P, Wells P, Agnelli G, Bounameaux H, Cohen A, Davidson BL, Piovella F, Schellong S. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010 Dec 23;363(26):2499-510. Epub 2010 Dec 3. [http://www.nejm.org/doi/full/10.1056/NEJMoa1007903 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21128814 PubMed]
 
−
# '''ROCKET AF:''' Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011 Sep 8;365(10):883-91. Epub 2011 Aug 10. [http://www.nejm.org/doi/full/10.1056/NEJMoa1009638 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21830957 PubMed]
 
−
# '''ATLAS ACS 2–TIMI 51:''' Mega JL, Braunwald E, Wiviott SD, Bassand JP, Bhatt DL, Bode C, Burton P, Cohen M, Cook-Bruns N, Fox KA, Goto S, Murphy SA, Plotnikov AN, Schneider D, Sun X, Verheugt FW, Gibson CM; ATLAS ACS 2–TIMI 51 Investigators. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med. 2012 Jan 5;366(1):9-19. Epub 2011 Nov 13. [http://www.nejm.org/doi/full/10.1056/NEJMoa1112277 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22077192 PubMed]
 
−
# '''EINSTEIN-PE:''' EINSTEIN–PE Investigators, Büller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, Chlumsky J, Verhamme P, Wells P, Agnelli G, Cohen A, Berkowitz SD, Bounameaux H, Davidson BL, Misselwitz F, Gallus AS, Raskob GE, Schellong S, Segers A. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012 Apr 5;366(14):1287-97. Epub 2012 Mar 26. [http://www.nejm.org/doi/full/10.1056/NEJMoa1113572 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22449293 PubMed]
 
−
# '''J-ROCKET AF:''' Hori M, Matsumoto M, Tanahashi N, Momomura S, Uchiyama S, Goto S, Izumi T, Koretsune Y, Kajikawa M, Kato M, Ueda H, Iwamoto K, Tajiri M; J-ROCKET AF study investigators. Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation – the J-ROCKET AF study –. Circ J. 2012;76(9):2104-11. Epub 2012 Jun 5. [https://www.jstage.jst.go.jp/article/circj/76/9/76_CJ-12-0454/_article link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22664783 PubMed]
 
−
# '''EINSTEIN CHOICE:''' Weitz JI, Lensing AWA, Prins MH, Bauersachs R, Beyer-Westendorf J, Bounameaux H, Brighton TA, Cohen AT, Davidson BL, Decousus H, Freitas MCS, Holberg G, Kakkar AK, Haskell L, van Bellen B, Pap AF, Berkowitz SD, Verhamme P, Wells PS, Prandoni P; EINSTEIN CHOICE Investigators. Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism. N Engl J Med. 2017 Mar 30;376(13):1211-1222. Epub 2017 Mar 18. [http://www.nejm.org/doi/full/10.1056/NEJMoa1700518 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28316279 PubMed]
 
−
==[[Tinzaparin (Innohep)]]==
 
−
''Note: this agent has been withdrawn from the US market.''
 
−
# '''LITE:''' Hull RD, Pineo GF, Brant RF, Mah AF, Burke N, Dear R, Wong T, Cook R, Solymoss S, Poon MC, Raskob G; LITE Trial Investigators. Long-term low-molecular-weight heparin versus usual care in proximal-vein thrombosis patients with cancer. Am J Med. 2006 Dec;119(12):1062-72. [http://www.sciencedirect.com/science/article/pii/S0002934306002634 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17145251 PubMed]
 
−
# '''CATCH:''' Lee AY, Kamphuisen PW, Meyer G, Bauersachs R, Janas MS, Jarner MF, Khorana AA; CATCH Investigators. Tinzaparin vs Warfarin for Treatment of Acute Venous Thromboembolism in Patients With Active Cancer: A Randomized Clinical Trial. JAMA. 2015 Aug 18;314(7):677-86. [http://jama.jamanetwork.com/article.aspx?articleid=2428955 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26284719 PubMed]
 
−
==[[Warfarin (Coumadin)]]==
 
−
# Meyer G, Marjanovic Z, Valcke J, Lorcerie B, Gruel Y, Solal-Celigny P, Le Maignan C, Extra JM, Cottu P, Farge D. Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study. Arch Intern Med. 2002 Aug 12-26;162(15):1729-35. [http://archinte.jamanetwork.com/article.aspx?articleid=754085 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12153376 PubMed]
 
−
# '''PREVENT:''' Ridker PM, Goldhaber SZ, Danielson E, Rosenberg Y, Eby CS, Deitcher SR, Cushman M, Moll S, Kessler CM, Elliott CG, Paulson R, Wong T, Bauer KA, Schwartz BA, Miletich JP, Bounameaux H, Glynn RJ; PREVENT Investigators. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med. 2003 Apr 10;348(15):1425-34. Epub 2003 Feb 24. [http://www.nejm.org/doi/full/10.1056/NEJMoa035029 link to original article]  [https://www.ncbi.nlm.nih.gov/pubmed/12601075 PubMed]
 
−
# '''CLOT:''' Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M; Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003 Jul 10;349(2):146-53. [http://www.nejm.org/doi/full/10.1056/NEJMoa025313 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12853587 PubMed]
 
−
# '''LITE:''' Hull RD, Pineo GF, Brant RF, Mah AF, Burke N, Dear R, Wong T, Cook R, Solymoss S, Poon MC, Raskob G; LITE Trial Investigators. Long-term low-molecular-weight heparin versus usual care in proximal-vein thrombosis patients with cancer. Am J Med. 2006 Dec;119(12):1062-72. [http://www.sciencedirect.com/science/article/pii/S0002934306002634 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17145251 PubMed]
 
−
# '''RE-LY:''' Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009 Sep 17;361(12):1139-51. Epub 2009 Aug 30. Erratum in: N Engl J Med. 2010 Nov 4;363(19):1877. [http://www.nejm.org/doi/full/10.1056/NEJMoa0905561 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19717844 PubMed]
 
−
# '''RE-COVER:''' Schulman S, Kearon C, Kakkar AK, Mismetti P, Schellong S, Eriksson H, Baanstra D, Schnee J, Goldhaber SZ; RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009 Dec 10;361(24):2342-52. [http://www.nejm.org/doi/full/10.1056/NEJMoa0906598 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19966341 PubMed]
 
−
# '''EINSTEIN-DVT:''' EINSTEIN Investigators, Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, Gallus AS, Lensing AW, Misselwitz F, Prins MH, Raskob GE, Segers A, Verhamme P, Wells P, Agnelli G, Bounameaux H, Cohen A, Davidson BL, Piovella F, Schellong S. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010 Dec 23;363(26):2499-510. Epub 2010 Dec 3. [http://www.nejm.org/doi/full/10.1056/NEJMoa1007903 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21128814 PubMed]
 
−
# '''ROCKET AF:''' Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011 Sep 8;365(10):883-91. Epub 2011 Aug 10. [http://www.nejm.org/doi/full/10.1056/NEJMoa1009638 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21830957 PubMed]
 
−
# '''ARISTOTLE:''' Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011 Sep 15;365(11):981-92. Epub 2011 Aug 27. [http://www.nejm.org/doi/full/10.1056/NEJMoa1107039 link to original article]  [https://www.ncbi.nlm.nih.gov/pubmed/21870978 PubMed]
 
−
# '''EINSTEIN-PE:''' EINSTEIN–PE Investigators, Büller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, Chlumsky J, Verhamme P, Wells P, Agnelli G, Cohen A, Berkowitz SD, Bounameaux H, Davidson BL, Misselwitz F, Gallus AS, Raskob GE, Schellong S, Segers A. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012 Apr 5;366(14):1287-97. Epub 2012 Mar 26. [http://www.nejm.org/doi/full/10.1056/NEJMoa1113572 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22449293 PubMed]
 
−
# '''J-ROCKET AF:''' Hori M, Matsumoto M, Tanahashi N, Momomura S, Uchiyama S, Goto S, Izumi T, Koretsune Y, Kajikawa M, Kato M, Ueda H, Iwamoto K, Tajiri M; J-ROCKET AF study investigators. Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation – the J-ROCKET AF study –. Circ J. 2012;76(9):2104-11. Epub 2012 Jun 5. [https://www.jstage.jst.go.jp/article/circj/76/9/76_CJ-12-0454/_article link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22664783 PubMed]
 
−
# '''RE-MEDY:''' Schulman S, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D, Kvamme AM, Friedman J, Mismetti P, Goldhaber SZ; RE-MEDY Trial Investigators; RE-SONATE Trial Investigators. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013 Feb 21;368(8):709-18. [http://www.nejm.org/doi/full/10.1056/NEJMoa1113697 link to original article] [[https://www.ncbi.nlm.nih.gov/pubmed/23425163 PubMed]
 
−
# '''AMPLIFY:''' Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Masiukiewicz U, Pak R, Thompson J, Raskob GE, Weitz JI; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013 Aug 29;369(9):799-808. Epub 2013 Jul 1. [http://www.nejm.org/doi/full/10.1056/NEJMoa1302507 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23808982 PubMed]
 
−
# '''RE-ALIGN:''' Eikelboom JW, Connolly SJ, Brueckmann M, Granger CB, Kappetein AP, Mack MJ, Blatchford J, Devenny K, Friedman J, Guiver K, Harper R, Khder Y, Lobmeyer MT, Maas H, Voigt JU, Simoons ML, Van de Werf F; RE-ALIGN Investigators. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med. 2013 Sep 26;369(13):1206-14. Epub 2013 Aug 31. [http://www.nejm.org/doi/full/10.1056/NEJMoa1300615 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23991661 PubMed]
 
−
# '''HOKUSAI-VTE:''' Hokusai-VTE Investigators, Büller HR, Décousus H, Grosso MA, Mercuri M, Middeldorp S, Prins MH, Raskob GE, Schellong SM, Schwocho L, Segers A, Shi M, Verhamme P, Wells P. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013 Oct 10;369(15):1406-15. Epub 2013 Aug 31. Erratum in: N Engl J Med. 2014 Jan 23;370(4):390. [http://www.nejm.org/doi/full/10.1056/NEJMoa1306638 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23991658 PubMed]
 
−
## '''Subset analysis:''' Raskob GE, van Es N, Segers A, Angchaisuksiri P, Oh D, Boda Z, Lyons RM, Meijer K, Gudz I, Weitz JI, Zhang G, Lanz H, Mercuri MF, Büller HR; Hokusai-VTE investigators. Edoxaban for venous thromboembolism in patients with cancer: results from a non-inferiority subgroup analysis of the Hokusai-VTE randomised, double-blind, double-dummy trial. Lancet Haematol. 2016 Aug;3(8):e379-87. Epub 2016 Jul 1. [http://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(16)30057-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27476789 PubMed]
 
−
# '''ENGAGE AF-TIMI-48:''' Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Špinar J, Ruzyllo W, Ruda M, Koretsune Y, Betcher J, Shi M, Grip LT, Patel SP, Patel I, Hanyok JJ, Mercuri M, Antman EM; ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013 Nov 28;369(22):2093-104. Epub 2013 Nov 19. [http://www.nejm.org/doi/full/10.1056/NEJMoa1310907 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24251359 PubMed]
 
−
# '''RE-COVER II:''' Schulman S, Kakkar AK, Goldhaber SZ, Schellong S, Eriksson H, Mismetti P, Christiansen AV, Friedman J, Le Maulf F, Peter N, Kearon C; RE-COVER II Trial Investigators. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014 Feb 18;129(7):764-72. Epub 2013 Dec 16. [http://circ.ahajournals.org/content/129/7/764.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24344086 PubMed]
 
−
# '''CATCH:''' Lee AY, Kamphuisen PW, Meyer G, Bauersachs R, Janas MS, Jarner MF, Khorana AA; CATCH Investigators. Tinzaparin vs Warfarin for Treatment of Acute Venous Thromboembolism in Patients With Active Cancer: A Randomized Clinical Trial. JAMA. 2015 Aug 18;314(7):677-86. [http://jama.jamanetwork.com/article.aspx?articleid=2428955 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26284719 PubMed]
 
  
−
==Additional information==
+
=[[Dabigatran (Pradaxa)]] reversal=
−
<references/>
+
==[[Idarucizumab (Praxbind)]]==
 +
*To be completed
 +
===References===
 +
# '''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. [https://doi.org/10.1056/NEJMoa1502000 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26095746/ PubMed] [https://clinicaltrials.gov/study/NCT02104947 NCT02104947]
 +
## '''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. [https://doi.org/10.1056/NEJMoa1707278 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28693366/ 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===
 +
# '''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. [https://doi.org/10.1056/NEJMoa1510991 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26559317/ PubMed] [https://clinicaltrials.gov/study/NCT02207725 NCT02207725]
 +
# '''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. [https://doi.org/10.1056/NEJMoa1510991 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26559317/ PubMed] [https://clinicaltrials.gov/study/NCT02220725 NCT02220725]
 +
# '''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. [https://doi.org/10.1056/NEJMoa1607887 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568772/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27573206/ PubMed] [https://clinicaltrials.gov/study/NCT02329327 NCT02329327]
 +
## '''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. [https://doi.org/10.1056/NEJMoa1814051 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6699827/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30730782/ PubMed]
 +
 
 +
=[[Warfarin (Coumadin)]] reversal=
 +
==Fresh frozen plasma (FFP)==
 +
==[[Prothrombin Complex Concentrate, Human (Kcentra)]]==
 +
 
 +
=Perioperative management=
 +
 
 +
=Bleeding risk calculators=
 
*Bleeding risk on anticoagulation: [http://www.globalrph.com/has-bled-score.htm HAS-BLED]; [http://www.globalrph.com/hemorr2hages-bleeding-risk.htm HEMORR2HAGES]
 
*Bleeding risk on anticoagulation: [http://www.globalrph.com/has-bled-score.htm HAS-BLED]; [http://www.globalrph.com/hemorr2hages-bleeding-risk.htm HEMORR2HAGES]
  
 
[[Category:General reference pages]]
 
[[Category:General reference pages]]
−
[[Category:Benign hematologic conditions]]
+
[[Category:Bleeding disorders]]
 +
[[Category:Supportive oncology]]

Latest revision as of 11:07, 6 July 2024

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

Warfarin (Coumadin) reversal

Fresh frozen plasma (FFP)

Prothrombin Complex Concentrate, Human (Kcentra)

Perioperative management

Bleeding risk calculators

Retrieved from "https://hemonc.org/w/index.php?title=Bleeding_with_anticoagulation&oldid=88716"