Indian Journal of Critical Care Medicine

Register      Login



Volume / Issue

Online First

Related articles

VOLUME 23 , ISSUE S3 ( September, 2019 ) > List of Articles


Reversal of Anticoagulants in Critical Care

John Victor Peter, Kandasamy Subramani

Keywords : Anticoagulant, Critical care, Direct thrombin inhibitors, Protamine, Reversal, Vitamin K antagonists

Citation Information : Peter JV, Subramani K. Reversal of Anticoagulants in Critical Care. Indian J Crit Care Med 2019; 23 (S3):0-0.

DOI: 10.5005/jp-journals-10071-23257

License: CC BY-NC 4.0

Published Online: 01-09-2019

Copyright Statement:  Copyright © 2019; The Author(s).


There has seen an increase in anticoagulant consumption worldwide over the past few decades. With this widespread utilization of anticoagulants, clinicians are increasingly likely to encounter situations where anticoagulants would need to be withheld. This includes emergency and elective procedures or surgeries as well as major or minor bleeding as a direct result of over anticoagulation or consequent to other intercurrent illnesses such as sepsis or trauma with multiorgan failure, where the anticoagulant may contribute to coagulation abnormalities. Clinicians are required to have a thorough understanding of the indications for anticoagulant prescription, drug interactions and monitoring, indications and options of reversal of anticoagulation and management of bleeding in the situations described above. Once the acute process is managed, the ongoing need and timing of reinitiation of anticoagulation is also crucial. This article provides an overview on the indications for reversal of anticoagulation, the agents used for reversal and the timing of reinitiation of anticoagulants.

PDF Share
  1. Barnes GD, Lucas E, Alexander GC, Goldberger ZD. National Trends in Ambulatory Oral Anticoagulant Use. The American Journal of Medicine. 2015 Dec;128(12):1300–1302.
  2. Wendelboe AM, Raskob GE. Global Burden of Thrombosis: Epidemiologic Aspects. Circ Res. Lippincott Williams & Wilkins Hagerstown, MD; 2016 Apr 29;118(9):1340–1347.
  3. Ustrell X, Pellisé A. Cardiac workup of ischemic stroke. Curr Cardiol Rev. 2010 Sep 17;6(3):175–183.
  4. Milling TJ, Frontera J. Exploring indications for the Use of direct oral anticoagulants and the associated risks of major bleeding. Am J Manag Care. 2017 Apr 1;23(4):S67–S80.
  5. Chai-Adisaksopha C, Crowther M, Isayama T, Lim W. The impact of bleeding complications in patients receiving target-specific oral anticoagulants: a systematic review and meta-analysis. Blood. 2014 Oct 9;124(15):2450–2458.
  6. Gómez-Outes A, Lecumberri R, Suárez-Gea ML, Terleira-Fernández A-I, Monreal M, Vargas-Castrillón E. Case Fatality Rates of Recurrent Thromboembolism and Bleeding in Patients Receiving Direct Oral Anticoagulants for the Initial and Extended Treatment of Venous Thromboembolism. J Cardiovasc Pharmacol Ther. 2015 Mar 31;20(5):490–500.
  7. Funk DMA. Coagulation assays and anticoagulant monitoring. Hematology Am Soc Hematol Educ Program. 2012;2012:460–465.
  8. Schulman S, Kearon C, Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. John Wiley & Sons, Ltd (10.1111); 2005 Apr;3(4):692–694.
  9. Beyer-Westendorf J, Förster K, Pannach S, Ebertz F, Gelbricht V, Thieme C, et al. Rates, management, and outcome of rivaroxaban bleeding in daily care: results from the Dresden NOAC registry. Blood. American Society of Hematology; 2014 Aug 7;124(6):955–962.
  10. Held C, Hylek EM, Alexander JH, Hanna M, Lopes RD, Wojdyla DM, et al. Clinical outcomes and management associated with major bleeding in patients with atrial fibrillation treated with apixaban or warfarin: insights from the ARISTOTLE trial. Eur Heart J. 2015 May 21;36(20):1264–1272.
  11. Carson JL, Guyatt G, Heddle NM, Grossman BJ, Cohn CS, Fung MK, et al. Clinical Practice Guidelines From the AABB. JAMA. American Medical Association; 2016 Nov 15;316(19):2025–2035. doi: 10.1001/jama.2016.9185
  12. Villanueva C, Colomo A, Bosch A, Concepción M, Hernandez-Gea V, Aracil C, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013 Jan 3;368(1):11–21.
  13. FACC GFTM, FACC KWMM, MS ACM, PharmD PPD, FACC JUDM, MBBS JWE, et al. 2017 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants. Journal of the American College of Cardiology. Elsevier; 2017 Dec 19;70(24):3042–3067.
  14. Lozano M, Cid J. Alternative strategies to platelet transfusion. ISBT Science Series. 2016;11(Suppl 1):93–99.
  15. Lubetsky A, Yonath H, Olchovsky D, Loebstein R, Halkin H, Ezra D. Comparison of Oral vs Intravenous Phytonadione (Vitamin K1) in Patients With Excessive Anticoagulation. Arch Intern Med. American Medical Association; 2003 Nov 10;163(20):2469–2473.
  16. Jones GM, Erdman MJ, Smetana KS, Mohrien KM, Vandigo JE, Elijovich L. 3-Factor Versus 4-Factor Prothrombin Complex Concentrate for Warfarin Reversal in Severe Bleeding: A Multicenter, Retrospective, Propensity-Matched Pilot Study. J Thromb Thrombolysis. 4 ed. Springer US; 2015 Dec 31;42(1):19–26.
  17. Goldstein JN, Refaai MA, Milling TJ, Lewis B, Goldberg-Alberts R, Hug BA, et al. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open-label, non-inferiority, randomised trial. Lancet. 2015 May 23;385(9982):2077–2087.
  18. Steiner T, Poli S, Griebe M, Hüsing J, Hajda J, Freiberger A, et al. Fresh frozen plasma versus prothrombin complex concentrate in patients with intracranial haemorrhage related to vitamin K antagonists (INCH): a randomised trial. The Lancet Neurology. 2016 May;15(6):566–573.
  19. Rosovsky RP, Crowther MA. What is the evidence for the off-label use of recombinant factor VIIa (rFVIIa) in the acute reversal of warfarin? ASH evidence-based review 2008. Hematology. American Society of Hematology; 2008;2008(1):36–38.
  20. Dager WE, King JH, Regalia RC, Williamson D, Gosselin RC, White RH, et al. Reversal of Elevated International Normalized Ratios and Bleeding with Low-Dose Recombinant Activated Factor VII in Patients Receiving Warfarin. Pharmacotherapy. John Wiley & Sons, Ltd; 2006 Aug;26(8):1091–1098.
  21. Greinacher A, Thiele T, Selleng K. Reversal of anticoagulants: an overview of current developments. Thromb Haemost. Schattauer GmbH; 2017 Nov 24;113(05):931–942.
  22. van Veen JJ, Maclean RM, Hampton KK, Laidlaw S, Kitchen S, Toth P, et al. Protamine reversal of low molecular weight heparin: clinically effective? Blood Coagul Fibrinolysis. 2011 Oct;22(7):565–570.
  23. Hirsh J, Bauer KA, Donati MB, Gould M, Samama MM, Weitz JI. Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;141S–159S.
  24. Pollack CV, Reilly PA, van Ryn J, Eikelboom JW, Glund S, Bernstein RA, et al. Idarucizumab for Dabigatran Reversal - Full Cohort Analysis. N Engl J Med. Massachusetts Medical Society; 2017 Aug 3;377(5):431–441.
  25. Pollack CV, Reilly PA, Weitz JI. Dabigatran Reversal with Idarucizumab. N Engl J Med. Massachusetts Medical Society; 2017 Oct 26;377(17):1691–1692.
  26. Stangier J, Rathgen K, Stähle H, Mazur D. Influence of Renal Impairment on the Pharmacokinetics and Pharmacodynamics of Oral Dabigatran Etexilate. Clin Pharmacokinet. Springer International Publishing; 2010 Apr;49(4):259–268.
  27. Connolly SJ, Crowther M, Eikelboom JW, Gibson CM, Curnutte JT, Lawrence JH, et al. Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors. N Engl J Med. Massachusetts Medical Society; 2019 Apr 4;380(14):1326–1335.
  28. Levi M, Moore KT, Castillejos CF, Kubitza D, Berkowitz SD, Goldhaber SZ, 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. John Wiley & Sons, Ltd (10.1111); 2014 Sep;12(9):1428–1436.
  29. Ansell JE, Bakhru SH, Laulicht BE, Steiner SS, Grosso MA, Brown K, et al. Single-dose ciraparantag safely and completely reverses anticoagulant effects of edoxaban. Thromb Haemost. Schattauer GmbH; 2017 Jan 26;117(2):238–245.
  30. Parsons-Rich D, Hua F, Li G, Kantaridis C, Pittman DD, Arkin S. Phase 1 dose-escalating study to evaluate the safety, pharmacokinetics, and pharmacodynamics of a recombinant factor Xa variant (FXa I16L). J Thromb Haemost. John Wiley & Sons, Ltd (10.1111); 2017 Apr 25;15(5):931–937.
  31. Witt DM, Nieuwlaat R, Clark NP, Ansell J, Holbrook A, Skov J, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy. Blood Adv. 2018 Nov 27;2(22):3257–3291.
  32. Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ, et al. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e152S–e184S.
  33. Khatib R, Ludwikowska M, Witt DM, Ansell J, Clark NP, Holbrook A, et al. Vitamin K for reversal of excessive vitamin K antagonist anticoagulation: a systematic review and meta-analysis. Blood Adv. 2019 Mar 12;3(5):789–796.
  34. Spyropoulos AC, Douketis JD. How I treat anticoagulated patients undergoing an elective procedure or surgery. Blood. American Society of Hematology; 2012 Oct 11;120(15):2954–2962.
  35. Rechenmacher SJ, Fang JC. Bridging Anticoagulation: Primum Non Nocere. Am Coll Cardiol. Elsevier Inc; 2015 Sep 22;66(12):1392–1403.
  36. Drumheller BC, Stein DM, Moore LJ, Rizoli SB, Cohen MJ. Thromboelastography and rotational thromboelastometry for the surgical intensivist: A narrative review. J Trauma Acute Care Surg. 2019 Apr;86(4):710–721.
  37. Hernandez I, Zhang Y, Brooks MM, Chin PKL, Saba S. Anticoagulation Use and Clinical Outcomes After Major Bleeding on Dabigatran or Warfarin in Atrial Fibrillation. Stroke. 2017 Jan;48(1):159–166.
  38. AlKherayf F, Xu Y, Gandara E, Westwick H, Moldovan ID, Wells PS. Timing of vitamin K antagonist re-initiation following intracranial hemorrhage in mechanical heart valves: Systematic review and meta-analysis. Thromb Res. 2016 Aug;144:152–157.
  39. Majeed A, Kim Y-K, Roberts RS, Holmström M, Schulman S. Optimal timing of resumption of warfarin after intracranial hemorrhage. Stroke. Lippincott Williams & Wilkins; 2010 Dec;41(12):2860–2866.
  40. Morgenstern LB, Hemphill JC III, Anderson C, Becker K, Broderick JP, Connolly ES Jr, et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage. Stroke. 2010 Sep;41(9):2108–2129.
  41. Doherty JU, Gluckman TJ, Hucker WJ, Januzzi JL Jr., Ortel TL, Saxonhouse SJ, et al. 2017 ACC Expert Consensus Decision Pathway for Periprocedural Management of Anticoagulation in Patients With Nonvalvular Atrial Fibrillation. Journal of the American College of Cardiology. 2017 Feb;69(7):871–898.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.