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Newest Antithrombotic Agents: Uses, Challenges, and Reversal Strategies for Surgical Procedures

  • Eisha Wali
  • Sandeep NathanEmail author
Chapter
First Online:
Part of the Difficult Decisions in Surgery: An Evidence-Based Approach book series (DDSURGERY)

Abstract

Management of antiplatelet and anticoagulant agents in patients requiring surgical intervention presents a unique challenge. Relative risks of bleeding and thromboembolism must be carefully assessed and readdressed at regular intervals. In the event of major bleeding complications, targeted transfusions and reversal may be required. This review offers an updated understanding regarding currently available agents, optimal timing and duration of therapy, perioperative management, and reversal strategies.

Keywords

Antithrombotics Antiplatelets Anticoagulation Bleeding 
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References

  1. 1.
    Thomas M, Shen KR. Coagulopathy and anticoagulation during thoracic surgery. Thorac Surg Clin. 2015;25(3):309–23.  https://doi.org/10.1016/j.thorsurg.2015.04.005.CrossRefPubMedGoogle Scholar
  2. 2.
    Bayer Inc. Aspirin product monograph. 2014. http://www.bayer.ca/omr/online/aspirinpmen16sep2014ctrl169398.pdf. Accessed 5 Mar 2018.
  3. 3.
    Guha D, Macdonald RL. Perioperative management of anticoagulation. Neurosurg Clin N Am. 2017;28(2):287–95.  https://doi.org/10.1016/j.nec.2016.11.011.CrossRefPubMedGoogle Scholar
  4. 4.
    Franchi F, Angiolillo DJ. Novel antiplatelet agents in acute coronary syndrome. Nat Rev Cardiol. 2014;12(1):30–47.  https://doi.org/10.1038/nrcardio.2014.156.CrossRefPubMedGoogle Scholar
  5. 5.
    Koenig-Oberhuber V, Filipovic M. New antiplatelet drugs and new oral anticoagulants. Br J Anaesth. 2016;117(S2):74–84.  https://doi.org/10.1093/bja/aew214.CrossRefGoogle Scholar
  6. 6.
    Food and Drug Administration. Plavix: full prescribing information. https://packageinserts.bms.com/pi/pi_plavix.pdf. Accessed 5 Mar 2018.
  7. 7.
    Food and Drug Administration. Prasugrel: full prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022307s003lbl.pdf. Published 2010. Accessed 5 Mar 2018.
  8. 8.
    Food and Drug Administration. Ticagrelor: full prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022433s020lbl.pdf. Published 2016. Accessed 5 Mar 2018.
  9. 9.
    Gurbel PA, Bliden KP, Butler K, et al. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation. 2009;120(25):2577–85.  https://doi.org/10.1161/CIRCULATIONAHA.109.912550.CrossRefPubMedGoogle Scholar
  10. 10.
    Ungar L, Rodriguez F, Mahaffey KW. Vorapaxar. Coron Artery Dis. 2016;27(7):604–15.  https://doi.org/10.1097/MCA.0000000000000409.CrossRefPubMedGoogle Scholar
  11. 11.
    Morrow DA, Braunwald E, Bonaca MP, et al. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med. 2012;366(15):1404–13.  https://doi.org/10.1056/NEJMoa1200933.CrossRefPubMedGoogle Scholar
  12. 12.
    Oprea AD, Noto CJ, Halaszynski TM. Risk stratification, perioperative and periprocedural management of the patient receiving anticoagulant therapy. J Clin Anesth. 2016;34:586–99.  https://doi.org/10.1016/j.jclinane.2016.06.016.CrossRefPubMedGoogle Scholar
  13. 13.
    Food and Drug Administration. Heparin: full prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/017037s158lbl.pdf. Accessed 5 Mar 2018.
  14. 14.
    Rauova L, Zhai L, Kowalska MA, Arepally GM, Cines DB, Poncz M. Role of platelet surface PF4 antigenic complexes in heparin-induced thrombocytopenia pathogenesis: diagnostic and therapeutic implications. Blood. 2006;107(6):2346–53.  https://doi.org/10.1182/blood-2005-08-3122.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Enriquez A, Lip GYH, Baranchuk A. Anticoagulation reversal in the era of the non-Vitamin K oral anticoagulants. Europace. 2016;18(7):955–64.  https://doi.org/10.1093/europace/euv030.CrossRefPubMedGoogle Scholar
  16. 16.
    Food and Drug Administration. Warfarin: full prescribing informatation. https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/009218s107lbl.pdf. Accessed 5 Mar 2018.
  17. 17.
    Hurlen M, Abdelnoor M, Smith P, Erikssen J, Arnesen H. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med. 2002;347(13):969–74.  https://doi.org/10.1056/NEJMoa020496.CrossRefPubMedGoogle Scholar
  18. 18.
    Yusuf S, Mehta SR, Chrolavicius S, et al. Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial. JAMA J Am Med Assoc. 2006;295(13):1519–30.  https://doi.org/10.1001/jama.295.13.joc60038.CrossRefGoogle Scholar
  19. 19.
    Phil D, Mehta SR, Chrolavicius S, et al. Comparison of fondaparinux and enoxaparin in acute coronary syndromes the fifth organization to assess strategies in acute ischemic syndromes investigators*. N Engl J Med. 2006;354:1464–76. https://www.nejm.org/doi/pdf/10.1056/NEJMoa055443. Accessed 1 Jun 2018.CrossRefGoogle Scholar
  20. 20.
    Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883–91.  https://doi.org/10.1056/NEJMoa1009638.CrossRefGoogle Scholar
  21. 21.
    Bauersachs R, Berkowitz SD, Brenner B, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363(26):2499–510.  https://doi.org/10.1056/NEJMoa1007903.CrossRefPubMedGoogle Scholar
  22. 22.
    Granger CB, Alexander JH, McMurray JJV, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981–92.  https://doi.org/10.1056/NEJMoa1107039.CrossRefGoogle Scholar
  23. 23.
    Center for Drug Evaluation and Research. Approved drugs – FDA approved betrixaban (BEVYXXA, Portola) for the prophylaxis of venous thromboembolism (VTE) in adult patients. https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm564422.htm. Accessed 1 Jun 2018.
  24. 24.
    Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139–51.  https://doi.org/10.1056/NEJMoa0905561.CrossRefGoogle Scholar
  25. 25.
    Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2016;134:e123–55.  https://doi.org/10.1161/CIR.0000000000000404.CrossRefPubMedGoogle Scholar
  26. 26.
    Douketis JD, Spyropoulos AC, Spencer FA, et al. Perioperative management of antithrombotic therapy. Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 SUPPL):e326S–50S.  https://doi.org/10.1378/chest.11-2298.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Angiolillo DJ, Firstenberg MS, Price MJ, et al. Bridging anti-platelet therapy with the intravenous agent cangrelor in patients undergoing cardiac surgery. JAMA. 2012;307(3):265–74.  https://doi.org/10.1001/jama.2011.2002.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Lip GYH, Nieuwlaat R, Pisters R, Lane DA, Crijns HJGM. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro heart survey on atrial fibrillation. Chest. 2010;137(2):263–72.  https://doi.org/10.1378/chest.09-1584.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Levi MM, Eerenberg E, Löwenberg E, Kamphuisen PW. Bleeding in patients using new anticoagulants or antiplatelet agents: risk factors and management. Neth J Med. 2010;68(2):68–76. http://www.ncbi.nlm.nih.gov/pubmed/20167958.PubMedGoogle Scholar
  30. 30.
    Sunkara T, Ofori E, Zarubin V, Caughey ME, Gaduputi V, Reddy M. Perioperative management of direct oral anticoagulants (DOACs): a systemic review. Heal Serv Insights. 2016;9(Suppl 1):25–36.  https://doi.org/10.4137/HSI.S40701.CrossRefGoogle Scholar
  31. 31.
    Douketis JD, Spyropoulos AC, Kaatz S, et al. Perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med. 2015;373(9):823–33.  https://doi.org/10.1056/NEJMoa1501035.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Healey JS, Eikelboom J, Douketis J, et al. Periprocedural bleeding and thromboembolic events with dabigatran compared with warfarin: results from the randomized evaluation of long-term anticoagulation therapy (RE-LY) randomized trial. Circulation. 2012;126(3):343–8.  https://doi.org/10.1161/CIRCULATIONAHA.111.090464.CrossRefPubMedGoogle Scholar
  33. 33.
    Garcia D, Alexander JH, Wallentin L, et al. Management and clinical outcomes in patients treated with apixaban vs warfarin undergoing procedures. Blood. 2014;124(25):3692–8.  https://doi.org/10.1182/blood-2014-08-595496.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Mauri L, Kereiakes DJ, Yeh RW, et al. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med. 2014;371(23):2155–66.  https://doi.org/10.1056/NEJMoa1409312.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Yeh RW, Secemsky EA, Kereiakes DJ, et al. Development and validation of a prediction rule for benefit and harm of dual antiplatelet therapy beyond 1 year after percutaneous coronary intervention. JAMA. 2016;315(16):1735–49.  https://doi.org/10.1001/jama.2016.3775.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Hornero F, Martin E, Paredes F, et al. Stroke after coronary artery bypass grafting: preoperative predictive accuracies of CHADS2 and CHA2DS2VASc stroke risk stratification schemes. J Thorac Cardiovasc Surg. 2012;144(6):1428–35.  https://doi.org/10.1016/j.jtcvs.2012.07.053.CrossRefPubMedGoogle Scholar
  37. 37.
    Lutz J, Jurk K, Schinzel H. Direct oral anticoagulants in patients with chronic kidney disease: patient selection and special considerations. Int J Nephrol Renovasc Dis. 2017;10:135–43.  https://doi.org/10.2147/IJNRD.S105771.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Dewilde WJM, Oirbans T, Verheugt FWA, et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet. 2013;381(9872):1107–15.  https://doi.org/10.1016/S0140-6736(12)62177-1.CrossRefPubMedGoogle Scholar
  39. 39.
    Gibson CM, Mehran R, Bode C, et al. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med. 2016;375(25):2423–34.  https://doi.org/10.1056/NEJMoa1611594.CrossRefPubMedGoogle Scholar
  40. 40.
    Eikelboom JW, Connolly SJ, Bosch J, et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med. 2017;377(14):1319–30.  https://doi.org/10.1056/NEJMoa1709118.CrossRefPubMedGoogle Scholar
  41. 41.
    Young PP, Cotton BA, Goodnough LT. Massive transfusion protocols for patients with substantial hemorrhage. Transfus Med Rev. 2011;25(4):293–303.  https://doi.org/10.1016/j.tmrv.2011.04.002.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Desborough M, Sandu R, Brunskill SJ, et al. Fresh frozen plasma for cardiovascular surgery. Cochrane Database Syst Rev. 2015;7:CD007614.  https://doi.org/10.1002/14651858.CD007614.pub2.CrossRefGoogle Scholar
  43. 43.
    O’Shaughnessy DF, Atterbury C, Bolton Maggs P, et al. Guidelines for the use of fresh-frozen plasma, cryoprecipitate and cryosupernatant. Br J Haematol. 2004;126(1):11–28.  https://doi.org/10.1111/j.1365-2141.2004.04972.x.CrossRefPubMedGoogle Scholar
  44. 44.
    Gulseth Michael P. Overview of direct oral anticoagulant therapy reversal. Am J Health Syst Pharm. 2016;73(10 Suppl 2):S5–S13.  https://doi.org/10.2146/ajhp150966.CrossRefPubMedGoogle Scholar
  45. 45.
    Franchini M, Lippi G. Prothrombin complex concentrates: an update. Blood Transfus. 2010;8(3):149–54.  https://doi.org/10.2450/2010.0149-09.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schünemann HJ. Executive summary: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 SUPPL):7–47.  https://doi.org/10.1378/chest.1412S3.CrossRefGoogle Scholar
  47. 47.
    Demeyere R, Gillardin S, Arnout J, Strengers PFW. Comparison of fresh frozen plasma and prothrombin complex concentrate for the reversal of oral anticoagulants in patients undergoing cardiopulmonary bypass surgery: a randomized study. Vox Sang. 2010;99(3):251–60.  https://doi.org/10.1111/j.1423-0410.2010.01339.x.CrossRefPubMedGoogle Scholar
  48. 48.
    Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M. Reversal of Rivaroxaban and Dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation. 2011;124(14):1573–9.  https://doi.org/10.1161/CIRCULATIONAHA.111.029017.CrossRefPubMedGoogle Scholar
  49. 49.
    Xu Y, Schulman S, Dowlatshahi D, et al. Direct oral anticoagulant- or warfarin-related major bleeding. Chest. 2017;152(1):81–91.  https://doi.org/10.1016/j.chest.2017.02.009.CrossRefPubMedGoogle Scholar
  50. 50.
    Smythe MA, Trujillo T, Fanikos J. Reversal agents for use with direct and indirect anticoagulants. Am J Heal Pharm. 2016;73(10):S27–48.  https://doi.org/10.2146/ajhp150959.CrossRefGoogle Scholar
  51. 51.
    Leitch J, van Vlymen J. Managing the perioperative patient on direct oral anticoagulants. Can J Anesth Can d’anesthésie. 2017;64(6):656–72.  https://doi.org/10.1007/s12630-017-0868-2.CrossRefGoogle Scholar
  52. 52.
    Tummala R, Kavtaradze A, Gupta A, Ghosh RK. Specific antidotes against direct oral anticoagulants: a comprehensive review of clinical trials data. Int J Cardiol. 2016;214:292–8.  https://doi.org/10.1016/j.ijcard.2016.03.056.CrossRefPubMedGoogle Scholar
  53. 53.
    Castillo DM. May 3, 2018 approval letter – ANDEXXA. 2018. https://www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM606693.pdf. Accessed 1 Jun 2018.
  54. 54.
    Wong JK, Chen PC, Falvey J, et al. Anticoagulation reversal strategies for left ventricular assist device patients presenting with acute intracranial hemorrhage. ASAIO J. 2008;2016:552–7.  https://doi.org/10.1097/MAT.0000000000000404.CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of MedicineUniversity of Chicago MedicineChicagoUSA
  2. 2.Section of CardiologyUniversity of Chicago MedicineChicagoUSA

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