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Prothrombin Complex Concentrate (4PCC): A Review of its Use in Reversal of Vitamin K Antagonists

  • Pharmacology of Acute Care (J. Fanikos, Section Editor)
  • Published:
Current Emergency and Hospital Medicine Reports Aims and scope Submit manuscript

Abstract

Bleeding continues to be a major adverse drug event associated with warfarin anticoagulation. The cornerstone of warfarin-related bleeding management involves repletion of affected plasma coagulation factor levels. Prothrombin complex concentrate (human) is a 4-factor prothrombin complex concentrate that contains vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S. It recently received Food and Drug Administration approval for warfarin reversal for patients with major bleeding or requiring urgent surgery or other invasive procedures. Its role in reversing target-specific oral anticoagulants appears to be limited to the Factor Xa inhibitors as an emergent intervention.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Johnson JA. Warfarin pharmacogenetics: a rising tide for its clinical value. Circulation. 2012;125:1964–6.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Jacobson A. Is there a role for warfarin anymore? Hematology. 2012;2012:542–6.

    Google Scholar 

  3. Chesebro JH, Wiebers DO, Holland AE, et al. Bleeding during antithrombotic therapy in patients with atrial fibrillation. Arch Intern Med. 1996;156:409–16.

    Article  Google Scholar 

  4. Schulman S, Beyth RJ, Kearon C, Levine MN. American College of Chest Physicians. Hemorrhagic complications of anticoagulant and thrombolytic treatment: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest. 2008;133(suppl 6):257S–98S.

    Article  CAS  PubMed  Google Scholar 

  5. Budnitz DS, Lovegrove MC, Shehab N. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med. 2011;365:2002–12.

    Article  CAS  PubMed  Google Scholar 

  6. Holbrook AM, Pereira JA, Labiris R, et al. Systematic overview of warfarin and its drug and food interactions. Arch Intern Med. 2005;165:1095–106.

    Article  CAS  PubMed  Google Scholar 

  7. Zareh M, Davis A, Henderson S. Reversal of warfarin-induced hemorrhage in the emergency department. West J Emerg Med. 2011;12(4):386–92.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Navgren M, Forsblad J, Wieloch M. Bleeding complications related to warfarin treatment: a descriptive register study from the anticoagulation clinic at Helsingborg Hospital. J Thromb Thrombolysis. 2013;Epub ahead of print.

  9. Hirsch J, Dalen JE, Anderson DR, et al. Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest. 2001;119:8S–21S.

    Article  Google Scholar 

  10. Gulati G, Hevelow M, George M, et al. International normalized ratio versus plasma levels of coagulation factors in patients on vitamin K antagonist therapy. Arch Pathol Lab Med. 2011;135:490–4.

    PubMed  Google Scholar 

  11. Stirling Y. Warfarin-induced changes in procoagulant and anticoagulant proteins. Blood Coagul Fibrinolysis. 1995;6(5):361–73.

    Article  CAS  PubMed  Google Scholar 

  12. Nutescu EA, Dager WE, Kalus JS, et al. Management of bleeding and reversal strategies for oral anticoagulants: clinical practice considerations. Am J Health Syst Pharm. 2013;70:1914–29.

    Article  CAS  PubMed  Google Scholar 

  13. CSL Behring. KcentraTM (prothrombin complex concentrate [Human]): prescribing information [online] 2014 01/28/2014 Available from: http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM350239.pdf.

  14. Kerebel D, Joly LM, Honnart D, et al. A French multicenter randomised trial comparing two dose-regimens of prothrombin complex concentrates in urgent anticoagulation reversal. Critical Care. 2013;17R4.

  15. Vang ML, Hvas AM, Ravn HB. Urgent reversal of vitamin K antagonist therapy. Acta Anaesthesiol Scand. 2011;55:507–16.

    Article  CAS  PubMed  Google Scholar 

  16. Kaatz S, Crowther M. Reversal of target-specific oral anticoagulants. J Thromb Thrombolysis. 2013;36(2):195–202.

    Article  CAS  PubMed  Google Scholar 

  17. Nitzki-George D, Wozniak I, Caprini JA. Current state of knowledge of oral anticoagulation reversal using procoagulant factors. Ann Pharmacother. 2013;47:841–55.

    Article  PubMed  Google Scholar 

  18. •• Sarode R, Milling TJ, Refaai MA, et al. Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin k antagonists presenting with major bleeding: a randomized, plasma-controlled, phase IIIb study. Circulation. 2013;128:1234–43. This is the only randomized, controlled trial comparing a 4 factor prothrombin complex concentration to plasma. Warfarin reversal was achieved significantly faster in 4 factor prothrombin complex concentrate group compared to plasma although there was no difference at 24 hours.

  19. Hollbrook A, Shulman S, Witt DW, et al. Evidence-based management of anticoagulation therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed. American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(Suppl 2):e152S–84S.

    Google Scholar 

  20. Schick KS, Fertmann JM, Jauch KW, et al. Prothrombin complex concentrate in surgical patients: retrospecitve evaluation of vitamin K antagonist reversal and treatment of severe bleeding. Crit Care. 2009;13:R191.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Pabinger I, Brenner B, Kalina U, et al. Prothrombin complex concentrate (Beriplex ® P/N) for emergency anticoagulation reversal: a prospective multinational clinical trial. J Thromb Haemost. 2008;6:622–31.

    Article  CAS  PubMed  Google Scholar 

  22. Pinner NA, Hurdle AC, Oliphant C, et al. Treatment of warfarin-related intracranial hemorrhage: a comparison of prothrombin complex concentrate and recombinant activated factor VII. World Neurosurg. 2010;74(6):631–5.

    Article  PubMed  Google Scholar 

  23. CSL Behring news release. Kcentra®, from CSL Behring, Receives FDA Approval for Use in Warfarin Reversal in Patients Undergoing Surgery. December 13, 2013. http://www.cslbehring.com/newsroom/Kcentra-Earns-FDA-Approval-for-Use-in-Patients-Undergoing-Surgery?tabSelections=1255923338766&currentPage=1. Accessed 28 Jan 2014.

  24. • Kalus JS. Pharmacologic interventions for reversing the effects of oral anticoagulants. Am J Health Syst Pharm. 2013;70(Suppl 1):S12–21. This article provides guidance for the reversal of all oral anticoagulants with the available treatments based on current literature and expert opinion.

  25. Tran HA, Chunilal SD, Harper PL, et al. An update of consensus guidelines for warfarin reversal. Med J Aust. 2013;198(4):198–9.

    Article  PubMed  Google Scholar 

  26. Keeling D, Baglin T, Tait C, et al. Guidelines on oral anticoagulation with warfarin—fourth edition. Br J Haematol. 2011;154:311–24.

    Article  PubMed  Google Scholar 

  27. •• 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;124:1573–79. This study reviewed the impact of 4 factor prothrombin complex in reversing laboratory parameters of anticoagulation in normal volunteers treated with dabigatran and rivaroxaban.

  28. 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:S141–5.

    Article  CAS  PubMed  Google Scholar 

  29. Kaatz S, Crowther M. Reversal of target-specific oral anticoagulants. J Thromb Thrombolysis. 2013;36(2):195–202.

    Article  CAS  PubMed  Google Scholar 

  30. Franchini M, Lippi G. Prothrombin complex concentrates: an update. Blood Transfus. 2010;8:149–54.

    PubMed Central  PubMed  Google Scholar 

  31. Riess HB, Meier-Hellmann A, Motsch J, et al. Prothrombin complex concentrate (Octaplex®) in patients requiring immediate reversal of oral anticoagulation. Thromb Res. 2007;121:9–16.

    Article  CAS  PubMed  Google Scholar 

  32. Song MM, Warne CP, Crowther MA. Prothrombin complex concentrate (PP, Octaplex®) in patients requiring immediate reversal of vitamin K antagonist anticoagulation. Thromb Res. 2012;129:526–9.

    Article  CAS  PubMed  Google Scholar 

  33. Leissinger CA, Blatt PM, Hoots WK, et al. Role of prothrombin complex concentrates in reversing warfarin anticoagulation: a review of the literature. Am J Hematol. 2008;83:137–43.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacy, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA, 02115, USA

    David P. Reardon

  2. Division of Hematology, Department of Medicine, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA, 02115, USA

    Jean M. Connors

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  1. David P. Reardon
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  2. Jean M. Connors
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Correspondence to David P. Reardon.

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Reardon, D.P., Connors, J.M. Prothrombin Complex Concentrate (4PCC): A Review of its Use in Reversal of Vitamin K Antagonists. Curr Emerg Hosp Med Rep 3, 50–54 (2015). https://doi.org/10.1007/s40138-014-0058-2

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  • DOI: https://doi.org/10.1007/s40138-014-0058-2

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