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International Journal of Emergency Medicine

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Open Access 01-12-2009 | Original Research Article

Activated prothrombin complex concentrate factor VIII inhibitor bypassing activity (FEIBA) for the reversal of warfarin-induced coagulopathy

Authors: Cezary Wójcik, Michelle L. Schymik, Eric G. Cure

Published in: International Journal of Emergency Medicine | Issue 4/2009

Abstract

Aims

The purpose of this study was to evaluate the effectiveness of a new, fixed, yet individualized dosing regimen of activated prothrombin complex concentrate factor VIII inhibitor bypassing activity (FEIBA) for warfarin reversal in the setting of a life-threatening bleeding in a secondary care center.

Methods

In this report we present a retrospective chart review of 72 patients who received FEIBA and 69 patients who received fresh-frozen plasma (FFP) to reverse the effects of warfarin in a setting of a life-threatening bleeding. In the FEIBA cohort, patients received 500 units of FEIBA when the initial INR was <5 or 1,000 units of FEIBA when initial INR was ≥5.

Results

FEIBA administration resulted in lower subsequent INR when compared with FFP and shorter time elapsed from drug administration to an INR ≤1.4 when compared with FFP. No significant differences in survival or in the length of hospital stay were observed. A higher FEIBA dose induced a bigger decrease in INR than the lower dose. We observed five adverse events (7%) that could potentially be related to FEIBA administration.

Conclusions

The presented dosing regimen results in safe reversal of warfarin-induced coagulopathy, which appears to be faster and more profound than following FFP. Moreover, the use of activated PCC (FEIBA) does not appear to carry an increased risk of thrombotic events when compared to the rate reported for several non-activated PCC preparations.

Wiedermann CJ, Stockner I (2008) Warfarin-induced bleeding complications—clinical presentation and therapeutic options. Thromb Res 122(Suppl 2):S13–S18PubMedCrossRef

Makris M (2005) Optimisation of the prothrombin complex concentrate dose for warfarin reversal. Thromb Res 115:451–453PubMedCrossRef

Connock M, Stevens C, Fry-Smith A, Jowett S, Fitzmaurice D, Moore D et al (2007) Clinical effectiveness and cost-effectiveness of different models of managing long-term oral anticoagulation therapy: a systematic review and economic modelling. Health Technol Assess 11:iii–66PubMed

Hylek EM, Evans-Molina C, Shea C, Henault LE, Regan S (2007) Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 115:2689–2696PubMedCrossRef

Levine MN, Raskob G, Beyth RJ, Kearon C, Schulman S (2004) Hemorrhagic complications of anticoagulant treatment: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 126:287S–310SPubMedCrossRef

Evans G, Luddington R, Baglin T (2001) Beriplex P/N reverses severe warfarin-induced overanticoagulation immediately and completely in patients presenting with major bleeding. Br J Haematol 115:998–1001PubMedCrossRef

Hanley JP (2004) Warfarin reversal. J Clin Pathol 57:1132–1139PubMedPubMedCentralCrossRef

Crowther MA, Ageno W, Garcia D, Wang L, Witt DM, Clark NP et al (2009) Oral vitamin K versus placebo to correct excessive anticoagulation in patients receiving warfarin: a randomized trial. Ann Intern Med 150:293–300PubMedCrossRef

Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G (2008) Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 133:160S–198SPubMedCrossRef

10.

Aguilar MI, Hart RG, Kase CS, Freeman WD, Hoeben BJ, Garcia RC et al (2007) Treatment of warfarin-associated intracerebral hemorrhage: literature review and expert opinion. Mayo Clin Proc 82:82–92PubMedCrossRef

11.

Fredriksson K, Norrving B, Stromblad LG (1992) Emergency reversal of anticoagulation after intracerebral hemorrhage. Stroke 23:972–977PubMedCrossRef

12.

Bruce D, Nokes TJ (2008) Prothrombin complex concentrate (Beriplex P/N) in severe bleeding: experience in a large tertiary hospital. Crit Care 12:R105PubMedPubMedCentralCrossRef

13.

Lankiewicz MW, Hays J, Friedman KD, Tinkoff G, Blatt PM (2006) Urgent reversal of warfarin with prothrombin complex concentrate. J Thromb Haemost 4:967–970PubMedCrossRef

14.

Blumel J, Schmidt I, Effenberger W, Seitz H, Willkommen H, Brackmann HH et al (2002) Parvovirus B19 transmission by heat-treated clotting factor concentrates2. Transfusion 42:1473–1481PubMedCrossRef

15.

Lorenz R, Kienast J, Otto U, Egger K, Kiehl M, Schreiter D et al (2003) Efficacy and safety of a prothrombin complex concentrate with two virus-inactivation steps in patients with severe liver damage. Eur J Gastroenterol Hepatol 15:15–20PubMedCrossRef

16.

Popovsky MA (2009) Transfusion-associated circulatory overload: the plot thickens. Transfusion 49:2–4PubMedCrossRef

17.

Triulzi DJ (2009) Transfusion-related acute lung injury: current concepts for the clinician. Anesth Analg 108:770–776PubMedCrossRef

18.

Steiner T, Kaste M, Forsting M, Mendelow D, Kwiecinski H, Szikora I et al (2006) Recommendations for the management of intracranial haemorrhage—part I: spontaneous intracerebral haemorrhage. The European Stroke Initiative Writing Committee and the Writing Committee for the EUSI Executive Committee. Cerebrovasc Dis 22:294–316PubMedCrossRef

19.

Junagade P, Grace R, Gover P (2007) Fixed dose prothrombin complex concentrate for the reversal of oral anticoagulation therapy. Hematology 12:439–440PubMedCrossRef

20.

Hughes DB, Ullery BW, Barie PS (2008) The contemporary approach to the care of Jehovah's witnesses. J Trauma 65:237–247PubMedCrossRef

21.

Guidelines on oral anticoagulation (1998) third edition. Br J Haematol 101:374–387CrossRef

22.

Aledort LM (2008) Factor VIII inhibitor bypassing activity (FEIBA)—addressing safety issues. Haemophilia 14:39–43PubMedCrossRef

23.

van Aart L, Eijkhout HW, Kamphuis JS, Dam M, Schattenkerk ME, Schouten TJ et al (2006) Individualized dosing regimen for prothrombin complex concentrate more effective than standard treatment in the reversal of oral anticoagulant therapy: an open, prospective randomized controlled trial. Thromb Res 118:313–320PubMedCrossRef

24.

Roddie PH, Stirling C, Mayne EE, Ludlam CA (1999) Thrombosis and disseminated intravascular coagulation following treatment with the prothrombin complex concentrate, DEFIX. Thromb Haemost 81:667PubMed

25.

Preston FE, Laidlaw ST, Sampson B, Kitchen S (2002) Rapid reversal of oral anticoagulation with warfarin by a prothrombin complex concentrate (Beriplex): efficacy and safety in 42 patients. Br J Haematol 116:619–624PubMedCrossRef

26.

Yasaka M, Sakata T, Naritomi H, Minematsu K (2005) Optimal dose of prothrombin complex concentrate for acute reversal of oral anticoagulation. Thromb Res 115:455–459PubMedCrossRef

27.

Yasaka M, Sakata T, Minematsu K, Naritomi H (2002) Correction of INR by prothrombin complex concentrate and vitamin K in patients with warfarin related hemorrhagic complication. Thromb Res 108:25–30PubMedCrossRef

28.

Levi M, Peters M, Buller HR (2005) Efficacy and safety of recombinant factor VIIa for treatment of severe bleeding: a systematic review. Crit Care Med 33:883–890PubMedCrossRef

29.

Deveras RA, Kessler CM (2002) Reversal of warfarin-induced excessive anticoagulation with recombinant human factor VIIa concentrate. Ann Intern Med 137:884–888PubMedCrossRef

30.

Taketomi T, Szlam F, Levy JH, Tanaka KA (2008) Warfarin reversal with prothrombin complex concentrate confers better antifibrinolytic activity compared with recombinant activated factor VII. Blood Coagul Fibrinolysis 19:106–108PubMedCrossRef

31.

Tanaka KA, Szlam F, Dickneite G, Levy JH (2008) Effects of prothrombin complex concentrate and recombinant activated factor VII on vitamin K antagonist induced anticoagulation. Thromb Res 122:117–123PubMedCrossRef

32.

Appelboam R, Thomas EO (2007) The headache over warfarin in British neurosurgical intensive care units: a national survey of current practice. Intensive Care Med 33:1946–1953PubMedCrossRef

33.

Pabinger-Fasching I (2008) Warfarin-reversal: results of a phase III study with pasteurised, nanofiltrated prothrombin complex concentrate. Thromb Res 122(Suppl 2):S19–S22PubMedCrossRef

34.

Alban S (2008) Pharmacological strategies for inhibition of thrombin activity. Curr Pharm Des 14:1152–1175PubMedCrossRef

35.

Schulman S, Bijsterveld NR (2007) Anticoagulants and their reversal. Transfus Med Rev 21:37–48PubMedCrossRef

Title: Activated prothrombin complex concentrate factor VIII inhibitor bypassing activity (FEIBA) for the reversal of warfarin-induced coagulopathy
Authors: Cezary Wójcik
Michelle L. Schymik
Eric G. Cure
Publication date: 01-12-2009
Publisher: Springer Berlin Heidelberg
Published in: International Journal of Emergency Medicine / Issue 4/2009
Print ISSN: 1865-1372
Electronic ISSN: 1865-1380
DOI: https://doi.org/10.1007/s12245-009-0125-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Activated prothrombin complex concentrate factor VIII inhibitor bypassing activity (FEIBA) for the reversal of warfarin-induced coagulopathy

Abstract

Aims

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Aims

Methods

Results

Conclusions

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