Free
Correspondence  |   January 2014
Factor Eight Inhibitor Bypass Activity for Novel Oral Anticoagulant Reversal
Author Affiliations & Notes
  • Anthony M.-H. Ho, M.D., F.R.C.P.C., F.C.C.P.
    Kingston General Hospital, Queen’s University, Kingston, Ontario, Canada. hoamh@hotmail.com
  • Competing Interests: The author declares no competing interests.
    Competing Interests: The author declares no competing interests.×
  • Accepted for publication September 16, 2013.
    Accepted for publication September 16, 2013.×
Article Information
Correspondence
Correspondence   |   January 2014
Factor Eight Inhibitor Bypass Activity for Novel Oral Anticoagulant Reversal
Anesthesiology 01 2014, Vol.120, 242-243. doi:10.1097/ALN.0000000000000060
Anesthesiology 01 2014, Vol.120, 242-243. doi:10.1097/ALN.0000000000000060
To the Editor:
In their excellent review on novel oral anticoagulants, Levy et al.1  seemed to have deliberately ignored the potential of factor eight inhibitor bypass activity (FEIBA; Baxter AG, Vienna, Austria) as a quick reversal agent in emergency situations. Levy et al. cited the study by Marlu et al.2  but made no mention of the results on FEIBA as a reversal agent reported in that study and chose only to discuss the results on prothrombin complex concentrate and recombinant factor VIIa, while acknowledging that there is an activated form of 4-factor prothrombin complex concentrate.
Factor eight inhibitor bypass activity consists of nonactivated factors II, IX, X, and activated VII, which means that it is similar to 3-factor prothrombin complex concentrate and recombinant factor VIIa combined. It is inexpensive and has been used extensively and successfully in the management of patients with hemophilia A with inhibitors for several decades in many countries, including the United States,3,4  although FEIBA appears not to have been approved by the Food and Drug Administration yet. In the ex vivo study in healthy white males by Marlu et al.,2  rivaroxaban reduced total and peak thrombin generation, as well as time to initiation of thrombin generation. Prothrombin complex concentrate normalized total thrombin generation but not the peak thrombin value or thrombin generation starting time. Recombinant factor VIIa corrected thrombin generation starting time but not total quantity or peak. Interestingly, FEIBA corrected all parameters at lower doses and overcorrected at higher doses. These authors also demonstrated a dose-dependent correction by FEIBA of the thrombin generation starting time prolonged by dabigatran. Their conclusion was that FEIBA at lower doses seems to be the most reasonable approach to novel oral anticoagulant reversal.2 
Published a month before Levy et al.’s review was a case report from Davis, California, of a middle-aged man on dabigatran 150 mg two times per day who sustained a transseptal perforation during atrial ablation.5  Within 60 min, approximately 4.5 l of blood was removed via pericardiocentesis. Intravenous low-dose FEIBA (3,159 units, 26 U/kg) over 15 min was administered. Hemostasis was noted within minutes of initiating the infusion with cessation of bleeding occurring soon after.
Several abstracts have also been published documenting improvement in bleeding parameters by FEIBA in novel oral anticoagulant–treated animals.6 
Anthony M.-H. Ho, M.D., F.R.C.P.C., F.C.C.P., Kingston
General Hospital, Queen’s University, Kingston, Ontario,
Canada. hoamh@hotmail.com
References
Levy, JH, Faraoni, D, Spring, JL, Douketis, JD, Samama, CM Managing new oral anticoagulants in the perioperative and intensive care unit setting.. A. (2013). 118 1466–74
Marlu, R, Hodaj, E, Paris, A, Albaladejo, P, Cracowski, JL, Crackowski, JL, Pernod, G Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban: A randomised crossover ex vivo study in healthy volunteers.. Thromb Haemost. (2012). 108 217–24 [Article] [PubMed]
Leissinger, C, Gringeri, A, Antmen, B, Berntorp, E, Biasoli, C, Carpenter, S, Cortesi, P, Jo, H, Kavakli, K, Lassila, R, Morfini, M, Négrier, C, Rocino, A, Schramm, W, Serban, M, Uscatescu, MV, Windyga, J, Zülfikar, B, Mantovani, L Anti-inhibitor coagulant complex prophylaxis in hemophilia with inhibitors.. N Engl J Med. (2011). 365 1684–92 [Article] [PubMed]
Hay, CR, Brown, S, Collins, PW, Keeling, DM, Liesner, R The diagnosis and management of factor VIII and IX inhibitors: A guideline from the United Kingdom Haemophilia Centre Doctors Organisation.. Br J Haematol. (2006). 133 591–605 [Article] [PubMed]
Dager, WE, Gosselin, RC, Roberts, AJ Reversing dabigatran in life-threatening bleeding occurring during cardiac ablation with factor eight inhibitor bypassing activity.. Crit Care Med. (2013). 41 e42–6 [Article] [PubMed]
Siegal, DM, Crowther, MA Acute management of bleeding in patients on novel oral anticoagulants.. Eur Heart J. (2013). 34 489–98 [Article] [PubMed]