doi: 10.1097/ALN.0000000000000061

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Levy, Jerrold H. M.D., F.A.H.A., F.C.C.M.

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I appreciate your comments; however, the review did not deliberately ignore the potential of Factor VIII Inhibitor Bypassing Activity (FEIBA; Baxter AG, Deerfield, IL) as you suggest, and FEIBA is mentioned but details were not provided. However, if you check table 2, there is further discussion on the use of activated prothrombin complex concentrates.1 The table legend specifically states that in patients receiving dabigatran, the use of an activated prothrombin complex concentrate such as FEIBA may be more effective, and there are no studies reporting the use of prothrombin complex concentrates on actual bleeding in patients. Further studies including the development of specific reversal agents are underway currently.1 Of note is the study by Marlu et al.2 that you describe is an in vitro study, and caution should be considered for extrapolating in vitro data to clinical application. You also reference a case report. Please note that case reports are interesting, but an n = 1 or 2 is not a case series. The authors also suggest that FEIBA appears not to be approved by the Food and Drug Administration, but this is not the case. Although using an activated prothrombin complex concentrate such as FEIBA appears to make sense, additional human data are needed before we can make definitive conclusions.
The studies described in more detail in the review article on prothrombin complex concentrates were actually performed in volunteers receiving therapeutic doses of the new oral anticoagulation agents including rivaroxaban and dabigatran.3 I am also a part of additional studies further investigating the role of prothrombin complex concentrates for reversal of rivaroxaban in volunteers.* Of note is a specific reversal agent has also been developed for dabigatran, using an immunospecific Fab fragment (BI 655075).4 This novel therapeutic approach is entering into clinical trials.
Clinicians when faced with life-threatening hemorrhage do indeed need to know all of the information and data available to manage these complex and critically ill patients.5 Further clinical studies are needed to best determine the optimal therapy for bleeding when it occurs in patients related to the novel oral anticoagulation agents.
Jerrold H. Levy, M.D., F.A.H.A., F.C.C.M.
, Duke University School of Medicine, Durham, North Carolina.
* Available at: Accessed October 9, 2013. Cited Here...
† Available at: Accessed October 9, 2013. Cited Here...
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1. 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

2. 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

3. 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;124:1573–9

4. Schiele F, van Ryn J, Canada K, Newsome C, Sepulveda E, Park J, Nar H, Litzenburger T. A specific antidote for dabigatran: Functional and structural characterization. Blood. 2013;121:3554–62

5. Karkouti K, Levy JH. Commentary: Recombinant activated factor VII: The controversial conundrum regarding its off-label use. Anesth Analg. 2011;113:711–2

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