Letter by Bernstein et al Regarding Article, “Reversal of Rivaroxaban and Dabigatran by Prothrombin Complex Concentrate: A Randomized, Placebo-Controlled, Crossover Study in Healthy Subjects
To the Editor:
We read with interest the report by Eerenberg et al1 showing failure to reverse the anticoagulant effect of dabigatran with a nonactivated prothrombin complex concentrate (PCC). We remind readers that not all preparations of PCC are equivalent. In particular, an activated PCC contains higher amounts of activated clotting factors and may be more potent (and more thrombogenic) than nonactivated PCC. Indeed, van Ryn and colleagues2 have reported that Factor Eight Inhibitor Bypass Agent, an activated PCC, reduced bleeding times in dabigatran-treated rats. Although the findings of Eerenberg et al are valuable, their study should not be considered the last word regarding PCC for dabigatran reversal. The end points they studied were surrogates for the clinically desired outcome (in vivo hemostasis), and they tested only 1 dose of 1 nonactivated PCC.
On the basis of these concerns, we suggest the establishment of a national or international registry to collect reports of bleeding events and their treatment in patients who are receiving novel oral anticoagulants for a variety of indications. Short of a randomized trial (which would be problematic because of the low incidence of such events), a registry would provide some insights into the safety and efficacy of various reversal therapies for novel oral anticoagulants.
Richard A. Bernstein, MD, PhD
Mark J. Alberts, MD
Feinberg School of Medicine of Northwestern University
David A. Garcia, MD
University of New Mexico Health Sciences Center
Dr Bernstein is a consultant and speaker for Boehringer Ingelheim, Janssen, Bristol Myers Squibb/Sanofi Partnership, and Pfizer; he has research funding from Bristol Myers Squibb and Pfizer. Dr Alberts has received speaking honoraria from Boehringer-Ingelheim and is a consultant for Ortho-McNeil-Janssen, Merck, Bristol Myers Squibb, Sanofi-aventis, and Pfizer. Dr Garcia has received research funding from Bristol Myers and Boehringer Ingelheim and is a consultant for Bristol Myers, Boehringer Ingelheim, OrthoMcNeil, and Daichii Sankyo.
- © 2012 American Heart Association, Inc.
- Eerenberg ES,
- Kamphuisen PW,
- Sijpkens MK,
- Meijers JC,
- Buller HR,
- Levi M
- van Ryn JRD,
- Priepke H,
- Hauel N,
- Wienen W