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Anticoagulant Reversal Protocols

From Scott Cornelius at Johnson & Johnson, I am interested in finding out if you have any samples of what good bleeding protocols for large teaching hospitals are like. With all of the new oral agents on the market there surely are many new challenges in managing patients with ICH and other serious bleeding complications. Thanks for your insight.

Hi, Scott, and thank you for a question that has grown in importance with the advent of the oral anticoagulants dabigatran, rivaroxaban, and apixaban. Your question probably is intended to focus on these new oral anticoagulants, but first, the standard reversal protocol for Coumadin using discontinuance and vitamin K appears in Ageno W, Gallus AS, Wittkowsky A, et al. Oral anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012; 141): e44S–e88S. This is available online for a fee from the American College of Chest Physicians We’ve reproduced the Coumadin overdose information from an earlier edition of the Chest guidelines (still accurate) in Marques MB, Fritsma GA. Quick Guide to Coagulation Testing, 2nd Edition, available from AACC Press.

Here also is a link to an April 29 Los Angeles Times article about Kcentra®, a new prothrombin complex concentrate designed to reverse Coumadin overdose. I’ve not been able to find reference to Kcentra on the FDA web site, but the LA Times article indicates it provides nearly instant reversal.

Bleeding incidence for dabigatran, rivaroxaban, and apixaban is equivalent to Coumadin, and there is no current means for reversing their anticoagulant effects, save for renal dialysis, so bleeding management is a problem, as documented in Miesbach W, Seifried E. New direct oral anticoagulants-current therapeutic options and treatment recommendations for bleeding complications. Thrombos and Haemost 2012;108:625–32, linked below. Pharmaceutical companies are scrambling to come up with a reversal agent for all three. I hope this helps.

Thrombos & Haemost 2012

Comments (1)
Anticoagulant Therapy
George Fritsma
May 3, 2013 12:18pm

From David McGlasson, Clinical Research Scientist:

From David McGlasson, Clinical Research Scientist:

PER977 is a small molecule that is being investigated by Perosphere as a antidote for multiple anticoagulants, including FXa inhibitors, direct thrombin inhibitors, LMWH and fondaparinux. They have signed an agreement with Daiichi Sankyo on a phase I clinical study testing the effectiveness of PER977 to reverse the anticoagulant activity of edoxaban.  A couple of articles of interest on this are as follows: Dolgin E. Nature Medicine 19:251.Laulicht B, Bakhru G, Lee C et al. Small molecule antidote for anticoagulants. Meeting abstract/11395, Circulation 126 (21 Suppl)

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