NEW YORK (Reuters Health) – In healthy volunteers, prothrombin complex concentrate reverses the anticoagulant effect of rivaroxaban. However, it does not alter the action of dabigatran, Dutch researchers report in a September 6th on-line paper in Circulation.

Dr. Elise S. Eerenberg told Reuters Health by email, “The new oral anticoagulants dabigatran and rivaroxaban are a welcome replacement for the vitamin K antagonists, known for their unstable antithrombotic properties and need for frequent monitoring.”

“Dabigatran and rivaroxaban,” she added, “can already be prescribed in Europe and Canada, and dabigatran is also already licensed in the United States. Nevertheless, up until our work, little was known about a proper antidote, necessary for potentially life threatening situations such as major bleeding or emergency surgery.”

To investigate, Dr. Eerenberg and colleagues at Academic Medical Center, Amsterdam conducted a crossover study in 12 healthy male volunteers. They were given rivaroxaban 20 mg or dabigatran 150 mg twice daily for 2.5 days followed by 50 IU/kg of prothrombin complex concentrate (Cofact, Sanquin Blood Supply) or saline.

Rivaroxaban induced a significant prolongation of the prothrombin time at baseline (15.8 versus 12.3 seconds). This was immediately and completely reversed by prothrombin complex concentrate. The endogenous thrombin potential was also significantly inhibited and normalized. Saline had no effect.

Dabigatran increased the activated partial thromboplastin time, ecarin clotting time and thrombin time. Administration of prothrombin complex concentrate did not reverse these effects.

“In this study in healthy volunteers,” continued Dr. Eerenberg, “we showed that Cofact reversed the anticoagulant effect of rivaroxaban as measured by coagulation assays, whereas there was no measurable effect on dabigatran treatment. Even though further investigation needs to be conducted in patients treated with either of these anticoagulant drugs, this is the first study assessing a possible antidote in humans treated with dabigatran and rivaroxaban.”

Reference:

Reversal of Rivaroxaban and Dabigatran by Prothrombin Complex Concentrate

Circulation 2011.