Reversing new oral anticoagulants

A small study on normal volunteers examined reversal of the new oral anticoagulants, Rivaroxaban and Dabigatran.

Rivaroxaban is a Factor Xa inhibitor and Dabigatran is a direct thrombin inhibitor.

Image from "Australian Prescriber" website. Click for Original

We should note that this was a study on the reversal of effects on various coagulation tests, not on reversal of bleeding, which is what we would be interested in for our ED/critical care patients.

Nevertheless, it’s helpful to note that prothrombin complex concentrate appeared to reverse the effects of Rivaroxaban, but not of Dabigatran.

Background Rivaroxaban and dabigatran are new oral anticoagulants that specifically inhibit factor Xa and thrombin, respectively. Clinical studies on the prevention and treatment of venous and arterial thromboembolism show promising results. A major disadvantage of these anticoagulants is the absence of an antidote in case of serious bleeding or when an emergency intervention needs immediate correction of coagulation. This study evaluated the potential of prothrombin complex concentrate (PCC) to reverse the anticoagulant effect of these drugs.

Methods and Results In a randomized, double-blind, placebo-controlled study, 12 healthy male volunteers received rivaroxaban 20 mg twice daily (n=6) or dabigatran 150 mg twice daily (n=6) for 2½ days, followed by either a single bolus of 50 IU/kg PCC (Cofact) or a similar volume of saline. After a washout period, this procedure was repeated with the other anticoagulant treatment. Rivaroxaban induced a significant prolongation of the prothrombin time (15.8±1.3 versus 12.3±0.7 seconds at baseline; P<0.001) that was immediately and completely reversed by PCC (12.8±1.0; P<0.001). The endogenous thrombin potential was inhibited by rivaroxaban (51±22%; baseline, 92±22%; P=0.002) and normalized with PCC (114±26%; P<0.001), whereas saline had no effect. Dabigatran increased the activated partial thromboplastin time, ecarin clotting time (ECT), and thrombin time. Administration of PCC did not restore these coagulation tests.

Conclusion Prothrombin complex concentrate immediately and completely reverses the anticoagulant effect of rivaroxaban in healthy subjects but has no influence on the anticoagulant action of dabigatran at the PCC dose used in this study.

Reversal of Rivaroxaban and Dabigatran by Prothrombin Complex Concentrate
Circulation. 2011 Oct 4;124(14):1573-9

So what do we do about bleeding patients who are taking Dabigatran? If you haven’t seen it already, take a look at this video from made by my heroes at Hennepin County Medical Centre:

Bleeding in the Patient on Dabigatran from on Vimeo.

They have an algorithm for the patient who is bleeding on dabigatran therapy that you can download a PDF of here