Summary.  Background:  One limitation of the direct thrombin inhibitor dabigatran is the lack of specific antidotes that allow acute bleeding events to be managed or urgent interventional procedures performed. Prothrombin complex concentrates (PCCs) have served as a standard treatment for the reversal of coumarin anticoagulation. Objectives:  This study was designed to determine in an animal model whether a PCC (Beriplex P/N) can effectively reverse the effects of dabigatran. An additional objective was to evaluate markers of dabigatran‐associated bleeding diathesis. Methods:  Anesthetized rabbits were treated with 0.4 mg kg−1 dabigatran followed by PCC doses of 20, 35 or 50 IU kg−1 or placebo. After a standardized kidney incision, volume of blood loss and time to hemostasis were determined. Results:  From an initial mean of 29 mL, blood loss progressively declined by 5.44 mL with a 95% confidence interval (CI) of 2.21–8.67 mL per 10 IU kg−1 increment in PCC dose (P = 0.002). At a PCC dose of 50 IU kg−1 blood loss was fully normalized. Increasing PCC doses shortened the median time to hemostasis from 20.0 to 5.7 min (P < 0.001). The rate of hemostasis was nearly trebled with each 10 IU kg−1 increment in PCC dose (rate ratio, 2.89; CI, 1.64–5.09). Conclusions:  In this animal study, PCC showed potential as an agent for reversing the effects of dabigatran. Further investigation is warranted.

In summary, in a rabbit model of acute bleeding, treatment with 4F-PCC reduced bleeding to control levels following rivaroxaban 150 μg/kg and 300 μg/kg administration.

In a rabbit model of hemostasis, four-factor prothrombin complex concentrate administration significantly decreased edoxaban-associated hemorrhage.

Dilutional coagulopathy produced a generalized decrease in coagulation factors and impaired platelet function. Substitution with PCC effectively normalized coagulation and significantly improved hemostasis after venous and arterial bleeding.