Tissue Factor-Mediated Activation of the Prothrombin Complex Concentrate (PCC) is Differently Inhibited by Dabigatran, Rivaroxaban, and Apixaban

Abstract

Currently, several newer oral anticoagulants namely dabigatran (anti-IIa), rivaroxaban (anti-Xa), and apixaban are available for various clinical implications. Another oral anti-Xa edoxaban is under development. A parenteral anti-Xa drug namely otamixaban is also under development for cardiovascular interventions. Bleeding complications have been reported in the new oral anticoagulants and have been managed by conventional approaches with limited success. Prothrombin complex concentrates (PCCs) are reported to neutralize the anticoagulant activity of these agents. The PCCs are also able to generate endogenous factor Xa and IIa along with other proteases that are capable of neutralizing the circulating anti-Xa or anti-IIa activities of the newer anticoagulants. The generation of Xa and IIa is also dependent on the type of tissue factor available for their activation. These reported studies suggest that different tissue factors differentially activate a PCC namely Profilnine SD. Furthermore, dabigatran differs from rivaroxaban and other factor Xa inhibitors in its inhibitory profile.