Portola Pharmaceuticals, Inc. announced new invitro data establishing the relationship between concentrations of the direct oral anticoagulants (DOACs) apixaban and rivaroxaban and the ability of four-factor prothrombin complex concentrate (4F-PCC) to correct inhibition of thrombin generation, compared with warfarin anticoagulation reversal by 4F-PCC. Data were presented on July 8, 2019 during a poster session at the Annual Congress of the International Society on Thrombosis and Haemostasis (ISTH 2019) in Melbourne, Australia. Results showed that, while effective in reversing inhibition of thrombin generation in plasma from patients treated with warfarin, 4F-PCCs did not appear to have an effect on the inhibition of thrombin generation by apixaban or rivaroxaban unless the Factor Xa inhibitor concentration was less than 75 ng/mL. In contrast, data from the same thrombin generation assay demonstrated that Andexxa® [coagulation factor Xa (recombinant), inactivated-zhzo] fully corrected the inhibition of thrombin generation by apixaban and rivaroxaban across a broad range of inhibitor concentrations. In this study, tissue factor (TF)-initiated thrombin generation was assessed using plasma from healthy donors or patients treated with warfarin. Reversal of warfarin anticoagulation by 4F-PCC (using commercially available Kcentra®/Beriplex®) was performed using individual plasma samples from warfarin-treated patients to which the equivalent of either the low or high therapeutic 4F-PCC dose was added. Reversal of apixaban or rivaroxaban anticoagulation by 4F-PCC and Andexxa was similarly measured using normal human plasma containing different concentrations of Factor Xa inhibitor (0-250 ng/mL for rivaroxaban and 0-125 ng/mL for apixaban). Finally, the effect of individual purified plasma components of 4F-PCC on thrombin generation in normal plasma was measured. The use of Factor Xa inhibitors is rapidly growing because of their efficacy and safety profile compared to warfarin and enoxaparin in preventing and treating thromboembolic conditions such as stroke, pulmonary embolism and venous thromboembolism (VTE). This growth has come with a related increase in the incidence of hospital admissions and deaths related to bleeding, the major complication of anticoagulation. In the U.S. alone in 2017, there were approximately 140,000 hospital admissions attributable to Factor Xa inhibitor-related bleeding. Andexxa is the first and only reversal agent approved for adult patients treated with the Factor Xa inhibitors apixaban or rivaroxaban when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding. It received both Orphan Drug and Breakthrough Therapy designations from the U.S. Food and Drug Administration (FDA), and it was approved on May 3, 2018, under the FDA's Accelerated Approval pathway. It is marketed in Europe as Ondexxya® (andexanet alfa).