Comparison of activated and 4-factor prothrombin complex concentrates for reversal of apixaban- and rivaroxaban-associated major bleeding.

Factor Xa inhibitor (FXaI)-associated major bleeding presents a critical management challenge. Although andexanet alfa is the targeted reversal agent, its limited availability and high cost has sustained the use of prothrombin complex concentrates (PCCs). Activated PCC (aPCC) may provide effective reversal at lower doses due to its inclusion of activated factor VII. This study compared the effectiveness and safety of aPCC versus 4-factor PCC (4 F-PCC) for reversal of apixaban- and rivaroxaban-associated major bleeding. A retrospective cohort study was conducted at Huntsville Hospital. Adult patients who received aPCC or 4 F-PCC for major bleeding while on apixaban or rivaroxaban were included. Major bleeding and clinical hemostasis were defined using International Society on Thrombosis and Haemostasis (ISTH) criteria. The primary outcome was hemostatic effectiveness; the secondary outcome was in-hospital thromboembolic complications. Among 293 patients (252 aPCC, 41 4 F-PCC), baseline characteristics were similar except for more intracranial hemorrhage in the 4 F-PCC group (75.6% vs. 46.8%, p < 0.001). Hemostasis was achieved in 77.0% of aPCC-treated and 70.7% of 4 F-PCC-treated patients (p = 0.376). Thromboembolic events were infrequent (1.6% vs. 4.9%, p = 0.156), with no significant difference between groups. In FXaI-associated major bleeding, aPCC and 4 F-PCC achieved comparable hemostatic outcomes with low thromboembolic event rates. These results support either agent as a reasonable reversal option when andexanet alfa is unavailable, with aPCC potentially effective at lower doses.