Four-factor Prothrombin Complex Concentrate for Reversal of Factor Xa Inhibitors versus Warfarin in Life-threatening Bleeding

Abstract

Introduction: Factor Xa (fXa) inhibitor reversal for life-threatening bleeding is controversial due to a lack of high-quality evidence. The purpose of this study was to determine the hemostatic efficacy of four-factor prothrombin complex concentrate (4F-PCC) for the reversal of fXa inhibitors compared to warfarin for life-threatening bleeding. Methods: This was a multicenter, retrospective cohort study at two academic medical centers between January 1, 2014-December 31, 2019, which included patients who presented to the emergency department with a life-threatening bleed necessitating anticoagulation reversal with 4F-PCC. The primary endpoint was achievement of hemostatic efficacy after 4F-PCC administration. Results: Of the 525 patients who had an order for 4F-PCC during the study period, 148 patients met the criteria for inclusion (n = 48 fXa inhibitor group; n = 100 warfarin group). Apixaban (52.1%) and rivaroxaban (45.8%) were the most commonly used fXa inhibitors. Effective hemostasis was similar between groups (79.2% fXa inhibitor group vs 85% warfarin group, p = 0.38). This was consistent across all types of bleeding. Thrombotic events were rare in both groups (2% vs 3%). Conclusion: This multicenter, retrospective cohort study demonstrated that using 4F-PCC for treatment of life-threatening bleeding produced effective hemostasis in patients on fXa inhibitors and warfarin. [

Is reversal of anticoagulants necessary in neurologically intact traumatic intracranial hemorrhage?

“…It is important to note that reversal is not benign, there are potential side effects attendant to the reversal agents and a high cost associated with them. Interestingly, andexanet alfa is FDA‐approved for DOAC reversal, however, 4F‐PCC is not, but 4F‐PCC was previously studied in patients with far more severe bleeds than included in this study 22,23 . Complications of 4F‐PCC include thromboembolic events, hypersensitivity reactions, headache, nausea, vomiting, and hypotension 24 .…”

“…Interestingly, andexanet alfa is FDA-approved for DOAC reversal, however, 4F-PCC is not, but 4F-PCC was previously studied in patients with far more severe bleeds than included in this study. 22,23 Complications of 4F-PCC include thromboembolic events, hypersensitivity reactions, headache, nausea, vomiting, and hypotension. 24 Andexanet alfa also presents the following possible adverse effects: thromboembolic events, urinary tract infections, pneumonia, and infusion-related reactions.…”