Clinical pathways and outcomes of andexanet alfa administration for reversal of critical bleeding in patients on oral direct factor Xa inhibitors

Background: Andexanet is FDA-approved for reversal of critical bleeding from factor Xa inhibitors and off-label for surgical reversal. Data are lacking on andexanet administration processes. Methods: We retrospectively studied patients at a 23-hospital system who received andexanet from November 2019 to March 2023. Abstractors coded demographics, comorbidities, anticoagulant use, andexanet indication, and process times. The primary outcome was presentation-to-andexanet time; diagnosis, ordering, and administration times were calculated. Secondary outcomes included in-hospital post-andexanet major thromboembolism/bleeding and mortality. Results: 141 patients were analyzed. Andexanet indications were predominantly neurologic bleeding (85.8%). 24 patients (17.0%) transferred from non-tertiary/academic centers to tertiary/academic centers. Median presentation-to-administration time was 192.5 minutes (interquartile range [IQR] 108.0 - 337.0 minutes). Components were: 72.5 minutes (IQR 39.0 - 137.5 minutes) for bleeding diagnosis; 35.5 minutes (IQR 0 - 96.5 minutes) for andexanet ordering; and 53.0 minutes (IQR 38.5 - 78.5 minutes) for administration, which was longer at tertiary/academic hospitals (Ratio 1.5, 95% Confidence Interval [CI] 1.2 – 2.0, p = 0.002). Gastrointestinal or other critical bleeding (Ratio 2.59, 95% CI 1.67 – 4.02, p < 0.001), and tertiary/academic center treatment (Ratio 1.58, 95% CI 1.15 – 2.18, p = 0.005), were associated with increased time. Major thromboembolism, bleeding, and mortality occurred in 10.6%, 12.0%, and 22.9% of patients, respectively. Conclusions: In our cohort, median presentation-to-administration time was over 3 hours. Cumulative times were longer at tertiary/academic hospitals and for gastrointestinal/other bleeding. Post-andexanet major thromboembolism/bleeding occurred more at tertiary/academic hospitals, possibly related to transfers. Prospective studies may elucidate clinical decision-making bottlenecks.