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CC BY 4.0 · TH Open 2024; 08(02): e209-e215
DOI: 10.1055/a-2306-0804
Original Article

Clinical Pathways and Outcomes of Andexanet Alfa Administration for the Reversal of Critical Bleeding in Patients on Oral Direct Factor Xa Inhibitors

Mark Goldin
1   Institute of Health System Science, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, United States
2   Department of Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, United States
,
Kolton Smith
3   Department of Medicine, Lenox Hill Hospital at Northwell Health, New York, New York, United States
,
Ioannis Koulas
1   Institute of Health System Science, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, United States
,
Tungming Leung
4   Biostatistics Unit, Office of Academic Affairs, Northwell Health, Hempstead, New York, United States
,
Mayuri Ravi
5   Department of Medicine, North Shore University Hospital, Manhasset, New York, United States
,
Sanjit Parhar
1   Institute of Health System Science, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, United States
,
Sejal Shah
3   Department of Medicine, Lenox Hill Hospital at Northwell Health, New York, New York, United States
,
Kayla Floyd
3   Department of Medicine, Lenox Hill Hospital at Northwell Health, New York, New York, United States
,
Lori Ohanesian
6   Clinical Pharmacy, Long Island Jewish Medical Center, New Hyde Park, New York, United States
,
Rachel Bain
7   Clinical Pharmacy, Long Island Jewish Valley Stream, Valley Stream, New York, United States
,
Daniella Defonte
8   Clinical Pharmacy, Glen Cove Hospital, Glen Cove, New York, United States
,
Kanta Ochani
1   Institute of Health System Science, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, United States
,
Amanda Lin
9   Clinical Pharmacy, North Shore University Hospital, Manhasset, New York, United States
,
Bhumi Patel
8   Clinical Pharmacy, Glen Cove Hospital, Glen Cove, New York, United States
,
Nikolaos Tsaftaridis
1   Institute of Health System Science, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, United States
,
Jack Jnani
5   Department of Medicine, North Shore University Hospital, Manhasset, New York, United States
,
Alex C. Spyropoulos 
1   Institute of Health System Science, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, United States
2   Department of Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, United States
› Author Affiliations Funding This work was supported by AstraZeneca Pharmaceuticals, PC, and by funding from the Broxmeyer Fellowship in Clinical Thrombosis. The funders had no role in study design or conduct; data collection or analysis; preparation, review, or writing of the manuscript; or decision to submit the manuscript for publication.
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Abstract

Background Andexanet is U.S. Food and Drug Administration (FDA) approved for the 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 postandexanet major thromboembolism/bleeding and mortality.

Results In total, 141 patients were analyzed. Andexanet indications were predominantly neurologic bleeding (85.8%). Twenty-four patients (17.0%) were transferred from nontertiary/academic centers to tertiary/academic centers. The median presentation-to-administration time was 192.5 minutes (interquartile range [IQR]: 108.0–337.0 minutes). Components were as follows: 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, the median presentation-to-administration time was over 3 hours. Cumulative times were longer at tertiary/academic hospitals and for gastrointestinal/other bleeding. Postandexanet major thromboembolism/bleeding occurred more at tertiary/academic hospitals, possibly related to transfers. Prospective studies may elucidate clinical decision-making bottlenecks.

Keywords

DOAC - critical bleeding - andexanet alfa - clinical pathway - thromboembolism

Disclosures

Dr. Spyropoulos reports honoraria from Janssen, Bayer, Bristol Myers Squibb, Pfizer, AstraZeneca, and Sanofi and research grants from Janssen and Boehringer Ingelheim. He also is a member of the ATLAS group, an academic research organization. Dr. Goldin reports grant support from Janssen outside of the submitted work. The other authors report no conflicts.


Supplementary Material



Publication History

Received: 16 January 2024

Accepted: 08 April 2024

Accepted Manuscript online:
15 April 2024

Article published online:
13 May 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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