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Efficacy of 4-Factor Prothrombin Complex Concentrates in Factor Xa Inhibitor-Associated Intracranial Bleeding

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Abstract

Background/Objective

Intracranial bleeding (ICB) is a feared complication of systemic anticoagulation. Factor Xa inhibitors (FXaI) are used frequently due to their improved safety profile and predictable kinetics. Andexanet alfa was recently approved for emergent reversal of FXaI agents but was not compared formally to 4-Factor Prothrombin Complex Concentrates (4FPCC) which are the current standard of care in many centers. The objective of this study is to formally evaluate the hemostatic efficacy of 4FPCC in patients with FXaI-associated ICB.

Methods

We performed a retrospective cohort study of patients receiving 4FPCC for the reversal of a FXaI in the setting of acute ICB. Hemostatic efficacy was adjudicated via evaluation of post-4FPCC CT scan using the criteria closely mirroring those outlined in Annexa-4 (excellent < 20% expansion, good > 20% but ≤ 35% expansion, poor > 35% expansion). Each image was reviewed by two neurointensivist attendings for grading. Mortality was assessed until date of discharge. Charts were screened for thrombotic events out to 30 days post-4FPCC administration.

Results

A total of 59 patients were included in the final analysis. The mean age in years was 78.5 ± 10.9 and 56% were male. Apixaban was the most common FXaI prescribed at the time of presentation (67.8%). Most patients were on FXaI therapy for stroke prevention in the setting of atrial fibrillation (81.3%). Median Glasgow Coma Scale at presentation was 15(IQR 12–15), with the most frequently presenting ICB type being intracerebral hemorrhage (52.5%). The mean dose of 4FPCC prescribed was 46.6 (± 8.2) units/kg. Of those receiving 4FPCC for FXaI ICB, 88% were graded as having an excellent or good hemostatic outcome with excellent interrater reliability. Survival was high at 89.8%, and thrombotic events were seen in seven patients (11.9%).

Conclusion

4FPCC appears to be an effective and safe option for FXaI-associated ICB with outcomes comparable to andexanet alfa. A formal prospective evaluation of this strategy versus andexanet alpha including cost analysis is warranted.

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Funding

There was no funding associated with this project.

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Authors and Affiliations

  1. Department of Critical Care Medicine, Mercy Hospital St. Louis, 615 S. New Ballas Road, St. Louis, MO, 63303, USA

    Matthew J. Korobey, Farid Sadaka, Muhammad Javed & Ahmed Alsaei

  2. St. Louis College of Pharmacy, St. Louis, USA

    Meghin Moynihan

Authors
  1. Matthew J. Korobey
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  2. Farid Sadaka
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  3. Muhammad Javed
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  4. Meghin Moynihan
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  5. Ahmed Alsaei
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Contributions

MK designed and directed this study, conducted data collection, data analysis and drafted the manuscript. FS and MJ participated in the conceptual framing of the study, data collection/analysis, and revision of the manuscript. MM and AA participated in data collection.

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Correspondence to Matthew J. Korobey.

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The authors declare that they have no conflict of interest.

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This was IRB approved by Mercy IRB as an except review and did not require informed consent as it was retrospective and did not include active treatment.

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Work performed at Mercy Hospital St. Louis.

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Korobey, M.J., Sadaka, F., Javed, M. et al. Efficacy of 4-Factor Prothrombin Complex Concentrates in Factor Xa Inhibitor-Associated Intracranial Bleeding. Neurocrit Care 34, 112–120 (2021). https://doi.org/10.1007/s12028-020-00968-6

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  • DOI: https://doi.org/10.1007/s12028-020-00968-6

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