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Andexanet alfa after 4-factor PCC administration for intracranial hemorrhage: a case series

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Abstract

The ongoing controversy regarding optimal reversal agent for factor Xa-inhibitors is mainly due to lack of comparative data of andexanet alfa (AA) to 4-factor prothrombin complex concentrate (4F-PCC), institutional formulary restrictions, and navigation of clinical scenarios involving patients clinically worsen despite initial reversal efforts. The combination use of 4F-PCC and AA has not been evaluated in clinical trials and the outcomes of such patients with FXA-inhibitor associated intracranial hemorrhage (ICH) are unknown. A total of five patients, including four outside hospital transfers, received 4F-PCC prior to AA for FXa-inhibitor associated ICH (n = 3 apixaban, n = 2 rivaroxaban; n = 4 ICH, n = 1 TBI). The doses of 4F-PCC ranged from 25 to 60 units/kg and were administered within a range of 1.5–4.2 h prior to AA. One patient required surgical intervention with craniotomy and three patients underwent external ventricular drain placement. Two of the five patients developed an ischemic or thromboembolic complication within one week from 4F-PCC and AA administration. This case series discusses multiple unique patient cases in which 4F-PCC and AA were both administered for FXa-inhibitor associated ICH. The results highlight the potentially increased thrombotic risk associated with combination use. Ongoing post-marketing data collection of real patient case scenarios are essential to the establishment of consensus guidelines on how to prioritize initial reversal efforts and manage these patients during the course of their bleed.

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Funding

No funding was received for this observational analysis.

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Authors and Affiliations

  1. Department of Pharmacy Services, University of Cincinnati Medical Center, Cincinnati, OH, USA

    Paige Garber Bradshaw, Shaun Keegan & Madeline Foertsch

  2. University of Cincinnati James L. Winkle College of Pharmacy, Cincinnati, OH, USA

    Paige Garber Bradshaw, Shaun Keegan & Madeline Foertsch

  3. University of Cincinnati Gardner Neuroscience Institute, Cincinnati, OH, USA

    George L. Yang & Laura B. Ngwenya

  4. Department of Neurosurgery, University of Cincinnati, Cincinnati, OH, USA

    George L. Yang & Laura B. Ngwenya

  5. Department of Emergency Medicine, University of Washington School of Medicine, Seattle, USA

    Vasisht Srinivasan

Authors
  1. Paige Garber Bradshaw
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  2. Shaun Keegan
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  3. Madeline Foertsch
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  4. George L. Yang
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  5. Laura B. Ngwenya
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  6. Vasisht Srinivasan
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Contributions

PGB research idea, data collection, manuscript composure, SK research idea, manuscript composure/review, MF data collection, manuscript composure/review, GLY manuscript composure/review, LBN manuscript review, VS CT head readings/gradings/data collection.

Corresponding author

Correspondence to Paige Garber Bradshaw.

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Conflict of interest

All authors have no conflicts of interests to disclose regarding participation in this project.

Ethical approval

IRB approval was obtained for ongoing analysis of andexanet alfa outcomes in ICH patients at University of Cincinnati Medical Center with waived patient consent due to retrospective research design. Collection of data may be used to generate hypotheses and observations that would lead to or validate a prospective clinical study, lead to clinical trial design, or adapt institutional treatment guidelines. Additionally, collected data under current IRB approval is used to generate metrics affiliated with quality improvement by allowing detailed post-hoc analysis of clinical and physiologic variables of patients who received andexanet alfa. Because the review will involve records several years remote, it is not felt to be feasible to obtain informed consent. This study involves reviewing medical documents and images. The risk of participation to the subjects is judged to be minimal and only related to the potential disclosure of protected health information – to which appropriate precautions have taken place with deidentification and secure data storage. Per University of Cincinnati IRB, removal of the consent process is judged not to adversely affect the participants’ rights and welfare beyond exposure to no more than minimum risk. No imaging will be included or presented in current case series.

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Bradshaw, P.G., Keegan, S., Foertsch, M. et al. Andexanet alfa after 4-factor PCC administration for intracranial hemorrhage: a case series. J Thromb Thrombolysis 54, 295–300 (2022). https://doi.org/10.1007/s11239-022-02658-w

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  • DOI: https://doi.org/10.1007/s11239-022-02658-w

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