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Andexanet alfa and four-factor prothrombin complex concentrate for reversal of apixaban and rivaroxaban in patients diagnosed with intracranial hemorrhage

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Abstract

Limited data exists regarding the clinical outcomes of andexanet alfa and four factor prothrombin complex concentrate (4F-PCC) for reversal of apixaban or rivaroxaban in the setting of intracranial hemorrhage (ICH). The objective of this study was to evaluate clinical outcomes of 4F-PCC and andexanet alfa for reversal of ICH associated with oral factor Xa inhibitors. This was a retrospective, single-center, case series evaluating hemostatic efficacy of patients receiving andexanet alfa) or 4F-PCC for reversal of apixaban or rivaroxaban after ICH. Secondary endpoints included in-hospital mortality, thrombotic complications, timing of reversal agents, intensive care unit and hospital length of stay, patient disposition, and 30-day readmission rate. During the study period, 21 patients received andexanet alfa and 35 received 4F-PCC. Hemostatic efficacy occurred in 64.7% of patients receiving andexanet alfa and 54.8% of receiving 4F-PCC. Thirty-day all-cause mortality was 45.2% for 4F-PCC and 30% for andexanet alfa. Thrombotic events were higher with 4F-PCC (31.4%) compared to andexanet alfa (14.3%). Median time from presentation to administration of reversal agent was 2.67 [1.75–4.13] hours with andexanet alfa and 1.73 [1.21–3.55] hours with 4F-PCC. Discharge to skilled nursing facilities and 30-day readmission were similar between groups. In this cohort, reversal with andexanet alfa and 4F-PCC differed in terms ofhemostatic efficacy and thrombotic events after ICH in patients anticoagulated with apixaban or rivaroxaban.

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Authors and Affiliations

  1. Department of Pharmacy, Duke University Medical Center, Durham, NC, USA

    Mark L. Vestal, Kimberly Hodulik & Jennifer Mando-Vandrick

  2. Department of Pharmacy, Duke Regional Hospital, 3643 North Roxboro Street, Durham, NC, 27704, USA

    Mark L. Vestal

  3. Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA

    Michael L. James, Matthew Fuller, Mark Friedland & Ian J. Welsby

  4. Department of Neurology, Duke University Medical Center, Durham, NC, USA

    Michael L. James

  5. Division of Hematology, Department of Medicine, Duke University Medical Center, Durham, NC, USA

    Thomas L. Ortel & Ian J. Welsby

  6. Clincial Laboratories, Duke University Medical Center, Durham, NC, USA

    Maria Notini

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Contributions

MLV contributed to the concept and design, data collection, data analysis, interpretation of the data, and composition of the manuscript. KH contributed to the concept and design, data collection/validation, interpretation of the data, and revision of the manuscript. JMV and TLO contributed to concept and design, interpretation of the data, and revision of the manuscript. MLJ contributed to the interpretation of the data, and revision of the manuscript. M. Fuller contributed to concept and design, and data analysis. MN contributed to the DUH dosing algorithm for coagulation factor Xa (recombinant), inactivated-zhzo. M. Friedland contributed to the concept and design and interpretation of the data. IJW contributed to the concept and design, interpretation of the data, and composition of the manuscript. All authors approved the manuscript prior to submission for publication.

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Correspondence to Mark L. Vestal.

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MLV, KH, JMV, M. Fuller, MN, M. Friedland, and IW have no relevant conflicts of interests to disclose. MLJ has received research funding from Bard, AegisCN, and NICO Corporation. TLO has received research grants from Instrumentation Laboratory, Stago, and Siemens, and has received consulting fees from Instrumentation Laboratory.

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Vestal, M.L., Hodulik, K., Mando-Vandrick, J. et al. Andexanet alfa and four-factor prothrombin complex concentrate for reversal of apixaban and rivaroxaban in patients diagnosed with intracranial hemorrhage. J Thromb Thrombolysis 53, 167–175 (2022). https://doi.org/10.1007/s11239-021-02495-3

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