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Impact of Factor Xa Inhibitor Reversal with Prothrombin Complex Concentrate in Patients with Traumatic Brain Injuries

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Abstract

Background

Anticoagulant use prior to trauma has been associated with increased incidence of traumatic brain injury (TBI), intracranial hemorrhage (ICH) progression, and mortality. Prothrombin complex concentrates (PCCs) are commonly used as off-label treatments for factor Xa inhibitor-associated life-threatening hemorrhage. At this time, there is no consensus regarding appropriate indication, target dose, or outcomes of PCC administration in patients presenting with traumatic ICH. This study seeks to evaluate the impact of reversal with PCC on hemorrhage progression and outcomes in patients with TBI on preinjury factor Xa inhibitors.

Methods

This single-center retrospective cohort study included patients ≥ 18 years presenting with an acute TBI of any severity on apixaban or rivaroxaban from September 1, 2016, to September 1, 2019. Patients were grouped on the basis of receipt of PCCs for reversal (i.e., reversal or no reversal). Exclusion criteria included spontaneous ICH or known coagulopathy. Propensity score matching was conducted with the following variables: age, Abbreviated Injury Scale (head) score, and Charlson Comorbidity Index score. The primary outcome was hemorrhage stability within 48 h. Secondary outcomes included degree of hemorrhage progression, in-hospital mortality, discharge disposition, and incidence of thromboembolic events.

Results

Of the 115 patients meeting inclusion criteria, 84 were included in the propensity score matched data set. Baseline characteristics, comorbidities, and TBI severity were similar. The majority of patients in the reversal group (35 [83.3%]) and the no reversal (NR) group (40 [95.2%]) experienced a mild TBI (admission Glasgow Coma Scale score of 14 to 15). In the reversal group, patients received 34.3 units/kg activated PCC, 30.5 units/kg four-factor PCC, or 54.9 units/kg four-factor PCC and activated PCC on average. There was no difference observed in the incidence of hemorrhage progression (10.8% NR vs. 15.0% reversal; p = 0.739) or in median change in ICH volume (0 mL NR vs. 1 mL reversal; p = 0.2199) between groups. Additionally, reversal did not affect in-hospital mortality (3 [7.1%] NR vs. 4 [9.5%] reversal; p > 0.999). One patient in the reversal group developed a deep vein thrombosis (DVT) during the hospitalization; however, this did not result in a statistically significant difference in the occurrence of DVT (p > 0.999).

Conclusions

This study demonstrated that PCC used for the treatment of factor Xa inhibitor-associated ICH related to mild TBI did not significantly impact the incidence or degree of hemorrhage progression, and PCC treatment did not result in increased thromboembolic events.

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Funding

There was no funding for this project.

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Authors and Affiliations

  1. University of Tennessee Medical Center, 1924 Alcoa Highway, Box 117, Knoxville, TN, 37938, USA

    Grace E. Cooksey, Leslie A. Hamilton, James C. McMillen & A. Shaun Rowe

  2. Atrium Health Wake Forest Baptist, Winston Salem, NC, USA

    Grace E. Cooksey

  3. University of Tennessee Health Science Center College of Pharmacy, Knoxville, TN, USA

    Leslie A. Hamilton & A. Shaun Rowe

  4. University of Tennessee Graduate School of Medicine, Knoxville, TN, USA

    Jared H. Griffard

Authors
  1. Grace E. Cooksey
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  2. Leslie A. Hamilton
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  3. James C. McMillen
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  4. Jared H. Griffard
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  5. A. Shaun Rowe
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Contributions

Authors GEC, LAH, JCM, JHG, and ASR contributed to the initial design, data collection, drafting, and review of the final manuscript. Authors ASR and GEC were also involved with data analysis.

Corresponding author

Correspondence to A. Shaun Rowe.

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Conflicts of interest

Author JCM is currently employed by Amgen. At the time of study development and conduct, JCM was not affiliated with Amgen. Amgen does not have a role in this project.

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This project is institutional review board approved and complies with ethical guidelines.

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Cooksey, G.E., Hamilton, L.A., McMillen, J.C. et al. Impact of Factor Xa Inhibitor Reversal with Prothrombin Complex Concentrate in Patients with Traumatic Brain Injuries. Neurocrit Care 37, 471–478 (2022). https://doi.org/10.1007/s12028-022-01521-3

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  • DOI: https://doi.org/10.1007/s12028-022-01521-3

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