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Variables associated with adequate INR reversal in warfarin treated patients receiving 4-factor prothrombin complex concentrate

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Abstract

Dosing of 4-factor prothrombin complex concentrate (4FPCC) in warfarin treated patients generally utilizes international normalized ratio (INR) and patient weight. The recommended maximum dosing for all INR categories is capped at 100 kg weight. Whether this affects INR reversal is unknown. Furthermore, characteristics associated with adequate INR reversal need to be further elucidated. This was a multi-center, retrospective cohort study of 186 patients who received 4FPCC for INR reversal in the setting of warfarin-associated hemorrhage or need for emergent INR reversal. Utilizing multiple regression analysis, we evaluated INR reversal, achievement of hemostasis, and 28-day all-cause mortality. A target INR < 1.4 was achieved in 132 of 186 patients (71%). Factors significantly affecting the odds of achieving target INR were age in years (OR 1.03; 95% CI 1.01–1.06; P = 0.01), weight-based 4FPCC dose (units/kg) (OR 1.04; 95% CI 1.00–1.08; P = 0.03), and 4FPCC dosing normalized to INR (units/kg/INR) (OR 1.18; 95% CI 1.03–1.35; P = 0.02). Hemostasis was achieved in 109 of 148 bleeding patients (73.6%). Blood transfusions were associated with not achieving hemostasis (OR 0.44; 95% CI 0.21–0.93; P = 0.03). All-cause 28-day mortality was 21.5% and was associated with intracranial hemorrhage (OR 2.83; 95% CI 1.38–5.8; P = 0.01). Adequate INR reversal was associated with age, weight-based 4FPCC dose, and dosing normalized to INR (units/kg/INR). Future studies should evaluate the appropriateness of current INR targets for warfarin reversal and alternative 4FPCC dosing strategies such as utilizing a 4FPCC dosing ratio of units/kg/INR.

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Authors and Affiliations

  1. Department of Pharmacy, Intermountain Medical Center, 5121 South Cottonwood St, Murray, UT, 84107, USA

    Sara Kjerengtroen, Stephanie Chauv, Abby W. Hickman & Gabriel V. Fontaine

  2. Department of Pharmacy, Nebraska Medicine, Omaha, NE, 68198, USA

    Sara Kjerengtroen

  3. Office of Research, Intermountain Healthcare, Murray, UT, 84107, USA

    Dave S. Collingridge

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  1. Sara Kjerengtroen
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  2. Stephanie Chauv
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  3. Abby W. Hickman
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  4. Dave S. Collingridge
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  5. Gabriel V. Fontaine
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by SK, SC, AH, and GF. The first draft of the manuscript was written by SK and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Gabriel V. Fontaine.

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Kjerengtroen, S., Chauv, S., Hickman, A.W. et al. Variables associated with adequate INR reversal in warfarin treated patients receiving 4-factor prothrombin complex concentrate. J Thromb Thrombolysis 54, 268–275 (2022). https://doi.org/10.1007/s11239-022-02646-0

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  • DOI: https://doi.org/10.1007/s11239-022-02646-0

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