Abstract
Non-activated four-factor prothrombin complex concentrate (4 F-PCC) has emerged as the preferred reversal strategy for patients on warfarin with life-threatening bleeding. Current dosing recommendations for 4 F-PCC require pre-treatment international normalized ratio (INR) and bodyweight values, resulting in ordering and administration delays. Studies have shown that alternative dosing regimens are safe and efficacious. This retrospective, single-center, pre- and post-protocol analysis was conducted to assess the efficacy of a pharmacist driven modified fixed-dose 4 F-PCC regimen versus package insert weight- and INR-based dosing regimen for warfarin reversal. The primary outcome was achievement of INR less than two. Secondary outcomes included dose and cost of 4 F-PCC, a time analysis, incidence of concomitant vitamin K administration, and incidence of thrombosis within seven days of 4 F-PCC. There were 195 patients included in the analysis, with 74 in the pre-cohort and 121 in the post-cohort. Baseline characteristics were similar between cohorts with the most common indication for warfarin use being atrial fibrillation (48.6% versus 47.1%) and reversal being intracerebral hemorrhage (68.9% versus 43.0%). Achievement of the primary endpoint occurred in 92% versus 95% (p = 0.097) of patients. A statistically significant difference was seen between cohorts regarding median dose and cost of 4 F-PCC administered (p < 0.001). Eleven thromboembolic events occurred with three events in the pre-cohort and eight events in the post-cohort (p = 0.453). A fixed-dose of 1500IU of 4 F-PCC was effective in reversing INR to less than two in most patients regardless of reversal indication with minimal thrombotic risks.
Highlights
No consensus exists for the ideal dosing scheme for 4 F-PCC for warfarin reversal.
We describe our experience with a pharmacist driven modified-fixed dose 4 F-PCC protocol for warfarin reversal.
No difference in reversal of INR < 2 was seen between package-insert weight and INR based dosing compared to modified fixed-dose 4 F-PCC dosing for warfarin reversal.
Future research regarding to establish non-inferiority between fixed-dose and package-insert dosing is warranted.
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MEP designed the study, collected and interpreted the data, and drafted the manuscript. MJ, SB, and CM contributed to interpretation of the data and critically revised the manuscript for important intellectual content. All authors approved the final version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work is appropriately investigated and resolved. All authors have reviewed and approved this manuscript prior to submission for publication.
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Peterson, M.E., Jaynes, M.P., Berardi, S. et al. Evaluation of modified fixed dose four-factor prothrombin complex concentrate for warfarin reversal. J Thromb Thrombolysis (2024). https://doi.org/10.1007/s11239-024-02969-0
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DOI: https://doi.org/10.1007/s11239-024-02969-0