(452) Evaluation of Modified Fixed-Dose Four-Factor Prothrombin Complex Concentrate for Warfarin Reversal

Introduction: Non-activated four-factor prothrombin complex concentrate (4F-PCC) has emerged as the preferred reversal strategy for patients on warfarin with life-threatening bleeding. Current dosing recommendations for 4F-PCC require pre-treatment international normalized ratio (INR) and bodyweight values, resulting in ordering and administration delays while awaiting results. However, previous studies have provided some evidence that alternative dosing regimens may be safe and efficacious.

Methods: This retrospective, single-center, pre- and post-protocol analysis was conducted to assess the efficacy of a pharmacist driven modified fixed-dose 4F-PCC regimen versus a 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 4F-PCC, a time analysis, incidence of concomitant vitamin K administration, and incidence of thrombosis within seven days of 4F-PCC.

Results: A total of 254 records were assessed for eligibility based on 4F-PCC administration and warfarin on a patient’s prior to admission medication list. Fifty-nine records were excluded, most commonly for pre-treatment INR less than 2 which occurred in 13% of records. Following this exclusion, 195 patients were analyzed, 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 indication being intracerebral hemorrhage (68.9% versus 43.0%). Achievement of the primary endpoint occurred in 92% versus 95% (p = .097) of patients. A statistically significant difference was seen between cohorts regarding median dose and cost of 4F-PCC administered (p < .001). There were no differences in the time analysis, incidence of vitamin K administration, or incidence of thrombotic events between groups.

Conclusions: A fixed dose of 1500 units of 4F-PCC was effective in reversing INR to less than 2 in most patients regardless of reversal indication with minimal thrombotic risks. Furthermore, this study demonstrated that a modified fixed dose 4F-PCC dosing regimen can effectively be implemented for urgent warfarin reversal, decreasing costs associated with this therapy.