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Publication Date
5-2021
Keywords
oregon; portland; psvmc
Disciplines
Pharmacy and Pharmaceutical Sciences
Abstract
Background
•4 Factor Prothrombin Complex Concentrate (4F-PCC) reverses anticoagulation of warfarin with weight-based dosing criteria supplied by manufacturer. INR must be processed before 4F-PCC is prepared. This regimen provides additional cost and delay of treatment to the patient as well as cost to the hospital and pharmacy department. •Fixed dose regimens of 4F-PCC have been described in literature1,2-4as having similar performance in achieving target INR compared to weight-based dosing, and can potentially have a decreased rate of thromboembolic events (TEE) compared to weight-based dosing, although large randomized-control trials on the comparison have not been conducted. •Fixed dosing of 4F-PCC is included in the American College of Cardiology 2020 consensus statement for emergency reversal of warfarin.5 •Fixed doses of 4F-PCC for warfarin reversal were recommended across 8 hospitals as an option alongside manufacturer weight-based dosing: •1500 units for all adult patients •500 additional units for patients presenting with INR > 7.5 and/or total body weight (TBW) > 100 kg
Purpose •To determine whether the treatment regimen of fixed dose 4F-PCC has similar outcomes in safety and efficacy when compared to manufacturer weight-based dosing for warfarin reversal
Objectives
•Identify percentage of eligible patients receiving 4F-PCC within emergency departments for warfarin reversal •Evaluate the percentage of patients reaching the primary endpoint of achieving an INR ≤ 2.0 after a single dose of 4F-PCC •Assess secondary outcomes of mortality, TEE, blood product use, achieving INR ≤ 1.5, repeat 4F-PCC use and potential cost-savings of fixed dose 4F-PCC
Methodology
Table 2. Outcomes •Electronic health record (EHR)-based retrospective and prospective study of patients treated in ED with 4F-PCC for warfarin reversal •Study was designed to replicate other retrospective studies and was implemented on January 19, 2021 •Study population: •Patients ≥ 18 years admitted to the ED requiring anticoagulation reversal with 4F-PCC •Exclusion criteria: •Admission INR < 2.0 or no initial INR •Repeat INR drawn ≥ 24 hours after 4F-PCC administration •Not on warfarin prior to admission or dose of 4F-PCC not fitting manufacturer weight-based dosing or fixed dose regimen
The primary outcome required repeat INR to be drawn within 6 hours as 10 mg of Vitamin K IV is part of the administration protocol for warfarin reversal and has shown to increase coagulation factors within 1-2 hours, having a peak effect in 12-14 hours. •Patients who did not have repeat INR drawn within 6 hours of 4F-PCC infusion were included in analysis. •INR was chosen as a common primary endpoint in past studies used to determine effective hemostability.2 •An INR of ≤ 1.5 was chosen as a secondary endpoint based on data that factor activity levels exceed 80% at this range, which is above the minimum hemostatic level. •TEE was defined as any thromboembolic event identified using imaging and listed in the diagnosis of acute problems within 7 days of 4F-PCC infusion.
Discussion
Clinical Outcomes •Similar safety and efficacy outcomes for fixed dose 4F-PCC can be seen when compared to weight-based dosing. •The median INR collection-to-result times for patients assessed was 34 minutes. •Baseline INR results are not required for the initiation of fixed dose 4F-PCC. Projected Savings •Using lowest to highest acquisition costs to hospitals projects $45,600 -$80,400 in annual savings using fixed dose 4F-PCC for 55 patients. Study Limitations •Retrospective, non-randomized study •The study did not reach the size required for adequate power to assess the primary outcome of INR reversal. •Patients were not matched for baseline characteristics, no patients assessed in higher fixed dose group. •INR not collected for all patients at 1 hour, 6 hour, and 24 hour mark. •Order set withdrawal after study implementation contributed to decreased fixed dose administration. •Number of patients seen at the emergency departments may be skewed with the ongoing COVID-19 pandemic.
Moving Forward
•Fixed dose 4F-PCC did not result in decreased efficacy or safety when compared to weight-based dosing. •Fixed dose 4F-PCC shows significant potential savings once implemented in a hospital.
Specialty/Research Institute
Graduate Medical Education
Specialty/Research Institute
Pharmacy
Conference / Event Name
Academic Achievement Day, 2021
Location
Providence St. Vincent Medical Center
