Off-label use of 4-factor prothrombin complex concentrate is common despite little known benefit: A retrospective study

Background/Objective: While four-factor prothrombin complex concentrate (4F-PCC) is FDA-approved for reversal of warfarin-induced major bleeding, its use in real-world settings is unclear. This study's objective was to identify indications leading to 4F-PCC use and associated outcomes at a single university hospital. Methods: This was a retrospective cohort study of patients receiving 4F-PCC over a 22-month period. A dose was “on-label” if given for reversal of warfarin-induced coagulopathy in patients with major bleeding or requiring urgent surgeries/procedures; other doses were “off-label”. Results: A total of 165 doses of 4F-PCC in 154 patients were given. Sixty-one percent of doses were on-label, while 39% were off-label. Intracranial hemorrhage was the most common indication (55% of doses). On-label patients had significantly higher rate of INR normalization and survival to hospital discharge than off-label patients. There was no difference in time to INR normalization, time to hemostasis, or incidence of thromboembolic complications. Conclusions: Off-label use of 4F-PCC is likely common, occurring in nearly 40% of drug administrations at our center. Larger-scale prospective trials studying specific indications are needed for validation in off-label settings. Until such evidence is available, given potential harms historically displayed by off-label use of other hemostatic agents, limiting off-label 4F-PCC use is recommended.