Four-factor prothrombin complex concentrate use for on-label versus off-label indications: a retrospective cohort study

This study aimed to characterize the utilization of four-factor prothrombin complex concentrate (4F-PCC) at a tertiary academic medical center and evaluate the incidence of thromboembolic events (TEs) and mortality when used in an on-label versus off-label context. All medical records for consecutive patients having received 4F-PCC over 61-months were retrospectively evaluated. On-label indications for 4F-PCC were defined per FDA guidance, with the remaining indications considered off-label. Three hundred sixty-nine 4F-PCC doses were administered to 355 patients, with 46.6% of administrations classified as off-label. On-label and off-label groups demonstrated similar rates of TEs (16.2% vs. 14%). On-label patients receiving repeated administrations of 4F-PCC or with a post-administration INR ≤ 1.5 had a significantly higher incidence of TE. Off-label patients with a prior history of TE were more likely to develop a TE following 4F-PCC administration. Off-label patients also had a significantly higher 30-day mortality relative to on-label patients (29.1% versus 18.3%). In conclusion, in a large cohort of patients, observed rates of off-label 4F-PCC use were high. Underlying prothrombotic risk factors were predictive of TEs in off-label patients. Moreover, patients receiving off-label 4F-PCC demonstrated higher transfusion rates. Overall, our study findings suggest that the utilization of 4F-PCC in an off-label context may convey a significant risk to patients with uncertain clinical benefits.