On-label compared to off-label four-factor prothrombin complex concentrate use: a retrospective, observational study

BACKGROUND Four-factor prothrombin complex concentrate (4F-PCC) is US Food and Drug Administration approved for the urgent reversal of coagulation factor deficiency induced by a vitamin K antagonist complicated by acute major bleeding or in situations in which invasive procedures are urgently needed. Although recent evidence suggests the superiority of 4F-PCC over plasma for on-label indications, the off-label use of 4F-PCC has not been rigorously studied. STUDY DESIGN AND METHODS Eighty-nine patients receiving 4F-PCC at a single institution from July 2016 to December 2017 were retrospectively analyzed. Two cohorts, "On-Label" and "Off-Label" uses of 4F-PCC, were evaluated, comparing patient characteristics, blood utilization, and clinical outcomes including in-hospital mortality. RESULTS Patients receiving 4F-PCC for off-label reasons (n = 46) were younger and sicker compared to those receiving 4F-PCC for on-label reasons (n = 43). Notably, the mortality rate for off-label use was approximately twofold greater than the mortality rate for on-label use (26 of 46 [56.5%] vs. 12 of 43 [27.9%]; p = 0.006). Patients receiving 4F-PCC for off-label reasons received more units per patient of each blood component than their on-label counterparts. The average cost estimate per patient for 4F-PCC was similar (approx. $4300) in each cohort. CONCLUSION 4F-PCC is an effective but expensive treatment option for those requiring urgent reversal of vitamin K antagonist-induced coagulopathy. However, providers should be conscious of the high costs and questionable efficacy when using 4F-PCC off-label.