safety, efficacy, and cost of four-factor prothrombin complex concentrate (4f-pcc) in patients with factor xa inhibitor-related bleeding: a retrospective study

Oral factor xa (fxa) inhibitor-related bleeding is a concerning drug safety problem. there is considerable controversy surrounding available reversal strategies. the recently approved reversal agent andexanet alfa has limited data, an unclear safety profile, and imparts a substantial financial burden. this has led to the off-label use of four-factor prothrombin complex concentrates (4f-pcc) for this indication. this study aimed to assess the safety and efficacy of 4f-pcc for the management of major bleeding related to oral fxa inhibitors. this observational, retrospective study included adult patients admitted from 2014 to 2018 who received 4f-pcc (kcentra®) for fxa inhibitor-related major bleeding. efficacy was assessed using criteria described by sarode et al. secondary outcomes included the incidence of thromboembolism, mortality, and a cost analysis comparing 4f-pcc to andexanet alfa for reversal of oral fxa inhibitors. thirty-one patients received 4f-pcc for major bleeding associated with apixaban (55%) or rivaroxaban (45%). intracranial hemorrhage (58%) and pericardial effusion (16%) accounted for the majority of bleeding events. most patients received a single weight-based 4f-pcc dose of 25 units/kg (38.7%) or 50 units/kg (51.6%). effective hemostasis was achieved in 80.6% of patients. five patients (16%) died due to acute bleeding and no thromboembolic events were observed. administration of 4f-pcc was effective for most patients requiring emergent reversal of anticoagulation with apixaban or rivaroxaban and was associated with a low risk of thromboembolic events. considerable cost differences limit the use of andexanet alfa and warrant further study of 4f-pcc for fxa inhibitor reversal.