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((R))) 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 may warrant further study of 4F-PCC for fXa inhibitor reversal.