Andexanet Alfa Versus Prothrombin Complex Concentrate in the Perioperative Setting

Introduction: Patients on factor Xa inhibitors (FXaI) who have or are at risk of perioperative bleeding pose a significant clinical challenge. Andexanet alfa and 4-factor prothrombin complex concentrate (4F-PCC) are key reversal options, but there is limited data regarding their use in this setting. The objective of this study is to evaluate the efficacy and safety of these agents in a real-world cohort of perioperative patients requiring FXaI reversal.


Methods: This retrospective cohort study included adult perioperative patients with reported FXaI use who received either andexanet alfa or 4F-PCC for urgent reversal over a 20-month period. The primary efficacy outcome was the need for additional procoagulant products within 24 hours. Secondary efficacy outcomes for non-intracranial hemorrhage (non-ICH) or procedural patients were excellent ( < 10% decrease in corrected hemoglobin/hematocrit) or good (≤20% decrease) hemostasis at 12 hours. For intracranial hemorrhage (ICH), efficacy was determined by reported hematoma volume expansion of ≤35%. Subjective worsening of bleeding and the incidence of any thrombotic event within 24 hours were also assessed.


Results: The study included 16 patients on apixaban (mean age 74.6 years), with 11 receiving 4F-PCC and 5 receiving andexanet alfa. For the primary outcome, no patients in the andexanet alfa group required additional procoagulants, in contrast to two patients (18%) in the 4F-PCC group (p = 1). In secondary efficacy analyses, four of six assessable 4F-PCC patients (66.7%) in the non-ICH/procedural cohort achieved excellent hemostasis, while the single assessable andexanet alfa patient did not (p = .42). Furthermore, both assessable ICH patients treated with 4F-PCC met their efficacy endpoint. Notably, all three instances of subjectively worsened bleeding (p = 0.49) and the single recorded thrombotic event (a 9.1% incidence, p = 1) occurred exclusively within the 4F-PCC group.


Conclusions: This study suggests a clinical trade-off between reversal agents. 4F-PCC achieved efficacy per the secondary endpoint but was associated with additional procoagulant use and the sole VTE occurrence. Andexanet alfa required no additional procoagulant therapy and had a preferable safety profile, though sample sizes were small in both cohorts.