Four-factor prothrombin complex concentrate (4F-PCC) appears to be effective for reversing oral factor Xa (fXa) inhibitor–related bleeding, according to research published in The American Journal of Emergency Medicine.
Frequently, fXa inhibitors are used to treat and prevent thromboembolic diseases, including venous thromboembolism. These therapies, which inhibit the coagulation cascade, may, however, increase the risk of bleeding, leading to a need for reversal. Yet the optimal method for inducing fXa inhibitor reversal is not well-established. While the U.S. Food and Drug Administration (FDA) approved andexanet alfa for reversing apixaban and rivaroxaban in 2018, safety and cost concerns remain.
In 2013, 4F-PCC, which contains clotting factors II, VII, IX, and X, as well as antithrombotic proteins C and S, received FDA approval for reversal of oral vitamin K antagonist–associated coagulopathy. For this retrospective study, researchers evaluated whether 4F-PCC is safe and effective for managing bleeding events related to fXa inhibitor use. The authors used criteria similar to those used in ANEXXA-4 (ClinicalTrials.gov Identifier: NCT02329327), a phase 3b/4 safety trial completed in 2019 that evaluated andexanet alfa.
Overall, data from 119 patients were included, of which 83 matched ANEXXA-4-like criteria. The overall mean age was 77 years, 55% of patients were men, and 59% and 41% of patients had received apixaban and rivaroxaban, respectively. A total of 85 patients (71%) needed reversal because of intracranial bleeding.
Reversal was successful in 106 (89%) patients overall, and in 74 (90%) patients in the ANNEXA-4-like subgroup, with an overall mortality rate of 13%.
Compared with 4F-PCC, the treatment costs per patient would have been higher had andexanet alfa been used instead. Among the 59 patients treated in 2018 whose data were evaluated in this study, the mean calculated therapy cost per patient was $5400; for low-dose and high-dose andexanet alfa, these figures would have been $27,500 and $49,500, respectively.
“Administration of 4F-PCC for the reversal of oral fXa inhibitors was effective with relatively low thrombotic risk,” the authors wrote. “4F-PCC appear to have similar clinical success rates when indirectly compared with andexanet alfa with reduced prothrombotic risk and cost.”
Lipari L, Yang S, Milligan B, Blunck J. Emergent reversal of oral factor Xa inhibitors with four-factor prothrombin complex concentrate. Emerg Med Am J. Published online August 19, 2020. doi:10.1016/j.ajem.2020.08.019