(88) Hemostatic Effectiveness of Four-factor Prothrombin Complex Concentrate for Treatment of Factor Xa Inhibitor-associated Acute Major Bleeds: A Meta-analysis

Publication Number: 762

Background: Four-factor Prothrombin Complex Concentrate Human (4F-PCC) is a blood coagulation factor replacement product indicated for the urgent reversal of acquired coagulation factor deficiency induced by Vitamin K antagonist (VKA, e.g., warfarin) therapy in adult patients with acute major bleeding or need for an urgent surgery/invasive procedure. 4F-PCC has also been used to treat patients with Factor Xa (FXa) inhibitor (e.g., apixaban, rivaroxaban) -associated acute major bleeding. However, the effectiveness of this treatment approach has not been established.

Objectives: To estimate the hemostatic effectiveness of 4F-PCC for the treatment of FXa inhibitor-associated acute major bleeding.

Methods: Observational studies identified in a previously published meta-analysis (Nederpelt CJ, et al. Crit Care Med. 2021;49:e1025-e1036) that were conducted exclusively among patients with a FXa inhibitor-associated acute major bleed treated with 4F-PCC or studies with results for 4F-PCC-treated patients reported separately were included in this meta-analysis. Estimates of hemostatic effectiveness were pooled using a Restricted Maximum Likelihood (REML) random effects model in STATA statistical software version 16.1 (StataCorp., 2019).

Results: Nine observational cohort studies with a total of 677 patients treated with 4F-PCC for Factor Xa inhibitor-associated acute major bleeding were identified; seven studies were conducted retrospectively and two were conducted prospectively. Studies were conducted in the United States (7), Sweden (1), and Canada (1). Two studies reported 12-hour effectiveness and seven studies reported 24-hour effectiveness. Four studies were conducted exclusively among patients with an intracranial hemorrhage (ICH) and five studies included patients with an ICH or other type of bleed. Overall, 79% (95% confidence interval [CI]: 74-84%) of 4F-PCC-treated patients were assessed as having a favorable hemostatic effectiveness. Favorable hemostatic effectiveness was 89% (95% CI: 81-94%) and 77% (95% CI: 72-82%) for patients measured at 12 and 24 hours, respectively. Favorable hemostatic effectiveness was 83% (95% CI: 75-90%) and 76% (95% CI: 69-82%) among studies including patients with only ICH or studies including patients with mixed bleed types, respectively.

Conclusions: This meta-analysis provides an assessment of hemostasis effectiveness of 4F-PCC used to treat FXa inhibitor-associated acute major bleeding. Clinical studies are needed to confirm the results seen in the real-world as 4F-PCC could provide an effective alternative to the currently available treatments.