Prothrombin complex concentrate for reversal of factor Xa inhibitor-associated acute major gastrointestinal bleeding

Factor Xa inhibitor-associated major gastrointestinal bleeding is life-threatening and requires rapid anticoagulation reversal. Andexanet alfa, a recombinant factor Xa decoy protein, is approved for reversal but is limited by high cost, restricted availability, and reported thromboembolic risk. Consequently, four-factor prothrombin complex concentrate (4F-PCC) is frequently used in clinical practice, although real-world data remain limited.

We conducted a single-center retrospective study at Meir Medical Center evaluating patients who received 4F-PCC for reversal of factor Xa inhibitor-associated major gastrointestinal bleeding between August 2016 and May 2025. The primary outcome was 12-hour hemostatic efficacy, assessed using methodology similar to the ANNEXA-4 trial. Safety outcomes included 30-day thromboembolic events and in-hospital mortality.

Of 72 screened patients, 62 were included in the final analysis. Median age was 80 years (interquartile range 76-88), and 33 patients (53.2%) were male. Apixaban was the most commonly used factor Xa inhibitor (74.2%). Hemostatic efficacy was achieved in 72.6% (45/62; 95% CI 60.4-82.1), including excellent responses in 51.6% and good responses in 21.0%. Efficacy was 70.2% in upper gastrointestinal bleeding and 80.0% in lower gastrointestinal bleeding (relative risk 1.14, 95% CI 0.83-1.56; P = 0.53). Thromboembolic events occurred in 4 patients (6.5%; 95% CI 2.5-15.4), and in-hospital mortality occurred in 8 patients (12.9%; 95% CI 6.7-23.4).

Prothrombin complex concentrate achieved 73% hemostatic efficacy in factor Xa inhibitor-associated gastrointestinal bleeding, with low thromboembolic rates and mortality similar to published data, supporting current guideline recommendations for reversal.