Comparing Hemostatic Efficacy of Four-Factor Prothrombin Complex Concentrate with Andexanet Alfa in an Apixaban-Treated Polytrauma Male Porcine Model

INTRODUCTION: This study directly compared the hemostatic efficacy of two first-line treatments for reversing the effects of direct oral anticoagulants in patients with massive bleeding, andexanet alfa and four-factor prothrombin complex concentrate (4F-PCC), in an apixaban anticoagulated male porcine polytrauma model. METHODS: Male pigs (N=32) received 20 mg/day apixaban for 3 days. Trauma was simulated by inducing standard liver injuries and bilateral femur fractures. After resuscitation, animals received control, 4F-PCC (25 or 50 IU/kg) or andexanet alfa (1000 mg bolus followed by 1200 mg infusion over 2 hours); n=8 animals per group. Blood loss, survival, and coagulation parameters were evaluated. RESULTS: Both 50 IU/kg 4F-PCC and andexanet alfa treatment achieved 100% survival. Blood loss was significantly reduced compared with the control group (3843 ± 406 mL), with the largest effects observed for andexanet alfa (1123 ± 197 mL) followed by 50 IU/kg 4F-PCC (1855 ± 372 mL) then 25 IU/kg 4F-PCC. Consistent with the mechanism of action, andexanet alfa led to significantly lower apixaban anti-factor Xa activity (15.6 ± 6.2 ng/mL) compared with control or 4F-PCC treatment until 180 minutes post trauma. However, 4F-PCC treatment was able to dose-dependently overcome the trauma induced reduction in coagulation factors II, VII, IX, and X in contrast to andexanet alfa. While andexanet alfa shortened lag time and increased peak thrombin generation, 4F-PCC dose-dependently improved peak height and endogenous thrombin potential. No thromboembolic complications were observed. CONCLUSIONS: In a male polytrauma porcine model of apixaban anticoagulation, both high-dose 4F-PCC and andexanet alfa were fully effective in achieving survival and hemostatic control. Andexanet alfa achieved hemostasis more rapidly, while 4F-PCC showed sustained restoration of factors II, VII, IX, and X levels, as well as thrombin generation.