Transient or extended reversal of apixaban anticoagulation by andexanet alfa is equally effective in a porcine polytrauma model.

Abstract

Andexanet alfa (andexanet) reverses the anticoagulant effects of factor Xa inhibitors, but it has not been assessed in clinical studies for apixaban reversal in trauma. This study evaluated andexanet for reversing apixaban anticoagulation in a porcine polytrauma model. Oral apixaban (20 mg q.d., n=21) or placebo (n=7; sham group) was administered to male pigs for 4 days before blunt liver injury and bi-lateral femur fracture. After trauma, animals were randomised 1:1:1 to a single andexanet bolus (1000 mg), a bolus (1000 mg) plus infusion (1200 mg over 2 h), or vehicle (control). Haemodynamic and coagulation variables were monitored for 5 h or until death. The primary endpoint was blood loss. Mean blood loss in sham animals was 472 (standard deviation, 58) ml 12 min after injury and 658 (98) ml at 300 min, with 100% survival. Anticoagulation with apixaban significantly increased blood loss 12 min after injury [888 (133) ml, P<0.01]. Controls exhibited total blood loss of 3403 (766) ml, with 100% mortality. Andexanet bolus or bolus plus infusion significantly reduced blood loss to 1264 (205) and 1202 (95) ml, respectively), and increased survival to 100%. Haemodynamic parameters and markers of shock recovered to pre-trauma levels in andexanet-treated animals. Andexanet effectively reversed apixaban anticoagulation and reduced blood loss induced by severe trauma. Andexanet bolus alone had a similar impact on survival and blood loss as bolus plus infusion. Therefore, a 2 h andexanet infusion after the bolus may not be necessary to restore normal haemostatic mechanisms.