Abstract 14657: Andexanet-alfa and PER977 (Arapazine) Correct Blood Loss in a Rabbit Liver Laceration Model - Only Andexanet Reverses Markers of fXa-mediated Anticoagulation

As use of oral fXa inhibitors has increased, so has the need for an antidote to treat the major side effect of these drugs - bleeding. Andexanet alfa (AnXa) (PRT064445), a recombinant fXa derivative, reverses fXa inhibitor-mediated anticoagulation in animals and humans by sequestering the fXa inhibitor in a 1:1 molar ratio, reducing both anti-fXa activity and plasma free fraction of fXa inhibitor, and restoring normal thrombin generation, PT, and aPTT. These parameters correlate closely with reduced blood loss in a rivaroxaban-treated rabbit liver laceration model. Aripazine (PER) (PER977; Perosphere, Inc.) is a small molecule that has been reported to reverse the anticoagulant effects of a broad range of anticoagulants (fXa and thrombin inhibitors; heparins) by direct binding. We synthesized PER and compared it to AnXa in this same liver laceration model at PER doses of 0.3, 3 and 30 mg/kg, and observed reductions in blood loss of 27%, 16% and 76%, respectively (p<0.02 for 30 mg/kg dose only). There was ...