Hypersensitivity reactions with faster administration of four-factor prothrombin complex concentrate for oral anticoagulant reversal

Background Four-factor Prothrombin Complex Concentrate (4F-PCC) is used for reversal of bleeding caused by warfarin and direct factor Xa inhibitors. The 4F-PCC products available in the United States recommend all doses be administered at 0.12 mL/kg/min, up to a maximum rate of 8.4 mL/min. Our hospital prepares all doses of 4F-PCC at the bedside in multiple syringes administered as an intravenous push at 20 mL/min. Objective This study aims to review the incidence of hypersensitivity reactions when 4F-PCC is administered at a rate of 20 mL/min as an intravenous push. Methods This was a single-center, retrospective, chart review of patients receiving 4F-PCC for reversal of an emergent bleed while on oral anticoagulation. The primary outcome was development of an infusion reaction defined by either receipt of rescue medications, requirement of escalating respiratory support, or written documentation of infusion reaction with a secondary outcome of thromboembolic complications. Results 404 patients received 4F-PCC for reversal of an emergent bleed between January 1, 2013 and January 1, 2023. Six patients (1.5%) received a prespecified rescue medication within one hour of receiving 4F-PCC. Thirty-seven patients (9.2%) had escalation in their respiratory support, with one patient having a documented reaction of erythema that was concerning for a possible infusion reaction. Thirty-nine patients (9.6%) developed a thromboembolic complication post infusion. Conclusion We found no evidence of substantially increased rates of hypersensitivity reactions or thromboembolic events when utilizing an increased infusion rate for 4F-PCC of 20 mL/min as an IV push.