LAUSR

Learning Objectives: Bleeding caused by oral anticoagulants is a concerning drug safety problem. Given the sparse data available to support an optimal management strategy, this study aims to perform a comprehensive analysis of the safety and efficacy of four-factor prothrombin complex concentrate (4F-PCC) for the management of serious bleeding related to oral factor-Xa inhibitors. Methods: This observational, retrospective study included patients 18 years and older who were admitted between July 1, 2014 and May 30, 2018 and subsequently received 4F-PCC (Kcentra®) for moderate to severe bleeding associated with an oral factor-Xa inhibitor. Exclusion criteria included pregnancy, perioperative reversal unrelated to bleeding, initial GCS less than 7, or acute coronary syndrome or ischemic stroke within 30 days prior to reversal. Efficacy was assessed using criteria described by Sarode et al. Safety outcomes included thromboembolism and death. Results: Thirty-one patients received 4F-PCC for major bleeding associated with apixaban (55%) or rivaroxaban (45%) and met inclusion criteria. Mean age was 74 years and atrial fibrillation was the indication for anticoagulation in 90% of patients. Intracranial hemorrhage (58%) and pericardial effusion (16%) accounted for the majority of bleeding events. Approximately one-third (n=10) required invasive interventions to manage bleeding. Most patients received a single weight-based 4F-PCC dose of 25 units/kg (39%) or 50 units/kg (55%). Both patients requiring repeat doses of 4FPCC were managed for cardiac tamponade during atrial fibrillation ablation. Effective hemostasis was achieved in 81% of patients. Patients with ineffective hemostasis had intracranial hemorrhages (n=2), pericardial tamponade (n=2) and intrathoracic bleeding (n=1). Five patients (16%) died because of the acute bleeding and no thromboembolic events were observed for the duration of hospital stay. Conclusions: Administration of 4F-PCC was effective for most patients requiring emergent reversal of anticoagulation with apixaban or rivaroxaban and was associated with a low risk of thromboembolic events.