Tolerability and effectiveness of 4-factor prothrombin complex concentrate (4F-PCC) for warfarin and non-warfarin reversals

Current guidelines favor 4F-PCC over plasma for warfarin reversal. Uncertainty remains on its thrombotic risk and hemostatic effectiveness when used for direct-acting oral anticoagulants (DOACs), transplants, massive transfusion protocols (MTP), and non-anticoagulated patients. This study sought to evaluate the tolerability and effectiveness of 4F-PCC in a real-world setting. This was a retrospective study of adults who received 4F-PCC from March 2014 to December 2015. The primary outcome was thromboembolic events within 14 days. The secondary outcome was hemostatic effectiveness within 24 h. The final analysis included 212 patients. Primary reversal indication was major bleed in 165 patients (77.8%) and emergent surgery in 47 patients (22.2%). Thromboembolism occurred in 22 patients (10.4%), more in emergent surgery than major bleed reversals (17% and 8.5%, respectively). MTP and heart transplant patients had the highest thromboembolic event rates (44.4% and 28.6%, respectively). Hemostatic effectiveness was 65.8% (68% in major bleed and 58.1% in emergent surgery). DOAC patients achieved hemostasis most often (78.9%). Administration of any reversal agent, major surgery within 14 days, and MTP activation were significant predictors of thromboembolism. Use of 4F-PCC in this real-world setting was associated with variable thromboembolic and hemostatic effectiveness rates based on the indication for reversal. •4F-PCC is standard care for warfarin reversal in major bleed and emergent surgery.•4F-PCC is also used in non-warfarin reversals despite limited evidence.•Significant thrombotic predictors were use of any reversal agent and major surgery.•Lower hemostatic effectiveness and higher thromboses than in prospective trials.•These data offer added risk/benefit evidence for 4F-PCC in non-warfarin reversals.