Discussion of “Protocolized warfarin reversal with 4-factor prothrombin complex concentrate versus 3-factor prothrombin complex concentrate with recombinant factor VIIa”

Introduction: Life-threatening bleeding is the most feared complication of warfarin therapy. Rapid anticoagulant reversal via replacement of vitamin K dependent clotting factors is essential for hemostasis. Methods: A retrospective cohort study of warfarin-treated patients experiencing a life-threatening bleed treated with a warfarin reversal protocol comprised of 4F PCC (post-implementation group) and those who received the prior reversal protocol of 3F PCC and rFVIIa (pre-implementation group) was performed. Demographic and clinical information, anticoagulant reversal information, and all adverse events attributed to warfarin reversal were recorded. Results: 195 patients were included in final analysis; 118 in the pre-implementation group, 77 in the post-implementation group. While baseline SOFA and GCS scores were similar between groups, the pre-implementation group had a longer ICU LOS and higher in-hospital mortality (p <.01,.01 respectively). The most common indication for anticoagulation reversal was intracranial hemorrhage in both groups. Pre-reversal INR was similar between both groups, but post-reversal INR was significantly lower in the pre-implementation group, 0.8 versus 1.3 (p <.01). Significantly more patients experienced thromboembolic complications (TEC) in the pre-implementation group than the post-implementation group, 27.9% versus 6.5% of patients (p <.01). The leading TEC in both groups was deep venous thrombosis. Differences in baseline characteristics (p ≤.2) were entered into a Poisson log-linear regression model for association with TECs. Receipt of rFVIIa was the only characteristic significantly associated with TECs. Discussion: A 4F PCC warfarin reversal strategy is efficacious at reversing INR while providing significantly lower thromboembolic risk as compared to 3F PCC with rVIIa.