Assessment of temporary warfarin reversal in patients with left ventricular assist devices: the KVAD study

Background Patients with left ventricular assist devices (LVAD) require interruption of warfarin for invasive procedures yet parenteral bridging is associated with many complications. Four-factor prothrombin complex concentrate (4F-PCC) can temporarily restore hemostasis in patients anticoagulated with warfarin. Objectives This pilot study evaluated the strategy of using variable dose 4F-PCC to immediately and temporarily reverse warfarin before invasive procedures without holding warfarin in patients with LVAD. The duration of effect of 4F-PCC on factor levels and time to re-establish therapeutic anticoagulation post procedure were assessed. Methods Adult patients with LVAD with planned invasive procedures were enrolled from a single center. Warfarin was continued uninterrupted. The 4F-PCC dose administered immediately pre-procedure was based on study protocol. INR and vitamin K dependent factor levels were collected before and over 48 hours after 4F-PCC administration. Use of parenteral bridging, International Society for Thrombosis and Haemostasis major and clinically relevant non-major bleeding (CRNMB), and thromboembolic events at 7 and 30 days were collected. Results In 21 episodes of 4F-PCC reversal, median baseline INR was 2.7 (IQR 2.2-3.2). Median dose of 4F-PCC administered was 1,794 units (IQR 1536-2130). At 24 and 48 hours post 4F-PCC administration, median INRs were 1.8 (IQR 1.7-2.0) and 2.0 (IQR 1.9-2.4). Two patients required post-operative bridging. One patient experienced major bleeding within 72 hours and two experienced CRNMB within 30 days. There were no thromboembolic events. Baseline and post 4F-PCC vitamin K dependent factor levels corresponded with changes in INR values. Median time to achieve therapeutic INR post-procedure was 2.5 days (IQR1-4). Conclusion Administration of 4F-PCC for temporary reversal of warfarin for invasive procedures in patients with LVADs allowed for continued warfarin dosing with minimal use of post-intervention bridging, limited bleeding, and no thromboembolic events.