Urgent Reversal of Warfarin Anticoagulation with Prothrombin Complex Concentrate.
Authors: Lankiewicz Michael W. , Hays John , Friedman Kenneth D. , Blatt Philip M. 
Published: April 2020

Abstract
Warfarin remains the primary agent used in long-term antithrombotic treatment and prophylaxis. The major adverse effect associated with its use is bleeding. When intracerbral or other life threatening hemorrhage occurs in patients on warfarin, or urgent surgical intervention is indicated, timely reversal may favorably impact outcomes. Warfarin effect is commonly reversed with fresh frozen plasma (FFP) and vitamin K. The efficacy of FFP in this setting has been questioned, and fluid overload is a common complication. In addition, thawing and administering significant volumes of FFP may delay correction. We instituted a policy for rapid delivery and administration of Prothrombin Complex Concentrate (PCC) in the setting of the need for urgent reversal of warfarin. Patients were triaged by emergency services to determine the need for urgent warfarin reversal. Hematology telephone consultation was obtained, and patients received 25–50 units/Kg of PCC, (Proplex-T, Baxter). PT/INR was recorded before and immediately (within 30 minutes) after dosing, and 24 hours post dosing. Urgent surgical interventions were performed immediately after PCC. We report data from retrospective chart review of 2 years experience with this protocol. 58 patients were treated, with a mean age of 71y (range 26–92). Indications for Warfarin: atrial fibrillation (38), DVT (5), pacer or defibrillator (3), prosthetic aortic valve (4), cardiomyopathy (1), A-V fistula clot (1), undetermined from chart review (6). Concomitant bleeding risks were identified in 15 patients, including renal failure (4), thrombocytopenia (4), anti-platelet therapy (3) and liver disease (4). 29 Patients received FFP in the course of their care as directed by their primary care service. 12 patients presented with extreme (&gt;10) elevations of their INR. INR results are reported below:
INR pre-PCC (Mean) INR post-pcc (Mean) INR 24 hr post-PCC (Mean) All Patients (N=58) 11.7 1.4 1.5 Pre INR &lt; 10 (N=46) 5.4 1.3 1.5 Pre INR ≥ 10 (n=12) 35.3 1.8 1.7 No FFP Used (N=29) 12.2 1.2 1.2
16 Patients underwent invasive or surgical procedures immediately after PCC. Hemostasis was judged to be normal in all cases. Patients were monitored throughout their hospital stay for thrombotic complications. 2 patients had non-Q myocardial infarction after their therapy. Both had catastrophic presentations and histories of cardiac revascularization. One patient had a line-associated thrombosis 17 days after PCC and one had possible extension of chronic calf thrombophlebitis by doppler evaluation 3 days after PCC. These events were felt to be more likely attributable to underlying disease than PCC. No patients experienced fluid overload related to PCC use. Patients with intracerebral hemorrhage (N=22) had a mortality rate of 45%, which compares favorably with the recently published figure of 52%. Responses to PCC were similar in patients not receiving plasma as part of their care (N=29). 30 patients had a higher INR at 24 hours when compared to the INR post infusion, however the change was small (Mean INR Δ=0.3). Recent protocol refinements include routine use of IV Vitamin K, No FFP use and Q6 hour PT/INR monitoring for possible additional PCC dosing in the first 24 hours. Immediate reversal and the absence of volume complications make the use of PCC superior to FFP for the reversal of warfarin effect in the urgent setting, and wider use of this intervention is appropriate.