Prothrombin Complex Concentrates Compared with Frozen Plasma for Urgent Reversal of Vitamin K Antagonists: A Single Centre Retrospective Review
Authors: Lee Lauren J. , Chi Jay , Chipperfield Kate M. , Yenson Paul R. 
Published: October 2019

Abstract

Background: Vitamin K antagonists (VKAs) are associated with a risk of major bleeding requiring urgent reversal with frozen plasma (FP) or prothrombin complex concentrates (PCC) and concurrent vitamin K administration. Several treatment guidelines currently recommend PCC over FP for urgent reversal in VKA-associated bleeding. Four-factor PCC (Octaplex®, Beriplex®) has been available in Canada since 2008 with a change in national dosing recommendations in 2012. We conducted a retrospective study to determine the efficacy and safety of PCC in comparison with FP in patients presenting with bleeding and requiring VKA reversal.
Methods: We retrospectively reviewed all consecutive bleeding episodes requiring VKA reversal at Vancouver General Hospital (VGH) for 2 cohorts of patients: i) those who received FP (July 28, 2008 to July 27, 2010); and ii) those who received PCC, during two time periods (July 28, 2008 to July 27, 2010; and September 1, 2011 to December 31, 2012) during which Canadian national dosing recommendations had changed. The PCC data however were pooled as no significant differences between the early and later PCC cohorts were found. Details of VKA reversal were reviewed, including patient demographics, bleeding type, indication for VKA therapy, dose of PCC or FP, admission hematologic parameters, INR value subsequent to completion of PCC or FP infusion, time to complete infusion, transfusion requirements, vitamin K dose and route of administration, transfusion reactions, thrombotic events (within 30 days) and mortality during hospitalization. The primary outcome was the proportion of patients achieving a target INR defined as ≤1.5 following the initial order of PCC or FP. Subject characteristics were compared using two-sided t-tests for continuous and Chi-square analysis for categorical variables. Predictors of mortality were analyzed with binary logistic regression.
Results: A total of 201 bleeding episodes occurred in 191 patients. PCC was used in 89 episodes (44%). The most common indication for VKA was atrial fibrillation (81%). Mean PCC dose was 1489 U (range 500-3000 U). Mean FP dose was 3.1 U (range 1-10 U). Target INR was achieved in 86% of episodes in the PCC group versus 60% with FP (p<0.001). Mean time to complete the reversal agent was 4.4 hours with PCC versus 8.7 hours with FP (p<0.001). There was no significant difference in thromboembolic events between FP and PCC with 4 thromboembolic events occurring in each treatment group: 2 strokes, 1 myocardial infarction, and 1 recurrent deep vein thrombosis occurred in the PCC cohort. No transfusion-related reactions occurred in the PCC group compared with 12.6% with FP (p<0.001). Mortality was significantly higher in the PCC group (25% vs. 11%, p=0.010); however, intracranial bleeding (ICH) was more common in the PCC group (62% vs. 31%, p<0.001) and was the only independent predictor of mortality. Vitamin K was not administered in 20% of episodes, including 17% of episodes of ICH.
Conclusion: PCC is effective in the urgent reversal of VKA with faster and more complete INR reversal, significantly fewer transfusion reactions and no increase in thromboembolic events in comparison to FP. Along with vitamin K, PCC should be the agent of choice for VKA reversal in bleeding patients.

Disclosures
Chipperfield: Boehringer Ingelheim: Honoraria. Yenson:Octapharma Canada: Unrestricted Education Grant Other; Alexion Pharmaceuticals: Honoraria.