Presentation Details
| Fixed-dosing of 4-factor prothrombin complex concentrate for reversal of anticoagulation: evaluating the effectiveness, safety, and cost savings Amer Al Homssi1, Ryan Lokkesmoe1, Ryan Powers1, Benjamin Jung2, Lisa Baumann Kreuziger3. 1Medical College of Wisconsin, Milwaukee, WI, USA.2Froedtert Health, Milwaukee, WI, USA.3Versiti Blood Research Institute, Milwaukee, WI, USA |
Abstract
Background: Reversal of anticoagulation is required in bleeding or emergent surgical procedures. Four-factor prothrombin complex concentrate (4F-PCC) is a common medication used to reverse warfarin or off-label management of bleeding in patients taking direct oral anticoagulants (DOACs). The ability to quickly mix and administer 4F-PCC is advantageous over other reversal agents, however, dosing strategies that optimize anticoagulant reversal and cost, such as fixed dosing of 4F-PCC, are still under evaluation. Objective: The primary objective of this study is to evaluate the effectiveness, safety, and cost savings of fixed dosing of 4F-PCC at 1500 units for warfarin reversal and 2000 units for DOAC reversal in urgent and emergent situations. Methods: Three hospitals of Froedtert and the Medical College of Wisconsin transitioned to fixed 4F-PCC (Kcentra) dosing in October 2018. We retrospectively reviewed patients from 10/1/2018-4/30/2021 who received fixed dosing. Cost-savings were defined as the difference in the cost between the administration of fixed dosing and the projected weight-based dosing based on the package insert for warfarin reversal or 50 units/kg in patients treated with DOACs. Results: 592 patients received Kcentra during the prespecified period, of whom 541 received Kcentra for warfarin reversal (n=414) or DOAC (n=127) management in emergency settings. The mean age was 71, 57% were males, and the mean weight was 86 kg. More than half of the patients were treated with anticoagulation for atrial fibrillation and 24% had venous thromboembolism. Reversal in patients on warfarin was needed in 32% of cases pre-procedure and 65% of cases for bleeding of which 42% was for intracranial hemorrhage (ICH) and 30% for gastrointestinal bleeding. Whereas for patients treated with DOAC, 87% of cases were reversed for bleeding of which 63% were for ICH. More than half of the patients on warfarin had a pre-reversal INR between 2 and 4 and almost a quarter over 6. Post-reversal INR below 2 and 1.5 was achieved in 89% and 56% of patients, respectively. The mean doses for warfarin and DOAC reversals were 1,636 and 2,106 units, respectively. Less than 5% in either group required repeat doses. 82% of patients treated with warfarin also received vitamin K. Within 30 days, both groups had similar bleeding (12%) and thrombotic (5%) events. All-cause 30-day mortality rates in patients treated with warfarin and DOAC, including patients who suffered from ICH, were 24% and 30%, respectively. The median cost savings of fix dosing per patient on warfarin and DOAC were $1,567 (IQR $455 - $2,947) and $3,936 ($2,716 - $5,632), respectively. The annualized median hospital cost savings for warfarin and DOAC were $176,239 and $146,733, respectively. Conclusions: Based on our real-world data over more than two years, fixed-dosing of 4F-PCC (Kcentra) for warfarin and DOAC hemorrhage management had significantly less cost than adjusted dose and is associated with similar rates of thrombosis and death compared to other studies.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.