Low-dose compared to manufacturer-recommended dose four-factor prothrombin complex concentrate for acute warfarin reversal

  • Wesley ZemrakEmail author
  • Francis Manuel
  • Kathryn E. Smith
  • Stephen Rolfe
  • Timothy Hayes
  • Robert L. Trowbridge
  • Brian Carlone
  • David Seder



Four-factor PCC is the recommended standard of care for acute warfarin reversal but optimal dosing is unknown. We aim to show that a low-dose strategy is often adequate and may reduce the risk of thromboembolic events when compared to manufacturer-recommended dosing.


A weight-based dosing strategy of 15–25 units/kg was established as the institutional standard of care in May 2015. This retrospective, before-and-after cohort analysis included patients receiving 4F-PCC according to a manufacturer-recommended (n = 122) or a low-dose (n = 83) strategy. The primary efficacy outcome was a combination of INR reversal on first check and hemostatic efficacy at 24 h.


Demographics, indications for warfarin, and presenting INR values were similar between the two groups. Patients in the manufacturer-recommended dose group received significantly more 4F-PCC than the low dose group (2110 units vs. 1530 units). More patients in the manufacturer-recommended dose group achieved the primary endpoint (75.4% vs. 61.4%), with more patients achieving the target INR on recheck in the manufacturer-recommended dose group (95.9% vs. 84.3%) and no difference in hemostatic efficacy between groups (79.5% vs. 74.7%). There was no difference in thromboembolic events at 72 h (4.1% vs. 1.2%) or at 30 days (8.2% vs. 4.8%). Significantly more patients in the manufacturer-recommended dose group died or were transferred to hospice care during hospitalization (21.3% vs. 9.6%).


Utilization of a low-dose 4F-PCC strategy resulted in fewer patients achieving target INR reversal, but no difference in hemostatic efficacy, thromboembolic events, or survival.


Warfarin Reversal Prothrombin complex concentrate Hemorrhage PCC 



No funding was received for this study.

Compliance with ethical standards

Conflict of interest

All authors have no conflict of interest to report in relation to this study.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PharmacyMaine Medical CenterPortlandUSA
  2. 2.Department of PharmacyMayo ClinicRochesterUSA
  3. 3.Department of PathologyMaine Medical CenterPortlandUSA
  4. 4.Department of MedicineMaine Medical CenterPortlandUSA
  5. 5.Department of Critical Care ServicesMaine Medical CenterPortlandUSA

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