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Comparison of 3-Factor Versus 4-Factor Prothrombin Complex Concentrate With Regard to Warfarin Reversal, Blood Product Use, and Costs

DeAngelo, Jessica PharmD, MBA1; Jarrell, Daniel PharmD1; Cosgrove, Richard PharmD1; Camamo, James PharmD1; Edwards, Christopher PharmD1; Patanwala, Asad E. PharmD, MPH2,*

American Journal of Therapeutics: May/June 2018 - Volume 25 - Issue 3 - p e326–e332
doi: 10.1097/MJT.0000000000000643
Original Article

Background: Prothrombin complex concentrates (PCCs) are drug products containing varying amounts of vitamin K-dependent coagulation factors II, VII, IX, and X. The evidence comparing 3-factor PCC (3-PCC) versus 4-factor PCC (4-PCC) for warfarin reversal is conflicting. It has been hypothesized that 3-PCC may be less effective than 4-PCC because of relatively lower factor VII content.

Study Question: The primary objective of this study was to compare international normalized ratio (INR) reversal between 3-PCC and 4-factor PCC (4-PCC) in warfarin-treated patients. The secondary objectives include comparing blood product use, total reversal costs, and cost-effectiveness between the groups.

Study Design: This was a retrospective cohort study conducted in 2 affiliated, academic institutions in the United States. Consecutive adult patients who received 3-PCC or 4-PCC for warfarin reversal were included.

Measures and Outcomes: The primary outcome was adequate INR reversal defined as a final INR ≤1.5. Secondary outcomes were the utilization of plasma, red blood cells and platelets, reversal costs, and the cost-effectiveness ratio.

Results: There were 89 patients who were included in the overall cohort (3-PCC = 57, 4-PCC = 32). Adequate INR reversal occurred less commonly with 3-PCC (45.6%) compared with 4-PCC (87.5%) (P < 0.001). There was no significant difference in the proportion of patients who received plasma (32% vs. 28%, P = 0.813), red blood cells (37% vs. 47%, P = 0.377), or platelets (16% vs. 28%, P = 0.180) between the 3-PCC and 4-PCC groups, respectively. The median reversal cost of 3-PCC ($3663) was lower than 4-PCC ($5105) (P = 0.001). The cost-effective ratio favored 4-PCC ($5105/87.5% = $5834) compared with 3-PCC ($3663/45.6% = $8033).

Conclusions: Four-PCC was more effective than 3-PCC with regard to INR reversal in patients taking warfarin, but blood product use was similar. Although 4-PCC is associated with increased reversal costs, it may be cost-effective in terms of INR reversal.

1Department of Pharmacy Services, Banner—University Medical Center Tucson, Tucson, AZ;

2Department of Pharmacy Practice & Science, College of Pharmacy, The University of Arizona, Tucson, AZ.

Address for correspondence: Asad E. Patanwala, PharmD, MPH, 1295 North Martin, PO Box 210202, Tucson, AZ 85721. E-mail:

This study was partially funded by a Publication and Research grant from CSL Behring who is the manufacturer of Kcentra.

The authors have no conflicts of interest to declare.

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.