Three- versus four-factor prothrombin complex concentrate for the reversal of warfarin-induced bleeding

Abstract

Objective:The objective of this study was to evaluate the effectiveness of 3-factor prothrombin complex concentrate (3F-PCC) compared to 4-factor PCC (4F-PCC) in warfarin-associated bleeding.Methods:This multicenter, retrospective, cohort study analyzed data from patients admitted between May 2011 and October 2014 who received PCC for warfarin-associated bleeding. The primary outcome was the rate of international normalized ratio (INR) normalization, defined as an INR ≤1.3, after administration of 3F-PCC compared to 4F-PCC. Other variables of interest included the incidence of additional reversal agents, new thromboembolic events, and mortality.Results:A total of 134 patients were included in the analysis. The average dose of PCC administered was 24.6 ± 9.3 units/kg versus 36.3 ± 12.8 units/kg in the 3F-PCC and 4F-PCC groups, respectively, P < 0.001. Baseline INR in the 3F-PCC and 4F-PCC groups was 3.61 ± 2.3 and 6.87 ± 2.3, respectively P < 0.001. 4F-PCC had a higher rate of INR normalization at first INR check post-PCC administration compared to 3F-PCC (84.2% vs. 51.9%, P = 0.0001). Thromboembolic events, intensive care unit and hospital length of stay, and mortality were similar among both groups.Conclusion:The use of 4F-PCC leads to a more significant reduction in INR compared to 3F-PCC though no difference in mortality or length of stay was observed. Thromboembolism rates were similar among both groups.

Propensity Score Adjusted Comparison of Three-Factor versus Four-Factor Prothrombin Complex Concentrate for Emergent Warfarin Reversal: A Retrospective Cohort Study

“…The proportion of patients who reached the goal INR was higher with PCC4 (87% vs. 31.6%, p < 0.001). Comparisons of PCC3 and PCC4 products for EWR have been done by others (17)(18)(19)(20)(21)(22)(23). Our study is similar to these other studies regarding retrospective design, PCC products compared, and the adult population.…”

“…Given the compositional differences in the PCC products, it is important to know if there are differences in clinical response for effective and safe use of these products. Studies evaluating the comparative effects of PCC3 and PCC4 head-to-head for EWR with the outcome of INR lowering response and/or clinical outcomes are few (17)(18)(19)(20)(21)(22)(23). The inclusion criteria for these studies vary, but all were in adult patients needing reversal of warfarin for bleeding, surgical intervention, and/or trauma associated bleeding.…”

Propensity score adjusted comparison of three-factor versus four-factor prothrombin complex concentrate for emergent warfarin reversal: a retrospective cohort study

“…However, given the critical need to reverse the effects of warfarin in the setting of an emergent bleeding episode, a randomized trial would be difficult to implement. Several previous studies compare the effectiveness of PCC3 and PCC4 for EWR with the outcome of INR lowering response and/or clinical outcomes [23][24][25][26][27][28][29]. The inclusion criteria for these studies vary, but all were in adult patients needing reversal of warfarin for bleeding, surgical intervention, and/or trauma associated bleeding.…”

“…Holt, et al studied multiple centers with warfarin reversal defined as an INR ≤ 1.3. Regardless, a greater proportion of PCC4 patients achieved goal INR compared to PCC3 patients (PCC4: 48/57 (84.2%) vs. PCC3:40/77 (51.9%), p < 0.001) (patient counts calculated from percentages and total patient number) [ 27 ]. DeAngelo, et al reported analysis from two centers with institutions with the same formulary and protocols.…”

A review of guidelines on anticoagulation reversal across different clinical scenarios – Is there a general consensus?

“…There is recent evidence that 4F-PCCs effectively reduce INR in patients with VKA-associated bleeding, with TEE rates ranging from 1.8 to 6.5% [48,49] data from a meta-analysis of PCC use in VKAassociated ICH support these findings [50]. 4F-PCC was shown to reduce INR more effectively compared with 3F-PCC alone [48], but not compared with 3F-PCC + rFVIIa [49]; however, 4F-PCC has also been associated with a significantly lower rate of TEEs compared with 3F-PCC + rFVIIa [49]. In contrast, one recent retrospective study of emergency department data reported an increased rate of TEEs in patients on warfarin who received 4F-PCC compared with FFP [51].…”