3-Factor Versus 4-Factor Prothrombin Complex Concentrate for Warfarin Reversal in Severe Bleeding: A Multicenter, Retrospective, Propensity-Matched Pilot Study

Abstract

Current guidelines recommend 4-factor prothrombin complex concentrate (4PCC) for emergent reversal of bleeding secondary to warfarin. While current research has demonstrated superiority of 4PCC over plasma, direct comparisons with 3-factor PCC (3PCC) are lacking. The purpose of this study is to compare the efficacy and safety of 3PCC and 4PCC. We conducted a retrospective analysis of patients who received PCC at one of four medical centers. All patients in the 3PCC group were treated at one center that utilizes a fixed, weight-based dosing protocol. After evaluation of all patients meeting inclusion criteria, propensity-score matching was used to adjust for differences in treatment characteristics. There was no difference in the primary outcome of INR ≤ 1.4 between 3PCC and 4PCC in both the unmatched (85.7 vs. 90.6 %; p = 0.37) and matched (84.2 vs. 92.1 %; p = 0.48) analyses. There was a significant difference in goal INR achieved favoring 4PCC (56.3 vs 90.0 %; p < 0.02) when baseline INR > 4.0. A total of three thrombotic events were documented, all in the 4PCC group. We found no difference in the rate of INR reversal in those treated with 3PCC and 4PCC. However, those with a baseline INR > 4.0 may experience more successful INR reversal with 4PCC.

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.…”

Reversal of Oral Anticoagulants for Intracerebral Hemorrhage Patients: Best Strategies

“…Three studies did find advantages of 4F-PCC over 3F-PCC. [49][50][51] The most recently published study by Fischer et al reviewed 103 patients with intracranial bleeds on warfarin who received either PCC agent, with 52 of these patients presenting specifically with an ICH. 52 There were no statistical differences observed in any outcomes between either products.…”

A surgeon's guide to anticoagulant and antiplatelet medications part one: warfarin and new direct oral anticoagulant medications

“…The observational experience with these agents, either alone or in retrospective comparison, is mixed, with some studies suggesting greater efficacy associated with four-factor PCC and others suggesting no difference in efficacy between the two formulations. 21–24 However, there is a recurring observation among many of these studies that three-factor PCC, which does not provide factor VII replenishment, is less effective at normalizing INR >4. This may be explained by the fact that only 10–20% level of factor VII activity is required for coagulation, and an INR>4 reflects factor VII activity under 5–10%.…”