Reduced Mortality with Use of Four-Factor Prothrombin Complex Concentrates vs. FFP for Warfarin Reversal: Meta-Analysis

Coagulation factor replacement with either prothrombin complex concentrate (PCC) or fresh frozen plasma (FFP) are treatment options for urgent reversal of warfarin in patients who experience major bleeding or need urgent surgery, but the optimal reversal strategy is unclear based on clinically relevant outcomes. Canadian investigators conducted a systematic review of the clinical literature through December 2015, and identified five randomized clinical trials and eight observational studies for evaluation.

PCC use was associated with a significant reduction in all-cause mortality compared to FFP (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.37 to 0.84; P = 0.006). Removing studies considered to have a high risk of bias did not importantly change this finding (OR, 0.59; CI, 0.39 to 0.89). Studies utilizing four-factor PCC accounted for 98% of the weight of evidence for this significant mortality difference.

PCC use additionally was more likely to achieve normalization of the international normalized ratio (INR) (OR, 10.80; CI, 6.12 to 19.07), resulted in a shorter time to INR correction (mean difference -6.50 hours; CI, -9.75 to -3.24) and was associated with a lower risk of posttransfusion volume overload compared to FFP (OR, 0.27; CI, 0.13 to 0.58). There was no significant difference in the risk of thromboembolism following administration of PCC or FFP (OR, 0.91; CI, 0.44 to 1.89).