Title:
Dosing of 3-factor prothrombin complex concentrate for international normalized ratio reversal.

Abstract:
Three-factor prothrombin complex concentrate (PCC) is commonly used for reversal of international normalized ratio (INR) in patients who are bleeding or require emergency surgery. However, there is little information regarding the optimal dosing strategy for achieving adequate INR reversal.
To determine whether patients with higher initial INR levels are less likely to achieve adequate INR reversal after receiving 3-factor PCC.
A retrospective cohort study was conducted in a tertiary care medical center in the US. Patients who received 3-factor PCC were grouped into 2 categories based on degree of INR reversal after PCC infusion: (1) adequate reversal (final INR ≤1.5) or (2) inadequate reversal (final INR >1.5). Initial INR was compared between the 2 groups using the Wilcoxon rank-sum test. A multivariate logistic regression analysis was used to adjust for confounders and determine predictors of adequate INR reversal.
Fifty patients met criteria for inclusion in the final analyses. Of these, 58% achieved adequate reversal after PCC. There were no significant differences in patient demographics or in vitamin K or fresh frozen plasma (FFP) use between the 2 groups. Median PCC dose was also similar between the adequate and inadequate reversal groups (25.2 vs 24.5 units/kg, respectively; p = 0.2). The group that did not achieve adequate reversal had a significantly higher initial INR (3.5 vs 2.5, p = 0.012) prior to PCC administration. In the multivariate logistic regression analysis, initial INR was a significant predictor of adequate INR reversal (ie, reversal less likely as INR increases) after adjusting for PCC dose and concurrent use of vitamin K or FFP (OR = 0.38; 95% CI 0.17 to 0.87; p = 0.02).
Patients with a higher initial INR are less likely to achieve adequate INR reversal after receiving 3-factor PCC and may require higher doses than were used in the study.