Summary

Prothrombin complex concentrates (PCC) are recommended for urgent warfarin reversal. However, disagreement exists regarding the proper dosing strategy (i.e. fixed vs. weight-based). We measured the in vitro effect of PCC dosing on international normalised ratio (INR) and factor activity. Plasma from warfarin-anticoagulated patients with stable INRs was collected. PCC doses of 1,000, 2,000 and 3,000 IU were added to the samples, and INR and factor activity were analysed before and after PCC. Twenty-three of thirty subjects enrolled had complete data for analysis. INRs were below 1.5 in all samples post-1,000 IU, and decreased further with subsequent doses (p<0.001). Factors II, VII, and X increased with consecutive doses (p<0.01). Linear correlation was seen between INR and factors II, VII and X. Factor IX did not increase consistently nor show correlation with INR reversal. Weight-based dosing was then estimated; INRs were all <1.2 (0.9–1.2) and activity >0.50 IU for factors II, VII and X (0.96–1.52, 0.51–1.45 and 0.81–1.38, respectively). Factor IX did not uniformly correct above 0.50 IU (0.31–1.31). We confirm in vitro that 1,000 IU of Octaplex® is able to correct INR to <1.5 but factors were not uniformly >0.50 IU until 2,000 IU, and not >1.00 IU until 3,000 IU. This suggests that INR correction alone may not accurately reflect factor activity, and lends support for weight-based dosing.