Study of Octaplex Dosing Accuracy: An In Vitro Analysis

Supratherapeutic INRs are common with warfarin therapy, and increase serious bleeding risk. Octaplex is a prothrombin complex concentrates (PCC) that is recommended for urgent warfarin reversal. However, disagreement exists regarding proper dosing strategies (fixed versus weight-based).

We sought to measure the in vitro effect of Octaplex on INR and factor levels, and to characterize this relationship.

Plasma samples from eligible patients on warfarin with stable INRs for ≥4 weeks were collected. Plasma volumes were calculated to approximate 1000, 2000 and 3000IU doses of Octaplex and these were added to the samples. INR and factor levels were measured pre- and post-Octaplex.

Twenty-three of the 30 subjects enrolled had complete data for analysis. INRs corrected <1.5 in all samples post-1000IU, and decreased further with subsequent doses (p<0.001). Similar changes occurred in factors II, VII, and X (p<0.01). Linear correlations were seen between INR and factors II, VII and X. Factor IX did not increase incrementally or show a correlation with INRs. Weight-based dosing was then estimated. All INRs were <1.2 (0.9–1.2), and factor levels >0.50IU for II, VII and X (0.96–1.52, 0.51–1.45 and 0.81–1.38, respectively). Factor IX did not uniformly correct >0.50IU (0.31–1.31).

We confirmed in vitro that 1000IU of Octaplex was able to correct INR to <1.5 but factor activity for II, VII and X was not uniformly >0.50IU until 2000IU, and >1.00IU not until 3000IU. Our study suggests that INR correction alone may not appropriately reflect sufficient factor activity, and lends support for weight-based PCC dosing.

No relevant conflicts of interest to declare.