A factor VII-based method for the prediction of anticoagulant response to warfarin

Warfarin dosing methods based on existing models for warfarin and the international normalised ratio (INR) give biased maintenance dose predictions at the upper and lower quantiles of dose requirements. The aim of this work is to propose a conceptually different approach to predict INR after warfarin dosing. Factor VII concentration was proposed as the principal driving force for the INR. The time to steady-state INR (t_SS,INR) was determined based on the INR response to changes in factor VII concentrations following warfarin initiation, and from this the steady-state INR (INR_SS) was derived. The proposed method requires timed, paired blood samples of INR and factor VII. At different simulated warfarin dose rates, the prediction error associated with the proposed method was shown to be within clinically acceptable limits for both the t_SS,INR (±2 days) and INR_SS (±0.2). The use of the method was demonstrated in two patients who were initiated with 5 mg of warfarin daily. The difference in predicted versus actual steady-state INR were 0.0 and -0.4. The proposed method represents a unique approach to predict the INR. It considers factor VII as the main driver for INR and provides valuable information about the time to steady state INR.