Determination of kinetic parameters for prothrombin complex activity during initiation of anticoagulation

A prospective determination of the kinetic parameters of prothrombin complex activity (PCA) during initiation of anticoagulation in seven adult patients (4 males and 3 females, age 62.9 +/- 5.8 years, mean SD) receiving anticoagulant therapy with warfarin.

All excluding one patient received a fixed daily dose of 5mg warfarin over an initial 3 days. Three successive daily doses of warfarin were recorded, together with the corresponding PCA. The kinetic parameters for elimination of PCA during the initiation of anticoagulation were estimated from the log PCA-time plot with a 1-compartment model.

The mean elimination rate constant (kp) of PCA was 0.377 day(-1) (range 0.242-0-588 day (-1)) during initiation of anticoagulation. The coefficient of variation in kp was about 28%, indicating the considerable inter-individual differences in PCA response to warfarin. The mean plasma half-life of PCA was 1.96 days. There were no significant relationships (by simple regression analysis) between kp and cumulative warfarin doses per kg of body weight or age during initiation of anticoagulation.

The results suggest that for a 50% reduction of PCA, one would need about 2 days after initiation of anticoagulation.