DETERMINATION OF KINETIC-PARAMETERS FOR PROTHROMBIN COMPLEX ACTIVITY DURING INITIATION OF ANTICOAGULATION

Objective: A prospective determination of the kinetic parameters of pr othrombin 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. Method: Al l excluding one patient received a fixed daily dose of 5 mg warfarin o ver an initial 3 days. Three successive daily doses of warfarin were r ecorded, together with the corresponding PCA. The kinetic parameters f or elimination of PCA during the initiation of anticoagulation were es timated from the log PCA-time plot with a l-compartment model. Results : The mean elimination rate constant (k(p)) of PCA was 0.377 day(-1) ( range 0 242-0.588 day(-1)) during initiation of anticoagulation. The c oefficient of variation in k(p) was about 28%, indicating the consider able inter-individual differences in PCA response to warfarin. The mea n plasma half-life of PCA was 1.96 days. There were no significant rel ationships (by simple regression analysis) between k(p) and cumulative warfarin doses per kg of body weight or age during initiation of anti coagulation. Conclusion: The results suggest that for a 50% reduction of PCA, one would need about 2 days after initiation of anticoagulatio n.