EVALUATION OF ORAL ANTICOAGULANT-THERAPY BY MEASURING PLASMA PROTHROMBIN FRAGMENT 1+2

To assess the degree of haemostatic system activation, plasma levels of prothrombin fragment 1 + 2 (F1+2), a direct indicator for thrombin generation in vivo, were measured in 49 patients with thrombotic disease undergoing long-term warfarin therapy (Thrombotest(R) values less-than-or-equal-to 40%). In these patients, vitamin K dependent coagulation factors (factors II, VII, IX and X) were decreased together with the anticoagulant proteins C and S, but the mean plasma concentration of F1+2 was significantly decreased compared with 48 healthy subjects. In warfarin-treated patients, F1+2 was positively correlated with the Thrombotest value, factors II, VII, IX and X. When analysed according to the intensity of anticoagulation, patients with Thrombotest values less than 30% showed a significant decrease in F1+2, but the mean F1+2 level was normal in patients with Thrombotests higher than 30%. These findings indicate that long-term oral anticoagulant therapy suppresses thrombin generation approximately in parallel to the decrease in coagulation factors, and levels of F1+2 lower than healthy subjects are observed when Thrombotest values are less than 30%.