Oral anticoagulation thresholds

Background-Monitoring patients on oral anticoagulation is essential to prev ent hemorrhage and recurrent thrombosis. We studied tissue factor-induced w hole-blood coagulation in patients, on warfarin therapy with similar intern ational normalized ratios (INRs). Methods and Results-Contact pathway-suppressed whole-blood coagulation init iated with tissue factor was studied in 8 male subjects (group W) and in I individual multiple times (subject A). Coagulation profiles for group W sho wed that subjects with similar INRs had widely varying clot times (6.2 to 2 3 minutes) and thrombin-antithrombin III (TAT) profiles with rates of 25 to 40 nmol . L-(1) . min(-1) and maximum levels varying from 192 to 349 nmol/ L. The normal control group exhibited clot times of 5.7 +/-0.3 minutes and TAT rates of 57 +/- 13 nmol . L-1 . min(-1), reaching maximum levels of 742 +/- 91 nmol/L. Subject A, who was stably anticoagulated at an INR of 2.1 /-0.4 for 6 months, had widely ranging profiles with clot times of 9.0 to 2 2.7 minutes, TAT maximums varying from 141 to 345 nmol/L, and TAT formation rates of 10 to 57 nmol . L-1 . min(-1). INR did not correlate with TAT for mation. Platelet activation was decreased by anticoagulants but also displa yed variability. Fibrinopeptide A generation showed threshold variability i ndependent of the INR. Factor VIII levels were increased (P=0.03) in group W (204 +/- 34.4%) compared with normal control subjects (149.4 +/- 37.4%). A significant correlation was identified between increasing factor VIII lev els and years on warfarin therapy (r=0.78, P=0.01), suggesting a possible f actor VIII compensatory mechanism. Conclusions-These results suggest that control of anticoagulation in patien ts to a set INR therapeutic range may be less secure than anticipated. Pati ents with similar INRs show significant individual variability in their tis sue factor coagulation response, suggesting different risks to anticoagulat ion when confronted with underlying vascular anomalies.