Standardizing the prothrombin time. Calibrating coagulation instruments as well as thromboplastin

Recently, indications for anticoagulation with warfarin have increased, prothrombin time (PT) monitoring at offices and homes has become available, and the international sensitivity index (ISI) has been recognized as a means of adjusting for differences in thromboplastins to standardize warfarin sodium dosing. However, different coagulation instruments may yield differences in PTs even after correcting for the ISI by means of the international normalized ratio (INR) (INR = [PT measured ISI/PT normal]). Because the PTs and INRs from our Anticoagulation Clinic (portable PT monitor, ISI = 2.04, normal PT = 12.0 seconds) differed from the hospital reference laboratory (ISI = 2.01, normal PT = 12.0 seconds) despite nearly identical ISIs and equivalent control or normal PTs, we systematically compared the two systems. During a 3-month period, we studied two groups of 50 consecutive patients who had been receiving a stable dose of warfarin. After a single venipuncture, PTs and INRs were measured independently, and regression lines were calculated. Within each group, the results from the different instruments were not identical, but they were highly correlated. In comparing INRs, the regression lines for the separate and combined groups were as follows: group 1 monitor INR = 0.49 reference INR + 0.81, r = .94; group 2 monitor INR = 0.57 reference INR + 0.86, r = .88; and combined monitor INR = 0.49 reference INR + 0.95, r = .89. Only 82% of the differences for all samples were within 1.0 INR units. We concluded that the instrumentation effect may be clinically meaningful, and coagulation instruments as well as thromboplastins should be calibrated to standardize warfarin therapy.