International normalized ratio for prothrombin times in patients taking oral anticoagulants: Critical difference and probability of significant change in consecutive measurements

Abstract

To determine when a change in serial measurements of prothrombin time in patients receiving oral anticoagulant therapy (ACT) is a statistically significant biological change necessitating dose adjustment, one must know the size of the 'critical difference' in statistical terms (i.e., probabilities). In a cohort of 32 ACT patients at pharmacological steady- state, we studied the within-subject total variation of prothrombin time, expressed as International Normalized Ratio (INR), over 6 months. The total within-subject variation (CV) of INR was 10.1%. The corresponding critical differences required for significance of change in serial INR results was 0.7 at a therapeutic target of 2.5 INR and 1.0 at a therapeutic target of 3.5 INR. The data presented allow generation of objective criteria for monitoring ACT patients and deciding dose adjustments. We recommend that estimations of critical differences for significant change of INR in ACT patients should be based on results obtained in the specific clinic investigated to mirror the routine total variation of INR measurements they obtain.