INTERNATIONAL NORMALIZED RATIO FOR PROTHROMBIN TIMES IN PATIENTS TAKING ORAL ANTICOAGULANTS - CRITICAL DIFFERENCE AND PROBABILITY OF SIGNIFICANT CHANGE IN CONSECUTIVE MEASUREMENTS

To determine when a change in serial measurements of prothrombin time in patients receiving oral anticoagulant therapy (ACT) is a statistica lly significant biological change necessitating dose adjustment, one m ust know the size of the ''critical difference'' in statistical terms (i.e., probabilities). In a cohort of 32 ACT patients at pharmacologic al steady-state, we studied the within-subject total variation of prot hrombin time, expressed as International Normalized Ratio (INR), over 6 months. The total within-subject variation (CV) of INR was 10.1%. Th e corresponding critical differences required for significance of chan ge in serial INR results was 0.7 at a therapeutic target of 2.5 INR an d 1.0 at a therapeutic target of 3.5 INR. The data presented allow gen eration of objective criteria for monitoring ACT patients and deciding dose adjustments. We recommend that estimations of critical differenc es for significant change of INR in ACT patients should be based on re sults obtained in the specific clinic investigated to mirror the routi ne total variation of INR measurements they obtain.