Reliability of the international normalized ratio for monitoring the induction phase of warfarin: Comparison with the prothrombin time ratio

The International Normalized Ratio (INR) was introduced to reduce the variability of prothrombin time (PT) reporting. One potential problem with the use of the INR is the assumption that its reliability is reduced when it is used to monitor patients during the induction phase of treatment. This shortcoming arises because the model used to establish the INR system is based on the use of pooled plasma from patients stabilized on warfarin for at least 6 weeks. Because the prolongation of the PT by warfarin during the induction phase mainly reflects reduction in factor VII levels (whereas the prolongation of the PT after 6 weeks of stabilization reflects reductions in factors X, II, and VII), there exists a potential for loss of accuracy of the INR during warfarin induction. To overcome this potential problem, it has been suggested that the PT ratio should be used to report results during the induction phase of treatment and that the INR system should be reserved for reporting results after the patient has been stabilized. This approach is confusing to the clinician. In addition, the validity of this approach has never been demonstrated in a clinical study. To address this issue, we studied 43 patients for the first 5 days after they started warfarin therapy. We measured the PT in the same plasma samples from each patient with five different commercial thromboplastins. The variance in the PT ratios among the five thromboplastins was compared with the variance obtained with the INR values derived from the PT ratios when using the international sensitivity indexes provided by the manufacturer. Our results indicate that, even during the induction phase, there is less variance with the INR system than with the PT ratio system.