The reliability of manufacturer-determined, instrument-specific international sensitivity index values for calculating the international normalized ratio

Some thromboplastin manufacturers are currently supplying the instrument-specific international sensitivity index (ISI) values of their reagents, allowing clinical laboratories to calculate instrument-specific international normalized ratio (INR) values on plasma samples from patients receiving coumarin therapy. However, the assumption that systematic interinstrument variability in the INR would be eliminated if manufacturer-determined ISI values were used remains unsubstantiated. This assumption was evaluated by comparing INR values obtained on one instrument that measures a mechanical endpoint (fibrometer) with one that measures a photo-optical endpoint (MLA-700). Three thromboplastin reagents with instrument-specific ISI values supplied by the manufacturer (ISI range, 1.23-2.79) were used. For two of three reagents, the fibrometer INR values were significantly higher than the MLA-700 INR values (P < .01). Analysis of log prothrombin time ratio plots showed that this systematic variability was caused by inaccurate manufacturer ISI values. Of clinical significance is that the inaccurate ISI values produced a high number of discordant INR values between these two instruments (> 47% of plasma samples had one INR value within and one out of the recommended therapeutic range). The implication of these findings for laboratory monitoring of oral anticoagulation is discussed.