Variability of INR in patients on stable long-term treatment with phenprocoumon and acenocoumarol and implications for analytical quality requirements.

Within each patient treated with vitamin K antagonist (VKA), variation of the international normalised ratio (INR) occurs over the treatment period. The purpose of the present study was to assess INR variation in selected patients on long-term treatment in whom the dose of VKA was not changed. This type of variation is considered as "biological variation" which is caused by many factors but not VKA dose changes or other medication. Four groups of long-term patients were examined: each group with a different VKA (acenocoumarol or phenprocoumon) or a different target intensity (INR 2.0-3.5 or 2.5-4.0). All patients were monitored with the same PT system (Hepato Quick, STA-R Evolution coagulation instrument) by one laboratory. The variation of the INR within each patient was expressed as coefficient of variation (CV, in %). The CV was corrected for the average imprecision of the INR measurement (CV, 2.4%). The mean corrected CV values for the four groups were: 10.9% (acenocoumarol, target INR 2.0-3.5); 10.5% (acenocoumarol, target INR 2.5-4.0); 10.4% (phenprocoumon, target INR 2.0-3.5); 9.1% (phenprocoumon, target INR 2.5-4.0). The analytical performance goal for the INR measurement (imprecision) can be derived from the within-subject biological variation. Desirable INR imprecision goals are <4.9% and <5.3% CV for monitoring of phenprocoumon and acenocoumarol, respectively. These goals were achieved using the aforesaid PT system.