Long-Term French Experience in INR Standardization by a Procedure Using Plasma Calibrants

Abstract

The International Normalized Ratio (INR) has not lowered the interlaboratory differences in prothrombin time (PT) values to the extent expected, mainly because of the instrument-dependency of the International Sensitivity Index (ISI) and other factors (eg, accurate determination of the ISI, the normal value used in the PT ratio). The procedure (PPC) using plasma calibrants (reference lyophilized plasmas with assigned activity) has been evaluated since 1977 in nine French national external quality assessment surveys (NEQAS) involving approximately 4,000 laboratories and numerous local thromboplastin technique combinations. The PPC was compared with the conventional procedure (using the manufacturer's ISI), and the efficiency of antivitamin K-calibrated (AK Cal) plasmas from patients receiving oral anticoagulants vs artificially depleted plasma calibrants was also evaluated. The PPC efficiently standardized PTs with AK Cal plasmas, reducing interlaboratory variability (eg, coefficient of variation, 12% to 6% for survey 92 D) and reagent-instrument effects. However, AK Cal plasmas have drawbacks, such as limited supply, cost, and batch-to-batch variability. The artificially depleted plasma calibrants were less efficient, but usable if carefully prepared. The value of this simple procedure is that local practices are considered in the determination of PT, thus correcting for coagulometer effects and avoiding use of the manufacturer's ISI and need for a normal control plasma. These large-scale French surveys have demonstrated the validity of PPC through 15 years of experience and have shown that it offers the best compromise available in PT standardization.