Why is the standardization of prothrombin time a problem?

The standardization of prothrombin time (PT) has been a problem for more than 50 years; by applying the methods to the same clinical material the analysis may explain why. The initial standardization by 2--3 times normal clotting time by Quick's PT assay did not standardize presently used PT assays. The ratio method accepted by the WHO in 1977 was not satisfactory because the intercept was neglected. The revised ratio method (WHO 1983) recommended calibration between log clotting times of normal and abnormal plasmas and a simplified conversion into ratios. However, by including a high proportion of normal plasmas (up to 1/3 of abnormal) an erroneous calibration material was introduced; the conversion from clotting times into ratios was also more complex than predicted. The international sensitivity index, which is based on the simplified method, produced international normalized ratios (INR) that were not more standardized than not corrected ratios. Not corrected coagulation activities showed poor standardization due to the different sensitivity of assays for the protein induced by vitamin K absence (Pivka) inhibitor. The corresponding therapeutic ranges of INR and coagulation activities covered 70 and 10--20% of their scales, respectively. Standardization by Pivka-corrected coagulation activities against an international reference assay may be the preferable method.