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.

Blood Coagulation Tests↗

PubMedDate not supplied

Simplified prothrombin time standardization.

An analysis of prothrombin time (PT) standardization methods is presented. The present recommended ratio method demonstrated complex calibration and wide therapeutic ranges. Standardization by coagulation activities resulted in different therapeutic ranges due to the different sensitivity of assays for the protein induced by vitamin K absence (Pivka) inhibitor. A new method--the modified coagulation activity method--applied a reference assay against which any PT assay can be calibrated by clotting times, and the results were expressed in coagulation activities by the reference assay. This method was preferable due to simple calibration, narrow therapeutic ranges and identical results by any PT assay.

Blood Coagulation↗

PubMedDate not supplied

Simplified calibration of prothrombin time assays.

The calibration of prothrombin time (PT) assays was studied. A simple calibration between pooled normal plasma and pooled stable plasma was as satisfactory as more complex calibration methods based on linear or orthogonal regression between log clotting times of abnormal and/or normal plasmas.

Blood Coagulation↗

PubMedDate not supplied

Prothrombin time standardization by correction of the Pivka inhibitor.

The standardization of prothrombin time (PT) assays needs two steps: (1) calibration of PT assays towards a reference assay or reference thromboplastin, (2) correction of PT assays according to the calibration. The present recommended calibration by clotting times is favored for the linearity between assays; the clotting times of abnormal plasma are partly prolonged due to the protein induced by vitamin K absence (Pivka) inhibitor. Calibration by coagulation activities also demonstrated linearity between PT assays; the regression line for abnormal plasma deviated from the line of identity due to differences in sensitivity of assays for the Pivka inhibitor. The corrected PT assays demonstrated similar results using calibration by clotting time or coagulation activities, but the correction was simpler for coagulation activities. Patient plasma was the preferable material in calibration by clotting times as well as by coagulation activities. The corrections between the reference assay and other PT assays were equal to the differences in sensitivities for the Pivka inhibitor. The corrected PT assays did not differ from the reference assay by statistical analysis; any of the six PT assays tested might be used as reference assay.

Biomarkers↗