Evaluation of International Normalized Ratios by a Controlled Field Survey with 4 Different Thromboplastin Reagents

Abstract

SummaryA nationwide survey has been performed in Japan involving 75 laboratories to assess the relative reliability of different methods of reporting prothrombin time results in anticoagulant control. The interchangeability of results using prothrombin time, prothrombin activity percentage, prothrombin ratio and international normalized ratios (INR) were compared with four different thromboplastin reagents and a range of coagulometers. A secondary batch of reference thromboplastin of human brain origin (BCT/454) was used to calibrate the local thromboplastins and for comparison of methods of reporting. The study revealed the closest agreement of the results between BCT and the other reagents, and the regression lines of these reagents were almost identical, when the results were reported as INR. Box-Whisker plot analysis showed that the distribution of the results was large with the more deficient plasmas with all methods of reporting. It was found by this analysis that the interchangeability of the results was greatest when the results were expressed by INR, because the mean values obtained of each plasma using different thromboplastin reagents gave the lowest CV and the frequency of the far-out data was least, compared with the other methods of expression. On the other hand, the type of coagulometer had almost as much effect as the thromboplastin reagent on the prothrombin time, even if INR was used. Interchangeability of INR would be further improved by providing ISI values for each reagent/ instrument combination.

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

“…Others 16,36/38 have reported that despite this deviation, lyophilized plasmas can be used to calculate the INR and to calibrate thromboplastins. Clearly, our study shows that calibration is more reliable with AK Cal plasmas than with ART Cal plasmas, 31 as also recently reported by Stevenson et al 39 However, AK Cal plasmas are limited in supply, costlier, and subject to ethical and regulatory issues and to possible batch-tobatch variability. Second, it is not easy to provide the wide range of INR values required for accurate ISI calibration on pooled AK Cal plasmas.…”

“…Moreover, the manufacturer's stated ISI of the thromboplastin is derived from World Health Organization recommendations and applies only to manual techniques, whereas automation is rapidly increasing and diversifying. 8 31 have suggested that manufacturers give the ISI of the thromboplastin-instrurnent system, and some express the ISI according to the type of clot-detecting system (optical or mechanical). Poggio et al 16 showed that the calibration of some commercial reagents tested on coagulometers against the reference material (manual testing) raises further problems in slope determination.…”

Oral Anticoagulants: Mechanism of Action, Clinical Effectiveness, and Optimal Therapeutic Range

“…106 Several investigators have noted incorrect ISI values provided by manufacturers of thromboplastin reagents. [107][108][109] Although local calibrations can be performed with plasma samples with certified PT values to determine the instrument-specific ISI, the process is tedious and beyond the scope of many laboratories.…”

American Heart Association/American College of Cardiology Foundation Guide to Warfarin Therapy

“…98 -103 In general, the College of American Pathologists has recommended that laboratories use responsive thromboplastin reagents (ISI Ͻ1.7) and reagent/instrument combinations for which the ISI has been established. 104 ISI values provided by manufacturers of thromboplastin reagents are not invariably correct, [105][106][107] and this adversely affects the reliability of measurements. Local calibrations can be performed by using plasma samples with certified PT values to determine the instrument-specific ISI.…”