Oral Anticoagulant Therapy Control: Evidence that INR Expression Improves the Inter-Laboratory Comparability of Results - The Bologna Oral Anticoagulant Control Exercise

Abstract

SummaryThe aims of the present study were: l) interlaboratory normalization of prothrombin time (PT) testing for anticoagulant therapy control through calibration of customary thromboplastins against international reference materials, and 2) “on field” validation of the advantages offered by expression of results as International Normalized Ratio (INR) as opposedto percentage activity. PT tests were carried out over 8 days on the same normal subjects (16) and patients on oral an ticoagulants (48) in the 9 laboratories of the Bologna area. The use of customary thromboplastins and coagulometers was maintained in all labs throughout the study. The main results were: 1) the interlaboratory CV of the prothrombin ratios obtained for each sample with all customary thromboplastins (5 different brands) was 15%, but was reduced to levels of 5.8 to 8.9 when using constant thromboplastin brands and batches; 2) the International Sensitivity Index (ISI) values obtained in the different labs were only slightly influenced by the use of different coagulometers; 3) comparable ISI values were obtained through direct calibration with the international reference material and through intermediate calibration with a locally selected standard; 4) use of INR values instead of percentage activity greatly reduced interlaboratory variability and significantly improved uniformity of anticoagulation level measurements. thus reducing the possibility of erroneous prescriptions. The Bologna exercise is therefore of educational value for laboratory and community doctors of the area in understanding and accepting the INR system.

How to report results of prothrombin and activated partial thromboplastin times

“…Conversely, small clotting time variations in healthy subjects translate into large variation of percentage activity, which may occasionally lead to values far higher than 100%, which might be erroneously interpreted as an index of hypercoagulability. Third, the percentage activity does not account for the different sensitivity of commercial thromboplastins to the defect induced by VKA, as earlier shown by Palareti et al [5]. Therefore, it became rather clear that the PT percentage activity could not be used to monitor patients on VKA and that scale was used for some years to express results for patients other than oral anticoagulation.…”

New oral antithrombotics: a need for laboratory monitoring. For

“…The inter‐laboratory variability of assay methods (Criterion #3) has been greatly reduced by the use of INR values instead of percentage activity, significantly improving the uniformity of anticoagulation level measurements. Several studies have demonstrated the validity of the INR/ISI system [3–5]. A further advantage of this laboratory test is that it does not depend on sampling time, due to the very long pharmacodynamic half‐life of VKA.…”

Quantitative Systems Pharmacology Model-Based Predictions of Clinical Endpoints to Optimize Warfarin and Rivaroxaban Anti-Thrombosis Therapy

“…PT is generally expressed as international normalized ratio (INR) to allow for comparison of results across laboratories and test kits ( Marshall et al., 1987 ; Palareti et al., 1987 ). The INR indirectly measures the activity of the extrinsic as well as common part of the coagulation network, evaluating the coagulation factors VII, X, V, II, and I (fibrinogen) ( Raber, 1990 ), making it the first choice to monitor warfarin efficacy.…”