Failure of the International Normalized Ratio to Generate Consistent Results Within a Local Medical Community

Abstract

Use of the International Normalized Ratio (INR) has been recommended as a means of standardizing prothrombin time (PT) results for management of oral anticoagulant therapy. During the evaluation of a new lot of thromboplastin reagent, however, INR values were obtained that were inconsistent with results obtained with the prior lot of reagent from the same manufacturer. A local normalized ratio (LNR) was substituted for the INR for the new reagent, based on a calculated local sensitivity index (LSI). Validation of the LSI was performed at the three hospitals in the medical community by testing an identical panel of aliquots from 64 plasmas obtained from patients who were chronically receiving oral anticoagulants. Each test result was classified according to the INR value as low, low therapeutic, high therapeutic, or high. Local normalized ratio values obtained at one hospital in the community were in reasonable agreement with INR determinations in the other two hospital laboratories. Classification mismatches occurred using the INR, however, in 84 of 280 (30%) of the paired samples. Thus, the inability to generate consistent INR values within a local medical community raises serious concern about the reliability of the INR concept in its current form.

Poor Agreement among Prothrombin Time International Normalized Ratio Methods: Comparison of Seven Commercial Reagents

“…Different reagents are known to vary with respect to source of thromboplastins and other reagent components, and these have likewise not been characterized in detail. Hence, the theoretical basis of the ISI principle is itself not necessarily sound, as has been emphasized by several critics (17)(18)(19). There are, moreover, very few, if any, published investigations in which good agreement between different INR-based PT methods has been demonstrated.…”

CalculationvsCalibration Curve for INR Determination: Results of an Interlaboratory Proficiency Scheme

“…Despite this standardization, difficulties still exist that are evident in testing through external quality assessment programs. 3,4 It is, therefore, believed that improved accuracy may achieve the goals of a lower risk of recurrence and reduced risk of bleeding. Attempts are being made to improve the performance by using instrument-specific ISI values or corrected ISI values for specific reagent and instrument systems by using a local calibration process.…”

Effect of 3.2%vs3.8% Sodium Citrate Concentration on Routine Coagulation Testing

“…[10][11][12] The various reasons for differences in INR values cited include biologic variation, ISI determination and standardization, instrument variation, and proper use of the equation to determine INR. Only one other study, by Duncan et al, 13 examined the effect of citrate concentration on INR.…”