Top-down and bottom-up approaches for the estimation of measurement uncertainty in coagulation assays

Abstract

Background: The assessment of measurement uncertainty (MU) in clinical laboratories is essential to the reliable interpretation of results in clinical laboratories. However, despite the introduction of various methods for the expression of uncertainty in measurement, the MUs of coagulation tests have not been extensively studied. The aim of this study was to quantify the MU of various coagulation assays according to international guidelines and to report an expected confidence in the quality of coagulation assays. Methods: We selected activated partial thromboplastin time, international normalized ratio (INR), protein C/S, antithrombin, fibrinogen, and Factor V/VIII/X to quantify the MUs of two coagulation testing systems: ACL TOP 750 CTS (Instrumentation Laboratory, Bedford, MA, USA) and STA Compact (Diagnostica Stago, Asnieres-sur-Seine, France). We used international standards and interlaboratory comparison results in accordance with international guidelines in a top-down approach to the assessment of MU. For INR, MU was estimated in a bottom-up approach using reference thromboplastin and certified plasmas. Results: Top-down approaches resulted in MUs between 3.3% and 21.3% for each measurand. In the bottom-up approach, MUs of INR values ranged from 10.9% to 26.4% and showed an upward trend as INR increased. Conclusions: In this study, we were successful in quantifying MU of coagulation assays using practical methods. Our results demonstrated that top-down and bottom-up approaches were adequate for coagulation assays. However, some assays showed significant biases against international standards; therefore, standardization would be necessary to ensure more reliable patient results.