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, Asnières-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.
Acknowledgments
The authors would like to thank Werfen Medical IL Ltd. (Seoul, Republic of Korea) for their technical support and the hematology department of Chung-Ang University Hospital, especially Young Dae Kwon and Kwang Il Park, for their contribution to this study. This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) and was funded by the Ministry of Education (NRF-2017R1A2B4011631).
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) and was funded by the Ministry of Education (funder id: http://dx.doi.org/10.13039/501100003725, NRF-2017R1A2B4011631).
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. EUROLAB. EUROLAB Technical Report No. 1/2002. EUROLAB Technical Report. Brussels, Belgium: EUROLAB, 2002.Search in Google Scholar
2. Padoan A, Sciacovelli L, Aita A, Antonelli G, Plebani M. Measurement uncertainty in laboratory reports: a tool for improving the interpretation of test results. Clin Biochem 2018;57:41–7.10.1016/j.clinbiochem.2018.03.009Search in Google Scholar PubMed
3. White GH. Basics of estimating measurement uncertainty. Clin Biochem Rev 2008;29(Suppl 1):S53–60.Search in Google Scholar
4. Qin Y, Zhou R, Wang W, Yin H, Yang Y, Yue Y, et al. Uncertainty evaluation in clinical chemistry, immunoassay, hematology and coagulation analytes using only external quality assessment data. Clin Chem Lab Med 2018;56:1447–57.10.1515/cclm-2017-1199Search in Google Scholar PubMed
5. ISO. ISO 15189:2012, Medical Laboratories – Requirements for Quality and Competence. Geneva, Switzerland: ISO, 2012.Search in Google Scholar
6. ILAC. Introducing the Concept of Uncertainty of Measurement in Testing in Association with the Application of the Standard ISO/IEC 17025. NSW, Australia: International Laboratory Accreditation Cooperation, 2002.Search in Google Scholar
7. CLSI. Expression of Measurement Uncertainty in Laboratory Medicine; Approved Guideline. CLSI document EP29-A. Wayne, PA: Clinical and Laboratory Standards Institute, 2012.Search in Google Scholar
8. JCGM. Evaluation of Measurement Data—Guide to the Expression of Uncertainty in Measurement. Paris, France: JCGM, 2008.Search in Google Scholar
9. EURACHEM/CITAC Guide CG 4. Quantifying Uncertainty in Analytical Measurement, 3rd ed. https://www.eurachem.org/images/stories/Guides/pdf/QUAM2012_P1.pdf. Accessed: 21 Nov 2019.Search in Google Scholar
10. Magnusson B, Näykki T, Hovind H, Krysell M. Handbook for Calculation of Measurement Uncertainty in Environmental Laboratories. Oslo, Norway: Nordic Innovation, 2012.Search in Google Scholar
11. Lim YK, Park AJ, Kweon OJ, Choi JH. Performance evaluation and measurement uncertainty determination of the new version of the Abbott ARCHITECT 25-OH Vitamin D 5P02 Assay. Am J Clin Pathol 2019;151:209–16.10.1093/ajcp/aqy131Search in Google Scholar PubMed
12. Lee JH, Choi J-H, Youn JS, Cha YJ, Song W, Park AJ. Comparison between bottom-up and top-down approaches in the estimation of measurement uncertainty. Clin Chem Lab Med 2015;53: 1025–32.10.1515/cclm-2014-0801Search in Google Scholar PubMed
13. Padoan A, Antonelli G, Aita A, Sciacovelli L, Plebani M. An approach for estimating measurement uncertainty in medical laboratories using data from long-term quality control and external quality assessment schemes. Clin Chem Lab Med 2017;55:1696–701.10.1515/cclm-2016-0896Search in Google Scholar PubMed
14. Matar G, Poggi B, Meley R, Bon C, Chardon L, Chikh K, et al. Uncertainty in measurement for 43 biochemistry, immunoassay, and hemostasis routine analytes evaluated by a method using only external quality assessment data. Clin Chem Lab Med 2015;53:1725–36.10.1515/cclm-2014-0942Search in Google Scholar PubMed
15. van den Besselaar AM, Witteveen E, van der Meer FJ. Uncertainty of international sensitivity index and international normalized ratio. J Thromb Haemost 2013;11:1615–7.10.1111/jth.12311Search in Google Scholar PubMed
16. Lim YK, Kweon OJ, Choi JH, Lee W, Park AJ. Measurement uncertainty of platelet concentration using the Sysmex XN automated hematology analyzer. Scand J Clin Lab Invest 2018;78:224–9.10.1080/00365513.2018.1437644Search in Google Scholar PubMed
17. JCGM. International Vocabulary of Metrology—Basic and General Concepts and Associated Terms (VIM), 3rd ed. Paris, France: JCGM, 2012.Search in Google Scholar
18. WHO. WHO Expert Committee on Biological Standardization, sixty-second report. WHO Technical Report Series, No 979. 2013:271–316.Search in Google Scholar
19. CLSI. Procedures for Validation of INR and Local Calibration of PT/INR Systems; Approved Guideline. CLSI document H54-A. Wayne, PA: Clinical and Laboratory Standards Institute, 2005.Search in Google Scholar
20. Tomenson J. A Statistician’s Independent Evaluation. Thromboplastin Calibration and Oral Anticoagulant Control. Springer, 1984:87–108.10.1007/978-94-009-5676-6_5Search in Google Scholar
21. Magnusson B, Ellison SL. Treatment of uncorrected measurement bias in uncertainty estimation for chemical measurements. Anal Bioanal Chem 2008;390:201–13.10.1007/s00216-007-1693-1Search in Google Scholar PubMed
22. Magnusson B, Ossowicki H, Rienitz O, Theodorsson E. Routine internal- and external-quality control data in clinical laboratories for estimating measurement and diagnostic uncertainty using GUM principles. Scand J Clin Lab Invest 2012;72:212–20.10.3109/00365513.2011.649015Search in Google Scholar PubMed
23. Tran MT, Hoang K, Greaves RF. Practical application of biological variation and Sigma metrics quality models to evaluate 20 chemistry analytes on the Beckman Coulter AU680. Clin Biochem 2016;49:1259–66.10.1016/j.clinbiochem.2016.08.008Search in Google Scholar PubMed
24. Hubbard AR, Heath AB. Standardization of factor VIII and von Willebrand factor in plasma: calibration of the WHO 5th International Standard (02/150). J Thromb Haemost 2004;2:1380–4.10.1111/j.1538-7836.2004.00838.xSearch in Google Scholar PubMed
25. Talstad I. Why is the standardization of prothrombin time a problem? Pathophysiol Haemos Thromb 2000;30:258–67.10.1159/000054142Search in Google Scholar PubMed
26. Mackie IJ, Kitchen S, Machin SJ, Lowe GD, Haemostasis, Thrombosis Task Force of the British Committee for Standards in H. Guidelines on fibrinogen assays. Br J Haematol 2003;121: 396–404.10.1046/j.1365-2141.2003.04256.xSearch in Google Scholar PubMed
27. Marlar RA, Gausman JN. Laboratory testing issues for protein C, protein S, and antithrombin. Int J Lab Hematol 2014;36: 289–95.10.1111/ijlh.12219Search in Google Scholar PubMed
28. Favaloro EJ, Hamdam S, McDonald J, McVicker W, Ule V. Time to think outside the box? Prothrombin time, international normalised ratio, international sensitivity index, mean normal prothrombin time and measurement of uncertainty: a novel approach to standardisation. Pathology 2008;40: 277–87.10.1080/00313020801911454Search in Google Scholar PubMed
29. Favaloro EJ, editor. How to generate a more accurate laboratory-based international normalized ratio: solutions to obtaining or verifying the mean normal prothrombin time and international sensitivity index. Seminars in thrombosis and hemostasis. Thieme Medical Publishers, 2019.10.1055/s-0038-1667342Search in Google Scholar PubMed
Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2020-0038).
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