Standardization of clinical enzyme analysis using frozen human serum pools with values assigned by the International Federation of Clinical Chemistry and Laboratory Medicine reference measurement procedures

Abstract

Variation in clinical enzyme analysis, particularly across different measuring systems and laboratories, represents a critical but long-lasting problem in diagnosis. Calibrators with traceability and commutability are imminently needed to harmonize analysis in laboratory medicine. Fresh frozen human serum pools were assigned values for alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), creatine kinase (CK) and lactate dehydrogenase (LDH) by six laboratories with established International Federation of Clinical Chemistry and Laboratory Medicine reference measurement procedures. These serum pools were then used across 76 laboratories as a calibrator in the analysis of five enzymes. Bias and imprecision in the measurement of the five enzymes tested were significantly reduced by using the value-assigned serum in analytical systems with open and single-point calibration. The median (interquartile range) of the relative biases of ALT, AST, GGT, CK and LDH were 2.0% (0.6–3.4%), 0.8% (−0.8–2.3%), 1.0% (−0.5–2.0%), 0.2% (−0.3–1.0%) and 0.2% (−0.9–1.1%), respectively. Before calibration, the interlaboratory coefficients of variation (CVs) in the analysis of patient serum samples were 8.0–8.2%, 7.3–8.5%, 8.1–8.7%, 5.1–5.9% and 5.8–6.4% for ALT, AST, GGT, CK and LDH, respectively; after calibration, the CVs decreased to 2.7–3.3%, 3.0–3.6%, 1.6–2.1%, 1.8–1.9% and 3.3–3.5%, respectively. The results suggest that the use of fresh frozen serum pools significantly improved the comparability of test results in analytical systems with open and single-point calibration.

Keywords:

• Enzyme
• standardization
• calibration
• bias
• reference system

Acknowledgments

We thank Prof. Zhenhua Yang from the National Center for Clinical Laboratories for his guidance and support in this study.

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This study was funded by Beijing Municipal Science and Technology Plan Projects (Grant no. Z141107006614010 awarded to Qing Tong).