Establishment of intra- and inter-laboratory reference change values for coagulation tests: PT, INR, and aPTT

Background Coagulation assays such as prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (aPTT) are widely used for patient monitoring. Accurate interpretation of sequential test results requires consideration of both biological and analytical variation. The reference change value (RCV) is a statistical tool that determines whether changes in serial results are clinically significant. While RCVs are typically calculated using intra-laboratory data, inter-laboratory variability remains largely unexplored for coagulation parameters. This observational study aimed to calculate intra- and inter-laboratory RCVs for PT, INR, and aPTT. Methods Internal quality control (IQC) data and external quality assessment (EQA) results were collected monthly throughout 2024. Intra-laboratory analytical imprecision (CV A ) was derived from IQC data, while inter-laboratory CV A was estimated using EQA results. RCVs were calculated using an asymmetric log-normal model incorporating within-subject biological variation (CV I ) and a Z-score of 1.64. Results Intra-laboratory CV A values were 5.1% (PT), 5.3% (INR), and 3.5% (aPTT), whereas inter-laboratory CVA values were substantially higher: 21.1%, 18.1%, and 13.6%, respectively. Corresponding intra-laboratory RCV increase values were 14.2% (PT), 14.6% (INR), and 11.0% (aPTT), while inter-laboratory RCV increase values reached 63.1%, 52.5%, and 37.9%. Individuality index values were <0.6 for all tests, highlighting the limited value of reference intervals and the clinical utility of RCVs. Conclusions The findings demonstrate that inter-laboratory RCVs for PT, INR, and aPTT are substantially wider than intra-laboratory RCVs, reflecting the impact of between-laboratory analytical variability. These results emphasize the need for context-specific RCV thresholds, particularly when interpreting serial coagulation test results across different laboratories.