ABSTRACT Introduction Hematological disorders, critical for diagnosis, and monitoring, rely on accurate complete blood count results from automated analyzers, the reliability of which depends on robust quality control (QC). However, the ability of commutability of commercial hematology QC materials (HQCM) to behave like patient samples across different systems, and the impact of analytical modes on results are not fully characterized. This study aimed to evaluate the analytical performance and commutability of two HQCM brands (Bioyuan and XC) across two hematology analyzers (Sysmex XN‐1000 and Mindray BC‐6800 Plus). Methods We systematically compared results between QC and sample measurement modes, between manual and autoloader sampling modes, and assessed commutability using clinical samples as a reference. Results The differences between QC and sample modes were analyzer and parameter specific, with WBC, HCT, and MCV most affected on the Sysmex system. Manual versus autoloader sampling on the Mindray analyzer introduced significant differences for most parameters across concentrations. Commutability assessment revealed that neither HQCM was universally commutable for all four directly measured parameters (WBC, RBC, HGB, PLT); noncommutability was frequent, particularly, at extreme concentrations, indicating significant matrix effects. Conclusion This study highlights that analytical (sampling mode and measurement mode) variables, along with material‐dependent matrix effects, can substantially influence QC results and their interpretation. Laboratories must standardize protocols and critically select QC materials to ensure reliable hematology testing and effective quality assurance. Future work should focus on developing more commutable reference materials and validating these findings in multicenter clinical settings.
Ren et al. (Wed,) studied this question.