B-299 Analytical performance, variant detection and result reportability of the CAPILLARYS 3 TERA HbA1c assay relative to the Siemens Atellica CH930

Abstract

Background Accurate hemoglobin A1c (HbA1c) measurement is key for diabetes diagnosis and monitoring. Many methods exist; however, immunoassay methods may be limited in detection of hemoglobin variants, abnormal fractions, and hemoglobin concentrations that impact result measurement. This study evaluated the analytical performance, variant detection, and result reportability of HbA1c measurement using the CAPILLARYS 3 TERA and Siemens Atellica CH930. Methods Studies included precision, accuracy, method comparisons, retesting of flagged samples, variant prevalence analysis, and precision of variant samples. CAPILLARYS 3 TERA within-run precision was evaluated using three residual samples (low, medium, high) analyzed in eight replicates per level and between-run precision was assessed in triplicate over three days. Accuracy was evaluated using 10 NGSP samples with assigned values. Six hundred and thirty-three residual EDTA samples with HbA1c values using the Atellica CH930 sent to McLendon Laboratory as part of routine care were tested using the CAPILLARYS 3 TERA within 24 hours of collection. Retesting of unreportable samples on the Atellica included specimens comprising flagged samples (n=64) and samples (n=65) with total hemoglobin concentrations of 7-12 g/dL. Results were compared to the Abbott Afinion 2 HbA1c diagnostic cartridge when HbA1c values were not generated by the Atellica. An enriched cohort (n=32) was used to challenge hemoglobin variant detection on both platforms. Variant precision was assessed in triplicate for nine specimens. Results CAPILLARYS 3 within-run, and between-run precision demonstrated CVs =1.5% across all levels. All measurements of NGSP samples on both platforms were within 6% relative bias. Slope, intercept, and mean absolute bias were 1.090, -0.373, 0.37% for CAPILLARYS 3 and 1.036, -0.12, and 0.18% for the Atellica compared to NGSP. Method comparison of the CAPILLARYS 3 versus Atellica using residual samples demonstrated a slope of 1.029, intercept of -0.05, correlation of 0.987 and mean bias of 0.12%. The CAPILLARYS 3 generated results for 96.9% (62/64) of Atellica flagged samples. These results showed good agreement (slope 1.025, bias -0.16) compared to the Afinion 2. The two remaining unreportable samples were flagged by the CAPILLARYS 3 as atypical and were previously known hemoglobin variants. For the variant enriched cohort, the CAPILLARYS 3 had a sensitivity of 100% versus 81% for the Atellica in flagging samples with possible interferences. The CAPILLARYS 3 correctly identified variant interferences despite calculating HbA1c values for 13 specimens collected from transfused patients. Six variant samples were not identified by the Atellica yet generated results; five were ß-globin related hemoglobinopathies, with Atellica values systematically lower than CAPILLARYS 3, showing 15-20% underestimation. Additionally, flagged and variant samples showed CV <1%, supporting the stability of HbA1c measurements on CAPILLARYS 3. Notably, in the 7-12 g/dL hemoglobin cohort on the Atellica, 30 samples had flags indicating total hemoglobin <7 g/dL, inconsistent with the total hemoglobin concentration measured. This discrepancy was independent of variant status Conclusion The CAPILLARYS 3 TERA demonstrated accurate resolution of problematic specimens originally tested using the Atellica enzymatic immunoassay. Furthermore, it may prevent inaccurate results in the patient population with hemoglobin variants.