Ensuring HbA1c Accuracy and Variant Detection in Hemoglobin G-Coushatta and Queens Using Variant Mode Analysis

Area of Science:

• Clinical Chemistry
• Laboratory Medicine
• Analytical Biochemistry

Background:

• Glycated hemoglobin (HbA1c) is crucial for monitoring glycemic control.
• Hb variants, particularly Hb G-Coushatta and Hb Queens, are prevalent in the Korean population.
• These variants can impact the accuracy and reliability of HbA1c assays.

Purpose of the Study:

• To evaluate the analytical performance of four HbA1c platforms in the presence of Hb G-Coushatta and Hb Queens.
• To assess the accuracy and flag detection rates of different HbA1c assay modes (fast, standard, variant).

Main Methods:

• Four HbA1c platforms (Arkray HA-8190V, Tosoh HLC-723 G11, Bio-Rad D-100, Sebia Capillarys) were tested.
• 33 samples with known Hb variants (26 Coushatta, 7 Queens) were analyzed.
• Performance was evaluated by comparing HbA1c results to a comparative method and assessing variant flag detection rates, with UPLC-MS/MS as the reference for variant identification.

Main Results:

• Hb G-Coushatta caused significant underestimation in fast assay modes (-28.4% to -17.6%).
• Hb Queens hindered automated detection in some standard modes (28.6% flag detection).
• Variant modes generally improved accuracy and detection (e.g., 100% flag detection for all platforms except G11 standard mode) but showed platform-dependent performance.

Conclusions:

• Hb G-Coushatta and Hb Queens present challenges for standard HbA1c assays, especially in rapid modes.
• Variant-aware HbA1c testing modes are essential for accurate results in populations with common Hb variants.
• Selection of the appropriate HbA1c platform and mode is critical for reliable glycemic control monitoring when Hb variants are present.