Vol. 4, Issue 2, Part A (2020)

Background: Hemoglobin A1c (HbA1c) is a standard marker for long-term glycemic control in diabetes mellitus. However, the incidental detection of hemoglobin variants during HbA1c testing poses diagnostic challenges, especially in multiethnic populations with high prevalence of hemoglobinopathies.

Objective: This study aimed to determine the incidence, types, and clinical implications of hemoglobin variants identified during routine HbA1c testing using ion-exchange high-performance liquid chromatography (HPLC) in a tertiary care center in South India.

Methods: A prospective observational study was conducted over 24 months, analyzing 10,200 unique HbA1c samples. Chromatograms were reviewed for abnormal peaks; samples with unidentified peaks exceeding 6% were further evaluated using the extended HbA2/F mode. Variants were categorized based on retention times. HbA1c values were reported only if variant interference was excluded.

Results: Hemoglobin variants were detected in 85 cases (0.83%). The most frequent variants were HbD heterozygous (27.1%), HbE heterozygous (25.9%), and HbS heterozygous (22.4%). A male predominance was observed across most variants. HbD heterozygous showed the widest HbA1c range (4.5%-13.8%). High HbF was identified in 12.9% of variant cases. No beta-thalassemia trait cases were detected due to method limitations.

Conclusion: The detection of hemoglobin variants during HbA1c testing highlights the need for chromatogram review to avoid misinterpretation of glycemic status. Identifying such variants provides an opportunity for earlier diagnosis of hemoglobinopathies and genetic counseling. Laboratories should establish protocols for variant detection and reporting to ensure accurate clinical decision-making.