HbA1c Measurement in Beta-Thalassemia

Mechanism of Interference

Any condition that shortens red blood cell survival or decreases mean red blood cell age produces falsely low HbA1c results, which is the primary mechanism in beta-thalassemia, according to the American Diabetes Association 1, 2
Hemolytic anemia, characteristic of beta-thalassemia, results in falsely low HbA1c levels because red blood cells have less time for glucose exposure and glycation, as reported by the American College of Physicians 3, 4
HbA1c cannot be measured and should not be reported in individuals with homozygous hemoglobin variants; alternative markers like fructosamine or glycated albumin must be used instead, as recommended by the American Association of Clinical Endocrinologists 1, 2, 5

Glucose testing will be necessary for screening, diagnosis, and management in individuals with disorders that affect red blood cell turnover, as HbA1c may provide spurious results, according to the American Diabetes Association 1, 2
Use fructosamine or glycated albumin in clinical settings where abnormalities in red blood cell turnover, hemoglobin variants, or other interfering factors compromise HbA1c interpretation, though these reflect a shorter period of average glycemia, as recommended by the American Association of Clinical Endocrinologists 1, 2, 5

Laboratories should be aware of potential interferences including hemoglobin variants that may affect HbA1c test results depending on the method used, and should consider the potential for interferences in their particular patient population when selecting assay methods, according to the American Association for Clinical Chemistry 1, 2, 5

Never base treatment decisions solely on a single HbA1c measurement without consideration of glucose monitoring results in beta-thalassemia patients, as this may lead to unnecessary initiation or intensification of therapy, as warned by the American College of Physicians 6, 7, 8
HbA1c should be interpreted with caution when there is a discrepancy with self-monitored blood glucose readings, especially in patients with suspected hemoglobinopathy, according to the American Association of Clinical Endocrinologists 6, 7