Management of Suspected HbA1c False Errors
Initial Verification Algorithm
- When HbA1c results appear discordant with clinical presentation or self-monitored blood glucose readings, immediately repeat the HbA1c test using the same laboratory method and simultaneously obtain fasting plasma glucose or perform glucose-based testing to confirm true glycemic status 1, 2
- The American Diabetes Association recommends repeating HbA1c without delay using the identical laboratory method to rule out laboratory error before making any diagnostic or treatment decisions, and simultaneously obtaining fasting plasma glucose (FPG) or performing oral glucose tolerance test (OGTT) for comparison 2
Diagnostic Workup for Discordant Results
- The American Diabetes Association suggests that conditions causing falsely low HbA1c include hemolytic anemia, recent acute blood loss or transfusion, pregnancy, and chronic kidney disease, while conditions causing falsely high HbA1c include iron deficiency anemia and occult malignancies affecting bone marrow function 1, 2
- Essential laboratory tests include complete blood count to assess for anemia, iron studies to evaluate for iron deficiency, reticulocyte count to assess RBC turnover, and hemoglobin electrophoresis if hemoglobin variant is suspected 1, 4
Critical Decision Points
- If HbA1c is ≥6.5% but FPG <126 mg/dL, repeat HbA1c immediately using same method, and if repeat HbA1c remains ≥6.5%, diabetes is confirmed even if FPG remains <126 mg/dL, according to the American Diabetes Association 2
- Absolute contraindications to using HbA1c for diagnosis include homozygous hemoglobin variants and conditions with abnormal RBC turnover, such as hemolytic anemia, recent blood loss or transfusion, and pregnancy, as stated by the American Diabetes Association 1, 2
Alternative Glycemic Markers
- When HbA1c is unreliable, use fructosamine or glycated albumin, which reflects 2-3 weeks of glycemic control and is unaffected by RBC disorders, or continuous glucose monitoring (CGM), which provides comprehensive glycemic patterns and identifies missed excursions, as recommended by the American Diabetes Association 1, 4
Special Populations Requiring Glucose-Based Testing
- Mandatory use of glucose criteria only (not HbA1c) is required for pregnant women, patients with hemolytic anemia of any cause, recent blood transfusion recipients, chronic kidney disease with shortened RBC lifespan, and known homozygous hemoglobin variants, according to the American Diabetes Association 1, 2
Laboratory Quality Considerations
- Ensure laboratory uses NGSP-certified methods traceable to DCCT reference standards, and laboratories must be aware of potential interferences in their specific patient population and select appropriate assay methods, as stated by the American Diabetes Association 1
Additional Interfering Factors
- Medications and supplements potentially affecting HbA1c include vitamins C and E, which may falsely lower HbA1c, and chronic salicylate use, which may falsely increase results with some methods, according to the American Diabetes Association 1, 4
- Age and race considerations include HbA1c increasing approximately 0.1% per decade after age 30 in people without diabetes, and African Americans may have HbA1c values 0.4% higher than whites for equivalent glycemia, as noted by the American Diabetes Association 4