What are the causes of falsely elevated Hemoglobin A1c (HbA1c) levels?

From the Guidelines

Falsely elevated Hemoglobin A1c (HbA1c) levels can be caused by several factors, including iron deficiency anemia, which prolongs erythrocyte life span and exposes the cell to glucose for a longer period 1.

Causes of Falsely Elevated HbA1c Levels

• Conditions that alter erythrocyte life span: Conditions such as iron deficiency anemia can lead to falsely elevated HbA1c levels, while conditions that shorten erythrocyte life span, such as hemolytic anemia, may result in falsely low HbA1c levels 1.
• Hemoglobin variants: Hemoglobin variants can result in falsely elevated or falsely lowered HbA1c levels, depending on the assay used 1.
• Chronic kidney disease: Chronic kidney disease may alter HbA1c measurement, and HbA1c results may not accurately reflect blood glucose control in patients with kidney disease, particularly those on dialysis 1.
• Oral hypoglycemic agents: Oral hypoglycemic agents, such as metformin or sulfonylureas, may alter the relationship between blood glucose and HbA1c levels, although the clinical significance is unclear 1.
• Laboratory methods: Certain laboratory methods, such as those using older assay techniques, may be more prone to interference and result in false high A1c readings 1. It is essential to consider these potential causes of false high readings when interpreting HbA1c results to ensure accurate assessment of blood glucose control 1.

From the Research

Causes of Falsely Elevated Hemoglobin A1c (HbA1c) Levels

• Hemoglobinopathies, such as Hemoglobin Wayne 2 and S-beta+-thalassemia 3, can cause falsely elevated HbA1c levels.
• Anemia, lead poisoning, chronic alcoholism, and opioid use can also lead to unreliable HbA1c results 2.
• Certain conditions that impair erythrocyte production or alter the normal process of glycation can affect HbA1c measurements 4.
• Patient ethnicity and normal aging can also cause variations in HbA1c results 4.
• Frequent HbA1c measurements can lead to unnecessary treatment modifications and falsely elevated results, which can be reduced by applying automated and educative HbA1c re-testing intervals 5.

Specific Conditions that Interfere with HbA1c Assays

• S-beta+-thalassemia can interfere with the Bio-Rad Variant II Turbo HbA1c assay, causing falsely elevated A1c results 3.
• Hemoglobin Wayne is a rare variant of hemoglobin that can result in false elevation of HbA1c 2.

Clinical Implications

• Clinicians should be aware of the underlying causes of falsely elevated HbA1c levels to avoid unexpected consequences and ensure accurate diagnosis and treatment of diabetes mellitus 2, 3, 4, 6.