A1C Test Errors

What causes A1C error? Changes in hemoglobin or red blood cells can have a detrimental impact on A1C testing. Conditions that affect the life span of red blood cells, such as blood loss, sickle cell disease, erythropoietin treatment, hemodialysis, or transfusion, bilirubin, and supplement use can affect A1C levels.  

Wise men learn from other men's mistakes; fools insist on learning from their own. ~ Albanian Proverb

9 Undesirable Factors Affecting the HbA1C Test

 Any variation in the RBC (or erythrocyte) or hemoglobin may cause hba1c errors. A1C can be increased or decreased by various factors; they are:

1. A decrease or increase in erythrocyte (RBC) makes your A1C lower or increase, respectively.
2. Hemoglobin Variants: Approximately 8% of African Americans have the hemoglobin S-trait. The hemoglobin C trait affects approximately 3% of African Americans. The hemoglobin E trait affects 10% to more than 50% of Southeast Asians in California. These Hb variants are all reported to affect some HbA1c assay methods. Elevated hemoglobin F is associated with thalassemia syndromes and affects some assay methods.
3. Hypertriglyceridemia interfered with some assay methods and increased results.
4. High bilirubin interferes with some assay methods and increases results.
5. Aspirin interfered with some assay methods and falsely increased results.
6. Chronic alcohol abuse produces a false high.
7. Splenectomy is a surgical procedure (removal of the spleen, either whole or partially); this raises A1C.
8. Chronic liver disease has a false A1C low.
9. Vitamin C & E ingestion interferes with some assay methods and decreases results.

A little doubt saves many a mistake. ~ Albanian Proverb

Causes of a decrease in erythrocytes that gives lower A1C results:

1. Anemia, Thalassemia or hemolytic anemia, and liver disease,
2. Hemorrhage or bleeding - heavy menstrual periods in women and stomach ulcers,
3. Hemolysis (RBC destruction) - due to transfusion, blood vessel injury, or other causes,
4. Erythropoietin deficiency - due to kidney diseases, Uremia (BUN more than 85 mg/dl), and Severe nephropathy.
5. Bone marrow conditions - include leukemia, multiple myelomas (plasma cell cancer), and lymphoma (blood cancer).
6. Medical conditions that lead to low RBC counts include cancer, rheumatoid arthritis, and HIV/AIDS.
7. Nutritional deficiencies, iron, copper, folate, and vitamins B6 & B12 can affect the result.
8. Some medications, such as drugs used for chemotherapy, chloramphenicol, hydantoins, and quinidine.
9. Overhydration
10. Pregnancy

Causes of an increase in erythrocyte (that gives high A1C)

1. Cigarette smoking
2. Congenital heart disease
3. Dehydration (due to severe diarrhea)
4. Kidney tumor (renal cell carcinoma)
5. Low blood oxygen level (hypoxia)
6. Pulmonary fibrosis
7. Polycythemia Vera
8. Medication: Gentamicin, Methyldopa

It is better to consider an alternative test if you encounter A1C interferences. These tests are glycated serum protein testing (fructosamine or glycated albumin). It helps assess glycemia better. Unfortunately, factors affecting the HbA1c accuracy cannot be recognized clinically.

A1C error chart

Unfortunately, factors that affect A1c accuracy cannot be clinically recognizable. Once you know the A1C interferences, go for an alternative test such as fructosamine or glycated albumin to help assess glycemia better. 

Understanding the Impact of Anemia on A1c Levels

Anemia can either cause false a1c low or high depending on the type and severity of the anemia. 

For instance:

• Increased RBC turnover: Hemolytic anemia can result in lower A1c levels because of the reduced lifespan of red blood cells, so less hemoglobin glycation.
• Decreased RBC production: Iron deficiency anemia or chronic disease anemia has an increase in A1c due to the prolonged lifespan of older red blood cells, so more glycation of hemoglobin over time.

Correction calculator for A1c in Anemia

Changes in red blood cell turnover impact the relationship between A1c and mean glucose concentration, which is the basis for the A1c correction in anemic patients.

This calculator is useful for iron deficiency, vitamin B-12, and folate deficiency anemias (false increase in a1c). This calculator is not for those with anemia (false low in a1c) from acute or chronic blood loss.

Corrected HbA1c = Measured HbA1c + (1.7 × (Measured Hemoglobin − 12))

Where: Measured HbA1c is the original HbA1c value obtained from the laboratory. Measured Hemoglobin is the patient's hemoglobin level in g/dL. 12 g/dL is the reference level of hemoglobin considered normal in adults.

Reference: Pitfalls in Hemoglobin A1c Measurement: When Results may be Misleading, Journal of General Internal Medicine 2013 Sep 4;29(2):388–394. 

Caution: This calculator is useful only if you are assessable to the fructosamine (which reflects average glucose levels over 2–3 weeks) or glycated albumin tests. Do not use this calculator value directly for diabetes management. Alternatively, you can use it as a reference.

A1C error correction calculator for Chronic liver disease patient

For liver cirrhosis patients, a low HbA1c did not indicate optimal glycemic control. In such situations, fructosamine and glycated albumin (GA) have been considered.

Chronic liver disease-HbA1c (CLD-HbA1c) = (A1c + GA/3)/2, 

The actual A1c = (2*CLD-HbA1c) – (GA/3)

where CLD-HbA1c represents the a1c value of the chronic liver disease patient. GA represents the portion of albumin glycated relative to the total albumin. The HbA1c, which is determined using average glucose, has been found to correlate well with it. Using the above relation, we can correct the A1c error for patients with chronic liver disease such as liver cirrhosis.

Reference: Inaccuracies of Hemoglobin A1c in Liver Cirrhosis: A Case Report, Journal of Endocrinology & Metabolism, Volume 6, Number 1, February 2016, pages 30-32.

Caution: This calculator is useful only if you are assessable to the fructosamine (which reflects average glucose levels over 2–3 weeks) or glycated albumin tests. Do not use this calculator value directly for diabetes management. Alternatively, you can use it as a reference.

A1c in chronic kidney disease

When it comes to chronic kidney disease (CKD), the accuracy of the A1c test can be affected. However, it's important to note that A1c may not be a reliable indicator of glycemic control in advanced CKD (eGFR < 60 mL/min/1.73 m² or on dialysis) patients.

Due to the changes in RBC lifespan, uremic conditions, and anemia associated with CKD, A1c may not accurately reflect glucose control. So, healthcare providers prefer using alternative methods to assess blood glucose control. 

Alternative method to assess blood glucose control

In patients with sickle cell disease or severe hemolysis, A1c may not be a reliable marker of long-term glucose control. In such cases, alternative methods such as fructosamine (which reflects average glucose levels over 2–3 weeks) or glycated albumin may be more useful for assessing glucose control.

You can click the following links to find the answers to any queries you may have.

• What are the benefits of the A1C test?
• What is the standard healthy A1C goal?
• What is an estimated average glucose (eAG)?
• What is the relation between A1C & glucose?
• Is there any chart for A1C to BS conversion?
• How can I lower my A1C?