How does anemia affect Hemoglobin A1c (HbA1c) levels?

Impact of Anemia on Hemoglobin A1c (HbA1c) Levels

Anemia significantly affects HbA1c measurements, with iron deficiency anemia typically causing falsely elevated HbA1c values while conditions that shorten red blood cell lifespan (such as hemolytic anemia) cause falsely decreased HbA1c values. 1, 2

Types of Anemia and Their Effects on HbA1c

Conditions That Falsely Lower HbA1c

• Shortened RBC lifespan conditions:
  • Hemolytic anemia
  • Sickle cell disease/trait (approximately 0.3% lower HbA1c than expected) 1, 2
  • Glucose-6-phosphate dehydrogenase deficiency
  • Recent blood loss or transfusion
  • Pregnancy (second and third trimesters)
  • Hemodialysis/end-stage kidney disease
  • Erythropoietin therapy 1, 2

Conditions That Falsely Elevate HbA1c

• Iron deficiency anemia - increases HbA1c despite normal blood glucose levels 1, 3, 4
• Vitamin B12 or folate deficiency - can increase HbA1c values 1

Clinical Implications and Detection

When to Suspect HbA1c Measurement Interference

• Marked discordance between measured HbA1c and plasma glucose levels 1
• Surprisingly high or low HbA1c readings
• Significant change in HbA1c coincident with a change in laboratory method 1
• HbA1c values that don't align with clinical presentation or self-monitoring blood glucose data 2

Diagnostic Approach

1. Determine hemoglobin level first:

   • If Hb ≥ 10 g/dL: HbA1c can be used with caution
   • If Hb < 10 g/dL: Use alternative testing methods 2

2. For suspected hemoglobin variants:

   • Use an A1c assay without interference from hemoglobin variants
   • Consider boronate affinity chromatography method which may be more reliable 1, 2

Alternative Testing Methods

When anemia affects HbA1c reliability, consider:

• Continuous glucose monitoring (CGM) - provides detailed glycemic patterns and can calculate estimated A1c 2
• Self-monitoring of blood glucose (SMBG) - helps validate HbA1c results 2
• Fructosamine - reflects glycemic control over 2-3 weeks and is less affected by red blood cell lifespan (though can be impacted by hypoalbuminemia) 2
• Glycated albumin - more reliable in patients with hemolytic conditions 2
• Plasma glucose criteria - particularly important for patients with glucose-6-phosphate dehydrogenase deficiency 1, 2

Treatment Considerations

• Iron deficiency anemia: Treatment with iron supplementation has been shown to significantly decrease falsely elevated HbA1c levels (from 5.75% to 5.44% in one study) 4
• Avoid setting treatment targets based solely on HbA1c in patients with known anemia until the anemia is corrected 3
• Use multiple methods to assess glycemic control when HbA1c reliability is questionable 2

Important Clinical Pitfalls

• Failing to recognize anemia as a cause of HbA1c discrepancies can lead to inappropriate diabetes treatment decisions 2, 5
• Over 700 hemoglobin variants can interfere with HbA1c measurements, with some variants affecting certain assay methods more than others 1, 2
• Recent blood transfusion can affect HbA1c for 2-3 months 2
• Ethnic variations exist - African Americans may have higher HbA1c levels than non-Hispanic whites with similar glucose levels 1, 2

By understanding how different types of anemia affect HbA1c values, clinicians can make more accurate diagnostic and treatment decisions for patients with diabetes or suspected diabetes.