Does Hemoglobin E (HbE) trait, heterozygous, affect HbA1c (hemoglobin A1c) measurement or interpretation?

Impact of Hemoglobin E Trait on HbA1c Measurement and Interpretation

Most assays used in the U.S. are accurate in individuals heterozygous for common hemoglobin variants, including Hemoglobin E trait, though clinicians should verify their specific assay method for potential interference. 1

Understanding HbA1c and Hemoglobin Variants

HbA1c is the primary tool for assessing glycemic control in diabetes management, reflecting average glycemia over approximately 2-3 months. However, certain factors can affect the accuracy of HbA1c measurements, including hemoglobin variants.

Hemoglobin E Trait and HbA1c Measurement:

• Assay Accuracy: Most National Glycohemoglobin Standardization Program (NGSP)-certified assays used in the United States provide accurate results in individuals who are heterozygous for common hemoglobin variants, including HbE 1

• Method-Specific Interference: The effect of HbE trait on HbA1c measurement varies by the specific laboratory method used:

  • Some assays show statistically significant interference but not clinically significant differences
  • Boronate affinity chromatography methods may be more reliable for patients with hemoglobin variants 2

• Potential for Misinterpretation: When using certain high-performance liquid chromatography (HPLC) methods, HbE trait may result in undetectable or falsely low HbA1c values 3

Clinical Approach to HbA1c Interpretation with HbE Trait

When to Suspect Interference:

• Discordant Results: Marked discrepancy between measured HbA1c and plasma glucose levels should raise suspicion of HbA1c assay interference 1

• Microcytosis: MCV of 80fl or below may serve as a rough guide to identify samples that might have hemoglobin variants affecting HbA1c measurement 3

• Unexpected Values: Unexpectedly low or undetectable HbA1c results despite elevated blood glucose levels 3

Management Algorithm:

1. Verify assay method compatibility:

   • Check the NGSP website (www.ngsp.org/interf.asp) for updated information on which assays are affected by HbE trait 1
   • Consult with the laboratory to determine if their specific assay is known to have interference with HbE

2. If interference is suspected:

   • Request an alternative assay method without interference with HbE trait 1
   • Consider using plasma glucose criteria for diagnosis instead 1

3. Consider alternative glycemic markers:

   • Fructosamine or glycated albumin can be used to assess glycemic control over 2-3 weeks 2, 4
   • Continuous glucose monitoring (CGM) provides detailed glycemic patterns and can calculate estimated A1c 1, 2
   • Self-monitoring of blood glucose (SMBG) can help validate HbA1c results 1

Important Caveats and Pitfalls

• Laboratory Notification: Inform the laboratory about the presence of HbE trait when ordering HbA1c tests

• Regular Monitoring: For patients with known HbE trait, consistent use of the same laboratory method is important for reliable trend monitoring

• Method Switching: Changing between different assay methods may result in apparent changes in HbA1c that do not reflect actual changes in glycemic control

• Documentation: Document the presence of HbE trait in the patient's medical record to ensure appropriate interpretation of HbA1c results

• Comprehensive Assessment: Use multiple methods to assess glycemic control when HbA1c reliability is questionable 2

By understanding these considerations, clinicians can appropriately interpret HbA1c results in patients with HbE trait and make informed decisions about diabetes management to optimize patient outcomes.