What causes falsely elevated or decreased Hemoglobin A1c (HbA1c) levels?

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From the Guidelines

False A1C levels can be caused by several factors, including conditions that alter erythrocyte life span, such as iron deficiency anemia, hemolytic anemia, and chronic kidney disease, as well as hemoglobin variants and certain medications, according to the most recent evidence 1. These factors can lead to falsely high or low readings, and it is essential to consider them when interpreting A1C results.

  • Conditions that prolong erythrocyte life span, such as iron deficiency anemia, can result in falsely elevated HbA1c levels 1.
  • In contrast, conditions that shorten erythrocyte life span, such as hemolytic anemia, may result in falsely low HbA1c levels 1.
  • Hemoglobin variants can also result in falsely elevated or lowered HbA1c levels, depending on the assay used 1.
  • Certain medications, such as oral hypoglycemic agents, may alter the relationship between blood glucose and HbA1c levels, although the clinical significance is unclear 1.
  • Additionally, racial/ethnic differences in HbA1c levels for a given level of glycemia have been observed, with African Americans having higher HbA1c values than white persons for any measure of glycemia 1.
  • Laboratory errors or differences in testing methods between facilities can also contribute to inconsistent results 1.
  • Vitamins C and E have been reported to lower HbA1c results falsely, possibly by inhibiting glycation of hemoglobin 1.
  • Iron-deficiency anemia is reported to increase test results 1.
  • Hypertriglyceridemia, hyperbilirubinemia, uremia, chronic alcoholism, chronic ingestion of salicylates, and opiate addiction are reported to interfere with some assay methods, falsely increasing results 1. It is recommended that healthcare providers consider these factors when interpreting A1C results and discuss alternative testing methods with patients if necessary, such as fructosamine tests or continuous glucose monitoring, which can provide more accurate assessments of glucose control 1.

From the Research

Causes of False A1C Levels

  • Hemoglobin variants, such as Hb Hirose (β-37Trp→Ser) and β-198A→G mutation, can cause falsely elevated HbA1c levels regardless of the measurement method used 2
  • Increased red blood cell lifespan can contribute to high HbA1c levels measured by various methods 2
  • Hemoglobin antigenicity due to gene mutations may affect HbA1c levels measured by immunoassay 2
  • Sickle cell disease can lead to unreliable HbA1c results, and alternative markers such as serum fructosamine may be used to monitor glycemic control 3
  • Clinical scenarios and interfering factors, such as hemolytic anemia and chronic transfusion therapy, can yield false A1c results 4

Factors Affecting A1C Measurement

  • Red blood cell lifespan and hemoglobin variants can impact A1c measurement 2
  • Chronic transfusion therapy can affect HbA1c levels in patients with sickle cell disease and diabetes 3
  • Hematological disorders, such as sickle cell disease, can lead to inaccurate A1c results 5, 6

Alternative Markers for Glycemic Control

  • Serum fructosamine can be used as an alternative marker for monitoring glycemic control in patients with sickle cell disease and diabetes 3
  • Continuous blood glucose monitoring and glycated albumin level can also be used to assess glycemic control 2

References

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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