gycosylated haemoglobin (HbA1c) and haemoglobin variants

Last reviewed 05/2021

• HbA1c is characterized and defined as hemoglobin that is irreversibly glycated at the N-terminal valine of the ß-chain
  • HbA1c is an index used in the management of patients with diabetes
  • HbA1c measurements rely on a predictable effect of glucose concentration on hemoglobin (Hb) over a normal red blood cell (RBC) life span - however any condition that alters RBC survival may invalidate HbA1c as an accurate measure of glycaemic control
    • risk of misdiagnosis in those with iron-deficiency anemia and increased red blood cell turnover (e.g., haemolytic anemia or major blood loss) (1)
    • iron-deficiency anemia is associated with higher concentrations of HbA1c among pediatric patients with type 1 diabetes despite similar levels of glycemia (1)
    • iron replacement therapy can also result in a substantial drop in HbA1c in both diabetic and non-diabetic subjects (1)
      
      
  • samples containing variant Hb cause erroneous results in measurement of HbA1c
  • comparative analyses of HbA1c in samples containing Hb variants have shown that different test systems may give different results
    • measurements of HbA1c percentages in subjects with Hb variants or high percentages of Hb derivatives may be affected differently in different methods
    • decreased exposure time of Hb to circulating glucose concentrations will lead to truly decreased percentages for HbA1c, with erroneous interpretation when the condition is not recognized (2,3)
      • for example with respect to sickle cell disease
        • heterozygous HbS
          • data from methods by HPLC and electrophoresis were variable, ranging from 'not detectable' to increased
        • homozygous HbS
          • will have a shortened red cell half-life
            • will show decreased HbA1c percentages that do not relate to mean blood glucose content

Please contact local laboratory service as to effect of haemoglobin variants and the measured value of glycosylated haemoglobin - this will depend on the particular test for glycosylated haemoglobin used.

Reference:

• (1) Lippi G, Targher G.A laboratory standpoint on the role of hemoglobin A1c for the diagnosis of diabetes in childhood: more doubts than certainties? Pediatr Diabetes. 2011 May;12(3 Pt 1):183-6.
• (2) Bry PC et al.Effects of hemoglobin variants and chemically modified derivatives on assays for glycohemoglobin. Clin. Chem.2001; 47:153-163
• (3) Clin Chem. 1993 ;39(8):1717-23