Haemoglobin molecules in red blood cells transport and distribute oxygen to cells throughout the body. Haemoglobin is composed of two portions – haeme (iron component) and globin (protein chain).

Haemoglobin variants occur when mutations in the globin genes result in changes in the globin protein chain. Haemoglobinopathy is the condition characterised by the presence of haemoglobin variants in the blood. The most common haemoglobin variants are HbS, HbC and HbE.

Haemoglobin Type Prevalence
Haemoglobin S (HbS) 8.3 % of African Americans
1 % of Hispanics
Haemoglobin C (HbC) 2.3 % of African Americans
(West African descent)
Haemoglobin E (HbE) 30 % of Southeast Asians
Haemoglobin D (HbD) 2 % of North Indians and descendants
from Pakistan and Afghanistan
Haemoglobin F (HbF) 1.5 % of patients have a persistence of
fetal haemoglobin ranging from 2–12 % HbF1

How do Haemoglobin Variants Affect HbA1c Results?

There are a variety of methods used to measure HbA1c and most methods are susceptible to interference from variant haemoglobins such as HbS and HbC. This interference may cause an abnormally high or low HbA1c result.

When Should a Healthcare Provider Suspect that a Diabetic Patient has a Haemoglobinopathy?

Healthcare providers and clinical laboratories need to be aware of the effects of haemoglobin variants upon HbA1c test results. A healthcare provider should suspect the presence of a haemoglobinopathy if the blood glucose monitoring results have a low correlation with HbA1c results, the HbA1c result is different than expected, the HbA1c result is more
than 15 % or if a patient’s HbA1c test result is radically different from a previous test result following a change in the method for measuring HbA1c.2

Clinical Implications of Haemoglobinopathy

In patients with haemoglobinopathy, HbA1c testing may result in high or low readings that can lead to the over-treatment or under-treatment of their diabetes. Patients suspected of having a haemoglobinopathy should have at least one HbA1c test using an HPLC or boronate affinity methodology in order to rule out the presence of variant haemoglobins.3

Further information regarding factors that influence HbA1c test results can be obtained from the National Glycohaemoglobin Standardisation Program (NGSP) website.


  1. Smaldone A. Glycemic Contorl and Hemoglobinopathy: When A1C May Not Be Reliable. Diabetes Spectrum 21:46–49, 2008.
  2. Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 48: 436–472, 2002.
  3. Sacks D. Hemoglobin Variants and Hemoglobin A1c Analysis: Problem Solved? Clin Chem 49: 1245–1247, 2003.