Hemoglobin A1c (HbA1c) is formed from the addition of a glucose residue to the N terminus of the Beta chain of a hemoglobin molecule via a non-enzymatic glycation pathway. Its levels correlate with the ambient plasma glucose concentration. The 120-day life span of red blood cells makes HbA1c a useful tool to approximate the diabetic control of patients over three to four months. It has also been found to be an accurate predictor of the microvascular and macrovascular complications of DM. The measurement of HbA1c works on the principle of separating and quantifying glycated hemoglobin chains. Several techniques have been developed for daily clinical use including High Pressure Liquid Chromatography (HPLC) via ion exchange and immunoassay techniques. However, there are caveats to their uses with some limitations. Several factors can cause assay interference including hemoglobinopathies. Hemoglobinopathies such as Thalessemia (HbH) disease can affect HbA1c results through both HPLC and immunoassay methods. We report a case of a patient with a falsely low HbA1c in a patient with known Thalessemia (HbH disease) and DM. The error occurred on both HbA1c assays available in our local hospital. His HbA1c was discordant with his home serial blood glucose monitoring (SBGM) and real-time interstitial glucose monitoring. This posed an important clinical management challenge. Further evaluation and analysis of the HPLC chromatogram revealed an inaccurate estimation of HbA1c via the HPLC method. It is important to recognise such pitfalls. While HbA1c may be a popular marker to assess patients long-term glycemic control, clinical judgement needs to be exercised in situations where serial blood glucose monitoring does not correlate. In patients with Thalessemia HbH disease, other markers of glycemic control such as fructosamine should be considered.
References: 1. Pravatmuang P, Sae-Ngow B, Whanpuch T, Leowattana W. Effect of HbE and HbH on HbA1C level by ionic exchange HPLC comparing to immunoturbidimetry. Clinica Chimica Acta. 2001; 313(12):171178.
2. Agilli M, Yaman H, Aydin FN, et al. Hb H interference on measurement of HbA1c with ion-exchange HPLC. Acta Inform Med. 2013;21:216218.
3. Khera R, Singh T, Khuana N, Gupta N, Dubey AP. HPLC in characterization of hemoglobin profile in thalassemia syndromes and hemoglobinopathies: a clinicohematological correlation. Indian J Hematol Blood Transfus. 2014;31(1):1105.
18 - 21 May 2019
European Society of Endocrinology