Unexpected high HbA1c results due to an unusual haemoglobin variant: an important clinical lesson

The measurement of glycated haemoglobin (Hb), reported as HbA1c, is recommended for the screening, diagnosis and monitoring of diabetes mellitus. HbA1c measurement usually provides an assessment of an individual’s glycaemic control over the previous 2–3 months and correlates with the development of diabetic complications. Standardisation of results attempts to ensure both intra- and inter-assay agreement so that an individual’s glycaemic control can be accurately monitored. Historically, standardisation was performed based on the Diabetes Control Complications Trial (HbA1c reported as a percentage), but more recently based on the International Federation of Clinical Chemistry (reported as mmol/mol). However, despite robust approaches towards measurement standardisation, it is recognised that HbA1c results might not necessarily provide a true reflection of glycaemic control. HbA1c can be falsely lowered by conditions that shorten erythrocyte survival or decrease mean erythrocyte age (eg, acute blood loss or haemolytic anaemia) irrespective of the assay method.1 Furthermore, other factors such as the presence of a haemoglobinopathy, iron deficiency anaemia, hypertriglyceridaemia, hyperbilirubinaemia, uraemia or exogenous toxins may interfere with some assay methods but not others. In these instances, alternative methods for monitoring long-term glycaemic control (including total HbA1c, plasma glucose or fructosamine measurement) are recommended.2 The presence of interfering factors is not always obvious, especially in the case of haemoglobinopathies that are not evident either clinically or within standard haematological indices. Here we report a rare and novel case of HbJ-CapeTown (plus an alpha chain triplicated 3.7 Kb mutation) resulting in falsely elevated HbA1c results and highlight the importance of visual analysis …