Hemoglobin variants and determination of glycated hemoglobin (HbA1c)

Abstract

Measurement of glycated hemoglobin in diabetic patients is an established procedure for evaluating long-term control of diabetes. The Diabetes Control and Complications Trial (DCCT), as well as the United Kingdom Prospective Diabetes Study (UKPDS), confirmed the direct relationship between the degree of glycemic control as estimated by glycohemoglobin (GHb) determinations and the development and progression of long-term complications in diabetic patients. Samples with known interferences of HbA(1c) determination as hemoglobinopathies are specifically excluded from certification testing and there are no guidelines or requirements for comparability of samples containing hemoglobin (Hb) variants. This paper reviews the interference of Hb variants on determination methods of glycated hemoglobin as they result in false HbA(1c) results.

HbA1c levels in individuals heterozygous for hemoglobin variants

“…26 New methods are being developed, such as mass spectrometry, which is based on the suppression of fluorescence of a boron eosin in acid solution, and shows minimal interference of the hemoglobin variants. [27][28][29][30] Despite these valuable attributes, cost of equipment and complexity of the operation limit its use. 31 According to studies, the presence of genetic variants of hemoglobin under heterozygous conditions may interfere with the measurement of HbA1c, resulting in falsely high or decreased values, depending on the type of test used.…”

A Case of Hemoglobin Beckman; An example of Hemoglobin Variants Interfering with HbA1c Measurement

“…To our knowledge, after Rahbar's and Kim's, this is the third case reported worldwide. [3,4]. HbA 1c analysing methods are mainly based on either molecular charge (ion exchange chromatography, electrophoresis) or structure (immunoassays, boronate affinity chromatography, mass spectrophotometry).…”

Glycated hemoglobin and liver disease in diabetes mellitus

“…It is conceivable that the interference is subtle in the normal range but increases with increasing HbA 1c . In general, a hemoglobin variant can be suspected in patients with HbA 1c results >15 %, HbA 1c measurements below the non-diabetic reference range, or when the HbA 1c result varies substantially from other indices of metabolic control and/or clinical impression [38]. Regardless of the assay method used, reduced erythrocyte survival or decreased mean erythrocyte age falsely lowers HbA 1c results [39,40].…”