Evaluation of the Interference of Hemoglobin Variant J-Bangkok on Glycated Hemoglobin (HbA1c) Measurement by Five Different Methods

Abstract

The interference of the hemoglobin variant (Hb J-Bangkok) was evaluated on 4 different glycated hemoglobin assays and compared with a reference immuno assay. An overall test of coincidence of 2 least-squares linear regression lines was performed to determine whether the presence of Hb J-Bangkok caused a statistically significant difference in HbA1c results compared with a reference immuno assay. Statistical analysis was performed on the difference of the estimated average glucose calculated from HbA1c values and fasting plasma glucose in the Hb J-Bangkok variant group using the different detection systems. Deming regression analysis was used to determinate whether Hb J-Bangkok had a significant interference on HbA1c results using an HbA1c±10% relative bias at 6% and 9% HbA1c as evaluation limits. Turbidimetric inhibition immunoassay method, and enzymatic methods were not affected by Hb J-Bangkok. However, Hb J-Bangkok showed statistically significant interference to the two ion-exchange high-performance liquid chromatography methods. When performing HbA1c tests, clinical laboratory personnel should identify the Hb variant and select the appropriate methods or use alternative indicators.

Case Report: Abnormally Low Glycosylated Hemoglobin A1c Caused by Clinically Silent Rare β-Thalassemia in a Tujia Chinese Woman

“…The principle of enzymatic determination of HbA1c is that glycated glycine glutamine from the β chain N-terminus of HbAlc is cut off by a specific protease. The specific cleavage site of HbA1c is not affected by Hb J-Bangkok ( 17 ).…”

“…The accuracy of HbA1c in patients with hemoglobinopathy is method dependent. It has been reported that immunoassay and enzyme methods are not affected by Hb J-Bangkok ( 17 ). Immunoassays use specific antibodies to bind to glycated sites on the N-terminus of the Hb β chain of HbA1c, which is far from the location of the amino acid substitution of Hb J-Bangkok.…”

“…Immunoassays use specific antibodies to bind to glycated sites on the N-terminus of the Hb β chain of HbA1c, which is far from the location of the amino acid substitution of Hb J-Bangkok. Therefore, Hb J-Bangkok does not affect antibody recognition ( 17 ). The principle of enzymatic determination of HbA1c is that glycated glycine glutamine from the β chain N-terminus of HbAlc is cut off by a specific protease.…”

Hemoglobin J in a patient with severe anemia, a case report from Nepal

“…Most cases of Hb J are clinically silent and mostly discovered incidentally during routine investigations or in conjunction with other hemoglobinopathies such as thalassemia [ 8 ] and sickle cell anemia [ 9 ] while investigating these diseases. Interestingly, there are many reports of Hb J interfering with glycated hemoglobin measurements in diabetics [ [10] , [11] , [12] ]. There are case report of Hb J being detected following transfusion as well [ 13 ].…”

Assessment of Glycemic Control in Patients With Diabetes in Northern Sudan Using Calculated HbA1c

“…In contrast, others interfere with immunoassay [ 18 ]. Being simple and cost-effective, the mathematical calculation of HbA1c is becoming of value in areas with insufficient resources [ 19 ]. In areas with low resources, such as our setting in northern Sudan, the availability of HbA1c assessment is a big issue; hence the calculated HbA1c is a reasonable solution to assess glycemic control [ 19 ].…”