Effects of hemoglobin (Hb) E and HbD traits on measurements of glycated Hb (HbA1c) by 23 methods.
BACKGROUND
Glycohemoglobin (GHB), reported as hemoglobin (Hb) A(1c), is a marker of long-term glycemic control in patients with diabetes and is directly related to risk for diabetic complications. HbE and HbD are the second and fourth most common Hb variants worldwide. We investigated the accuracy of HbA(1c) measurement in the presence of HbE and/or HbD traits.


METHODS
We evaluated 23 HbA(1c) methods; 9 were immunoassay methods, 10 were ion-exchange HPLC methods, and 4 were capillary electrophoresis, affinity chromatography, or enzymatic methods. An overall test of coincidence of 2 least-squares linear regression lines was performed to determine whether the presence of HbE or HbD traits caused a statistically significant difference from HbAA results relative to the boronate affinity HPLC comparative method. Deming regression analysis was performed to determine whether the presence of these traits produced a clinically significant effect on HbA(1c) results with the use of +/-10% relative bias at 6% and 9% HbA(1c) as evaluation limits.


RESULTS
Statistically significant differences were found in more than half of the methods tested. Only 22% and 13% showed clinically significant interference for HbE and HbD traits, respectively.


CONCLUSIONS
Some current HbA(1c) methods show clinically significant interferences with samples containing HbE or HbD traits. To avoid reporting of inaccurate results, ion-exchange chromatograms must be carefully examined to identify possible interference from these Hb variants. For some methods, manufacturers' instructions do not provide adequate information for making correct decisions about reporting results.
Little
Randie R
RR
Department of Pathology & Anatomical Sciences, University of Missouri-Columbia School of Medicine, Columbia, MO 65212, USA. littler@health.missouri.edu
Rohlfing
Curt L
CL
Hanson
Steve
S
Connolly
Shawn
S
Higgins
Trefor
T
Weykamp
Cas W
CW
D'Costa
Mario
M
Luzzi
Veronica
V
Owen
William E
WE
Roberts
William L
WL
D000704:Analysis of Variance; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D003920:Diabetes Mellitus / Q000097:blood*; D019075:Electrophoresis, Capillary; D014644:Genetic Variation; D006442:Glycated Hemoglobin / Q000032:analysis*; D006446:Hemoglobin E / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D016018:Least-Squares Analysis; D016014:Linear Models; D012680:Sensitivity and Specificity
D006442:Glycated Hemoglobin; D006446:Hemoglobin E; D006455:Hemoglobins, Abnormal; C032001:hemoglobin D