HbA1c Assay Interferences
HbA1c methods: Effects of Hemoglobin Variants (HbC, HbS, HbE and HbD traits) and Elevated Fetal Hemoglobin (HbF)
Updated March 2013
More comprehensive information regarding HbA1c assay interferences
HbA1c, also called A1C, is a measure of the amount of glucose attached to hemoglobin (Hb) in red blood cells. The higher the glucose levels over the previous 2-3 months, the higher the A1C. The A1C test is used to monitor the glucose levels of patients who have been diagnosed with diabetes. In people who have hemoglobin variants such as HbS (sickle cell trait), some A1C tests give falsely high or low readings that can lead to the over-treatment or under-treatment of diabetes.
Laboratories use many different methods for measuring A1C, but some of these methods can give inaccurate results when the patient has a hemoglobin variant such as sickle cell trait or if there is an elevated level of fetal hemoglobin (HbF). Doctors or patients interested in getting information about the accuracy of a particular A1C method for patients with hemoglobin variants should first find out which method your laboratory is using.
The following table lists the 20 methods most often used to measure A1C and whether the method is affected by HbC, HbS, HbE or HbD trait or by elevated HbF. Methods are listed in alphabetical order by manufacturer. The criteria used to determine whether or not a method shows interference that is clinically significant (indicated by “Yes”) is >±7% at 6 and/or 9% A1C. If your diabetes patient has a hemoglobin variant, your lab should use a method that does not show interference from that variant in order to produce an accurate A1C result.
Method |
Interference from HbC |
Interference from HbS |
Interference |
Interference |
Interference |
Abbott Architect/Aeroset |
Yes |
Yes |
@ |
@ |
$ |
Arkray ADAMS A1c HA-8180V (Menarini) |
No |
No |
HbA1c not quantified |
HbA1c not quantified |
No |
Axis-Shield Afinion |
No |
No |
No |
No |
$ |
Bayer A1cNOW |
Yes |
Yes |
No |
No |
$ |
Beckman AU system |
Yes |
Yes |
No |
No |
$ |
Beckman Synchron System |
No |
No |
No |
No |
$ |
Bio-Rad D-10 (A1c program) |
No |
No |
No |
No |
Yes >10% HbF |
Bio-Rad Variant II NU |
- |
- |
No |
No |
Yes >10% HbF |
Bio-Rad Variant II Turbo |
No |
No |
Yes |
Yes |
Yes >5% HbF |
Bio-Rad Variant II Turbo 2.0 |
No |
No |
No/Yes |
No |
Yes >25% HbF |
Bio-Rad in2it |
Yes |
No |
Yes |
No |
$ |
Ortho-Clinical Vitros |
No |
No |
No |
No |
$ |
Roche Cobas Integra Gen.2 |
No |
No |
No |
No |
$ |
Roche/Hitachi (Tina Quant II) |
No |
No |
No |
No |
$ |
Sebia Capillarys 2 Flex Piercing |
No |
No |
No |
No |
No |
Siemens Advia HbA1c (original version) |
Yes |
Yes |
@ |
@ |
$ |
Siemens Advia A1c (new version) |
No |
No |
@ |
@ |
$ |
Siemens DCA 2000 |
No |
No |
No |
No |
Yes >10% |
Siemens Dimension |
No |
No |
No |
No |
$ |
Tosoh G7 |
Yes |
No |
Yes |
No |
No |
Tosoh G8 |
No |
No |
Yes |
No |
No |
Trinity (Primus) HPLC (affinity) |
No |
No |
No |
No |
Yes >15% HbF |
@ In the absence of specific method data, it can generally be assumed that immunoassay methods do not have clinically significant interference from HbE and HbD because the E and D substitution are distant from the N-terminus of the hemoglobin beta chain (1).
$ In the absence of specific method data, it can generally be assumed that both immunoassay and boronate affinity methods show interference from HbF levels above ~10-15% (2,3).
More comprehensive information regarding HbA1c assay interferences
More (from the NIDDK web site):
Sickle Cell Trait and Other Hemoglobinopathies and Diabetes: Important Information for Physicians
References:
1. Little RR, Rohlfing CR, Hanson S, Connolly S, Higgins T, Weykamp C, D'Costa M, Luzzi V, Owen WE, Roberts WL. Effects of hemoglobin E and D traits on glycated hemoglobin (HbA1c) Measurements by twenty-three methods. Clin Chem 2008;54:1277-82.
2. Little RR, Rohlfing CL, Hanson SE, Schmidt RL, Lin C-N, Madsen RW, and Roberts WL. The Effect of Increased Fetal Hemoglobin on 7 Common Hb A1c Assay Methods. Clin Chem 2012 58: 945-6.
3. Rohlfing C, Connolly S, England J, Hanson S, Moellering C, Bachelder J, Little R. The effect of elevated fetal hemoglobin on HbA1c results: five common HbA1c methods compared to the IFCC reference method. Amer J Clin Path 2008;129:811-4.