HbA1c Assay Interferences

HbA1c methods: Effects of Hemoglobin Variants (HbC, HbS, HbE and HbD traits) and Elevated Fetal Hemoglobin (HbF)

Updated June 2022

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 >±6% 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
from HbE

Interference
from HbD

Interference
from elevated HbF

Abbott Architect c Enzymatic

No

No

No

No

-

Alere Afinion

No

No

No

No

$

Arkray ADAMS A1c HA-8180V (Menarini)

No

No

HbA1c not quantified (no for ver. EU 1.41

HbA1c not quantified (no for ver. EU 1.41

No <30%

Beckman HbA1c Advanced B00389 Manual Application on DxC 700 AU AU system

No

No

No

No

$

Beckman HbA1c Advanced B93009 Online Application on DxC 700 AU

No

No

No

No

$

Beckman Synchron System Unicel DxC

No

No

No

No

$

Bio-Rad D-100 (A1c program)

No

No

No

No

-

Bio-Rad Variant II Turbo 2.0

No

No

No

No

No <25% HbF

Ortho-Clinical Vitros

No

No

No

No

$

Roche Cobas c513

No

No

No

No

$

Sebia Capillarys 2 Flex Piercing

No

No

No

No

No <15% HbF

Siemens DCA Vantage

No

Yes↑/ No*

Yes↑/ No*

No

No <10% HbF

Siemens Atellica

No

No

No

No

$

Siemens Dimension

No

No

No

No

$

Tosoh G8 ver. 5.24, 5.28

No

No

No

No

No <30% HbF

Trinity HPLC

No

No

No

No

No <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 immunoassay, boronate affinity and enzymatic methods show interference from elevated HbF levels (2,3).

# When HbE trait is detected there is no significant interference. In cases where the presence of HbE trait is not detected, HbA1c results are artificially lowered.

* Conflicting data in the literature

Interference causes a higher result
Interference causes a lower result

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 

For People of African, Mediterranean, or Southeast Asian Heritage: Important Information about Diabetes Blood Tests

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.