HbA1c Assay Interferences

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

Updated September 2014

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
from HbE

Interference
from HbD

Interference
from elevated HbF

Abbott Architect/Aeroset

Yes

Yes

@

@

$

Arkray ADAMS A1c HA-8180V (Menarini)

No

No

HbA1c not quantified

HbA1c not quantified

No <30% HbF

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

No <10% HbF

Bio-Rad Variant II NU

-

-

No

No

No <10% HbF

Bio-Rad Variant II Turbo

No

No

Yes

Yes

No <5% HbF

Bio-Rad Variant II Turbo 2.0

No

No

No/Yes
(conflicting reports)

No

No <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 <15% HbF

 Siemens Advia A1c (new version)

No

No

@

@

$

Siemens
DCA 2000/Vantage

No

No

No

No

No <10% HbF

Siemens Dimension

No

No

No

No

$

Tosoh G7

Yes

No

Yes

No

No ≤30% HbF

Tosoh G8

No

No

Yes

No

No ≤30% HbF

Trinity (Primus) HPLC (affinity)

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 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 

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.