Factors that Interfere with HbA1c Test Results
Updated 4/2010
Information for physicians and patients regarding HbS, HbC, HbE and HbD traits
More about hemoglobin variants and HbA1c can also be found at 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
Hemoglobin Variants and Derivatives: Genetic variants (e.g. HbS trait, HbC trait) and chemically modified derivatives of hemoglobin (e.g. carbamylated Hb in patients with renal failure, acetylated Hb in patients taking large amounts of aspirin) can affect the accuracy of HbA1c measurements. The effects vary depending on the specific Hb variant or derivative and the specific HbA1c method. Table 1 contains information for most of the commonly used HbA1c methods for some of the more common Hb variants and derivatives. Interferences from less common Hb variants and derivatives are discussed in Bry, et al (1). All entries in Table 1 are based on published information. In addition, if a product insert indicates clearly that there is inference from a particular factor, then the interference is entered as “yes” and the product insert is cited. When selecting an assay method, laboratories should take into consideration characteristics of the patient population served, (e.g. high prevalence of hemoglobinopathies or renal failure).
Shortened Erythrocyte Survival: Any condition that shortens erythrocyte survival or decreases mean erythrocyte age (e.g., recovery from acute blood loss, hemolytic anemia) will falsely lower HbA1c test results regardless of the assay method used (23). HbA1c results from patients with HbSS, HbCC, and HbSC must be interpreted with caution given the pathological processes, including anemia, increased red cell turnover, transfusion requirements, that adversely impact HbA1c as a marker of long-term glycemic control. Alternative forms of testing such as glycated serum protein (fructosamine) should be considered for these patients.
Other factors: Vitamins C and E are reported to falsely lower test results, possibly by inhibiting glycation of hemoglobin (24, 25); vitamin C may increase values with some assays (25). Iron-deficiency anemia is reported to increase test results (26). Hypertriglyceridemia, hyperbilirubinemia, uremia (see carbamylated Hb in Table 1), chronic alcoholism, chronic ingestion of salicylates, and opiate addiction are reported to interfere with some assay methods, falsely increasing results (3, 5, 9, 11, 12, 14, 16-18, 21-22, 27-30).
Table 1: Effects of frequently encountered Hb variants and derivatives on HbA1c measurement |
Method |
Interference (Yes/No) |
|||||
Hb C trait |
Hb S trait |
Hb E trait |
Hb D trait |
Elevated |
Carbamyl-Hb |
|
*Abbott Architect (Seradyn Reagents) |
Yes 35 |
Yes 35 |
- |
- |
- |
- |
*Axis-Shield Nycocard (Primus Nycocard) |
No 4 |
No 4 |
- |
- |
- |
- |
*Axis-Shield Afinion |
No 38 |
No 38 |
No 40 |
No 40 |
- |
- |
*Bayer (previously Metrika) A1c Now |
Yes 31 |
Yes 31 |
No 40 |
No 40 |
- |
- |
*Beckman Synchron |
No 4 |
No 4 |
No 40 |
No 40 |
- |
- |
*Bio-Rad D-10 (short Program) |
Yes/No 31, 38 |
No 31, 38 |
No 40 |
No 40 |
- |
- |
*Bio-Rad D-10 (extended program) |
No 38 |
No 38 |
No 40 |
No 40 |
- |
- |
*Bio-Rad Variant A1c |
No 1, 2, 38 |
Yes/No 1, 2, 38 |
No 1,7, 40 |
No 40 |
- |
Yes 1, 3, 11, 12, 14 |
*Bio-Rad Variant II A1c |
Yes/No 31, 4, 32, 38 |
Yes/No 31, 4 ,32, 38 |
No 40 |
No 40 |
No 33, 39 |
No 11 |
*Bio-Rad VARIANT II TURBO A1c (270-2415/2417) |
No 38 |
No 38 |
Yes 40 |
Yes 40 |
- |
- |
*Bio-Rad Deeside MicroMat (previously Provalis; also sold by Cholestech as GDX) |
Yes4 |
No4 |
- |
- |
- |
|
*Dade Dimension |
No 31 |
No 31 |
No 40 |
No 40 |
- |
- |
Diazyme Direct Enzymatic HbA1c |
No 38, 43 |
No 38, 43 |
No 40, 43 |
No 40 |
- |
- |
Drew Scientific DS5 |
No 31 |
Yes 31 |
- |
- |
- |
- |
Helena Glyco-Tek |
Yes 4, 5 |
No 4, 5 |
- |
- |
- |
- |
*Menarini HA8140 |
No 4 |
Yes 4 |
Yes 1, 15 |
Yes 44 |
No 1, 15 |
Yes/No 1, 3, 16, 17 |
*Menarini HA8160 (Diabetes Mode) |
No 31 |
No 31 |
Yes 40 |
Yes 40 |
- |
- |
*Menarini HA8160 (Thalassemia Mode) |
- |
- |
No 40 |
Yes 40 |
- |
- |
Microgenics |
No 38 |
No 38 |
- |
- |
- |
- |
* Olympus |
Yes 35, 36, 38 |
Yes 35, 36, 38 |
No 40 |
No 40 |
Yes (>10%) 36 |
- |
Ortho-Clinical Vitros |
No 32, 38 |
No 32, 38 |
No 40 |
No 40 |
- |
- |
Pointe Scientific Hemoglobin A1c |
No 32, 38 |
No 32, 38 |
No 40 |
No 40 |
- |
- |
*Primus Boronate Affinity HPLC |
No 1, 2, 31, 38 |
No 1, 2, 31, 38 |
No 1, 7, 40 |
No 40 |
Yes 33, 39 |
No 1, 3, 9, 18 |
Randox Haemoglobin A1c |
Yes 37 |
Yes 37 |
- |
- |
Yes (>10%) 37 |
- |
*Roche Cobas Integra |
Yes 4 |
Yes 4 |
- |
- |
- |
- |
*Roche Cobas Integra Gen2 |
No 38, 41, 42, |
No 38, 41, 42 |
No 40 |
No 40 |
- |
- |
*Roche Tina-quant II |
No 1, 2, 19 |
No 1, 2, 19 |
No 1, 19, 40 |
No 40 |
No (<30% HbF) 19 |
No 1, 3, 16 |
*Roche Unimate |
Yes 1, 20 |
Yes 1, 20 |
- |
-- |
- |
No 1, 3, 11 |
*Siemens (previously Bayer) Advia HbA1c (original version) |
Yes 34 |
Yes 34 |
- |
- |
- |
- |
*Siemens Advia A1c (new version) |
No 45, 46 |
No 45, 46 |
- |
- |
- |
- |
*Siemens (previously Bayer) DCA 2000 |
Yes/No 1, 5, 6, 13 |
No 1, 5 |
No 1, 7, 8, 40 |
No 40 |
Yes 33, 39 |
No 3, 9 |
*Tosoh A1c 2.2 Plus |
No 1, 2, 31 |
No 1, 2, 31 |
Yes 1, 7, 40 |
No 40 |
Yes 33, 39 |
Yes/No 1, 3, 11, 14, 16, 21, 22 |
*Tosoh G7 (Variant Analysis Mode) |
No 31, 38 |
No 31, 38 |
Yes 40 |
No 40 |
No 33, 39 |
- |
*Tosoh G8 (Variant Analysis Mode) |
No 46 |
No 46 |
Yes 40 |
No 40 |
- |
- |
* indicates NGSP certification at the time of this update (August 2009) Yes/No indicates that there is conflicting data in the literature. The indicator in bold is the opinion of the NGSP based on review of the literature cited. |
NOTE:
- Many other publications have been reviewed. Only those with conclusions that are reasonably supported by data are included.
- For ion-exchange HPLC methods, interference from Hb variants and adducts may be dependent on the lot of reagents used (2).
References:
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