Clinical Chemistry
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Clinical Chemistry 44: 1999a-2000a, 1998;
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(Clinical Chemistry. 1998;44:1999-2000.)
© 1998 American Association for Clinical Chemistry, Inc.

Letters

Hemoglobin D [ß 121(GH4)Glu->Gln] Causing Falsely Low and High HbA1c Values in HPLC

Wolfgang J. Schnedl1,a, Rainer W. Lipp1, Martin Trinker1, and Pierre Hopmeier2

1 Department of Internal Medicine, Karl-Franzens University, Auenbruggerplatz 15, 8036 Graz, Austria,
2 Central Laboratory, City Hospital Rudolfstiftung, 1030 Vienna, Austria
a Author for correspondence. Fax 43-316-385-3062; e-mail wolfgang.schnedl{at}kfunigraz.ac.at.


To the Editor:

Despite advances in the standardization of methods for glycohemoglobins (1) , hemoglobinopathies may falsely lower glycohemoglobin values and may cause falsely high hemoglobin (Hb)A1c values and/or additional peaks in HPLC chromatograms (2)(3) . We report a 66-year-old female Caucasian diabetic patient, treated with diet, whose HbA1c was repeatedly 3.2% (reference interval in nondiabetics, 4.2–6.1%) as measured with the Diamat HPLC (Bio-Rad Laboratories). The chromatogram contained no anomalous peaks, and neither low blood glucose values nor symptoms of hypoglycemia were detectable. The Diamat HPLC uses a borate-containing buffer and a step gradient of three phosphate buffers with increasing ionic strength.

The patient's HbA1c value with a second HPLC method (Hi-Auto A1c, HA-8140, Menarini Diagnostics) was repeatedly 8.4% (reference values, 4.5–5.7%), and the HPLC chromatogram showed an additional peak at HbAo. This analyzer system denoted the chromatogram as abnormal separation. This HPLC method uses cation-exchange and reversed-phase chromatography on a solid phase of methacrylic acid and methacrylate ester. The hemoglobin fractions are eluted by varying the pH of the mobile phase.

The mean blood glucose of our patient was near the upper limit if the reference interval is at 7 mmol/L (126 mg/dL), based on a mean of 3–4 daily home measurements during 1 week before HbA1c evaluation. The serum fructosamine was 256 µmol/L (reference values <285 µmol/L). Electrophoretic analysis on cellulose acetate membranes (Helena Laboratories) of a blood sample from our patient revealed an abnormal hemoglobin anodal to HbS. Citrate agar electrophoresis of hemoglobin using citrate buffer at pH 6.2 demonstrated a hemoglobin variant co-migrated with HbA. Identification of HbD was performed with the ß-Globin StripAssay (Vienna Lab) using reverse-hybridization with the patient's amplified DNA and probes for HbD. Routine hematological indices were within reference values.

We conclude that HbD, a common hemoglobinopathy (4) , may cause diagnostic confusion because of falsely low and high HbA1c values when measured by these two HPLC methods. This supports the suggestion that fructosamine measurement is a suitable alternative to control diabetes in patients with hemoglobin variants (5) .


References

  1. Eckfeld JH, Bruns DE. Another step toward standardization of methods for measuring hemoglobin A1c [Editorial]. Clin Chem 1997;43:1811-1813. [Free Full Text]
  2. Schnedl WJ, Reisinger EC, Katzensteiner S, Lipp RW, Schreiber F, Hopmeier P, et al. Haemoglobin O Padova and falsely low haemoglobin A1c in a patient with type I diabetes. J Clin Pathol 1997;50:434-435. [Abstract/Free Full Text]
  3. Schnedl WJ, Reisinger EC, Lipp RW, Krejs GJ, Hopmeier P. Hemoglobin variants recently detected in Austria. Ann Hematol 1995;71:185-187. [Medline] [Order article via Infotrieve]
  4. Fioretti G, De Angioletti M, Pagano L, Lacerra G, Viola A, De Bonis C, et al. DNA polymorphism associated with HbD-Los Angeles [beta 121(GH4)Glu->Gln] in southern Italy. Hemoglobin 1993;17:9-17. [Medline] [Order article via Infotrieve]
  5. Halwachs-Baumann G, Katzensteiner S, Schnedl W, Pürstner P, Pieber T, Wilders-Truschnig M. Comparative evaluation of three assay systems for the automated determination of hemoglobin A1c. Clin Chem 1997;43:511-517. [Abstract/Free Full Text]




This Article
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