Erroneous HbA1c results in a patient with elevated HbC and HbF.
BACKGROUND
HbA1c is used in the diagnosis and monitoring of diabetes mellitus (DM). Interference from hemoglobin variants is a well-described phenomenon, particularly with HPLC-based methods. While immunoassays may generate more reliable HbA1c results in the presence of some variants, these methods are susceptible to negative interference from high concentrations of HbF. We report a case where an accurate HbA1c result could not be obtained by any available method due to the presence of a compound hemoglobinopathy.


METHODS
HbA1c was measured by HPLC, immunoassay, and capillary electrophoresis. Hemoglobinopathy investigation consisted of a CBC, hemoglobin fractionation by HPLC and electrophoresis, and molecular analysis.


RESULTS
HbA1c analysis by HPLC and capillary electrophoresis gave no result. Analysis by immunoassay yielded HbA1c results of 5.9% (Siemens DCA 2000+) and 5.1% (Roche Integra), which were inconsistent with other markers of glycemic control. Hemoglobinopathy investigation showed HbC with the hereditary persistence of fetal hemoglobin-2 Ghana deletion.


CONCLUSIONS
Reliable HbA1c results may be unobtainable in the presence of some hemoglobinopathies. HPLC and capillary electrophoresis alerted the laboratory to the presence of an unusual hemoglobinopathy. Immunoassays generated falsely low results without warning, which could lead to missed diagnoses and under treatment of patients with DM.
Department of Laboratory Medicine and Pathology, University of Alberta, Canada.
Joy
J
Adekanmbi
Department of Laboratory Medicine and Pathology, University of Alberta, Canada; DynaLIFE(Dx), Edmonton, Canada.
Trefor
T
Higgins
Department of Laboratory Medicine and Pathology, University of Alberta, Canada; DynaLIFE(Dx), Edmonton, Canada.
Karina
K
Rodriguez-Capote
Department of Laboratory Medicine and Pathology, University of Alberta, Canada; DynaLIFE(Dx), Edmonton, Canada.
Dylan
D
Thomas
WestEd Medical Clinic, Edmonton, Canada.
Jeffrey
J
Winterstein
Department of Laboratory Medicine and Pathology, University of Alberta, Canada.
Tara
T
Dixon
Calgary Lab Services, Calgary, Canada.
Jessica L
JL
Gifford
Calgary Lab Services, Calgary, Canada.
Richard
R
Krause
Department of Laboratory Medicine and Pathology, University of Alberta, Canada; Alberta Health Services, Red Deer, Canada.
Allison A
AA
Venner
Department of Laboratory Medicine and Pathology, University of Alberta, Canada.
Gwen
G
Clarke
Department of Laboratory Medicine and Pathology, University of Alberta, Canada; DynaLIFE(Dx), Edmonton, Canada. Electronic address: mathew.estey@dynalifedx.com.
Mathew P
MP
Estey
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D019075:Electrophoresis, Capillary; D005319:Fetal Hemoglobin / Q000032:analysis* / Q000235:genetics; D006442:Glycated Hemoglobin / Q000032:analysis*; D006444:Hemoglobin C / Q000032:analysis* / Q000235:genetics; D006453:Hemoglobinopathies / Q000097:blood* / Q000235:genetics; D006801:Humans; D007118:Immunoassay; D008297:Male; D016133:Polymerase Chain Reaction
D005319:Fetal Hemoglobin; D006442:Glycated Hemoglobin; D006444:Hemoglobin C; C517652:hemoglobin A1c protein, human
HbA1c; Hemoglobin C; Hemoglobinopathy; Hereditary persistence of fetal hemoglobin; High performance liquid chromatography; Immunoassay