The haemoglobin variant Hb Tacoma [HBB:c.93G > T;CD30(Arg > Ser) was detected in approximately 1 in 1000 patients tested for HbA1c at Karolinska University Hospital, Stockholm. Incidentally, five homozygous individuals were found, none of them presenting with severe haematological abnormalities. When the cation exchange chromatographic method Bio-Rad Variant II was used, chromatograms representing Hb Tacoma heterozygotes were easily misinterpreted as normal, although the HbA1c results were about 40% lower than those obtained by immunoassays. This is explained by the fact that the glycated form of Hb Tacoma coelutes with the LA1c fraction, while the main fraction of Hb Tacoma is not separated from normal HbA. Automatic calculation of the ratio LA1c/HbA1c was soon introduced and samples, where this ratio exceeded certain limits, were further investigated. In case of Hb Tacoma, HbA1c results were obtained from immunoassays. Several other HbA1c methods were evaluated using samples from Hb Tacoma heterozygotes. Unlike the Variant II method, the HbA1c results from the Bio-Rad D-100 method did not significantly differ from immunoassay. However, the results for Hb Tacoma samples deviated in an unpredictable way. The cation exchange chromatographic method Tosoh G11 constantly showed a positive bias. Hb Tacoma did not significantly affect the HbA1c results using immunoassays like Tina-quant Gen. 3 (Roche) and DCA Vantage (Siemens), an affinity method (Afinion 2, Abbott) or an enzymatic method (Alinity c, Abbott). Although the capillary electrophoresis HbA1c method (Sebia Capillarys 3 Tera) did not demonstrate any significant bias, the imprecision for this method was unacceptably high for samples with Hb Tacoma.
Keywords: Glycated hemoglobin; chromatography, ion exchange; electrophoresis, capillary; hemoglobin Tacoma; hemoglobinopathies; immunoassay; point-of-care testing.