Falsely elevated hemoglobin A1c due to S-β⁺-thalassemia interference in Bio-Rad Variant II Turbo HbA1c assay

Background: Hemoglobin (Hb) S-β⁺-thalassemia is a relatively mild form of S-β-thalassemia, but it may interfere with HbA1c (A1c) assay. We report a falsely elevated A1c due to S-β⁺-thalassemia interference in the Bio-Rad Variant II Turbo cation-exchange HPLC assay (Bio-Rad Turbo). Methods: A1c was determined with Bio-Rad Turbo and turbidimetric inhibition immunoassay (TINIA, Siemens) respectively. The former measured the A1c fraction only of glycated HbA, while the latter measured all Hb variants that are glycated at the beta chain N-terminus and have epitopes identical to that of A1c. S-β⁺-thalassemia was confirmed with the Bio-Rad Classic Variant HPLC method using the beta thalassemia short program. Results: The A1c levels of 4 patients were 30.3%, 26.3%, 25.3%, and 27.6% by Bio-Rad Turbo, while the levels were 5.8%, 4.8%, 4.7%, and 4.9% by TINIA. Hemoglobinopathy analysis showed a typical S-β⁺-thalassemia pattern: the fraction of HbS is greater than that of HbA with increased HbA2 and F. Conclusions: S-β⁺-thalassemia interferes with Bio-Rad Turbo assay causing falsely elevated A1c. If significantly increased A1c is detected and HbS is > 50%, S-β⁺-thalassemia should be suspected. In this case, A1c should be measured with other assays not significantly subject to S-β⁺-thalassemia interference.