Role of HbA1c in The Diagnosis of Hemoglobinopathies

Abstract

Introduction: Hemoglobinopathies are common genetic disorders resulting from qualitative (hemoglobinopathies) or quantitative (thalassemias) abnormalities affecting hemoglobin. The Hb S variant is of particular concern, as it causes severe sickle cell syndromes. Screening for these conditions is essential, especially in regions such as Morocco, where consanguinity increases the prevalence of genetic disorders.

Patients and Methods: This study included 17 patients, aged between 23 and 70 years, who were followed at the Cheikh Zaid University Hospital in Rabat from 2018 to 2022. Among them, six were from Morocco, and eleven were from sub-Saharan Africa. All patients underwent comprehensive hemoglobin testing and HbA1c measurement. Two primary methods were used for analysis. The first was alkaline agarose gel electrophoresis with the Hydrasys® analyzer, which identifies normal hemoglobins (A, A2) and abnormal variants (S, D, C, E). The second was high-performance liquid chromatography (HPLC) using the D-10® and G7® analyzers. Although primarily designed for HbA1c measurement, these analyzers can also detect hemoglobin variants. The D-10® identifies the Hb S variant but may occasionally confuse it with Hb D.

Results : Electrophoresis identified Hb S as the only abnormal variant. One patient had homozygous sickle cell disease (S/S), and ten were heterozygous carriers (A/S). The remaining six patients showed no hemoglobin abnormalities. The D-10® analyzer detected the Hb S variant in several patients but misidentified one case as Hb D. Additionally, the G7® analyzer detected some variants, although it lacked clear differentiation. The correlation between HPLC and electrophoresis for HbA and HbS measurements was generally acceptable. However, the correlation for HbA was weaker, likely due to differences in the detection of specific hemoglobin fractions.This study highlights that while HPLC is primarily used for diabetes management, it also serves as a valuable complementary tool for the incidental detection of hemoglobin variants, such as Hb S. This approach is particularly useful in asymptomatic patients, enabling the early identification of carriers and sickle cell syndromes. Integrating HPLC with electrophoresis could improve patient care and reduce diagnostic delays, especially in high-prevalence regions such as Morocco. However, it is important to account for HPLC’s limitations, including its inability to distinguish certain variants accurately.

Conclusion: In conclusion, although HPLC is not specifically intended for the diagnosis of hemoglobinopathies, it represents a useful complementary tool. It facilitates the detection of variants such as Hb S, guiding further diagnostic investigations. A combined strategy using both HPLC and electrophoresis could enhance patient care and minimize diagnostic delays, particularly in regions with high prevalence. Special attention should be given to HPLC’s limitations, notably its difficulty in distinguishing between certain hemoglobin variants.