Hemoglobin A2 Levels in Indian Patients with Sickle Cell Disease Reveal Heterozygosity Open Access

Sickle cell disease (SCD) is characterized by the presence of homozygous hemoglobin S (HbS) or variants associated with HbS. We used hemoglobin A2 (HbA2) levels of >4% as indicative of thalassemic traits. This study investigated variations in HbA2 levels and their correlations with hematological parameters. This study enrolled 691 patients, including 575 patients with homozygous HbS and HbA2 <4% and 116 patients (17%) with HbS >50% and HbA2 ≥4%. The median (interquartile range [IQR]) HbA2, HbS, and hemoglobin F (HbF) levels were 1.900% (1.400%–2.700%), 67.900% (62.900%–72.700%), and 26.200% (21.500%–30.900%), respectively. In 104 patients, the HbA2 level ranged 4%–8.9%. Patients with HbA2 >4% had median (IQR) HbA2, HbS, HbF, and hemoglobin A0 levels of 5.100% (4.500%–6.300%), 65.400% (60.025%–71.200%), 23.250% (16.800%–29.375%), and 6.600% (4.450%–8.275%), respectively. Patients with elevated HbA2 levels had median (IQR) hemoglobin level, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) level, and mean corpuscular hemoglobin concentration (MCHC) of 7.637 g/dL (6.025–9.175), 71.400 fL (66.800–76.600), 22.650 pg (21.100–24.400), and 31.400 g/dL (29.900–32.975), respectively. By contrast, for patients with HbA2 <4%, the median (IQR) MCV, MCH level, and MCHC were 86.100 fL (77.225–93.800), 28.250 pg (24.725–31.500), and 33.100 g/dL (31.500–34.300), respectively. An increase in HbA2 levels led to a significant decrease in MCV and MCH, as expected. The dataset revealed a notably high incidence (17%) of HbA2 elevation, necessitating a reclassification of HbA2 levels to meet heterozygosity criteria.