Major Types of Hemoglobin and Their Physiological and Pathological Relevance

Hemoglobinopathies: Sickle Cell Disease and Thalassemia

Hemoglobin (Hb) plays a crucial role in oxygen transport within the human body. It is composed of protein subunits that form different types of hemoglobin throughout life, including HbA, HbF, HbA2, and pathological variants such as HbS and HbE.

Normal Hemoglobin Types

• Hemoglobin A (HbA): The predominant adult hemoglobin (α2β2), accounting for about 95% of total Hb.
• Hemoglobin F (HbF): The fetal hemoglobin (α2γ2) with higher oxygen affinity, replaced by HbA postnatally.
• Hemoglobin A2 (HbA2): A minor fraction (α2δ2), important in beta-thalassemia screening.

Hemoglobinopathies

Sickle Cell Disease (SCD)

SCD results from a mutation in the β-globin gene, leading to hemoglobin S (HbS) formation. Under deoxygenated conditions, HbS polymerizes, causing red blood cells to assume a sickle shape. This leads to vascular occlusion, chronic hemolysis, and multisystem complications.

Thalassemia

Thalassemias are inherited disorders characterized by reduced or absent synthesis of α- or β-globin chains. Beta-thalassemia major requires lifelong transfusion therapy, while milder forms, such as beta-thalassemia minor, are asymptomatic.

Diagnosis and Treatment

Electrophoresis, HPLC, and molecular testing are used to diagnose hemoglobinopathies. Management includes hydroxyurea for SCD, transfusion, iron chelation therapy, and potential gene therapy for severe cases.

Conclusion

Understanding hemoglobin types and their associated disorders is critical for early diagnosis and optimal patient management.