The deficiency in alpha-globin results in the formation of Hemoglobin H (Hb H), an abnormal hemoglobin composed of four beta-globin chains. Hb H is unstable and prone to forming precipitates in red blood cells. This instability causes red blood cells to undergo premature destruction in the spleen, a process known as hemolysis, leading to chronic hemolytic anemia. The severity of anemia can range from mild to moderate, depending on the residual alpha-globin gene activity.
Patients with Hemoglobin H disease often experience fatigue, pallor, and jaundice due to anemia. Splenomegaly (enlarged spleen) and hepatomegaly (enlarged liver) are common due to increased red blood cell turnover. Complications such as gallstones, caused by excessive breakdown of red blood cells, and episodes of acute hemolysis triggered by infections, certain medications, or oxidative stress are also frequent. In severe cases, growth delays and skeletal abnormalities may arise due to increased bone marrow activity attempting to compensate for anemia.
Diagnosis of Hemoglobin H disease typically involves blood tests such as a complete blood count, peripheral blood smear, and hemoglobin electrophoresis, which reveals the presence of Hb H. Genetic testing confirms deletions or mutations in alpha-globin genes. Imaging studies may evaluate organ enlargement or other complications.
Management focuses on symptom alleviation and complication prevention. Regular monitoring is crucial, along with folic acid supplementation to support red blood cell production. Blood transfusions may be necessary during severe anemia episodes, especially in pregnancy or illness. In refractory cases, splenectomy can reduce hemolysis and the need for transfusions. Advances in gene therapy hold promise for curative approaches by restoring alpha-globin gene function, though these are still under investigation.
Public health initiatives and genetic counseling programs are essential in regions where alpha-thalassemia is prevalent, particularly Southeast Asia, the Mediterranean, and the Middle East. Carrier screening and prenatal testing have significantly reduced the incidence of severe alpha-thalassemia syndromes, emphasizing the role of preventive strategies alongside improved clinical care.
Hemoglobin H Disease: Causes, Symptoms, and Management
