From the Guidelines
Alpha thalassemia is the abnormal form of hemoglobin linked to alpha thalassemia, resulting from mutations in the alpha globin genes (HBA1 and HBA2) and leading to reduced or absent production of alpha globin chains. This condition is a common cause of nonimmune hydrops fetalis (NIHF), particularly in Southeast Asian populations, where it accounts for 28-55% of NIHF cases 1. The severity of alpha thalassemia depends on the number of affected alpha globin genes, ranging from silent carrier status to Hemoglobin H disease to Hemoglobin Bart hydrops fetalis, which is typically fatal before birth.
Some key points to consider in alpha thalassemia include:
- The abnormal hemoglobins that can be detected include Hemoglobin H (four beta chains) and Hemoglobin Bart (four gamma chains), which appear when there aren't enough alpha chains to pair with beta or gamma chains 1.
- These abnormal hemoglobins function poorly in oxygen transport because they bind oxygen too tightly and don't release it effectively to tissues.
- Diagnosis typically involves hemoglobin electrophoresis, complete blood count, and genetic testing.
- Treatment depends on severity, with mild forms often requiring no intervention while more severe forms may need blood transfusions, iron chelation therapy, and in some cases, stem cell transplantation.
It's essential to note that parents can be screened by evaluation of the mean cell volume, which will be <80 fL in thalassemia carriers 1. This screening can help identify individuals at risk of having a child with alpha thalassemia, allowing for early diagnosis and management. Overall, alpha thalassemia is a significant cause of NIHF, and its diagnosis and treatment require a comprehensive approach to manage the condition effectively and improve outcomes.
From the Research
Abnormal Form of Hemoglobin Linked to Alpha Thalassemia
- Alpha thalassemia is caused by reduced or absent synthesis of alpha globin chains, leading to imbalances of globin chains and resulting in hemolysis and impaired erythropoiesis 2.
- The clinical presentation of alpha thalassemia varies depending on the genotype, ranging from a silent or mild carrier state to severe, transfusion-dependent or lethal disease 3.
- Alpha thalassemia major, also known as hemoglobin Bart's, usually results in fatal hydrops fetalis 2, 4.
- Alpha thalassemia intermedia, or hemoglobin H disease, causes hemolytic anemia and has a variable presentation based on gene mutation or deletion 4, 5.
- Unstable and thalassemic alpha chain hemoglobin variants can cause Hb H disease and thalassemia intermedia, resulting in anemia and hemolysis 6.
Clinical Manifestations and Management
- Clinical manifestations of alpha thalassemia range from no symptoms to severe transfusion-dependent anemia 5.
- Management of patients with alpha thalassemia is primarily supportive, addressing either symptoms or complications of the disease, or its transfusion-dependence 3.
- Treatment options include transfusions, iron chelation therapy, hydroxyurea, hematopoietic stem cell transplantation, and luspatercept 4.
- Novel therapies, such as curative gene manipulation techniques and disease-modifying agents, are also in development 3.