Alpha Thalassemia: Diagnosis and Treatment
Diagnosis
Alpha thalassemia should be suspected in patients presenting with microcytic anemia and normal or elevated ferritin levels, distinguishing it from iron deficiency anemia. 1
Diagnostic Workup
- Complete blood count (CBC) reveals microcytic anemia with normal or elevated red blood cell count 1
- Ferritin levels are normal or elevated, which differentiates alpha thalassemia from iron deficiency 1
- Hemoglobin electrophoresis may show characteristic patterns but cannot definitively diagnose alpha thalassemia 1
- Genetic testing is mandatory to confirm the diagnosis and determine the specific number of alpha-globin gene deletions 1
Clinical Phenotypes by Genotype
The severity correlates directly with the number of deleted alpha-globin genes:
- Silent carrier (1 gene deletion): Asymptomatic, no treatment needed 1, 2
- Alpha thalassemia trait (2 gene deletions): Asymptomatic, no treatment or monitoring required 1, 2
- Hemoglobin H disease (3 gene deletions): Variable severity ranging from mild to severe transfusion-dependent anemia 3, 4
- Alpha thalassemia major (4 gene deletions): Results in hydrops fetalis, usually fatal at birth without intrauterine intervention 1, 3, 5
Treatment
Alpha Thalassemia Trait and Silent Carrier
No treatment is required for silent carriers or alpha thalassemia trait, as these individuals are asymptomatic with normal life expectancy. 1, 2
- Genetic counseling is recommended for family planning purposes 1
- Partners should undergo genetic testing if considering pregnancy 2
Hemoglobin H Disease
Treatment depends on disease severity, which is largely determined by whether mutations are deletional or non-deletional:
Mild Forms
- Monitoring only with periodic CBC and ferritin levels 1
- Avoid iron supplementation unless true iron deficiency is documented 1
- Folic acid supplementation may be considered for chronic hemolysis 4
Moderate to Severe Forms
- Intermittent blood transfusions when symptomatic anemia develops 1, 4
- Iron chelation therapy if transfusion-dependent or evidence of iron overload develops 1, 4
- Hydroxyurea may reduce transfusion requirements in some patients 1
- Luspatercept is an emerging therapy under investigation 1
Common pitfall: Non-deletional mutations cause more severe disease with greater transfusion burden and complication risks compared to deletional mutations, requiring more aggressive monitoring and earlier intervention. 4
Alpha Thalassemia Major (Hydrops Fetalis)
In utero transfusions are required for fetal survival, with postnatal management consisting of either chronic transfusions or hematopoietic stem cell transplantation. 5
Prenatal Management
- Intrauterine blood transfusions starting when fetal anemia is detected 5
- In utero stem cell transplantation is currently under investigation in phase 1 clinical trials 5
- Chorionic villus sampling should be offered to at-risk pregnancies for early diagnosis 2
Postnatal Management
- Chronic transfusion therapy every 3-4 weeks, similar to beta thalassemia major 5
- Iron chelation therapy must begin as soon as regular transfusions are established 5
- Hematopoietic stem cell transplantation (HSCT) is the only curative option and should be performed as early as possible, ideally before significant iron-related organ damage develops 5
Monitoring for Complications
For transfusion-dependent patients with HbH disease or alpha thalassemia major:
- Cardiac monitoring: Annual echocardiography and cardiac MRI T2* to detect iron deposition before symptoms develop 6, 7
- Liver assessment: Liver function tests every 3 months and periodic MRI to measure liver iron concentration 6, 7
- Endocrine screening: Annual screening for diabetes, thyroid dysfunction, and hypogonadism 6
- Infection prevention: Hepatitis B vaccination before starting transfusions 6, 7
Key Clinical Caveats
Critical distinction: Alpha thalassemia trait requires no cardiac monitoring, iron overload assessment, or chelation therapy—these interventions are only relevant for transfusion-dependent forms. 8
Pregnancy risk: Pregnant women with alpha thalassemia trait carrying a fetus with alpha thalassemia major face increased risk of toxemia and postpartum bleeding, requiring specialized obstetric care. 2
Prognosis: With optimal adherence to transfusions and chelation in severe forms, patients can expect survival into their 40s-50s with reasonable quality of life, compared to death in infancy without treatment. 6, 7