Alpha Thalassemia Workup and Treatment
Screen parents with mean corpuscular volume (MCV) <80 fL to identify carriers, then proceed with DNA testing for specific deletions or point mutations to confirm diagnosis, followed by supportive care for mild forms or transfusion therapy with iron chelation for severe disease. 1
Diagnostic Workup
Initial Screening
- Check parental MCV: Values <80 fL indicate possible alpha thalassemia carrier status and warrant further investigation 2, 1
- Consider ethnicity: Alpha thalassemia is most prevalent in Southeast Asian (28-55% of non-immune hydrops fetalis cases), Mediterranean, Middle Eastern, and African populations 2, 1
Confirmatory Testing
- DNA testing for deletions or point mutations: This is the definitive diagnostic test to identify the specific genetic defect (one to four alpha-globin gene deletions) 2, 3
- Hemoglobin electrophoresis: May reveal characteristic patterns but genetic testing is required for confirmation 3, 4
- Complete blood count: Shows microcytic hypochromic anemia with reduced MCH and MCV 5, 4
Prenatal Diagnosis
- Amniocentesis or fetal blood sampling: Recommended when both parents are carriers to detect severe forms like Hb Bart's hydrops fetalis (four-gene deletion), which is typically fatal 2, 1
- Middle cerebral artery Doppler: To assess for fetal anemia in cases of suspected hydrops fetalis 2
Treatment by Clinical Severity
Silent Carrier (One Gene Deletion) and Alpha Thalassemia Trait (Two Gene Deletions)
- No treatment required: These individuals are generally asymptomatic and require only monitoring 5, 6
- Genetic counseling: Essential for reproductive planning 1, 5
HbH Disease (Three Gene Deletions)
Deletional HbH Disease:
- Primarily preventative care: Transfusions are uncommon 6
- Intermittent transfusions: May be needed during intercurrent illness or periods of increased hemolysis 5, 6
- Avoid oxidative stressors: Prevent hemolytic crises 6
Non-deletional HbH Disease (e.g., HbH Constant Spring):
- Regular transfusions: Approximately one-third require chronic transfusion therapy due to more severe anemia 6
- Maintain pre-transfusion hemoglobin 9-10 g/dL and post-transfusion 13-14 g/dL 7, 8
- Iron chelation therapy: Must be initiated concurrently with transfusion therapy to prevent iron overload 7, 8
Hb Bart's Hydrops Fetalis (Four Gene Deletions)
- Typically fatal: Most pregnancies are terminated due to high maternal and fetal morbidity risk 1, 5
- No alpha-globin synthesis: Results in severe intrauterine hypoxia and non-immune hydrops fetalis presenting in late second or early third trimester 2
- Intrauterine transfusion: Considered investigational and not generally recommended outside research settings 2
Monitoring for Complications (For Transfusion-Dependent Patients)
Cardiac Surveillance
Hepatic Monitoring
- Liver function tests every 3 months 7, 8
- MRI for liver iron concentration: Guide chelation therapy adjustments 7, 8
Endocrine Screening
- Annual screening: For diabetes, thyroid dysfunction, and hypogonadism 7
Hematologic Monitoring
- Hemoglobin levels every 2 weeks: Especially during antiviral treatment or periods of increased transfusion requirements 7, 8
Common Pitfalls
- Failing to screen based on ethnicity: Missing diagnosis in high-risk populations (Southeast Asian, Mediterranean, Middle Eastern) 1
- Not initiating iron chelation with transfusions: Leads to iron overload and organ damage 8
- Confusing with iron deficiency anemia: Alpha thalassemia presents with microcytic anemia but normal or elevated ferritin 3
- Inadequate genetic counseling: Cascade testing should start with the affected individual, then extend to at-risk family members 1