Thalassemia is caused by impaired globin gene production, which can result in decreased or absent alpha or beta globin chains. This leads to various forms of thalassemia depending on which chain is affected and how severe the deficiency is. Alpha thalassemia traits typically do not require treatment, while more severe forms can cause anemia. Beta thalassemia major requires lifelong red blood cell transfusions and iron chelation therapy.

1. Thalassemia

2. Thalassemia: Impaired globin gene
production
Hgb A tetramer
globin globin
globin globin

3. Globin chain synthesis
cluster - chromosome 16
Gower 1
Portland Embryonic
Gower II
F Fetal
<1%
G A
A2
cluster - chromosome 11

4. Thalassemia
• Organization of globin genes
cluster - chromosome 16 cluster - chromosome 11
G A
2 1
G A
2 1
• Decreased production of normal globin
chains
– thalassemia—deficiency of gene(s)
– thalassemia—deficiency of gene(s)

5. Alpha Thalassemia: Clinical
Features
• Absence of 1–2 alpha X X
chains XX X
– Common
– Asymptomatic
– Does not require therapy X
• Absence of 3 alpha chains XX
(Hgb H disease)
– Microcytic anemia (Hgb 7–10)
– Splenomegaly XX
• Absence of 4 alpha chains XX
– Hydrops fetalis (non-viable)

6. Alpha Thalassemia: Laboratory
Findings
Hgb MCV
Chains (g/dl) (fl) Hgb Analysis
/ Normal Normal Normal
/- 12–14 75–85 Normal
Normal with Hgb Barts (
-/ - or --/ 11–13 70–75
4); Hgb H ( 4) (small)
Normal with Hgb Barts (
-/-- 7–10 50–60
4); Hgb H ( 4) (large)
--/-- - - Not viable

7. Hypochromic Microcytic RBCs:
Alpha Thalassemia
Alpha thalassemia trait Alpha thalassemia ( -/--)
Photomicrographs from American Society of Hematology Slide Bank

8. Beta Thalassemia
Clinical Genotype Hgb (g/dl) Hgb A2 Hgb F
syndrome
Minor (Trait) +
or ° 10–13 + +
Intermedia +
/ +
7–10 + ++
Major +
or
(Cooley’s <7 + +++
°
anemia)

9. Beta Thalassemia Major
Skeletal
– Osteoporosis due to bone marrow expansion
– Pneumatization of the sinuses is delayed by
expanded hematopoiesis
• Dilated cardiomyopathy secondary to severe
anemia
• Growth and development delayed
• Hepatomegaly due to extramedullary hematopoiesis

10. Microcytic Hypochromic Anemia:
Beta Thalassemia Major

11. Approach to Beta Thalassemia
• thalassemia trait
– Screening/counseling
• thalassemia intermedia/major
– Screening/counseling
– RBC transfusion therapy (+ iron chelation therapy)
– Agents to increase hemoglobin F (hydroxyurea)
– Bone marrow transplantation