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