1. "Pleasure in the job puts perfection in the
work." -- Aristotle :

2. Hemoglobinopathies
are disorders affecting the structure, function or
production of hemoglobin

3. Thalassemia
is one of them

4. Thalassemia
• Hemoglobin
• Haem + Globin
• Globin – 4 chains - , , ,■
- 3 Types
• HbA (Normal Hemoglobin- 2 2)
• HbF ( o
• HbA2 (A2• 2 )
• Each chain has specific aminoacid combination
• When aminoacids altered by deletion or addition, mutation –
abnormal hemoglobins are formed.

5. Thalassemia
• Hemoglobin critical for normal oxygen delivery to
tissues
• Normal RBC life span – 120 days
• Hemoglobin is present in erythrocytes in such high
quantities that it can alter red cell shape, deformability and
viscosity.

7. Hemoglobin Review
• Each complex consists of :
– Four polypeptide chains, non-covalently
bound
– Four heme complexes with iron bound
– Four O2 binding sites

8. Globin Chains
• Alpha Globin
– 141 amino acids
– Coded for on Chromosome 16
– Found in normal adult hemoglobin, A1 and A2
• Beta Globin
– 146 amino acids
– Coded for on Chromosome 11, found in Hgb A1
• Delta Globin
– Found in Hemoglobin A2--small amounts in all adults
• Gamma Globin
– Found in Fetal Hemoglobin
• Zeta Globin
– Found in embryonic hemoglobin

9. Hemoglobin Types
Hemoglobin Type Globin Chains
• Hgb A1—92%--------- α2β2
• Hgb A2—2.5%-------- α2δ2
• Hgb F — <1%--------- α2γ2
• Hgb H ------------------ β4
• Bart’s Hgb-------------- γ4
• Hgb S-------------------- α2β26 gluval
• Hgb C------------------- α2β26 glulys

10. Thalassemia
• Thalassemias are genetic disorders in which synthesis
of normal polypeptide chain forming adult hemoglobin
is suppressed.
• Selective deficiency of one or more polypeptide
chains have two consequences
• 1. R Hb – Anemia & e
• 2. Cell Membrane damage leading to premature
destruction of cells

11. 2 -Thalassemia
• Decreased production of chains.
• Total 4 genes code for 4 chains
• 2 genes on each chromosome 16

12. Types of Thalassemia
• 2 Classifications
• First Type
a. Thalassemia Major (Profound Anemia)
b. Thalassemia Intermediate
c. Thalassemia Minor
d. Thalassemia Minima
• Second Type
a. Alpha Thalassemia
b. Beta Thalassemia

13. > -Thalassemia
-Thalassemia
• Classification
- -Thalassemia 2 trait (One of 4 genes deleted)
- -Thalassemia 1 trait (Two of 4 genes deleted)
- HbH disease
> Three genes deleted
> No specific treatment required
> Avoid iron therapy
> Folic acid if necessary
- Hydrops fetalis (Hb Bart’s)
> All 4 genes deleted
> In utero death of foetus
> No treatment available

14. Alpha Thalassemias
• Result from gene deletions
• One deletion—Silent carrier; no clinical
significance
• Two deletions—α Thal trait; mild
hypochromic microcytic anemia
• Three deletions—Hgb H; variable
severity, but less severe than Beta Thal
Major
• Four deletions—Bart’s Hgb; Hydrops
Fetalis; In Utero or early neonatal
death

15. Alpha Thalassemias
• Usually no treatment indicated
• 4 deletions incompatible with life
• 3 or fewer deletions have only mild
anemia

16. Beta Thalassemia
• Point mutation in gene for non alpha producing chain in
chromosome 11
- Two types
• Beta Thalassemia Major ( r 0 )
• Beta Thalassemia Minor ( r - )

17. Beta Thalassemia Major
Also called Cooley’s Anemia
• Clinical Features
- Severe hypochromic anemia
- Erythroblastosis
- Grossly b l HbA
- Increase in HbF

18. Beta Thalassemia Major
• Treatment
- Bone Marrow transplantation
- Avoid Iron therapy
- If iron overload, Desferoximine therapy
- Splenectomy

19. Beta Thalassemia Minor
• Clinical Features
- Mild anemia
- Some target cells
- Punctate basophilia
- resistance of RBC to osmotic lysis

20. β-Thalassemia Major--Treatment
• Chronic Transfusion Therapy
– Maximizes growth and development
– Suppresses the patient’s own ineffective erythropoiesis and
excessive dietary iron absorption
– PRBC transfusions often monthly to maintain Hgb 10-12
• Chelation Therapy
– Binds free iron and reduces hemosiderin deposits
– 8-hour subcutaneous infusion of deferoxamine, 5 nights/week
– Start after 1year of chronic transfusions or ferritin>1000 ng/dl
• Splenectomy--indications
– Trasfusion requirements increase 50% in 6mo
– PRBCs per year >250cc/kg
– Severe leukopenia or thrombocytopenia

21. β-Thalassemia Major
Complications and Emergencies
• Sepsis—Encapsulated organisms
– Strep Pneumo
• Cardiomyopathy—presentation in CHF
– Use diuretics, digoxin, and deferoxamine
• Endocrinopathies—presentation in DKA
– Take care during hydration so as not to
precipitate CHF from fluid overload

22. How to Prevent Thalassemia
This disease is inherited. Blood tests and
family genetic studies will show if you are
a carrier. A genetic counselor can discuss
risks of passing on the disease. They can
also give you information on testing.