1. What hematologists should know
about thalassemia
• Correct diagnosis
• Counselling
• Complications and prevention
• Plan of management

2. Hb electrophoresis
A2 E A H
<10% = A2 F Bart’s
>10% = E

3. Thalassemia
• globin
• Alpha thalassemia
– alpha globin
– globin , beta globin
• Beta thalassemia
– beta globin
– delta, gamma globin
– Alpha

4. • Hb E A2 report
– Peak 10% A2
– Peak 10% E
•E F Hb
beta chain
• Bart H Hb
alpha chain

5. alpha thalassemia
• Hb typing rule out Hb H disease
• Bart H CS
Hb H disease
• Alpha thal 1 trait MCV
• Alpha thal 2 trait family history
• DNA analysis rule in, rule out
100%

6. MCV IB Hb H Bart’s Bart’s in
cord blood
thal 2 trait Low Neg - - 1-2 %
- / normal
thal 1 trait 60-70 1:10,000 - - - 10%
--/ 1:50,000
Hb H disease 55-70 20-50% 0-20% 0-10% 20-30%
--/-
CS
--/ + CS 3-5%

7. Hb Constant Spring (CS)
1 Normal
Normal globin
Stop codon mutated
1
CS (unstable)

8. Hb CS
• Genotype CS
(never CS CS or - CS)
• Phenotype : resemble thal 2 (- )
• Typing
– CS trait: CS 1%
– CS homozygous: CS 5%
– CS/ thal1 : clinical = Hb H, CS 3-5%

9. Globin synthesis in
thalassemia
Normal thal trait thal major

10. beta thalassemia
• Beta trait A2
< 3 = normal
> 4 = Beta trait
• Beta major F A2

11. Abnormal splicing
Beta globin gene with mutation = beta E
Exon 1 Intron 1 Exon 2
Exon 1 Exon 2
Normal splicing
beta E
Exon 1 Exon 2
Abnormal splicing
Abnormal globin, will be degraded in cytoplasm

12. Globin synthesis in Hb E
Hb E trait Hb E homozygous

13. Globin synthesis in thal/Hb E

14. Hb E
• E 80% F E/ E
• E 60-80% F 0/ E
• E 40-60% FA +/ E
• E 25-40% A / E
• E 15-25% A / E alpha thal
trait

15. Typing in beta thalassemia
genotype MCV A2 F+alkF E A
trait / 0 low > 3.5 <3%
E trait / E low with E 1% 25-30% 70-75%
normal
thal 0/ 0, low 2-10% >90% - 0
+/ +
0/ +
0/ E, low with E 20-25% 60-70%
thal/HbE +/ E 10-50% 40+% 10-50%
HbE E/ E low with E 0-20% >80% 0
homo normal

16. Alpha and beta thalassemia
• Alpha thal beta major
• Hb H E homozygous = EF Bart
• Hb H E trait = AE Bart

17. alpha thalassemia with Hb E
genotype MCV IB E F Bart’s
thal1 trait/ --/ Low + 14-22% - -
E trait / E
thal2 trait/ - / Normal Neg 25-30% - -
E trait / E
Hb H/ --/- 60-69 + 13-16% - 2-8%
E trait / E
HbH/ --/- Low Neg 80% 10% 3-4%
E homo / E

18. Father Mother Child 1 Child 2
Hb/Hct 14.2/40 11/32.9 10.4/30.1 9.8/27.4
Retic 0.3 0.2 0.2 1.7
IB - - - -
Hb typing
A 75.5 69.0 71 -
E 24.5 31.0 28.6 100
Alk F 0.26 1.2 1.1 2.8

19. Father Mother Child 1
Hb/Hct 11.8/38 13.5/39.2 9.9/32.6
Retic 0.5 1.1 0.6
IB 1:10,000 - >50%
MCV 52 82 66
Hb typing
A 85.8 96.8 95.0
A2 3.2 1.6
E 14.2
Alk F 1.5 1.0 5.5

20. Father Mother Child 1 Child 2
Hb/Hct 16.2/51 11.4/31.4 8.7/27.7 6.4/23
Retic 1.0 1.0 5% 6.4
IB rare > 1:20,000 1:5,000 > 50%
MCV 81 61 62 67
Hb typing
A 73.2 95.9 70.1 67.0
A2 3.1 2.7
F - - - -
E 26.8 14.4
H - - - 11.6
Bart’s - - 15.5 16.7
Alk F 1.6 1.7 7.4 5.6

21. Father Mother Child 1
Hb/Hct 14.3/41.5 12.5/35.5 8.1/24.5
Retic 0.7 0.2 5.5
IB - - -
MCV 62 83 49
Hb typing
A 92.7 65.9 -
A2 7.29
F - - 27.2
E 34.0 72.7
Alk F 1.89 1.81 20.95

22. Father Mother Child 1
Hb/Hct 14.5/42.5 13.6/39.6 10.6/31.9
Retic 1.2 3.6 7.9
IB - - 1:20,000
MCV 79 81 77
Hb typing
A 96.9 94.2 95.4
A2 3.1 2.5 2.3
CS 3.3 2.3
Alk F 0.3 1.0 1.9

23. Father Mother Child 1 Child 2
Hb/Hct 13.5/40 12.0/35 8.7/25 13/41
Retic 1.2 2.2 5.6 1.5
IB - - - -
MCV 72.4 77.8 67.4 85
Hb typing
A 96.0 77.0 25.0 98.5
A2 4.0 1.5
F 20.0
E 23.0 55.0

24. Types of transfusion program
• Hypertransfusion program
– normalize growth and endocrine function
– pre transfusion Hb level 9.5-10 mg/dl
• Symptomatic transfusion

25. Blood products for transfusion
• Leucodepleted red cells
– less than 5 x 106 WBC/cumm
– pre storage or post storage filtration
– decrease alloimmunization
• Washed red cells
• Blood products should be used within 2
weeks after colllection

26. Adverse reaction of
transfusion
• Febrile non-hemolytic transfusion
reaction
• Allergic reaction
• Acute hemolytic reaction
• Delayed hemolytic transfusion reaction
• TaGVH
• Transfusion transmitted diseases

27. Allo-immunization
• 3%
• antibody Rh, Duffy, Kell, Kidd
blood group
• leucodepleted blood products

28. Autoimmune hemolytic
anemia
•
• thalassemia
•
– Steroid
– IVIG
– Splenectomy

29. Post transfusion hypertension
•
30% cerebral
hemorrhage
• 3-7 units
• 1-15

30. Iron overload
• Source of Fe
– Blood products (5-10 gm/ year)
– Fe in food (1-2 gm/ year)
• Defined by total body iron of more than 20
gm.
• Gold standard in diagnosis : liver biopsy
• Serum ferritin may be useful as non-invasive
test.
• MRI: T2*

31. Complications from Fe
overload
• Endocrine dysfunction
– hypothyroidism
– DM
– adrenal gland dysfunction
• Cardiovascular problems
• Liver fibrosis

32. Iron chelation
• Desferrioxamine (Desferol ®)
– subcutaneous infusion
– infusion pump (20,000+ )
– 500-1500 mg 3-7
– 200 / 500 mg
• Oral Iron chelator
– Deferiprone
– Deferasirox

33. Comparison of iron chelators

34. Advantages of oral chelators
• More compliance
• More effective for cardiac iron
deposition

35. Consideration before initiating chelation
• Organ damage from Fe overload is not
reversible. ???
• Compliance is the most important
factors for success.
• Complete vision and auditory function
should be done.

36. Desferrioxamine
administration
Initiation
• After 10-20 transfusions
• Serum ferritin more than 1,000
microgram/L
Dose
• 20-40 mg/kg subcut. infusion over 8-12
hours
6 times a week.

37. Thromboembolic problems
• : Pulmonary
thromboembolism
• hypoxemia 20%
hypoxemia 50%
• Post splenectomy : increased
thrombosis, increased platelet
aggregrability
• Daily ASA might be helpful.

38. Bone marrow transplantation
• The only current technique to ‘cure’
thalassemia
• donor HLA
thalassemia
–
– Unrelated donor
• :
hepatomegaly portal fibrosis
hemochromatosis ( )

39. Modulation of gene productivity
• Increase gene activity will lessen
anemic symptoms
• Agents proved to increase gene
activity
– Hydroxyurea
– Butyrates

40. Frontiers in thalassemia
• Iron chelation
• Epigenetics
• Transplantation