Thalassemia in Pediatric Hematology and Oncology ward.

1. WELCOME TO SEMINAR
Presenters:
Dr. ReneshaIslam
Dr. umme nusraT ara
Resident (Phase B)
Pediatric Hematology and Oncology
Bangabandhu Sheikh Mujib Medical University

2. Case scenario 1 Case scenario 2

3.  Rima, a 11 years old girl of consanguineous parents
and Siam a 9 years old boy of consanguineous
parents presented with complaints of not growing
well, gradual pallor & abdominal distension for 7 & 5
years respectively.
 On examination both were severely pale, facial
dysmorphism & hepatosplenomegaly were present.
Both had history of repeated blood transfusion.
History

4. Hereditary hemolytic anemia
Diagnosis

5. SEMINAR ON

6. Introduction
"Thalassemia" is a Greek term
derived from “Thalassa”, which
means "the sea" and “Emia” means
"related to blood.“
The term “Thalassemia” refers to a
genetic disorder of hemoglobin
synthesis characterized by a lack or
decreased synthesis of one or more
of the four Globin chains causing
excessive breakdown of RBC.
Thomas cooley

7. Worldwide:
• β-Thalassemia is most prevalent
in Africa, all Mediterranean
countries, the Middle East, Indian
subcontinent & Southeast Asia.
• Affects– 4.4/10,000 live birth.
• β thalassemia trait - 8% of
population.
• Carrier - >100 million.
• Hb E - 53 millions.
• About 60 000 new patients born
annually.
• Most common blood group
observed is O +ve.
Epidemiology

8. Some facts about Bangladesh
Consanguineous marriage
- 14% parents of affected child.
• β thalassemia trait- 4.1%
• Hb E trait - 6.1%
• Hb E Beta thalassemia-10.2%
• Carrier of Beta thalassemia &
HbE - 3% & 4% respectively.
• HbE-β Thalassemia - commonest
type.
• Average life expectancy is about
30 years.
• Critical knowledge gaps and
societal misperceptions present.

9. In BSMMU
IN OUR DEPARTMENT 2020
Disease No. Of
patients
Percentage%
Hb E beta
Thalassemia
19 9.5
Beta
Thalassemia
Trait
14 7
Hb-E Trait 11 5.5
Beta
Thalassemia
Major
2 1
Alpha
Thalassemia
2 1
Hb-H
Disease
1 0.5

10. Hemoglobin molecule

12. Site of synthesis of globin

13. Normal hemoglobin component
Hb type Name Components
Adult A α2β2
A2 α2δ2
Fetal F α2γ2
Embryonic Portland ξ2γ2
Gower 1 ξ2ε2
Gower 2 α2ε2
Hemoglobin in normal adult

14. Types of thalassemia
α Thalassemia
β Thalassemia

15. • Transfusion dependent thalassemia
- β-Thalassemia major
- Hb E - β-Thalassemia (severe).
• Non transfusion dependent thalassemia (NTDT)
- β-Thalassemia intermedia
- β-Thalassemia trait
- Hb E - β-Thalassemia (mild ,moderate)
- Alpha-Thalassemia intermedia(Hb H disease)
- Hb E disease
- Hb E trait
- Alpha-Thalassemia carrier.

16. Inheritance

17. Inheritance

18. α Thalassemia

19. Chromosome 16 defect
a2 a1 a2 a1 a2 a1
a1
a2 a1 a2 a1
a1
Normal Hb
One α gene deletion
silent carrier
Two α gene deletions- α-Thal. Minor
Three α gene deletions
Hb-H disease

20. Chromosome 16 defect
a2 a1 a2 a1
CS
CS
a2 a1
CS
a2 a1
a2 a1
CS a1
a2 a1
a1
Normal Hb Four α gene deletions
Hydrops fetalis or also
called: Erythroblastosis
Fetalis.
Hb constant spring
Hb-H disease

21. CLINICAL PRESENTATION
Variants of alpha
thalassemia
Signs &Symptoms
Silent carrier Asymptomatic
Trait Asymptomatic
Hb H disease
Moderate to severe hemolytic anemia
Modest degree of ineffective erythropoiesis
Splenomegaly
Variable bone changes
Hb Bart's Born with massive generalized edema, usually fatal
Other Variants : Hb CS, Hb PS

22. Diagnosis of α-Thalassemia
CBC:
• Silent Carrier: no microcytosis , no anaemia.
• α-Thalassemia trait: microcytosis, hypochromia,
mild anaemia.
• Hb H disease: variable severity
of anaemia & hemolysis.
PBF: Hb H inclusion body
(brilliant cresyl blue) in Hb H disease.

23. Hb electrophoresis –
Hb H:
• (2-40%) Hb H
• others Hb A
• Hb F & Hb A2
Hb Bart's:
• (80-90%) Bart's,
• no Hb A, Hb F, Hb A2
Diagnosis of α-thalassemia

24. Treatment of α-thalassemia
• Silent carrier & trait: do not require treatment.
• Hb H disease: usually does not require regular
transfusions. But, with intercurrent illnesses,
patient may require transfusion .

25. β-Thalassemia

26. With a mutation on one of the 2 beta globin
genes , a carrier is formed with lower protein
production but enough hemoglobin
Without a mutation
enough hemoglobin
No
carrier
With one mutation
less hemoglobin
Beta
thalassemia
carrier but less
hemoglobin
Slight anemia
With two mutation
No beta globin
Beta
thalassemia
major pt with
severe anemia
Gene from father
Gene from mother
Chromosome 11 gene defects

27. Clinical syndrome Genotype Sign & symptom
Minor
/ 
+
or
/ °
Asymptomatic
Intermedia 
+
/
+
Variable degree of severity
Major

+
/°
or
°/°
- Present within 1 year of age
- Severe anemia
- Growth retardation
- Organomegaly
- Skeletal deformities
-Transfusion require within 2 year
Variants of β-thalassemia
Other variants of β-thalassemia:
-delta-beta thalassemia
- Hb Lepore.

28. An absence or deficiency of β-
chain synthesis of adult HbA
Pathophysiology of β-thalassemia
β Chain synthesis Hb-A
α , γ and δ chain
Hb A =
α2β2

29. Pathophysiology of β-thalassemia

31. Thalassemia Major
Child with no
transfusion or
inadequate transfusion
Child with regular
blood transfusion but
no chelation
Child with regular
blood transfusion &
chelation
Leads natural course
of disease, may die
within 5 yrs of age
Manifestation of iron
overload at the end of
1st decade
May enter into normal
puberty & have
normal life expectancy
Clinical features

32. Natural course
General
features
Weakness
Gradual Pallor
Fatigue
Dyspnoea on
exertion
Poor appetite
Palpitation
Poor growth
Features of
marrow
expansion

33. Features of
extramedullary
hematopoiesis
Features of
hemolysis
Jaundice
Hyperurecemia-
Gout
Gallstone
Scoliosis,Kyphosis,vertebral collapse
with cord compression

34. Cirrhosis
Diabetes
Infertility
Pituitary failure
Hypothyroidism
Arrythmia
Heart failure
Dark skin
Liver Heart Endocrine organs
Features of iron overload

35. Hb E β-Thalassemia
• Most prevalent thalassemia variant in Southeast Asia &
Bangladesh.
• Double heterozygous state.
• Lysine substitutes glutamic acid in 26th position.
• Divided into mild, moderate & severe form with clinical
features varying from thalassemia intermedia to
thalassemia major.

36. Types Sign & symptom
Mild Hb E β
Thalassemia
Asymptomatic , Hb :9 -12 gm/ dl , require no treatment .
Moderately severe Hb E
β Thalassemia
Majority of patient are in this group, Hb : 6 -7 gm/dl ,
resemble Thalassemia intermedia.
Severe Hb E β -
Thalassemia
Clinical manifestation resemble Thalassemia major
(severe anaemia, growth retardation,
hepatosplenomegaly, skeletal deformities).
Hb: 4-5 gm/dl , treated as thalassemia major.
Variants of Hb E β-Thalassemia

37. Complications of thalassemia
 Excessive erythropoiesis.
 Iron overload.
 Chronic hemolysis.
 Hypercoagulable disease.
 Infection.
 Treatment of related complications.

38. Facial changes:
• Maxillary over growth
• Malocclusion of teeth
• Frontal bossing
• Chronic sinusitis
• Impaired hearing.
A. Excess erythropoiesis

39. • Medullary expansion –
cortical thinning, risk of
fracture, osteopenia,
osteoporosis, back
ache.
• Vertebral expansion
lead to spinal cord
compression –
neurological
manifestations.
Bone Changes

40. • Hepatosplenomegaly
• Lymphadenopathy.
Extramedullary

41. Endocrine failure:
• Short stature
• Delayed puberty
• Estrogen/ testosterone
deficiency
• Diabetes mellitus
• Hypoparathyroidism.
B. Iron Overload

42. B. Iron overload
Cardiac involvement:
• Cardiomyopathy
• Pericarditis
• Arrhythmia
• CCF.
• Hepatic involvement:
• Cirrhosis
• Hepatic fibrosis.

43. C. Chronic hemolysis
• Gallstone 50-70% by around
15 years.
D. Hypercoagulable disease
Impaired platelet function Deep venous thrombosis
Elevated endothelial
adhesion protein level
Pulmonary embolism
Activation of coagulation
cascade by damage RBC
Cerebral ischemia

44. E. Infection
• Anemia.
• Iron overload – Yersinia, Klebsiella.
• Hypersplenism.
• Splenectomy – Pneumococci,
Meningococci, Hemophilus
influenzae.
• Transfusion related – HBV, HCV, HIV
etc.

45. F. Complications due to blood
transfusion
• Acute hemolytic reactions.
• Delayed transfusion reaction.
• Autoimmune hemolytic anemia.
• Febrile transfusion reaction.
• Allergic reaction.
• Transfusion related acute lung injury
(TRALI).
• Graft versus host disease (GVHD).
• Volume overload.
• Transfusion of disease – HAV, HBV,
HIV.

46. Causes of death in thalassemia
• Congestive heart failure.
• Arrhythmia.
• Sepsis due to increase susceptibility to infection.
• Multiple organ failure due to hemochromatosis.

47. History taking
Physical findings
Lab investigations
 Symptoms of anemia
 Positive family history
 History of blood
transfusion
 Failure to thrive
• Severe Anemia
• Thalassemic facies
• Hepatosplenomegaly
• Growth retardation, etc.
An approach to thalassemia

48. Investigations
CBC:
• Hb level - Depends on severity
– β-thalassemia minor: 10-13 gm/dl
– β-thalassemia intermedia: 7-10 gm/dl
– β-thalassemia major: 3-6 gm/dl
• TC/DC– normal / increased / decreased
• Platelet- normal / decreased.
• RBC Indices- MCV, MCH, MCHC are low
• RDW- Normal or raised
• Reticulocyte count- Increased (5-10%)

49. Abnormal RBCs in PBF
1. Target cell
2. Tear drop cell
3. Elliptocyte
4. Hypochromic
5. Microcyte
PBF:
Microcytic hypochromic cells with marked anisocytosis,
poikilocytosis and other abnormal cells.

50. PBF: Normal vs Hypochromia

51. Poikilocytosis

52. Anisocytosis

53. Target cell

54. Nucleated RBC vs lymphocyte

55. PBF: β-thalassemia minor

56. PBF: β-thalassemia minor vs IDA

57. PBF: β-thalassemia major

58. Investigations
• Osmotic fragility: Decrease.
• Iron Profile:
 S. Iron & ferritin- Increased
 TIBC- Decreased
 High % saturation of transferrin.
• S. bilirubin (indirect): Increased.

59. Hb electrophoresis
Hb NORMAL MAJOR MINOR INTERMEDIATE
Hb F <1% 90-98% 1-5 % Variable
Hb A 97% Absent 90-95% Variable
Hb A2 1-3% Variable 3.5-7% >3.5%

61. • Widened diploic
spaces.
• Hair-on-end
appearance.
• Thinning of
cortex.
X-ray Skull

62. • Rectangular appearance.
• Medullary portion of bone is
widened.
• Bony cortex thinned out.
• Coarse trabecular pattern in
medulla.
X-ray of hand

63. Investigations
• DNA analysis:
Determine specific
defect at molecular
DNA level.
• HPLC (High Performance
Liquid Chromatography):
Identify & quantify
large number of
abnormal Hb.

64. Flow chart for Thalassaemia diagnosis
<77fl

65. To see complications
• Liver function test.
• Thyroid function test.
• FSH, LH, Testosterone, Estradiol.
• Blood Sugar.
• Bone profile.
• Ca, Phosphate, PTH.
• Liver Iron Concentration (LIC): T2 MRI, Liver Biopsy.
• Cardiac Iron Measurement by: T2 MRI.

66. • Bright areas represent high iron concentration.
• Dark areas represent low iron concentration.
Monitoring iron overload by MRI

67. MANAGEMENT OF
THALASSEMIA

68. Treatment modalities
A. Supportive
B. Curative
C. Preventive

69. A. Supportive management
• Multi-disciplinary approach
• Focus on each patient’s clinical course
Transfusion
Iron Chelation
Fetal Hb Induction
Splenectomy

70. Objectives of supportive management
• Maintenance of growth and development
• Correction of anemia
• Prevention of iron overload
• Treatment of complications
• Counseling and Prevention

71. Blood Transfusion

72. Whom to transfuse?
•Confirmed diagnosis of thalassemia major
• Laboratory criteria:
Hb < 7gm/dl on 2 occasions > 2 weeks apart
• Laboratory and clinical criteria:
Hb > 7gm/dl with:
• Facial changes
• Poor growth
• Fractures
• Extramedullary hematopoiesis
• Cardiac complication
• Decrease normal physical activity
• Hypersplenism
ref.TIF

73. Target in 
Hb
Haematocrit of Donor Red Cells
50% 60% 75% 80%
1 gm/dl 4.2 ml/kg 3.5 ml/kg 2.8 ml/kg 2.6 ml/kg
2 gm/dl 8.4 ml/kg 7.0 ml/kg 5.6 ml/kg 5.2 ml/kg
3 gm/dl 12.6 ml/kg 10.5 ml/kg 8.4 ml/kg 7.8 ml/kg
4 gm/dl 16.8 ml/kg 14.0 ml/kg 11.2 ml/kg 10.4 ml/kg

74. Recommended Transfusion
To maintain pre transfusion Hb >9–10.5 gm/dl –
 Transfusion volume usually 10–15 cc/kg of
packed Leuko-depleted red cells
Lifelong regular blood transfusions, every 3–5
weeks interval
Interval depend on patients work/school schedule
and other lifestyle issue

75. A higher target pre-transfusion hemoglobin level
of 11- 12 gm/dl may appropriate for patients with
*Heart disease or other medical condition
*Patients who do not achieve adequate
suppression of bone marrow activity at
lower Hb level.
Keep post transfusion Hb not higher than 14-
15g/dl
patient with cardiac failure or very low initial Hb
levels should receive smaller amount of red cells
at slower rate of infusion

76. Recommendations
Careful donor selection and screening
Confirm laboratory and clinical criteria before initiation of
transfusion
Before first transfusion, extended red cell antigen typing of
patients (at least for C, E and kell)
Before each transfusion, give ABO, Rh(D),C, E, and Kell
compatible blood
Before each transfusion, full cross-match and screen for new
antibodies

77. Keep record of annual transfusions requirements ,red cell
antibodies and transfusion reactions for each patient
Use leucoreduced packed red cells. Pre-storage filtration is
recommended.
Washed red cells for patients who have severe allergic reactions.
Use red cells stored in CDPA , as fresh as possible(less than one
week)
Avoidance of transfusion first-degree relative donors

78. Regularly
Transfused
Irregularly
Transfused

79. • Normal growth and developments
• Normal physical activities
• Minimizes extra medullary
haematopoiesis
• Minimizes iron accumulation
• Reducing and/or delaying the onset
of complications
Regular transfusion allows

80. Thalassemic diet

81. CHELATION THERAPY

82. Chelator Metal
Chelator
Toxic
Excretion
Metal
What is chelation therapy?

83. Iron overload occurs either as a result of RBC
transfusions or increased absorption of iron through GIT.

84. Transfusion Induced Iron Overload
• A unit of transfused blood contains approximately 200 mg
of iron.
• When transferrin is oversaturated, the excess iron
circulates as relatively free non-transferrin-bound
iron(NTBI)
• A specific portion of NTBI is the chelatable labile plasma
iron(LPI)
• This LPI is most toxic component due to high redox
potential that generates oxygen-free radicles such as
superoxide anion.
• This Superoxide anion damages DNA, proteins and
membrane lipids in the cell.

88. Evaluation of iron overload
Serum ferritin concentration
Liver iron concentration (LIC)
- liver biopsy
- MRI
- SQUID
Cardiac iron estimation by T2* MRI
NTBI ( by LPI assay)
Guideline- Thalassemia International Federation-2008

91. • Myocardial T2* is associated with LV function.
• T2* >20ms – very low chance of decrease LVF
• T2* 10-20ms- 10% chance of decrease LVF
• T2* 8-10ms- 18% chance of decrease LVF
• T2* 6ms- 38% chance of decrease LVF
• T2* 4ms- 70% chance of decrease LVF

92. Primary goals of chelation therapy
Complete
chelation
The primary goals of iron chelation therapy are to remove excess iron and provide
protection from the effects of toxic iron
Iron
balance
Removal of iron
at a rate equal
to transfused iron
input
Prevents end-
organ damage due
to iron
Normalization of
stored tissue iron
May take years
in established iron
overload
Safe levels of
tissue iron differs
between organs
Control of toxic iron
over 24-hr period
24-hr control
of NTBI/LPI and
intracellular labile
iron
Prevents end-
organ damage due
to iron

93. Guidelines for starting treatment of iron
overload in patients with β-thalassemia major
Thalassemia International Federation
guidelines for the clinical management of
thalassemia (2008)1 recommend that chelation
therapy is considered when patients:
Have received 10–20 transfusion episodes
OR
Have a serum ferritin level of >1000 ng/mL
1Thalassemia International Federation. Guidelines for the clinical management of thalassemia, 2nd Edition revised
2008; 2Angelucci E et al. Haematologica 2008;93:741–752

94. • Iron balance with “safe” tissue iron levels by removal of iron
from the body.
– 0.4–0.5 mg/kg day excretion
– Slow process
•
Detoxification of iron
– Extracellular (NTBI)
– Intracellular (Labile Iron Pools)
– Iron-chelate complex
• It is clear that symptoms of iron overload, such as cardiac
arrhythmia and heart failure, can be improved well before
local tissue levels of iron have decreased by continual
presence of a chelator in the plasma.
Goals of Chelation Treatment

95. Iron chelating agents
Desferrioxamine(DFO)
Deferiprone
Defrasirox

96. Management: iron chelators
Agent Dose Route T1/2
hours
Schedule Clearance
Desferrioxamine 20-40
mg/kg
IV/SQ
Slow
infusion
0.3 8-24 hours
5-7 days
per week
Renal and
hepatic
Deferiprone 75-100
mg/kg
Oral 2-3 3 times
daily
Renal
Deferasirox 20-40
mg/kg
Oral 12-16 Once daily Hepatic

97. Desferrioxamine

98. Desferrioxamine
• Desferrioxamine has been in clinical use since the 1970s and
widely used since about 1980.
• The process of iron chelation ceases soon after an infusion is
complete
• Efficacy of chelation is 14%
• With adequate dose and duration Desferrioxamine monotherepy
effectively control serum ferritin,liver iron, cardiac iron and hence
total body iron store.
• Vitamin C(2-3 mg/kg/day) increases iron excretion by increasing
the availability of chelatable iron
• Can be used in pregnancy.

99. Desferrioxamine
• The most common
sites of infusion are
abdomen, thighs and
upper arms.

100. Intensive chelation with Desferrioxamine –
continuous 24-hourly infusions IV or SC.
Indications:
a) Persistently high serum ferritin;
b) LIC > 15 mg/g dry weight;
c) Significant heart disease, and;
d) Prior to bone marrow transplantation
Dose: 50 mg/kg/day (up to 60 mg/kg/day)

101. Adverse effects
Local skin reactions
Hearing impairment
Ophthalmologic impairment
Growth retardation
Skeletal changes
Rare complications

102. Combined therapy: DFO and DFP
• DFP given on each day of the week, and subcutaneous
DFO infusions given on some or all of these days was
introduced in 1998 for patients inadequately chelated by
maximum tolerated doses of DFP
• The effect of the combined drugs on iron excretion has been
found on the basis of urine iron excretion and iron balance
studies : additive or even synergistic.
• This has been explained as a shuttle mechanism with DFP
entering cells and removing iron, which is then passed on to
DFO for excretion in urine or feces. The DFP may reenter
cells and extract more iron.
• In addition, recent studies show that DFP is capable of
rapidly accessing NTBI fractions in plasma and transferring
this iron to DFO. Shuttling of iron from DFP to DFO also
applies to iron removed from transferrin.

103. The “shuttle”
mechanism by which
DFP given orally
binds iron from
transferrin (TF),
NTBI, and
intracellular
compartments and
transfers some of
this iron to DFO. The
free DFP is then
available to bind
more iron. Some
DFO also enters
cells to bind iron
directly.

109. Iron chelating agents
Deferiprone

110. Deferiprone

111. Deferiprone
• Orally absorbed iron chelator that began clinical trials in UK in the
1980
• At currently used doses ,about 6% of the drug binds iron before it
is excreted or metabolised (6% efficiency)
• There is no significant difference in reducing serum ferritin, liver
iron or cardiac iron in between deferiprone and desferrioxamine
• Contraindicated in pregnancy

112. Adverse effects
agranulocytosis
Gastrointestinal symptoms
Arthropathy
Elevation o liver enzymes

113. Deferasirox

114. Deferasirox
• Deferasirox was developed by Novartis as a once daily oral
monotherapy
• It has been licensed as first line monotherapy for thalassaemia in
over 70 countries.
• Efficiency of chelation is 28%
• Use in children >2 years of age
• Contraindicated in pregnancy and in significant renal dysfunction.

115. Adverse effects
Gastrointestinal effects
Renal impairment
Liver dysfunction
Skin rashes

123. Fetal Hb Induction

124. Induction of fetal hemoglobin
Hb F enhancement..
• Hydroxyurea
• Butyrate derivatives
• Erythropoietin
• Decitabine
• 5-Azacytadine

125. • Increasing the synthesis of fetal hemoglobin can help to alleviate
anaemia and thereby improve the clinical status of patients with
thalassemia intermedia.
• Agents including cytosine arabinoside and hydroxyurea may alter
the pattern of erythropoiesis and increase the expression of foetal
gamma globin gene.
• Erythropoietin has been shown to be effective, with a possible
additive effect in combination with hydroxyurea.
• Butyrate (short chain fatty acid derivatives) acts as a foetal globin
gene promoter and rises two to six fold high foetal globin.

126. SPLEECTOMY

127. SPLENECTOMY
Deferred as long as possible. At least till 5-6 yrs age.
• Splenectomy reduces the transfusion requirements in patients with
hypersplenism.
• Splenectomy is avoided if possible due to the risk of infection,
pulmonary hypertension and thromboembolism

128. Indications for splenectomy include:
• Persistent increase in blood transfusion requirements by
50% or more over initial needs for over 6 months.
• Annual packed cell transfusion requirements in excess of
250 ml/kg/year in the face of uncontrolled iron overload
(ferritin greater than 1,500 ng/ml or increased hepatic
iron concentration).
• Evidence of hypersplenism (cytopenia )
• Massive splenomegaly causing mechanical discomfort
or concern about splenic rupture.

129. The risk of splenectomy
Overwhelming infection
Age—(<2 years of age)
Time since splenectomy (1-
4 years after surgery)
Immune status of patient
Commonly associated pathogen
Streptococcus pneumoniae
Haemophilus influenzae
Neisseria meningitidis

130. Preventative measures
Immunoprophylaxis–
 At least 2 weeks before splenectomy
 Pneumococcus/meningococcus/Hemophilus
Chemoprophylaxis-
 Chemoprophylaxis with life-long oral penicillin.
Education

131. B. Curative treatment in thalassemia
• Hematopoietic Stem cell transplantation
• Gene therapy

132. •Only curative option available.
•Outcome is best for children <17 years
with HLA identical sibling donor
•Overall survival is greater than 90%
•Overall outcome depends on-
• Inadequate chelation therapy,
• hepatomegaly,
• presence of liver fibrosis.
•Treatment-related mortality is
approximately 10%.
Hematopoietic stem cell transplantation
Guideline- Thalassemia International Federation-2008

133. Stem cell transplantation

134. Whom to offer?
Stem cell transplantation

135. Cost Vs Risk benefit
of patient
and
Availability of
DONOR
Stem cell transplantation

136. Gene therapy
• Stable transfer of a normal functioning copy of a beta-globin
therapy gene unit into the patient’s own HSC via retrovirus
delivery vector ,resulting in the permanent splicing or integration
of the therapy gene into the HSC DNA generates normal rather
than diseased RBC for life long.
• HSC are isolated from the patient’s bone marrow and infected or
transduced with the beta-globin lentiviral vector.
• The corrected cells are then returned to the patient, who
in the meantime undergone chemotherapy to partially or
completely destroy their diseased bone marrow.
Guidelines for the Management of transfusion dependent Thalassemia,3rd

137. Role of surgery in thalassemia
• Cholelithiasis – Cholecystectomy
• Choledocholithiasis – Choledocholithotomy
• Cirrhosis (due to iron overload) – Liver biopsy and liver
transplantation
• Leg ulcer – Surgical dressing
• Pathological fracture – Surgical correction
• Spinal cord compression - Laminectomy

138. Follow up
Monthly:
• Complete blood count
• Complete blood chemistry (including liver function tests,
BUN, creatinine) if taking deferasirox
• Record transfusion volume.
Every 3 months:
• Measurement of height and weight
• Measurement of ferritin (trends in ferritin used to adjust
chelation);
• Complete blood chemistry, including liver function tests

139. Follow up
Every 6 months:
• Complete physical examination including Tanner
staging,
• Monitor growth and development
• Dental examination

140. Follow up
Every year:
• Cardiac function – echocardiograph, ECG, Holter
monitor (as indicated)
• Endocrine function (TFTs, PTH, FSH/LH, fasting
glucose, testosterone/estradiol, FSH, LH, IGF-1,
Vitamin D levels)
• Ophthalmological examination and auditory acuity
• Viral serologies (HAV, HBV panel, HCV (or if HCV1,
quantitative HCV RNA PCR), HIV)
• Bone densitometry
• Ongoing psychosocial support.

141. Follow up
Every 2 years:
• Evaluation of tissue iron burden
• Liver iron measurement – R2 MRI, SQUID, or biopsy
• T2* MRI measurement of cardiac iron (age .10 years).

142. C. Prevention and control
 Career detection/Screening
 Genetic counseling
 Prenatal diagnosis
 Health education

143. Screening
• RBC indices (MCV, MCH, MCHC)
• NESTROFT
• HbA2

144. Career detection/screening
Automated CBC:
• Thalassemic red cells are microcytic and hypochromic
• WHO recommends MCV <77fl and MCH <27 pg as
screening tools to pick up cases for confirmation by
electrophoresis
DCIP (Di Chloro phenol indol phenol): Screening for Hb
E

145. Career detection/screening
Mass screening: NESTROFT (Necked Eye Single Tube
Red Cell Osmotic Fragility Test)
• Very cheap and easy to perform require small
amount of blood
• Based on principle that Thalassemic red cell resists
hypotonic solution more than that of normal person
• Give positive result on NESTROFT
• Sensitivity 90-98% and specificity 85-90%

146. NESTROFT

147. Genetic counseling
• Index case parents and relatives.
• Antenatal visits of pregnant mothers.

148. Genetic counseling

149. • β/α ratio: <0.025 in fetal
blood
• Chorionic villous biopsy
(10-12 weeks)
• Cordocentesis
• Amniocentesis (15-18th
week) Analysis of fetal DNA
• PCR to detect β globin
gene
Prenatal diagnosis

150. Chorionic Villus Biopsy

151. Health education/awareness
• Knowledge of genetic nature of thalassemia
• Transmission of the disease
• Ways to avoid to have further child with the disease
• Aware about economic burden to the family and govt.

152. Thalassemia major-life expectancy:
• Without regular transfusion - Less than 10 years
• With regular transfusion and no or poor iron chelation -
Less than 25 years
• With regular transfusion and good iron chelation - 40
years, or longer?
The commonest cause of death is iron overload
Prognosis

153. Conclusion
• Management needs extensive hands
• Prevention program is rudimentary
• Awareness about thalassemia is though increasing still
very much lacking
• Manpower is developing-good news
• Thalassemia center dedicated to children to be
established

154. Thalassemia day
8th May is the international Thalassemia Day. This day is
dedicated to Thalassemia, to raise public awareness for
prevention of Thalassemia and to highlight the
importance of clinical care for Thalassemia patients in all
countries.