THALASSEMIA

THALASSEMIA
Muhammad Riza

Departement Of Child Health, Faculty Of Medicine,

University Of Sebelas Maret, Moewardi Hospital
Surakarta
Thomas cooley & Perl Lee (1925)  children of
Italian with severe anemia, splenomegaly &
characteristic bone change

Whipple and Bradford (1932) All early cases

reported in children of mediterranean origin the
Greek word thalassa = sea and hemia = blood
EPIDEMIOLOGY

• The most common genetic disorder in the world

• Approximately 250 millions of people (4.5% of

the world population) carry hemoglobinopathy
gene

• In Indonesia (2005) 2000 thalassemia major

patients

• Annual birth rate 20%  carrier of β thalassemia

5% 2020  22. 500 affected children
 How thalassaemia is inherited

• Autosomal recessive pattern of inheritance

• Autosomal chromosome other than a sex

chromosome  can affect males and females

• Recessive that the child needs to inherit the

defective gene from both the father and the
mother
Thalassemia  inherited disorders of hemoglobin
synthesis characterized by a reduced or absent
output of one or more of the globin chains of
adult hemoglobin

The α chains
The non α chains β,
δ,γ, ε, ζ
Normal Developmental Switching of Human Globin
β chain chromosome 11

α chain chromosome 16
 ERITROID cell NORMAL

a - chains b
Gen - a
b - chains a
Gen - b
a2b2  HbA > 96%
Gen - d
d - chains
Gen - g
g - chains d a2d2  HbA2 < 3,5%
g a2g2  HbF < 2%

a = b+ d +g
 ERITROID cell β Thalassemia

a - chains Free a globin chains

Gen - a
b - chains a b
Gen - b
a2b2 ---> HbA1
Gen - d b
d - chains
Gen - g a2d2 --> HbA2
d
g - chains g
Denaturation + precipitation a2g2 --> HbF
Pathophisiology
Clinical Forms
Type Globin-gene Hematological Clinical Hemoglobin
of thallasemia expression features expression findings
β0 homozygous β0/β0 severe anemia Cooley An HBF>90%

no HbA

HbA2 ↑
β+ homozygous β+/β+ moderate anemia Thal. intermedia HbA 20-40%

HbF 60-80%
β0 heterozygous β/β0 mild to moderate anemia spleenomegaly ↑HbF and HbA2

jaundice
β+ heterozygous β/β+ mild anemia normal ↑HbF and HbA2
δβ heterozygous δβ/δβ0 same normal HbF 5-20%
as above
HbA2
N/low
ά silent carrier -,α/αα mild anemia normal normal
α trait --/αα mild anemia normal Hb Barts(γ) 5 – 10%

-α/-α
HbH disease -,α/-,- Moderate Thal intermed Hb Bart 20-
anemia 40%,ChildHbH(b4) 4-
20%
Α -,-/-,- Severe anemia Hydrops fetalis Hb Barts80 – 90%
hydrops
no HbA or HbF
 ...Clinical Forms

• Severe Anaemia
• Hepatosplenomegaly
(Extramedullary Haematopoiesis)
 ...Clinical Forms

• Bone Marrow Expansion

• Classical Thalassaemic
Facies Bossing of Skull
 ...Clinical Forms

•Hair on End appearance in Skull X Rays

•Bone deformities
•Tendency to Fracture
 Haematological methods commonly used to
diagnose thalassaemia major
(i) Haematological indices (ii) Blood film and RBC morphology
MCV – DECREASED
MCH – DECREASED
MCHC – DECREASED
RDW – INCREASED

(iii) Haemoglobin electrophoresis

Electrophoresis á There is a lack in HbA1 but

an increase in HbA2 and HbF
The treatment of -thalassaemia major
1. Blood transfusion therapy

• When transfusion therapy should begin

• How to ensure safe transfusions
• What to transfuse
• How to establish the most appropriate
blood transfusion therapy regime
 ...The treatment of -thalassaemia major
2. Iron Overload and Iron Chelation
Nama Obat Desferrioxamine (DFO) Deferiprone Deferasirox

Dosis (mg/kg/hari) 25-60 75 20-30

Rute Pemberian s.c;i.v (dalam 8-12 jam; Oral Oral

5hari/minggu) 3 kali/hari 1 kali/hari

Waktu paruh 20-30 menit 3-4 jam 12-16 jam

Ekskresi Urin,feses urin Feses

Efek samping Reaksi lokal, gangguan Gangguan GIT, Gangguan GIT, rash,
optalmologis, auditoris agranulositosis, peningkatan kreatinin
(hearing loss), gangguan netropenia, athralgia ringan, gangguan
pertumbuhan, alergi optalmologis, gangguan
auditoris

Status Licensed Licensed diluar Approved

USA/Canada
 ...The treatment of -thalassaemia major
3. Splenectomy

Should be considered when:

• Transfusion requirement >200-220 ml/kg/year
• Massive splenomegaly (possible splenic rupture)
• Age > 5 yo
!!! Imunization (hep.B, HIB)
 ...The treatment of -thalassaemia major

4. Folate supplements to ensure adequate

nutrients for synthesis of red cells
5. Ascorbic Acid (Vitamin C) aids chelating
agent in increasing urinary excretion of iron
6. Endocrinal therapy to allow normal growth
and sexual development
7. Bone Marrow Transplantation (BMT)
8. Psychosocial issues
The importance of prevention

1. Genetic counselling

2. Testing a foetus for thalassaemia