UPDATE ON THALASSAEMIA

Epidemiology of thalassemia
 THALASSAEMIA
 Di Malaysia
 Pembawa thalassaemia (Thalassaemia minor/trait)
 600,000 – 1 juta orang
 5% daripada populasi penduduk
 Thalassaemia Major
 2500 pesakit
 Melayu, Cina & Bumiputera Sabah &
Sarawak
 Objectives

1. To promote awareness on β-thalassemia

disease & carrier status

2. To provide population screening on

voluntary basis for those age 16 years &
above

3. To provide counseling for all those

confirmed as β-thalassemia carriers
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 WHAT IS THALASSEMIA ?

 Inherited disease of
blood that reduces
the amount of
haemoglobin body
can make and so
can cause anaemia.

GENETIC DISEASE
What is Haemoglobin (Hb)?
Blood vessel

Platelet White blood cell Red blood cell

The hemoglobin molecule
 Resides in RBCs,
responsible for carrying
and transporting O2
 Is a tetramer, consist of
four polypeptide
groups, 2 α and 2 β
chains (α2β2)
 Up to 4 O2 molecules
can bind to the 4 heme
groups.
Haemoglobin Molecule
Genes for Haemoglobin
 BETA THALASSEMIA
Lack of beta chain

 Most of  thalassemia result

from point mutation within or
close to the  globin gene
complex.
 Each mutation result in
reduction or abolition of 
globin chain function.
BETA THALASSEMIA
CLINICAL SYNDROME
o Thalassemia Minor or Thalassemia Trait (ß+/ßa) or
(ßo/ßa)
o Thalassemia Intermedia (ß+/ß+) or (ß+/ßo)
o Thalassemia Major or Cooley's Anemia (ßo/ßo)
Beta Thalassaemia
Beta Thalassaemia Trait (Minor)
 Beta Thalassaemia Major
 Both parents thalassaemia major = 100%
fetal thalassaemia major.
 1 parent thalassaemia major + 1 parent
thalassaemia trait = 50% thalassaemia
major, 50% thalassaemia trait
 1 parent thalassaemia major + 1 normal
parent = 100% thalassaemia trait
 ALPHA THALASSEMIA

 Lack of Alpha Chain

 More than 95% of  thal are due to
deletion of one or both of the
tandem  globin genes located on
chromosome 16.
Alpha Thalassaemia
Alpha Thalassaemia
 ALPHA THALASSEMIA
5 possible genotypes:

Type Genotype
Normal /
+ heterozygote -/
+homozygote -/-
o heterozygote --/ 
ohomozygote --/--

o +double hetero --/-

 LAB INVESTIGATIONS

Screening Test
1. Full Blood Count
2. Full Blood Picture
3. Reticulocyte count.
4. S. Iron/TIBC, S. Ferritin

Diagnostic Test
1. Hb Analysis

Confirmatory Test

1. DNA Analysis
INVESTIGATIONS
FBC
 INVESTIGATIONS
FBP - smear

Thalassemia trait Thalassemia major

Immune haemolytic A
 INVESTIGATIONS
Reticulocytes count

Reticulocytes
- are juvenile red cells.
- Number of reticulocytes in
periperal blood is a fairly
accurate reflection of Range of retic count in
erythropoietic activity. health =
50-100x109/l
(0.5 – 2.5%)
INVESTIGATIONS
Hb Analysis
 THALASSEMIA SYNDROMES

SEA α0 α-thal 2 , 3.7 del

 Molecular diagnosis
 Methods are based on the polymerase chain
reaction.
 dot blot analysis,
 reverse dot blot analysis,
 the amplification refractory mutation system (ARMS),
 denaturing gradient gel electrophoresis,
 mutagenically separated PCR,
 gap-PCR and
 Restriction endonuclease analysis.
 Confirmatory Diagnosis
Currently molecular diagnosis available in
Malaysia at:

1. IMR
2. HUKM
3. UMMC
4. Some private labs outsource to Singapore or
Australia
5. HKL to commence next year
 Management of Thalassaemia
Intermedia/Major
 Transfusions
 Should be avoided
 Indicated if situations of poor growth or abnormal facies
 Splenectomy
 In the presence of hypersplenism or decline in Hb levels
 Iron chelation
 When ferritin exceeds 1000 micrograms/L
 Less frequent than the thalassaemia major patients
 Supplements
 Folate
SETIAP
BULAN

SEPANJANG
HAYAT
 Complications of Thalassamia and
Treatment
 Acute febrile illness
 Complications due to iron overload
 Cardiac complications
 Endocrine complications – DM, hypothyrodism, delayed puberty,
short stature
 Skin
 Other organs
 Complications from excessive erythropoiesis
 Challenge on the facial appearance
 Osteoporosis and osteopenia
 Transfusion related complications – Hep B/C/ HIV
 Psychosocial problems
 Lack of self-esteem, lack of confidence, adjustment, etc.
 Poor academic results (due to absence)
 Discrimination against employment, relationships, etc.
Treatment – Iron chelation
 Giving Desferrioxamine

Peralatan Membancuh ubat Ubat dalam syringe

Cucuk bawah kulit Tampal plaster Mesin dalam sarung

(Sarawak Thalassaemia Association)
 Haematopoietic cell transplant (BMT)
 The only curative option
 A form of gene therapy
 Replace defective haematopoietic system from
compatible donors
 Acute mortality rate
 Chronic morbidity
 Must be offered to all transfusion dependent patients
as early as possible
 ? ??? ?
CURE ? ?
?
vs ? ?
DEATH

CURE
Class 1: 91 %
Class 2: 83 %
Class 3: 58 % DEATH
Adults : 62 % Class 1 7%
Class 2 13%
Class 3 21%
Adults 34%
 Βeta-Thalassaemia Carrier Voluntary Screening
RESPONSIBILITY
Walk-in for voluntary
screening

Algorithm (KK/KPL)

Register – “Thalassaemia Screening”

Pembantu Tadbir

Perkhidmatan
Pembantu Rendah Am
(PER-PL102) (PRA)
Pembantu Perawatan
Kesihatan (PPK)

Penolong Pegawai
Pre-test counseling Perubatan
Jururawat Terlatih
Blood taking

Juruteknologi Makmal
FBC Perubatan (JTMP)
Penolong Pegawai
Perubatan
a a a Jururawat Terlatih
Hb – normal Hb – normal Hb↓ a
MCH <27 Return for Hb & MCH
MCH >27 MCH <27
results
(Keep blood for HPLC)

1
1 Penolong Pegawai
Post-test 2
Check & treat for Perubatan
counseling Iron Deficiency 1
Jururawat Terlatih
Anaemia 2
Pegawai Perubatan
2
Pakar Perubatan Keluarga
3 No response 3
Register Penolong Pegawai
Recall Register Perubatan

Within normal limit;

alpha-thalassaemia
cannot be excluded Pegawai Perubatan
HPLC Pakar Perubatan Keluarga

Counseling & Beta-thalassaemia /

Send blood for Hb E carriers
DNA Analysis to
IMR
Pakar Perubatan Keluarga
Pegawai Perubatan
Counseling & Penolong Pegawai
Beta-Thalassaemia Carrier Perubatan
National Registry Jururawat Terlatih 34
Kad Status Pembawa

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 Prenatal Diagnosis
 To diagnose whether the fetus has
Thalassaemia.
 Why do we want to diagnose?
 If fetus is normal, increased surveillance is not
required. Reassuring to the parent.
 If fetus is affected, surveillance is increased.
 ? Termination of pregnancy
 Prenatal Diagnosis
 Chorionic Villus Sampling (CVS)
 Amniocentesis
 Fetal Blood Sampling (FBS)
 Pre-implantation Genetic Diagnosis (PGD)
 Chorionic Villus Sampling
 Sampling of placental
tissue.
 10-13 weeks gestation.
 Transvaginal /
Transabdominal.
 Amniocentesis
 Aspiration of amniotic fluid (15-20ml).
 15-16 weeks gestation.
 Fetal Blood Sampling
Can be done during 16-18 weeks of gestation
Hydrops Fetalis
Thank you