Thalassaemia

Lecture II
Dr. KAW Karunasekera
Haemoglobinopathies
Due to structural abnormality of one of the
chains
- sickle cell (
2

2
6
valine for glutamic acid )
- haemoglobin C (
2

2
6
lysine)
- haemoglobin E (
2

2
26
lysine for glutamic
acid)
Due to reduce synthesis
- thalassaemia and

Thalassaemia syndrome
Are characterised by decreased
synthesis of one of the two types
of polypeptide chains.

thalassaemia

thalassaemia
thalassaemia
one affected allele (11 chromosome)-
heterozygous carrier or thalassaemia
trait/minor
two affected genes Phenotypes
thalassaemia major and thal. intermedia

0
,
+
,
++
in thal. major
other structural Hb. Variants
behaving similar to thal. such as HbE and
HbE thalassaemia. Both common in SE
Asia and Indian subcontinent
thalassaemia
Human genes are duplicated and located
in chromosome 16.
/ normal
-/ silent carrier, haematology is
normal
--/ or-/- thalassaemia trait
--/- HbH disease (mod. anaemia,
splenomegaly, haemolytic crisis

with drugs and infections)
--/-- Hb Bart disease (hydrops
fetalis)
thalassaemia -
pathophysiology

Clinical features
thalassaemia
presents at 2
nd
6 months of infancy
with features of progressive chronic
haemolytic anaemia including mild
jaundice & FTT
progressively enlarging spleen and
liver
skeletal deformities
features of iron overload
Clinical features
thalassaemia
Clinical features
thalassaemia
Skeletal deformities
skull bossing
scaphocephaly
prominent maxilla typical
flat nasal bridge
thalassaemic
malocclusion of teeth facies
pigmentation of the skin
bone tenderness and fractures
deformities in legs similar to rickets

How to investigate a case
of haemolytic anaemia?
FBC including Hb & blood picture
reticulocyte count
HPLC (high performance liquid
chromatography)/Hb electrophoresis
osmotic fragility test
G6PD levels
Coombs test and other relevant tests

X-ray changes
thalassaemia
HPLC / electrophoresis
HbF 90% in a 6 month old fetus, then
reduces to 70% at birth. By 6-12
months only traces present.
Normal child - HbA 98%, HbF
traces, HbA
2
2%

Type HbA HbF HbA
2

0
nil >90%

+
10% 80%

++
- 40% 60%



Hb electrophoresis
regular blood transfusion
iron chelation therapy
splenectomy
general management
management of complications
genetic counselling
prevention
Management of
thalassaemia (transfusion
dependent chronic
haemolytic anaemia)
Regular blood transfusion

Why? To correct anaemia
To improve physical and
mental well being
To suppress extramedullary
erythropoiesis
Regular blood transfusion
ctd
every 3-4 weeks
pre-transfusion Hb be at 9 g/dl
post-transfusion Hb be at 12 g/dl
ABO, Rh & other blood group
compatible, if not available O blood
can be given.
blood be < 2 weeks old

Deficit X wt in kg X 4
20 ml/kg for 2-3 hrs, 5 ml/kg for 3-4 hrs
if in Ht. failure
Hb drops by 1 g/dl/wk in
splenectomised patients, and by 1.5
g/dl/wk in non-splenectomised patients.
leukocyte depleted blood

Regular blood
transfusion ctd
complications of blood
transfusion

iron overload
transfusional reactions
infections

Iron overload
As a result of regular blood transfusion
(500 ml of blood give 200 mg of iron)
Increased intestinal absorption of iron

Why iron is toxic to the body
free iron (non transferrin bound)
causes cell death and fibrosis.
Features of iron overload
organomegaly, cirrhosis, hepatic
fibrosis
skin pigmentation
cardiomegaly, CCF & arrythmias
diabetes mellitus
pituitary failure - hypothyroidism
- growth failure and
delayed pubert
- hypoparathyroidism


Iron chelation
from 10
th
transfusion or depending on
serum ferritin levels >1000 g/l
Dry weight of liver iron
desferrioxamine is the drug of choice,
first introduced in 1970s
other drugs deferiprone
Desferrioxamine therapy
chelates iron & has a very short half life
so ideally should give as a slow infusion
(s.c.) over 8-10 hours daily for at least 6
days a week
dose 20-40 g/kg/d
expensive
vit C 2-3 mg/kg/d with infusion
monitoring -ferritin levels
liver dry iron concentration
local pain and tenderness
abscess formation
hypersensitivity
infection with Yersinia
visual impairment
hearing defects
skeletal abnormalities

Desferrioxamine - side
effects
Deferiprone
registered in Sri Lanka in year 2000
given orally as a second line therapy
the dose varies from 50-75 mg/kg/d
combine therapy with desferrioxamine is
a method of current treatment
5% have side effects including GIT
irritation, arthropathy, agranulocytosis
Transfusional reactions

Acute intravascular due to major blood group
incompatibility
Intravascular delayed due to Ag Ab reaction
Acute extravascular due to IgG attached to red
cells
Febrile non-haemolytic due to donor
lymphocytes cytokines (Leukocyte
depletion)
Allergic due to plasma proteins
Autoimmune haemolytic anaemia

Infections through blood
Hepatitis C
Hepatitis B - vaccination is mandatory
HIV
CMV
Malaria
Splenectomy
Indications
evidence of hypersplenism
Hb drop > 1.5 g/dl/wk
Thrombocytopaenia & recurrent infection
massive splenomegaly rupture
delay until 5 years
polyvalent pneumococcal, Hib,
meningococcal vaccines 2 weeks before
post op prophylactic penicillin
education of patient and parents
General management
no food very rich in iron, plain tea after meals
normal schooling & normal exercise
folic acid 1 mg/d
more calcium
vitamin C - no excess and only during
desferrioxamine therapy
Hepatitis B vaccination
psychological support
social support group
Other forms of therapy
bone marrow transplantation from a
histocompatible donor
gene therapy
pharmacological modulation of fetal
Hb
Causes of death
cardiac failure and arrhythmia 70%
infections
hepatoma
complications of bone marrow
transplantation
Prevention
genetic counselling
carrier detection MCH <21, MCV <70, blood
picture, HPLC/Hb electrophoresis >90% have
mild elevation of HbA
2
(3.4-7%). Those with
normal HbA
2
have increased HbF (5-15%)
discourage consanguineous marriage
antenatal diagnosis by chorionic villi biopsy

Other chronic haemolytic
anaemia
Thalassaemia intermedia
free chain is less
disease could behave as a mild
nontransfusional dependent haemolytic
anaemia or as thal. major
live longer therefore long term
complications are common
Haemoglobin E disease
there is ineffective erythropoiesis
common in SE Asia and Indian
subcontinent
Clinical spectrum is extremely
variable from mild to severe
haemolytic anaemia
could co-inherit with beta thal. gene
Congenital spherocytosis
Autosomal dominant
Anaemia varies and tends to be similar in
family
Presents as neonatal jaundice, anaemia,
mild jaundice and splenomegaly
Diagnosed by blood picture and osmotic
fragility
Treatment splenectomy, exchange
transfusion

G6PD deficiency
sex link recessive
presents with neonatal jaundice, acute
haemolysis with drugs and infections,
chronic haemolytic anaemia with
splenomegaly
diagnosed by G6PD assay
treatment : blood transfusion,
avoidance of drugs, exchange
transfusion