THALASSEMIA

THALASSEMIA

Some children are born with defective

limbs. Some with a defect in the senses.
Yet, very little of us know that some
children are born with a disorder of the
red blood cell- a disorder that requires
lifelong treatment and lifelong need to
cope with a multitude of complications.
Thalassemia is such a disorder

- Mindanao Thalassemia Foundation, Inc., 2002

WHAT IS THALASSEMIA?
COMES FROM 2 GREEK WORDS
Thalas meaning Sea
+
Emia meaning blood
Origin: Found in people in areas bordering
the Mediterranean Sea
IT IS A CONGENITAL HEMOLYTIC ANEMIA

THALASSEMIA
HEME + GLOBIN = HEMOGLOBIN
Main defect: globin synthesis
Two

major types
Alpha Thalassemia
Beta Thalassemia

INHERITANCE OF THALASSEMIA

Epidemiology of Thalassemia
Carrier frequencies of Thalassemia alleles (percent)
Region

-Thalassemia

0-Thalassemia

+-Thalassemia

Americas

03

05

040

Eastern
Mediterranean

218

02

160

Europe

019

12

012

Southeast Asia

011

130

340

Sub-Saharan
Africa

012

1050

Western Pacific

013

260

Weatherall D, Akinyanju O, Fucharoen S, Olivieri N, and Musgrove P, Inherited Disorders of Hemoglobin." 2006. Disease Control
Priorities in Developing Countries (2nd Edition). http://www.dcp2.org/pubs/DCP

CLASSIFICATION OF LPHA - THALASSEMIA

Silent Carriers

Trait

Hemoglobin H

Hydrops Fetalis

CLASSIFICATION OF ETA - THALASSEMIA

Minor

Major

CLINICAL MANIFESTATIONS
Pale
Stunted

growth
Dark skin
Enlarged abdomen ( enlarged liver &
spleen)
Bulging cheekbones
Frontal bossing
Widening of the bridge of the nose

PERIPHERAL SMEAR

TREATMENT
Blood

transfusion (prbc)
Folic acid
Vitamin B 1-6-12
Vitamin E
Splenectomy
Chelation therapy ( removal of excess
iron) either subcutaneous or oral route

IRON OVERLOAD
Accumulation

of excess iron in the body

Causes damage to the heart
liver
and other vital tissues in the body
Non specific symptoms of fatigue,
weakness, weight loss, abdominal
discomfort

Organ Systems Susceptible to

Iron Overload
Clinical sequelae of iron
overload
Pituitary impaired growth, infertility
Thyroid hypoparathyroidism,
Heart

cardiomyopathy

Liver

hepatic cirrhosis

Pancreas diabetes mellitus

Gonads hypogonadism

The build-up of iron in major organ

systems can lead to serious organ
dysfunction if not properly treated

Transfusion Therapy Results in

Iron Overload

1 blood unit contains 200 mg

iron

Overload can occur after 1020

transfusions ( estimated 1 year
of monthly prbc transfusion)

Porter JB. Br J Haematol 2001;115:239252

M5.2

What is Iron Chelation Therapy?

Toxic

Chelator

Iron

Chelator Iron

Excretion

The Challenge of Compliance

+
For most patients with iron overload, transfusion must be accompanied by chelation
therapy which requires the use of subcutaneous needles and infusion pumps.

The Challenge of Compliance

100
90
80
SURVIVAL

70
60
50

0-75 infusions/yr

40

75-150

"

30

150-225

"

20

225-300

"

10

300-365

"

10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40
YEARS

Gabutti and Piga, Acta Haematologica. 1996;95:26

Drugs for Iron Chelation Therapy:

1.

Deferoxamine (Desferal)

2.

Deferasirox (Exjade)

3.

Deferiprone (Brand F)

Deferoxamine (Desferal, DFO)

First-line

treatment of transfusional iron overload

Administered as slow subcutaneous infusion 57
nights/week
Side effects
localized

redness, swelling, itchiness and pain

reduced visual acuity, impaired color vision
Hearing loss
Growth retardation and bone changes in
children
Disadvantage:

non-compliance

Porter JB. Br J Haematol 2001;115:239252

Deferasirox (Exjade, ICL670)

Tridentate* iron chelator

An

oral, dispersible
tablet

Administered

once
daily (24 hr iron body
chelator)

Highly

iron1

specific for

Deferiprone (Ferriprox, L1)

Second-line

treatment of iron overload when DFO

therapy is contraindicated or inadequate1
Tablet, three times a day
Side effects of treatment
Agranulocytosis/neutropenia
Arthralgia
Nausea,

vomiting, abdominal pain

Increased levels of serum liver enzymes

IS THERE HOPE FOR A

THALASSEMIC CHILD?
YES
Supportive

anemia

treatment in correcting

( Periodic packed red cell transfusion)

Chelation

therapy to address
complications of iron overload
Goal:
Make

children with thalassemia live long

useful lives