Thalassaemia syndromes Treatment - PowerPoint Presentation

Slide1

Thalassaemia syndromes

Treatment1 Regular blood transfusions are needed to

maintainthe

haemoglobin

over 10 g/

dL

at all times.

This usually requires 2-3 units every 4-6 weeks

Fresh blood

, filtered to

remove white

cells, gives the

best red

cell

survival

with the fewest

reactions

.

The patients

should be

genotyped

at the start of the

transfusion program

in case red cell antibodies

against transfused red cells develop.

2-

Regular folic acid (e.g. 5 mg/day) is given if the

diet is

poor.

3 -Iron

chelation

therapy is used to treat iron overload.

The most established drug,

deferoxamine

, is

inactive orally

.

It

may be given by a separate

infusion bag

1-2 g with each unit of blood transfused

and by subcutaneous infusion 40 mg/kg over

8-12

h, 5-7 days weekly.

It

is commenced in infants

after 10-15

units

of blood have been transfused.

Deferiprone

is an orally active iron

chelator

which causes

predominantly urine iron excretion.

It is

usually

given in three doses

daily .

more

effective than

deferoxamine

at

removing cardiac iron

Deferasirox is the newest

oral

chelator

.

It

is given once daily and causes

faecal

iron excretion

only.

Skin

rashes and transient

changes in

liver enzymes have been reported.

The

ease

of administration

and its lack of major side-effects

are likely

to result in its widespread use.

4-

Vitamin C, 200 mg/day, increases excretion of

iron produced by

deferoxamine

.

5

-

Splenectomy

may be needed to reduce blood

requirements. This should be delayed until the

patient is over 6 years old because of the high

risk of

dangerous infections post-

splenectomy

.

vaccinations and

antibiotics

should

be

given

6-

Endocrine therapy is given either as replacement

because of end-organ failure or to stimulate the

pituitary if

puberty is delayed

.

Diabetics

will require

insulin therapy.

Patients with osteoporosis may need additional

therapy with increased calcium and vitamin

D in their diet, together with a

bisphosphonate

and appropriate

endocrine therapy.

7 -Immunization against hepatitis B should be

carried out in all non-immune patients.

Treatment for

transfusion-transmitted hepatitis C with

alpha interferon and

ribavirin

is needed if viral

genomes are

detected in plasma.

8-

Allogeneic

bone marrow

transplantation

offers

the prospect of permanent cure.

The

success

rate(long-term

thalassaemia

major-free survival)

is over

80% in well-

chelated

younger patients

without liver

fibrosis or

hepatomegaly

.

A

human

leucocyte

antigen

(HLA) matching sibling (or rarely

other family

member or matching

unrelated

donor)

acts as

donor

.

Failure

is mainly a result of

recurrence

of

thalassaemia

, death (e.g. from infection) or

severe chronic

graft-versus-host disease

Beta Thalassaemia trait (minor)

This

is a common, usually symptomless,

abnormality characterized

like

؛

alpha-

thalassaemia

trait by

a

hypochromic

,

microcytic

blood picture (

MCV and

MCH very low) but high red cell

count (>

5.5 x 1012/L) and

mild

anaemia

(

haemoglobin

10-12.g/

dL

).

I

t

is usually more severe

thanalpha

trait

.

A

raised

Hb

A2 (>3.5%) confirms the diagnosis

.

One of

the most important indications for making

the diagnosis

is that it allows the possibility of

prenatal

counselling

to patients with a partner who also

has a

significant

haemoglobin

disorder.

If

both carry

beta

thalassaemia

trait

there is a 25% risk of a

thalassaemia

major child

Thalassaemia intermedia

Cases

of

thalassaemia

of moderate

severity (

haemoglobin

7.0-10.0 g/

dL

) who do not need

regular transfusions

are called

thalassaemia

intermedia

This

is a

clinicnl

syndrome which may

be

caused

by a variety of genetic defects

:

homozygous beta-

thalassaemia

with

production of more

Hb

F than

usual

or with mild defects in

beta-chain

synthesis,

by beta-

thalassaemia

trait alone of

unusual

severity

('dominant'

beta-

thalassaemia

)or

beta-

thalassaemia

trait in

association with mild

globin

abnormalities

suchas

Hb

Lepore

.

.

The coexistence of alpha-

thalassaemia

trait improves the

haemoglobin

level in homozygous beta-

thalassaemia

by reducing the degree of chain imbalance and thus of alpha-chain precipitation and ineffective

Erythropoiesis

Conversely, patient with beta

thalassaemia

trait who also have excess (five or six) a genes tend to be more

anaemic

than usual.

The

patient with

thalassaemia

intermedia

may

show bone deformity, enlarged liver

and spleen

,

extramedullary

erythropoiesis

and

features of iron overload caused by

increased iron

absorption

.

Hb

H disease (three-gene

deletion alpha-

thalassaemia

) is a type of

thalassaemia

intermedia

without iron overload or

extramedullary

haemopoiesis

.

Thalassaemia

intermedia

.

Homozygous

beta-

thalassaemia

Homozygous mild

β

+

-

thalassaemia

Coinheritance of

alpha

thalassaemia

Enhanced ability to make fetal

haemoglobin

(ɣ-chain production)

Heterozygous

beta-

thalassaemia

Coinheritance of additional

alpha-

globin

genes

(α

αα

/

αα

) or (

ααα

/

ααα

)

Dominant beta-

thalassaemia

trait

δβ

-

Thalassaemia

and hereditary persistence

of fetal

haemoglobin

Homozygous

δβ

thalassaemia

Heterozygous

δβ

thalassaemia

/beta-

thalassaemia

Homozygous

Hb

Lepore

(some cases

)

Haemoglobin

H disease

δβ-Thalassaemia

This involves failure of production of both

β

and

δ

chains

.

in the heterozygous state

Fetal

haemoglobin

production is

increased to

5-20

%

which resembles

thalassaemia

minor

haematologically

.

In

the

homozygous state

only

Hb

F is present and

haematologically

the

picture is of

thalassaemia

intermedia

.

Haemoglobin Lepore

This

is an abnormal

haemoglobin

caused by

unequal

crossing-over of the

beta

and

delta

genes to

produce:

a polypeptide chain consisting of the

delta

chain

at its amino end and

beta

chain at its carboxyl end.

The

δβ

-fusion

chain is synthesized inefficiently and

normal

delta-

and

beta-chain

production is abolished.

The

homozygotes

show

thalassaemia

intermedia

and

the

heterozygotes

thalassaemia

trait.

Hereditary persistence of fetal haemoglobin

These

are a heterogeneous group of genetic

conditions caused by:

deletions or cross-

overs

affecting

the production of

β

and

ɣ

chains

or

, in

non-deletion forms

, by point mutations upstream from the

ɣ

globin

genes

.

Association of beta-thalassaemia trait with other genetic disorders of haemoglobin

The

combination of

β

-

thalassaemia

trait with

Hb

E

trait usually causes a transfusion-dependent

thalassaemia

major syndrome, but some cases are

intermediate.

β

-

Thalassaemia

trait with

Hb

S

trait

produces the clinical picture of sickle cell

anaemia

rather than of

thalassaemia

β

-

Thalassaemia

trait

with

Hb

D

trait causes a

hypochromic

,

microcytic

anaemia

of varying

severity