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‫ميسم مؤيد علوش‬.‫د‬
Hematology
Lec3
Thalassaemias
Objectives:
1-Define thalassemia and its main types(βand α)
2- Know the genet ic lesions of each of β and α thalassemia
3-Know the difference between thalassemia minor and major.
4-Know the main features of each subtype of thalassemia.
5-Define anemia of chronic diseases and its causes.
6-Define sideroblastic anemia.
Thalassaemias
These are a heterogeneous group of genetic disorders in which
there is reduced rate of synthesis or abscent synthesis of α
or β chains. This leads to a reduced rate of synthesis of
haemoglobin and therefore microcytosis.
β -Thalassaemia :
-Normal cell have two β globin genes (β).
- β –Thalassaemia is a condition resulting from mutation in one
or both of the β globin genes, which leads to a reduced rate ,or
even a total absence ,of synthesis of β globins.
The β-globin mutations associated with β-thalassemia fall into
two categories: Either
no β chain
→
(β o)
or
small amounts
are synthesized
→
.
(β +)
1- β –Thalassaemia major: ( homozygosity )
-There is a mutation in both β genes .
-Synthesis of β globin is totally abscent (β o β o
Thalassaemia)
or
severly reduced (β o β + Thalassaemia or
β + β + Thalassaemia)
-The majority of genetic lesions are point mutations.
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‫ميسم مؤيد علوش‬.‫د‬
Hematology
Lec3
- Severe anaemia becomes apparent at 3-6 months after birth as
haemoglobin F synthesis declines but haemoglobin A synthesis
does not take over,
- Excess α chains precipitate in erythroblasts causing the severe
ineffective erythropoiesis and in mature red cells causing
haemolysis that are typical of this disease.
- Enlargement of the liver and spleen occurs as a result of
excessive red cell destruction, extramedullary haemopoiesis and
later because of iron overload.
So the mechanism of sever anaemia is threefold :
1) inadequate synthesis of globin and therefore of haemoglobin
leading to a microcytic anaemia.
2) ineffective haemopoiesis- death of red cell precursors in the
bone marrow when they are damaged by excess α chains.
3) shortened red cell survival .
- The splenomegally further aggravates the anaemia as red cells
are pooled in the spleen.
- Expansion of bones caused by intense marrow hyperplasia
leads to a thalassaemic facies and to thining of the cortex of
many bones and bossing of the skull with a 'hair-on-end'
appearance on X-ray.
- The patient can be sustained by blood transfusions but iron
overload caused by repeated transfusions and deposition of iron in
the heart, pancrease,liver and pituitary gland.
Laboratory Findings:
-severe hypochromic, microcytic anaemia, with normoblasts
(nuclested red blood cells) , target cells and basophilic stippling in
the blood film.
- A raised reticulocyte percentage
-Haemoglobin electrophoresis reveals severly reduced amount
or almost complete absence of Hb A, with Hb F being the major
haemoglobin.
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‫ميسم مؤيد علوش‬.‫د‬
Hematology
Lec3
2.β –Thalassaemia minor or trait :( heterozygosity)
-There is a mutation in only one of the two β globin genes ,
So there is reduced rate of synthesis of β globin and
it is usually symptomless .Only occasionally , e.g. during
pregnancy or infection , anaemia occur.
- A hypochromic, microcytic blood picture (MCV and MCH are
low) but high red cell count.
- A raised Hb A2 (>3.5%) confirms the diagnosis.
3.Thalassaemia intermedia:
Cases of thalassaemia of moderate severity who do not need
regular transfusions are called thalassaemia intermedia.
α-Thalassaemia
-There are normally four copies of the α-globin gene (α α/ α α)
- The genetic lesion is usually caused by gene deletions.
*Loss of all four genes completely (--/--) suppresses α-chain
synthesis
When no α-chain can be produced there can be no production of
haemoglobin s F, A or A2 .Instead there is production of
haemoglobin Bart's , a non –functional haemoglobin with four γ
chains (γ4 ) and this is incompatible with life and leads to
death of the severly anaemic and oedematous fetus in utero or
shortly after birth (hydrops fetalis)
* Loss of three genes (-α/ --) causes haemoglobin H
disease .
-A moderately sever microcytic anaemia with haemolysis and
splenomegally.
-Haemoglobin H is of four β chains (β4).
- Haemoglobin H (β4) can be detected in red cells of these patients
by 1.electrophoresis
or
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‫ميسم مؤيد علوش‬.‫د‬
Hematology
Lec3
2.I n reticulocyte preparations ( golf ball' cells) caused by
precipitation of aggregates of β -globin chains.
* Loss of one or two genes ( -α / α α , - -/ α α , - α/ - α) .
-The α -thalassaemia traits
-It is harmless to the individual.
-Usually not associated with anaemia.
-The mean corpuscular volume (MCV) and mean corpuscular
haemoglobin (MCH) are low and the red cell count is increased.
- Haemoglobin electrophoresis is normal and DNA analyses are
needed to be certain of the diagnosis.
(- -/ α α) ,is of no clinical significance but genetically significant
(since this condition in both parents leads to a one in four of
haemoglobin Bart's hydrops fetalis.
Consequences of loss of one or more α genes
Alpha genes
Consequences
α α/ α α
Normal
- α/ α α
Haematologically normal or mild microcytosis
- α/ - α
Microcytosis, no clinical or genetic significance
- -/ α α
Microcytosis, no clinical significance but
genetic ally significant
- -/ -α
Haemoglobin H disease
--/--
Haemoglobin Bart's hydrops fetalis
-Anaemia of chronic disease :
-One of the most common anaemias .
-It occurs patients with a variety of chronic inflammatory and
malignant diseases .
-Causes include :
tuberculosis, osteomyelitis, rheumatoid arthritis, systemic lupus
erythematosus and other connective tissue diseases ,
sarcoidosis, Crohn's disease) Carcinoma , lymphoma, sarcoma
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‫ميسم مؤيد علوش‬.‫د‬
Hematology
Lec3
-The mechanism is synthesis of an inflammatory cytokines and
their effect on erythropoiesis.
-Initially Normochromic, normocytic the become hypochromic
microcytic .
- Both the serum iron and TIBC are reduced.
- The serum ferritin is normal or raised.
Sideroblastic anaemia
This is a refractory anaemia with hypochromic cells in the
peripheral blood and increased marrow iron.
It is defined by the presence of many pathological ring
sideroblasts in the bone marrow.
These are abnormal erythroblasts containing numerous iron
granules arranged in a ring or collar around the nucleus instead of
the few randomly distributed iron granules seen when normal
erythroblasts are stained for iron.
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