HAEMATOLOGY

RED BLOOD CELLS

DISORDERS

‫ميسم مؤيد علوش‬.‫د‬.‫م‬.‫أ‬

LEC.2
Assistant Professor Dr.Maysem Alwash/Hematopathologist
 HYPOCHROMIC MICROCYTIC
ANAEMIAS
OBJECTIVES:
1-Define hyochromic microcytic anaemia
2-Know the differential diagnosis of hyochromic microcytic anaemia
3-.Know the main dietary sources of iron ,site of absorption of iron ,distribution of iron in the
body and daily requirement.
4-Know the causes of iron deficiency anaemia.
4-Know the clinical and laboratory findings of iron deficiency anaemia.
5-Define thalassemia and its main classification
6-Understand the pathophysiology of alpha and beta thalassemia

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 HYPOCHROMIC MICROCYTIC ANAEMIAS

A Hypochromic Microcytic Anaemia is one in which

the erythrocytes are smaller than normal (i.e.
microcytic), often they also hypochromic (i.e. they
appear paler than normal in a stained blood film

Assistant Professor Dr.Maysem Alwash/Hematopathologist

Normal blood film Hypochromic microcytic anemia

Assistant Professor Dr.Maysem Alwash/Hematopathologist

MICROCYTIC ANAEMIAS
RESULT FROM A REDUCED
RATE OF SYNTHESIS OF
HAEMOGLOBIN.

THIS, IN TURN RESULTS

FROM A REDUCED RATE OF
SYNTHESIS OF EITHER HAEM
OR GLOBIN.

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 Causes of a hypochromic
microcytic anaemia:

-Iron deficiency anaemia

- -Thalassemia.
-Anaemia of chronic disease.
-Sideroblastic anaemia
Assistant Professor Dr.Maysem Alwash/Hematopathologist
1.Iron Deficiency Anaemia:

Iron deficiency is the most common cause of

anaemia in every country of the world. it is
the most important cause of a microcytic
hypochromic anaemia.

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 Iron :

 -Itis an element of crucial importance in the human body

,being essential for the synthesis of haemoglobin ,cytochromes
,and ribonucleaotide reductase (needed for DNA synthesis).

Iron is absorbed from the diet with that of animal origin (red
meat, fish , egg) being the richest source.

Iron is released from food in the stomach , and passes into the
duodenum where absorption is maximum. some absorption
also occurs in the jejunum
Assistant Professor Dr.Maysem Alwash/Hematopathologist


Uptake of about 1 mg a day is needed

in adult men while menstruating woman
needs about 2 mg per day.
Pregnant and lactating women need higher
amount.
-Growing infants, children and adolescents
have greater requirement than adult man.
Very little iron is normally lost from the body
in desequamating cells from the skin or
Assistant Professor Dr.Maysem Alwash/Hematopathologist

gastrointestinal tract or red blood cells..

 Body iron can be viewed as belonging to
three pools :

1.The functional pool :

such as Haemoglobin and Myoglobin .
Most of the iron in the body is contained in
circulating haemoglobin.

Assistant Professor Dr.Maysem Alwash/Hematopathologist

2.The storage pool :
Ferritin and Haemosiderin.
-Ferritin is a water-soluble protein-iron complex, is not
visible by light microscopy.
-Haemosiderin is an insoluble protein-iron complex and
is visible in macrophages and other cells by light
microscopy after staining by perl s' (prussian blue)
reaction.

3. The transit pool of iron

bound to transferrin in plasma

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 IRON IN THE BODY

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 Causes of iron deficiency:

I.Chronic blood loss

Uterine ,gastrointestinal, e.g. peptic ulcer, oesophageal varices
, non-steroidal anti inflammatory drugs ingestion, carcinoma
,hookworm.
II.Increased demand
Prematmity
Growth
Pregnancy
III.Malabsorption
Gluten-induced enteropathy , gastrectomy
IV.Poor diet
Assistant Professor Dr.Maysem Alwash/Hematopathologist

infants and children (iron poor milk), vegetarian diet

 Clinical features:

1.General symptoms and signs

of anaemia ( pallar ,fatigue,
tachycardia, and poor exercise
tolerance).
Assistant Professor Dr.Maysem Alwash/Hematopathologist
 Pallar

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 PALLAR

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 2.Special clinical featurs suggestive of iron
deficiency:

A Glossitis, angular stomatitis

Spoon nails (koilonychias).
Dysphagia as a result of pharyngeal webs
(Patersonkelly or Plummer-Vinson Syndrome)
-Unusual dietary cravings (PICA) .
-In children, it can cause irritability and a decline
in psychomotor development.
Assistant Professor Dr.Maysem Alwash/Hematopathologist
ANGULAR CHEILOSIS:
FISSURING AND ULCERATION OF THE
CORNER OF THE MOUTH.

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 KOILONYCHIA

Assistant Professor Dr.Maysem Alwash/Hematopathologist

PATERSON-KELLY (PLUMMER-VINSON) SYNDROME:
BARIUM SWALLOW X-RAY SHOWING A FILLING
DEFECT
(ARROW) CAUSED BY A POSTCRICOID WEB.

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 Laboratory Findings:

 -Peripheral blood:
 COMPLETE BLOOD COUNT: RBCS COUNT , HB , RBCS, HCT ,MCV,
MCH , MCHC All are reduced.

WBCS :Normal or increased or reduced

Platelets: may be increased in count.
 BLOOD FILM:

Hyochromic microcytic red blood cells, anisocytosis

(variation in size), poikilocytosis (variation in shape) ,
Assistant Professor Dr.Maysem Alwash/Hematopathologist

pencil cells and target cells

 HYPOCHROMIC MICROCYTIC

Assistant Professor Dr.Maysem Alwash/Hematopathologist

Scanning Electron Microscope Photograph

Normal red cells. Iron deficiency anaemia

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 Serum ferritin is low .
-
-Serum iron is low.
-Serum transferin receptor increased
-Transferrin concentration and total
iron binding capacity are elevated.

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 THE SENUN IRON; LTNSATURATED SENUN IRON-BINDING
CAPACITY (UIBC) AND SERUM FERRITIN IN NORMAL
SUBJECTS AND
IN THOSE WITH IRON DEFICIENCY

ferritin

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 :
BONE MARROW
Bone marrow examination is not essential to assess
iron stores except in complicated cases.
There is a complete absence of iron from stores
(macrophages) and from developing erythroblasts
The erythroblasts are small and have a ragged
cytoplasm.
Iron stain Bone marrow aspirate

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 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.

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 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
Assistant Professor Dr.Maysem Alwash/Hematopathologist

small amounts are synthesized → (β +)

 1- β –Thalassaemia major:
( homozygosity )
-There is a mutation in both β genes.
-The majority of genetic lesions are point
mutations.
Synthesis of β globin is:

Totally abscent (β o β o Thalassaemia)

or
Severly reduced (β o β + Thalassaemia
or
Assistant Professor Dr.Maysem Alwash/Hematopathologist
β + β + Thalassaemia)
 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
Assistant Professor Dr.Maysem Alwash/Hematopathologist
of iron overload.
 So the mechanisms of sever
anaemia are:

2) Ineffective
3) shortened
1)Inadequate haemopoiesis
red cell
synthesis of death of red
survival . The
globin and cell
splenomegaly
therefore of precursors in
further
the bone
haemoglobin aggravates
marrow when
leading to a the anaemia
they are
as red cells
microcytic damaged by
are pooled in
Assistant Professor Dr.Maysem Alwash/Hematopathologist excess α
anaemia. the spleen.
chains.
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.
'Hair-on-end' appearance on X-
Thalassaemic face RAY.

Assistant Professor Dr.Maysem Alwash/Hematopathologist

The patient can be sustained by blood
transfusions but iron overload occurs
caused by repeated transfusions
and deposition of iron in the heart,
pancrease,liver and pituitary gland.

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 Clinical features

1-Severe anaemia becomes apparent at 3–6 months after birth Typically the infant
presents in the first year with failure to thrive, pallor and a swollen abdomen.

2-Enlargement of the liver and spleen

3-Expansion of bones leads to a thalassaemic facies and to thinning of the cortex of

many bones, with a tendency to fractures and bossing of the skull.

4-Features of iron overload due to frequent blood transfusion

•
5-Infections: due to anaemia ,splenectomy (if has been carried out), and blood born
viruses transmitted by blood transfusion .

6-Liver disease: as a result of hepatitis C, hepatitis B , Human immunodeficiency virus

(HIV) and also iron overload is a cause of liver disease.

7-Osteoporosis :
Assistant Professor Dr.Maysem Alwash/Hematopathologist

It is more common in diabetic patients with endocrine abnormalities, including those resulting
from iron-related injury to the pituitary gland.
 LABORATORY FINDINGS:
Complete blood count: HGB, HCT, MCV, MCH, MCHC all are low

Reticulocyte count : increased

- film: severe hypochromic, microcytic anaemia, with
Bood
normoblasts (nucleated red blood cells) , target cells and
-
basophilic stippling in the blood film.

Hemoglobin fraction quantification: by hemoglobin

electrophoresis, cation-exchange HPLC, and capillary zone
electrophoresis .
These reveal severly reduced amount or almost complete
absence of Hb A, with Hb F being the major haemoglobin.
Assistant Professor Dr.Maysem Alwash/Hematopathologist
Bood film:severe hypochromic, microcytic anaemia, with
normoblasts (nucleated red blood cells) , target cells and
basophilic stippling in the blood film.

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 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.
Assistant Professor Dr.Maysem Alwash/Hematopathologist
 Β –THALASSAEMIA
MINOR OR TRAIT

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 3.Thalassaemia intermedia:

Cases of thalassaemia of
moderate severity who do
not need regular
transfusions are called
thalassaemia intermedia.
Assistant Professor Dr.Maysem Alwash/Hematopathologist
 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

Assistant Professor Dr.Maysem Alwash/Hematopathologist

Loss of all four genes completely (--/--)

suppresses α-chain synthesis when no α-

chain can be produced there can be no
production of haemoglobins 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
Assistant Professor Dr.Maysem Alwash/Hematopathologist

in utero or shortly after birth (hydrops fetalis

 HYDROPS FETALIS

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 Loss of three genes (-α/ --)

• Haemoglobin H (β4) can

be detected in red cells
Haemoglobin H disease .
of these patients by
-A moderately sever
1.Electrophoresis
microcytic anaemia with
or
haemolysis and
splenomegally. 2. In reticulocyte
preparations
-Haemoglobin H is of four
β chains (β4). ( golf ball' cells) caused
by precipitation of
Assistant Professor Dr.Maysem Alwash/Hematopathologist
aggregates of β -globin
chains.
 Supravital staining with brilliant
Marked hypochromic, cresyl blue reveals multiple fine,
deeply stained deposits ('golf ball‘
microcytic cells with target cells) caused by precipitation of
cells and poikilocytosis aggregates of p-globin
chains.
.

Assistant Professor Dr.Maysem Alwash/Hematopathologist

Loss of one or two genes ( - α / α α , - -/ α α ,
- α / - α) .
-
-
*
- α -thalassaemia traits
 The

 It is harmless to the individual.

 It 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.
Assistant Professor Dr.Maysem Alwash/Hematopathologist
(- -/ αα) ,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.

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 The genetics of a-thalassaemia. .
the orange boxes represent normal genes,
and the blue boxes represent gene deletions or
dysftmctional genes..

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 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
Assistant Professor Dr.Maysem Alwash/Hematopathologist
--/-- Haemoglobin Bart's hydrops fetalis
• REFERENCES:
1-Rodak s hematology:
Clinical principles and Applications , 6 th edition
2-Hoffbrand s essential haematology 8th edition

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 THANK YOU

Assistant Professor Dr.Maysem Alwash/Hematopathologist