List of contents

— Objectives
— Contents
I.Definition
II.General evidences of hemolysis
III.Classification of hemolytic anemias
VI.Hereditory spherocytosis
V.G6PD –deficiency.
— Conclusions
objectives
— To define and classify Hemolytic anemias
— To explain the general evidences of hemolysis.
— To discuss hereditory membrane defect in
spherocytosis and enzymopathy in G6PD-deficiency
 Definition
u r e
e m at ion l s
Pr ruct c e l
t d
des he re
t
of
• Anaemias which result from an increase in the rate of
the red cell destruction; the life span of normal red cell is
120 days,
• in severe haemolysis the cell survive only a few days,
the haemolysis occurs either extravascularly by the
macrophages of the spleen leading to anaemia, jaundice and
splenomegaly.
Or
directly in the circulation intravascularly
General evidence of haemolysis:
ž1. Evidence of RBC and Hb breakdown :
- Increased unconjugated (Indirect) Bilirubin.
- Increased urinary Urobilinogen.
- Absent Hb binding protein (Haptaglobin).
ž2. Evidence of increased red cell
production:
- Reticulocytosis – blood.
- Erythroid hyperplasia – marrow.
INCREASED IN:
Hemolytic anemia or Bleeding
General evidence of haemolysis
(Cont.):
•3. Evidence of RBC Damage :
- Spherocytes, fragmented red cells.
.

•4. If intravascular haemolysis :

- Hemoglobinuria.

Hemoglobinaemia.
 Classification:
A- Hereditary Hemolytic Anemia

1- Membrane defect: e.g. hereditary spherocytosis,

hereditary elliptocytosis.

2- Defect in metabolism: e.g. G6PD deficiency

3- Genetic defect of haemoglobin: e.g. Thalassaemias

and sickle cell anaemia.
Elliptocytosis is a
hereditary disorder of the
Hereditary spherocytosis is an inherited blood red blood cells (RBCs). In
disorder. It happens because of a problem this condition, the RBCs
with the red blood cells (RBCs). Instead of assume an elliptical shape,
being shaped like a disk, the cells are round rather than the typical
like a sphere. round shape
 HS

Membrane HE

Hb
Thalassemia
Enzymes G6PD ↓
Hemoglobinopathies
Sickle PK ↓

ALL CONGENITAL
B- Acquired Hemolytic Anemia:
1- Immune Idiopathic
a. Autoimmune
• Warm antibody type. Lymphoma, S.L.E

• Cold antibody type.

b. Alloimmune
• Haemolytic transfusion reactions
• Haemolytic disease of the newborn
2- Drug associated
3- Red cell fragmentation syndromes
e.g. Arterial grafts, cardiac valves and
MAHA.
4- Infections: e.g. Malaria
5- Chemical (e.g. industrial agents)
and physical agents (Burns).
6- Secondary as in liver and renal
disease.
Hereditary spherocytosis (HS):

Inheritance: Autosomal Dominant

Pathogenesis: HS is due to a defect in the main

structural protein (spectrin) of the red cell
membrane.
The marrow produces cells of normal
biconcave shape but they lose membrane
as they circulate in the spleen →

they become spherical, spherocytes are

unable to pass through splenic
microcirculation where they die
prematurely inside spleen.
Clinical Features of
Hereditary Spherocytosis:
Anaemia
Jaundice
Splenomegally.

Laboratory finding:
The blood film shows (a) microspherocytes
(densely stained cells, smaller than normal
RC)
(b) Reticulocytosis.
G6PD deficiency:
Inheritance: sex linked disorder affecting
males and carried by females

Pathogenesis:
G6PD normally functions to reduce NADP
(nicotinamide-adenine-dinucleotide-
phosphate) to form NADPH
which is necessary for production of reduced
glutathione (GSH)
by which RBC are protected from damage by
oxidant stress.
In G6PD deficiency there is impaired reduction
of glutathione leading to acute haemolytic
anaemia in response to oxidant stress e.g.
(drugs, fava beans and infections, oxidant
chemicals).

Clinical features:
features of anemia with jaundice
Intravascular haemolysis with
haemoglobinuria.
conclusions
— Hemolytic anemias result from premature destruction of
red cells.

— Hemolysis is either inherited or acquired.

— Hemolysis is Extravascular or intravascular.

— Reticulocytosis,jaundice,hemoglobinaemia and
haemoglobinurea are among the general evidences of HA.
Nawsherwan Sadiq
Hawler Medical University
College of Medicine
List of contents
— Objectives

— contents
I.Definition and classification
II.B-thalassaemias
III. α-thalassaemias
VI.Sickle cell anaemias

— Conclusions
— question
objectives

— To define and classify hemoglobinopathies.

— To discuss the pathophysiology and genetic lesions of

thalassaemias and sickle cell anaemia

— To learn about clinical, laboratory features and treatment.

Are inherited disorders of globin synthesis
Haemoglobin abnormalities result from
the followings
Reduced rate of synthesis of normal α- or β-
globin chains e.g α-thalassaemia and β-
Thalassaemia.

Synthesis of an abnormal haemoglobin e.g Hb S

(Sickle cell anaemia)
1- Function:
The main function of Haemoglobin is to carry O2 to the tissues
and to return carbon dioxide (CO2) from the tissues to the
lungs.

2- Structure:
Each molecule of haemoglobin is composed of a tetramer of
four globin (polypeptide) chains each with its own haem group.
 Hb A2: α 2δ2
2.2 – 3.2 %
Hb A: α2β2
96 – 98 %

Hb F: α2γ2
0.5 – 0.8
Are heterogeneous
group of genetic
disorders which result
from reduced rate of
synthesis of α or β
globin chains.

Inheritance; Mendelian
recessive fashion
1- Thalassaemia major: which is transfusion dependent.

2- Thalassaemia intermedia: moderate anaemia with

splenomegally and iron overload

3- Thalassaemia minor : symptomless carrier with mild

or no anaemia.
 Are the most important types of thalassaemia
Because they are so common and usually produce
severe anaemia in their homozygous state

The majority of genetic lesions are point mutation.

Distribution: occur widely in Mediterranean region,
and parts of north and west Africa, Middle East, India
and South East Asia
 Genetics of b thalassemia
— There is one Beta globin gene on each chromosome 11
in human genome.

— The inheritance of this disorder is autosomal

recessive,

— so that heterozygous (minor) are usually

symptomless, while homozygotes are severely or
moderately affected.
B-thalassaemia major

Thalassaemia major is often due to

inheritance of two different mutations;
either no β chain synthesized (βº) or small
amount synthesized (β+).
Excess α chains precipitate in erythroblasts
and mature red cells causing haemolysis.
Severe anaemia becomes apparent at 3 – 6 months
after birth, Pallor, poor feeding ,failure to thrive

Enlargement of the liver and spleen due

to excessive red cell destruction;
extramedullary haemopoiesis and iron
overload
 Expansion of bones due to intense marrow
hyperplasia leads to thalassaemic face (bossing
of skull bones) and Hair on end in the skull

thalassaemic face Hair on end

 Iron overload due to repeated blood
transfusion which leads to multiple organ
failure and eventually death
Hypochromic microcytic
anaemia (decrease MCV
and MCH)

Increased reticulocyte
count

Anisocytosis and
poikilocytosis mainly Hb electrophoresis
target cells reveals absent or ↓ HbA
levels with increased
HbF.
Regular blood transfusions are needed to maintain
Hb > 10 g/dl.

Folic acid.

Iron chelation therapy to prevent iron overload

(Desferrioxamine).

Splenectomy to reduce blood requirements.

Bone marrow transplantation

No or mild anemia
hypochromic
microcytic anaemia

Low MCH and MCV

with raised HbA2
level.
 Blood Film in thal minor

Normal
Thalassemia minor
blood film
α- Thalassemia
— The majority of genetic lesions results from gene
deletion

Inheritance: Autosomal recessive.

1- Deletion of 4 genes lead to completely suppressed α-chain
synthesis since the α- chain is essential in foetal as well as
adult haemoglobin this will lead to death in utero (hydrops
foetalis). no Hb F but g4 (Hb Barts) which is
ineffective as an Oxygen carrier

αα/αα
--/--
Hydrops
2- Deletion of 3 genes leads to Hb H disease which is a moderate
hypochromic microcytic anaemia (both MCV and MCH are
reduced) and splenomegally
Hb H (made by union of 4 B globin chain B4) can be
detected by electrophoresis.

--/-α

HbH
3- Deletion of 2 or single gene (α-thalassaemia trait) not associated
with anaemia.
The red cells are hypochromic microcytic

The MCV and MCH are reduced.

-α/αα --/αα
Silent α- thal minor
HbS (Hb-α2βs2) is insoluble, forms crystals when
exposed to low oxygen tension. Deoxygenated
sickle haemoglobin arrange into long fibers with
cross linking the red cells, sickle and block the
microcirculation causing infarction of different
organs.

Hb S results from replacement of glutamic acid by

valine at position 6 of β-globin chain
 Inheritance:
Autosomal recessive

Distribution:
Africa,Asia (Saudi Arabia and Iraq mainly In
Basrah)
1- Haemolytic anaemias: but symptoms are
mild in relation to the severity of anaemia
because HbS have low oxygen affinity. (gives
O2 easily to the tissues compared with HbA)
2- Crisis may be:
Painful vascular – occlusive crisis; infarction may
occur in a variety of organs including bones
precipitated by (Infection, acidosis, dehydration
and deoxygenation)

Vascular sequestration crisis: due to sickling within

the organs and sequestration of the blood.

Aplastic crisis;due to folate deficiency and or parvo-

virus infection characterized by fall in haemoglobin
as well as reticulocytes.

Haemolytic crisis; characterized by increased rate of

haemolysis with a fall in Hb and increased
reticulocytes.
Low Hb level with sickle cells and target cells in
blood film.

Positive sickling test when the blood is

deoxygenated.

Hb –electrophoresis reveals no HbA

Benign condition with no anaemia and normal blood
film but crisis can be caused by extreme stress as
in surgical operations.
summary
— B-thalassaemia major is transfusion dependent .
— Hb-electrophoresis reveals absent or reduced Hb-
A with raised Hb-F in B-thalassaemia major.
— In B-thalassaemia minor there is mild or no
anemia with low MCV and MCH and raised Hb-
A2.
— Hb-electrophoresis is usually normal in α-
thalassaemia minor with low MCV and MCH.