Dr. Mehdi Ashik Chowdhury M.B.B.S. MD. (BSMMU) Assistant Professor & Head of the Department of Pathology Tairunnessa Memorial Medical College

1. Haemolytic Anaemia
Dr. Mehdi Ashik Chowdhury
M.B.B.S. MD. (BSMMU)
Assistant Professor &
Head of the Department of Pathology
Tairunnessa Memorial Medical College

2. Red blood cell
Haemoglobin
• Each molecules of haemoglobin consist of two pair of
globin polypeptide chain. Each globin chain combine
with a haem group whose central iron atom is the site at
which oxygen attaches to haemoglobin. Adult
haemoglobin A consist of two α chain and two β chain.
Synthesis of haemoglobin A commences just before the
beginning of the third trimester. The proportion of
haemoglobin A (Hb-A) then progressively increases to
make up 25% of total haemoglobin at birth and about
97% at 1 year. Fetal haemoglobin Hb-F (α2 γ2) makes up
less than 2% and the remaining portion consist of
haemoglobin A2 (α2 δ2).

6. Normal Human haemoglobin.
Haemoblobin Structural
Formula
Adult Hb-A
Hb-A2
α2β2
α2δ2
Fetal Hb-F
Hb-Bart’s
α2γ2
γ4
Embryonic Hb-Gower 1
Hb-Gower 2
Hb-Portland
ζ2ε2
α2ε2
ζ2γ2
α :alpha
β : beta
γ : gamma
δ : delta
ε : epsilon
ζ : zeta

7. • Haemolytic anaemia are those anaemia that result
from an increase in the rate of red cell destruction
due to shortened red cell lifespan. The premature
destructon of red cell may result from two
fundamental defects :
• Haemolytic anaemia due to intracorpuscular defect.
• Haemolytic anaemia due to extracorpuscular effect.
The normal cells transfused to a patient with
intracorpuscular defect will survive for normal length
of time but the patient cell transfused to a normal
person have a shortened lifespan. The opposite
feature will be seen in extracorpuscular effect.

8. The aetiological classification of haemolytic anaemia :
1)Haemolytic anaemia due to intracorpuscular defect:
It may be Congenital defect or Acquired defect.
Congenital
a) Membrane defect
i) Hereditary spherocytosis.
ii) Hereditary elliptocytosis.
b) Haemoglobin defect
i) Haemoglobinopathies :
Sickle cell anaemia
Other Homozygous disorder (Hb-C,Hb-D, Hb-E)
Unstable haemoglobin disease.

9. • ii) Thalssaemia
β- Thalssaemia
α- Thalssaemia
iii) Double heterozygous disorder
Sickle cell β-Thalssaemia
c) Enzyme defect
i) Deficiency of pyruvate kinase or other enzyme
of Embden-Meyerhof pathway.
ii) Deficiency of Glucose-6-phosphate dehydrogenase
or other enzyme of pentose phosphate pathway.
iii) Drug induced haemolytic anaemia and favism.
Acquired
Paroxysmal nocturnal haemoglobinuria.

10. • Haemolytic anaemia due to extracorpuscular
effect
• Immune mechanisms
• Auto-immune acquired haemolytic anaemia
• (a) Warm antibody
• (b) Cold antibody.
• Haemolytic disease of the newborn
• Incompatible blood transfusion.
• Drug-induced haemolytic anaemia.
• Non-Immune mechanisms
• Mechanical haemolytic anaemia
(a) Cardiac hemolytic anaemia
• (b) Micro-angiopathic haemolytic anaemia.

11. • Miscellaneous
Haemolytic anaemia due to direct action of
chemicals and drugs.
Haemolytic anaemia due to infection.
Haemolytic anaemia due to burns
Lead poisoning.

12. • Disorder of haemoglobin
• The disorder of haemoglobin can be classified into
two broad groups :
• Haemoglobinopathies and
• Thalassaemia.
• Haemoglobinopathies
• Characterized by production of structurally defective
haemoglobin due to abnormalities in the formation of
the globin moiety.
• Thalassaemias are characterized by reduced rate of
production of normal haemoglobin due to absent or
reduced production of one or more types of globin
polypeptide chain.

13. Haemoglobinopathy
• The majority of abnormal haemoglobin differ from
normal haemoglobin by the substitution of single amino
acid in globin polypeptide chain. When one globin
polypeptide chain in a pair is affected it is heterozygous
state and when both globin polypeptide chain in a pair is
affected it is homozygous state. The homozygous state is
referred to as disease and the heterozygous state is
referred as trait.

14. • The common abnormal Haemoglobin :
• Haemoglobin Structural formula
• Hb-S α2β2
6glu--val
• Hb-C α2β2
6glu--lys
• Hb-E α2β2
26glu--lys

15. Sickle cell anaemia
• Sickle cell anaemia are hereditary disorder in which red
cell contain Hb-S. They include sickle cell trait
(heterozygous state) and sickle cell disease (homozygous
state). In the deoxygenated state the solubility of Hb-S is
ten percent of that of Hb-A. In the deoxygenated state the
cells containing Hb-S become rigid and deformed,
assuming a sickle or crescent shape.The sickling of red
cells has two major pathological effects : (i) the distorted
cells block small blood vessels impairing flow and
causing ischaemia and infarction (ii) repeated ‘sickle-
unsickle’ cycles lead to injury to cells whch are
prematurely removed either by reticuloendothelial system
or destroyed in the circulaion resulting in both
extravascular and intravascular haemolysis.

16. Thalassaemias
• Thalassaemia are heterogenous group of disorders with
genetically determined reduction in the rate of synthesis
of one or more types of normal haemoglobin
polypeptide chain.
• Classification :
• Alpha thalassaemia : Alpha thalassaemia minor (Trait)
Alpha thalassaemia major (Disease)
Beta thalassaemia : Beta thalassaemia minor (Trait).
Beta thalassaemia major (Disease).

17. β-Thalassaemia
• The genetic mutation of β-Thalassaemia leads to a
reduced rate or absent production of β-chain and
consequently a reduction in the amount of normal
Hb-A in the red cells. The total haemoglobin is
maintained in part by the production of γ and δ-
chain and thus increased Hb-F and Hb-A2 is usually
found. The lack of β-chain leads to accumulation of
free uncombined α-chains within the developing
red cells. These chain aggregate and interfere with
erythroid cell maturation and function resulting in
premature destruction of cells in the marrow and
consequent ineffective erythropoisis. β-Thalassaemia
are of two types : (1) β-Thalassaemia minor (trait)
(2) β-Thalassaemia major (Disease).

18. • β-Thalassaemia minor (trait) : This is the heterozygous
state for β-Thalassaemia gene. It is characterized by
moderate reduction in β-chain synthesis.
• Clinical feature :
• Little or no anaemia, No symptoms, and a normal life
expectancy.
• Blood picture : Haemoglobin level is usually normal or
mildly reduced but rarely less than 10 gm/dl.
• RBC count is normal or increased.
• MCV : Reduced
• MCH : Reduced
• MCHC : Reduced or normal.

19. • Blood film :
• RBC : Microcytic hypochromic with variable number
of target cell.
• WBC and platelets are normal.
• Reduction of MCV and MCH are relatively marked
considering the degree of anaemia in thalassaemia
trait.
• There is a closer correlation between MCV and MCH
with the degree of anaemia in iron deficiency
anaemia.

20. β-Thalassaemia major
• β-Thalassaemia major is the homozygous state
for β0 or β+ thalassaemia gene.
• Clinical feature :
• Sign symptoms of anaemia.
• Marked spleenomegaly
• Moderate to marked hepatomegaly.

21. • Blood Picture :
• MCV : Reduced
• MCH : Reduced
• MCHC : Reduced
• Blood film :
• RBC : Microcytic hypochromic with marked
anisopoikilocytosis. Tear drop cells are often present.
Target cells are prominent. There is leptocytes,
fragmented RBC, occasional spherocytes,
Polychromatic RBC and Nucleated RBC.
• WBC count is usually raised. Platelets are normal.
• Reticulocyte count is increased.

22. • Biochemical test:
• Serum bilirubin : May be raised.
• Serum iron : Increased.
• Serum ferritin : Increased.
• Transferrin : Completely saturated.
• Diagnosis is confirmed by :
Haemoglobin electrophoresis.

23. General evidence of haemolysis
• Evidence of increased haemoglobin breakdown :
• Jaundice and hyperbiirubinaemia
• Reduced plasma haptoglobin and haemopexin
• Increased plasma lactate dehydrogenase
• Haemoglobinaemia Evidence of
• Haemoglobinuria intravascular
• Methaemalbuminaemia haemolysis
• Haemosiderinuria

24. • Evidence of compensatory erythroid hyperplasia
• Reticulocytosis
• Macrocytosis and polychromasia
• Erythroid hyperplasia of bone marrow
• Radiological changes of skull and tubular bone
(Congenital anaemia only)
Evidence of damage to the red cells
Spherocytosis and increased red cell fragility
Fragmentation of red cells
Heinz bodies.
Demonstration of shortened red cell lifespan.