This document provides an overview of different types of anaemia, including classifications based on red blood cell size (MCV) and the underlying causes and mechanisms of haemolytic anaemias. Specific examples discussed include hereditary spherocytosis, G6PD deficiency, sickle cell disease, and microangiopathic haemolytic anaemia. Diagnostic findings and key features are outlined for each condition.

1. CLASSIFICATION OF ANAEMIA:
NORMOCHROMIC NORMOCYTIC
ANAEMIA

2. Chapter outline
• Membrane defects: Hereditary spherocytosis
• Metabolic defect: pyruvate kinase deficiency,
G6PD deficiency
• Haemoglobinopathies: sickle cell disease
• Extrinsic abnormalities: antibody mediated
transfusion reaction
• Mechanical destruction: MAHA, infections

3. • Underlying causes:
1. Loss of RBC:Haemorrhage
2. Increased destruction of RBC
3. Reduced erythropoieisis
4. Reduced RBC’s survival
Haemolytic anaemia can be classified into:
1. Congenital and acquired
2. Intrinsic or extrinsic
3. Intravascular or extravascular haemolysis

4. Morphologic classification of Anaemia – MCV based
N or h RETIC
Normocytic - MCV 80-100 fl Bone marrow
Acellular
Hypercellular
h RETIC Normocellular
Haemolytic
anaemia
Intrinsic Extrinsic
PNH
Membrane
Chemical & Mechanical -
Antibody Infection MAHA
Physical
Enzyme mediated
damage
Haeme/globin

5. Anaemia - Diagnostic Overview
Clinical Symptoms
Haemolysis
Bilirubin hh
Haptoglobin i
Review Blood Film
other biochem
tests
Morphology
None
PNH Spherocytes
Variable findings *DAT Positive
*Blister cells
Sickle cells Immune mediated
Stomatocytes Oxidative haemolysis
Elliptocytes G6PD *DAT Negative
Target cells *Fragments Hereditary Spherocytosis,
Burns, C. perfringens
Spur cells MAHA septicaemia
Source; modified from AH Turner, 2004 Burr cells
Malaria

6. Hereditary Spherocytosis
• Characterized by numerous spherocytes in
blood film
• Common in Northern European but can be
found all over the world
• Due to deficiency of RBC membrane structural
proteins leading to loss of membrane surface
are----- causing the RBCs to become
spherocytes

7. Pathophysiology
• Defect in membrane skeletal proteins that
connect the membrane skeleton to the lipid
bilayer ( spectrin, ankyrin, protein 4.2, band 3)
• Cause RBCs progressively to lose unsupported
lipid membrane because of the local
disconnection
• RCs become rigid and their survival in the
spleen decrease

8. Clinical Features
• Symptoms of anaemia
• Splenomegaly
• Jaundice
• Megaloblastic crisis – folic acid deficiency due
to increase need

9. Lab Findings
• FBE- hallmark is d increase spherocytes
• Hb normal, unless in crisis, MCV, MCH normal
• Bone marrow- erythroid hyperplasia
• Biochemistry – increased unconjugated
bilirubin, fecal urobilinogen and decreased
haptoglobin
• DAT test- negative
• Osmotic frafility test – curve shift to left
• Spectrin immunoassay
• Family history and genetic studies

10. Treatment & differential diagnosis
• Splenectomy – post splenectomy cause the
appearance of target cells, howell jolly bodies,
pappenheimer bodies
• Differential diagnosis – other causes of
spherocytes must be ruled out AIHA,
PNH,sepsis, pyropoikilocytosis

12. Metabolic defect: G6PD Deficiency
• The gene for G6PD is located on X-
chromosome & show a characteristic X-linked
pattern
• Affect more males than females
• G6PD fx – maintain gluthathione (GSSG) in
reduced state (GSH) to protect RBC from
oxidative stress

13. RBC Membrane damage
Oxidant
Hb Heinz bodies
GSH GSSG
NADP NADPH
G-6P 6PG
G6PD

14. Clinical Features
• G6PD deficiency is usually asymptomatic but:
1.Acute haemolytic anaemia in response to
oxidative stress such as drugs, fava beans,
infections, etc.
2.Neonatal jaundice
3.Congenital non-spherocytic haemolytic
anaemia

15. Lab Findings
• FBE – depends on severity – normochromic
normocytic, marked anisocytosis,
poikilocytosis with bite cells and blister cells
• Biochemical - haptoglobin severely ,
unconjugated bilirubin and plasma Hb
• G6PD screening test – G6PD fluoresence spot
test, G6PD enzyme detection kit, PCR analysis
of mutations.

16. Differential Diagnosis
• Drug induced HA
• Other enzymopathies eg Pyruvate kinase
deficiency
• Haemoglobinopathies due to oxidative stress

18. Haem defects: Sickle Cell Disease
• Hb S is defined by structural formula α2β2Glu-val
which indictaes that on the B chain at 6th
position, glutamic acid is replaced by valine
• resulting in a structural change in RBC shape
relates to the amount of O2 bound to the Hb
molecules

19. Pathophysiology
• When HbS is fully oxygenated it remains soluble in the
erythrocyte similar to Hb A, maintaining its normal
shape
• On deoxygenation, Hb S becomes less soluble and
causing sickling
• The blood becomes more viscous when sickle cells are
created. Results in reduced blood flow which prolongs
the exposure of HbS containing erythrocytes to a
hypoxic environment which further promotes sickling,
• The end result is occlusion of capillaries and arterioles
by sickled RBCs and infarction of surrounding tissues

20. Clinical Features of SCD
• Hallmark feature is vaso occlusive
• Gradual loss of splenic fx
• Splenic sequestration
Laboratory diagnosis of SCD
•Peripheral blood smear – poikilocytosis
&anisocytosis, sickle cells, target
cells, nRBCs, spherocytes, basohilic stippling, Howell-
jolly bodies
•Moderate leukocytosis & neutrophilia
•thrombocytosis

21. Lab Diagnosis (Cont)
• BM- erythroid hyperplasia
• Elevated Indirect & direct bilirubin
• Solubility & sickling test
• Hb Electrophoresis
TREATMENT
1. BM transplantation
2. Transfusion
3. Hydroxyurea therapy

23. Microangiopathic Haemolytic
Anaemia (MAHA)
• Due to mechanical destruction
• It is a group of clinical disorders characterized by
RBC fragmentation in the circulation, resulting
from IV haemolysis
• The fragmentation occurs as RBCs passed through
fibrin deposits inside the lumen of arterioles &
capillaries or through damaged epithelium &
vessel walls
• RBCs being forced through a fibrin clot, attaching
to fibrin, folding around the strands &
fragmenting by the force of the flowing blood

24. • Disorders include
1) Thrombocytic thrombocytopenic purpurea
(TTP)
2) Haemolyric uraemic syndrome (HUS)
3) Disseminated intravascular coagulation (DIC)
4) Haemolysis Elevated Liver enzymes & Low
Platelet (HELLP)