Classification of Anaemia

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)