Pathology
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Hematology Lec.3 Haemolytic Anaemias
Haemolysis:
Shortening of red cell survival with premature red cell death.
When the life span of the red cells is shortened to less than 20 days, Hb drops and
anaemia develops (Haemolytic anaemia ), with longer life spans the marrow can
compensate by hyperactivity &/or expansion keeping Hb within normal limits
(Compensated haemolysis )
Classification
❖ H. Anaemias due to intrinsic red cell defects
❖ H. Anaemias due to extrinsic defects:
• Haemolysis is called intravascular when RBCs are destroyed in the
circulation, while it is called extravascular when destruction occurs by the
cells of the RES in the( spleen, liver & B.M ).
General Features of Haemolysis
❖ Features due to Hb degradation:
• Indirect hyperbilirubinaemia ( clinically; Jaundice, gall stones )
• Hyperurobilinogenuria
• Splenomegaly
• Iron overload
❖ Featurs due to marrow compensation:
• Reticulocytosis
• Skeletal abnormalities due to marrow expansion.
• Folate deficiency.
❖ Features specific of intravascular haemolysis:
• Haemoglobinaemia & hypohaptoglobinaemia.
• Haemoglobinurea & haemosiderinuria.
Hereditary Spherocytisis ) HS )
A hereditary haematological disorder characterized by:
❖ Autosomal dominant inheritance.
❖ Excessive red cell fragility.
❖ Microspherocytes in the peripheral blood.
❖ Reticulocytosis
❖ Marked improvement ( usually cure ) of anaemia after splenectomy.
Pathology
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Molecular defects and pathogenesis
A genetic mutation resulting in abnormality of the cytoskeletal protein; spectrin will cause
excessive leakiness of the cell membrane to cat-ions (Na & K ) »» Hyperactivity of Na-K
pump »» excessine utilization of glucose & O2 ( hypermetabolism )….. In the spleen.
Haematological Featurs
G6PD Deficiency
❖ G6PD normally provides reducing potentials through the production of NADPH
during the conversion of G6P to 6PG in the pentose pathway.
❖ NADPH neutralizes the effects of H2O2 & other oxidants by reducing them to water.
Accumulation of intracellular oxidants will damage the cell through.
Molecular defects and pathogenesis
❖ G6PD deficiency results from point mutations affecting G6PD gene on
chromosome
– X, mutations will result in isoenzymes that are either:
• Unstable.
• Reduced catalytic function.
❖ The pathological effects of the deficiency depends on the residual activity
of the enzyme:
• Activities of 3-5% normal are sufficient to maintain normal red cell
metabolism under normal conditions but will lead to intravascular haemolysis
under conditions of extra-oxidant stresses ( infections, drugs & ingestion of
fava beans ).
• Activities lower than 3% are associated with chronic haemolysis.
Clinical presentation
❖ Neonatal jaundice
❖ Chronic haemolytic anaemia ( rare presentation )
Pathology
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❖ Most individuals with G6PD deficiency are asymptomatic unless exposed to oxidant
stresses, such as infections, drugs and fava beans ingestion, the latter is called
Favisim where there will be a sudden bout of intravascular haemolysis
characterized by:
Haematological &other Lab. Features
❖ Normoch. Normocytic anaemia
with contracted &blister cells.
❖ Heinz bodies formation.
❖ Marked reticulocytosis.
❖ haemoglobinaemia, & Hb-uria.
❖ Indirect hyperbilirubinaemia.
❖ Demonstration of G6PD deficiency:
• Screening tests ( MRT)
• Enzyme assay