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Thalassaemia: Pathogenesis and Lab Diagnosis. Dr. M Sadequel Islam Talukder MBBS, M Phil (Pathology), MACP Assistant Professor Department of Pathology Dinajpur Medical College. Presentation at Seminar on observation of World Thalassaemia Day 2009

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Thalassaemia pathogenesis and lab diagnosis l.jpg

Thalassaemia:Pathogenesis and Lab Diagnosis

Dr. M Sadequel Islam TalukderMBBS, M Phil (Pathology), MACPAssistant ProfessorDepartment of PathologyDinajpur Medical College

Presentation at Seminar on observation of World Thalassaemia Day 2009

Presentation: 10 May 2009, Dinajpur Medical College

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Genetically determined

Heterogenous group of disorder

Reduced synthesis of one or more types of normal haemoglobin polypeptide chain

Reduced haemoglobin involving affected chain

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Normal Haemoglobin

  • HbA - α2β2

  • HbA2 - α2δ2

  • HbF – α2γ2

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Each goblin chain have separate genetic control

α –thalassaemia affect α-chain synthesis

β –thalassaemia affect β-chain synthesis

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β Chain synthesis

An absence or deficiency of β-chain synthesis of adult HbA


γ and δ chain

Hb-A = α2β2

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On the basis of synthetic ability β-genes are designated as

  • β gene – can synthesize normal amount of β-chain

  • β+ gene – can synthesize reduced amount of β-chain

  • β0 gene – cannot synthesize β-chain

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  • β-thalassaemia major

    • Mutation of normal β-gene β0-gene  absence HbA  increased HA2 and HbF

    • genotype – β0β0

  • β-thalassaemia intermedia

    • ↑HbA2

    • ↑HbF

    • ↓HbA

    • Genotype β+β+ or β0β

  • β-thalassaemia minor

    • ↑HbA2

    • HbA normal

    • HbF normal

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Pathophysiology of β-Thalassaemia

Various mutation in β-gene

Complete or partial absence of β-chain

Decreased adult HbA

α-chain synthesis remain normal

Free complementary α-chain – unstable and precipitate within normoblasts as insoluble inclusions

Cell membrane damage & impaired DNA synthesis apoptosis i.e. ineffective erythropoeisis

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70-80% marrow normoblasts undergo apoptosis

Inclusion bearing red cells undergo sequestration & destruction in spleen

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Partial or lack of HbA synthesis ↓MCHC & MCH Hypochromia & microcytosis



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Reticulocytes undergo intramedullary death

Inadequate production + ineffective erythropoiesis + haemolysis Anaemia

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↑Haemolysis ↑demands of phagocytic function  hyperplasia of phagocytes Hepatosplenomegaly

To compensate anaemia extramedullary haemopoiesis in liver, spleen & brain Organomegaly

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↑Erythropoiesismarrow expansion & thinning of cortex of skull bone Thalassaemia facies

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An absence or deficiency of α-chain synthesis due to delation of α-genes.

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Pathogenesis of α-Thalassaemia

  • In normal individual HbA, HbA2 and HbF need α-chain for their formation.

  • 4 genes of α-chain, each pair on short arm of chromosome 16 present with genotype α,α/α,α.

  • In α-thalassaemia, delation of α-genes reduction or absence of synthesis of α-chain depending on number of α-gene delation.

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  • α-chain synthesis free γ-chain in the fetus & β-chain in infant of 6 months, and continue in the rest of life.

  • Complementary 4γ and 4β are aggregated  Hb Bart (4γ ) and HbH (4β ), respectively.

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Variants of α-Thalassaemia

  • Silent carrier

    • Delation of single α-gene

    • Genotype α/αα

    • Asymptomatic

    • Absence of RBC abnormality

  • Thalasaemia trait

    • Delation of 2 α-genes

    • Genotype --/αα

    • Asymptometic, minimal or no anaemia

    • Minimal RBC abnormalities

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  • Hb H disease

    • Delation of 3 α-genes

    • Genotype --/- α

    • 75% reduction of α-chain

    • 25% α-chain synthesis small amount of HbF, HbA, & HbA2

    • Fetus can survive

    • Severe anaemia

    • Severe RBC abnormalites

  • Hydrops fetalis

    • Delation of all α-genes

    • Genotype --/--

    • Absence of α-chain synthsis

    • Only Hb Bart (γ4) is produced (High affinity for O2 and can not dissociate O2 to tissue)

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Laboratory Findings

  • Hb concentration – Decreased

  • ESR – Mild increased

  • WBC – Neutrophilic leucocytosis or normal

  • RBC count – Markedly decreased

  • PCV – Markedly decreased

  • MCV, MCH, MCHC – reduced

  • Reticulocyte count – Increased

  • Platelet count – May be increased

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Marked anisocytosis, polikilocytosis, microcytosis, frequent target cells, basophilic stippling, fragmented cells or schistocytosis, polychromatic macrocytes and nucleated cells


Whin normal or neutrophilic leucocytosis


Normal or increased

Morphology of PBF

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Haemoglobin Electrophoresis

  • Different types of haemoglobins contain different surface charge which determine the elecrtrophoretic mobility and gives a specific bands on the electrophoretic papers when haemolysate is undergone eletrophoresis.

  • HbF, HbA, HbA2, HbC, HbE, HbD, HbS, HbH and Hb Bart can be measured accurately by electrophoresis