HEMOLYTIC ANEMIA

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HEMOLYTIC ANEMIA
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LEARNING OBJECTIVES

• Genetic defect in ß and alpha thalassemia
• immune hemolytic anemias

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ß - THALASAEMIAS

• CHARACTERISTIC FEATURES
• - Diminished synthesis of ß globin
• chains
• - Un impaired synthesis of a globin
• chains
• - Heterogeneous causative gene mutations

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ß THALASSAEMIA MOLECULAR PATHOGENESIS

• 1. PROMOTOR REGION MUTATION
• - Reduced transcription of mRNA by
• 75 - 80
• - 20 - 25 normal ß globin chain
• synthesis

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ß THALASSAEMIA MOLECULAR PATHOGENESIS

• 2. ECTOPIC SLIPLICING MUTATION
• - Occurs at abnormal sites within intron
• - Abnormal splicing of mRNA
• - Normal splicing sites co exist

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ß0 THALASSAEMIA MOLECULAR PATHOGENESIS

• 1. CHAIN TERMINATION MUTATION
• - Premature termination of mRNA
• translation
• a. NON SENSE MUTATION
• Within exon changes amino acid codon to
  a stop codon (UAG, UAA, UGA)
• ( contd)

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ß0 THALASSAEMIA MOLECULAR PATHOGENESIS

• b. FRAME SHIFT MUTATION
• - Small insertions or deletion, shifts mRNA
• reading frame
• - Termination of ß globin chain synthesis

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ß0 THALASSAEMIA MOLECULAR PATHOGENESIS

• 2. SPLICING MUTATION
• - Most common mutations in ß thal
• i) Introns
• ii) Within exons
• iii) Normal splice junction
• - Normal splicing of mRNA does not occur at
  all
• - Degradation of unspliced mRNA within the
  nucleus

Site of mutation
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IMMUNE HAEMOLYTIC ANAEMIA (IHA)

• Antibody mediated hemolysis
• Diagnosed by Coombs antiglobulin test
• a. Direct antiglobulin test (Red
  cells)
• - Antibody
• - Compliment
• b. Indirect antiglobulin test (serum)
• - Antibody specificity

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WARM ANTIBODY IMMUNE HAEMOLYTIC ANAEMIA

• Most common type (48 70)
• 50 are idiopathic
• Antibodies IgG (common)
• IgA (rare)
• specificity Rh system

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WARM ANTIBODY IMMUNE HAEMOLYTIC ANAEMIA (CONTD..)

• MECHANISM OF HAEMOLYSIS
• Antibody binds to red cells at 37 C
• Antibody coated red cells bind to FC receptors on
  splenic macrophages
• Partial phagocytosis
• Spherocytosis
• Splenic sequestration/ destruction
• Moderate splenomegaly is characteristic

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COLD AGGLUTININ IMMUNOHAEMOLYTIC ANAEMIA

• Less common (16 - 32)
• IgM antibody bind to red cells at 0 4 C
• Compliment fixation to red cell membrane
• Post Injection
• - Mycoplasma pneumonia
• - Infectious mononucleosis
• - Cytomegalovirus
• - Influenza virus
• - HIV

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COLD AGGLUTININ IMMUNOHAEMOLYTIC ANAEMIA (CONTD)

• Extravascular haemolysis
• Acute, severe I/V haemolysis
• ( rarely after mycoplasma pneumonae)

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DRUG INDUCED IHA

• HAPTEN MODEL
• a. Penicillin / cephalosporin type
• - Drug absorption on red cell membrane
• - Antibody directed against drug
• - Large dosage
• - Prolonged duration ( 1 2 weeks)
• - Haemolysis is extravascular

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HAPTEN MODEL (CONTD)

• QUINIDINE TYPE
• - Antibody against drug - membrane complex
• - Very low dose
• - Short duration
• - Compliment mediated intravascular haemolysis
• - Acute onset

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CHRONIC CAIHA

• Idiopathic
• Associated with lymphoma
• Compliment mediated E/V haemolysis in spleen/
  liver
• Haemolysis of variable severity
• Vascular obstruction
• - Pallor
• - Cyanosis
• - Raynauds phenomenon