1. HEMOLYTIC ANEMIA

2. LEARNING OBJECTIVES Genetic defect in β and alpha thalassemia
immune hemolytic anemias

3. β - THALASAEMIAS CHARACTERISTIC FEATURES
- Diminished synthesis of β – globin
chains
- Un – impaired synthesis of α – globin
- Heterogeneous causative gene mutations

4. β+ THALASSAEMIA MOLECULAR PATHOGENESIS
1. PROMOTOR REGION MUTATION
- Reduced transcription of mRNA by
75% - 80%
- 20% - 25% normal β – globin chain
synthesis

6. β+ THALASSAEMIA MOLECULAR PATHOGENESIS
2. ECTOPIC SLIPLICING MUTATION
- Occurs at abnormal sites within intron
- Abnormal splicing of mRNA
- Normal splicing sites co – exist

7. β0 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………)

8. β0 THALASSAEMIA MOLECULAR PATHOGENESIS
b. FRAME – SHIFT MUTATION:
- Small insertions or deletion, shifts mRNA
reading frame
- Termination of β globin chain synthesis

9. β0 THALASSAEMIA MOLECULAR PATHOGENESIS
2. SPLICING MUTATION
- Most common mutations in β –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

12. 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

14. WARM ANTIBODY IMMUNE HAEMOLYTIC ANAEMIA
Most common type (48% – 70%)
50% are idiopathic
Antibodies : IgG (common)
IgA (rare)
specificity : Rh system

15. 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

16. 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

17. COLD AGGLUTININ IMMUNOHAEMOLYTIC ANAEMIA (CONTD…)
Extravascular haemolysis
Acute, severe I/V haemolysis
( rarely after mycoplasma pneumonae)

18. 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

19. HAPTEN MODEL (CONTD) QUINIDINE TYPE
- Antibody against drug - membrane complex
- Very low dose
- Short duration
- Compliment mediated intravascular haemolysis
- Acute onset

20. CHRONIC CAIHA Idiopathic Associated with lymphoma
Compliment mediated E/V haemolysis in spleen/ liver
Haemolysis of variable severity
Vascular obstruction :
- Pallor
- Cyanosis
- Raynaud’s phenomenon