Hereditary spherocytosis

hereditary hemolytic anemias.
lecture for:
BSc. MLT.
BSN
3rd Year MBBS.
2nd year BDS.
Pathophysiology.
Hematology

1. Hereditary Spherocytosis Dr . Umme Habiba MBBS, M . Phil , CHPE FCPS. Hematology PGR

2. Learning Objectives • Describe mode of inheritance of hereditary spherocytosis • Describe pathogenesis of hereditary spherocytosis • Describe morphological features and lab diagnosis of hereditary spherocytosis

3. Normal Red Cell Destruction RBC completes 120 days of life span Changes in cell membrane occurs Enzyme activity declines Effected cells less deformable than normal Recognized by macrophages Phagocytosis and cell death

4. Composition of Red Cell membrane The red cell membrane consists of: Proteins: 50% Lipids :40% Carbohydrates: 10%

5. Functions Of Red Cell Membrane Erythrocyte membrane that is normal in structure and function is essential to survival of red cell Maintains stability and normal discoid shape of cell Preserve cell deformability Retain selective permeability

6. Structure of RBC membrane

7. Hereditary Spherocytosis A genetically determined hemolytic anemia characterized by spherical shaped RBC Characteristic appearance, round cells with smaller diameter and less flexible Lack of area of central pallor Decrease surface to volume ratio Due to genetic defect in RBC membrane proteins Ankyrin Spectrin Band 3.1 protein

8. Epidemiology Most common inherited membrane disorder o 75% autosomal dominant fashion o 25% Rarely autosomal recessive

9. Cytoskeletal defects in HS

10. Spherocyte Formation

11. Pathophysiology

12. On Examination Marked anemia Pallor Marked splenomegaly Gall bladder stones

13. Diagnosis Complete blood picture: Hb = 7-14g /dl May fall below 7 in crises Red cell indices MCV =N or slightly reduced  MCH= Normal MCHC= Increased Plt = normal or decreased

14. Peripheral smear Spherocyte Polychromatic cells Target cells Nucleated RBC can be present severe cases Plt decreased if splenomegaly Retic Usually 5-20% even low to 50-70%

15. Spherocytosis in peripheral smear

16. Routine chemistry testing Bilirubin: Increased Indirect bilirubin Urine urobilinogen: increased Methaemalbumin: Increased LDH : Increased Haptoglobin: Decreased

17. Osmotic fragility test Principle When an erythrocyte is placed in a hypotonic sodium chloride-( NaCl ) solution, a net influx of solvent (water) into the cell-will occur and the cell will swell If the cell size reaches a certain point, the cell membrane will become leaky and hemoglobin will diffuse out (hemolysis) If the NaCl solutions hypotonic enough, the cell will rupture The degree of hemolysis can be measured by determining the absorbance of the supernatant using a spectrophotometer Confirmation on protein studies

18. Summary Genetic disorder of red cell membrane Mainly due to ankirin deficiency Extravascular hemolysis Severity depend on mutation in gene Diagnosis on routine lab investigations, osmotic fragility test and protein studies