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Hereditary spherocytosis
G6PD deficiency
Erythrocyte membrane
15 major proteins
Integral
Cross lipid bilayer
Glycophorins, Rh proteins, band 3, ATP-ases
Peripheral
Inside the lipid bilayer (Membrane skeleton)
Membrane skeleton provides support to lipid bilayer
Spectrin is major protein of membrane skeleton
Alpha and beta chains
These chains intertwine to form heterodimers
Erythrocyte membrane
Elliptocytes
Hereditary elliptocytosis
Poikilocytes
Hereditary elliptocytosis
Stomatocytes
Vinca alkaloids, Alcohol
Target cells
Iron deficinecy,
Thalassemias
Hepatic dysfunction
Acanthocytes
Abetalipoprotienemia
Echinocytes
Uremia
Vitamin K deficiency
Normal RBCs
Hereditary spherocytosis
Erythrocyte membrane disorder characterized by
Normal
membrane
cytoskeleton
Hereditary spherocytosis
Spectrin deficiency
Ankyrin deficiency
Band 3 deficiency
Combined deficiency
Erythrocyte abnormalities
Increased Na and K flux across membrane
RBCs are dehydrated, and less deformable
This makes RBCs more fragile
Pathogenesis of HS
Spectrin,ankyrin,band 3 defect
Decreased spectrin incorporation into
membrane/band 3 deficiency
Destabilisation of lipid bilayer
Microspherocytosis-Decreased RBC deformability
Stagnation in splenic cords and contact with
macrophages
Phagocytosis of spherocytes/Conditioning of
spherocytes
Further loss of membrane surface area
Pathogenesis of HS
ATP depletion
Increased glycolysis
Decreased 2,3 dpg,Ph falls
Passive cation leak
Increased Na/K Pump activity
Water leak and cell dehydration
Clinical features
Pallor
Icterus
Splenomegaly
Lab findings
Peripheral Smear :
Spherocytes
Reticulocytosis
Nucleated RBCs
Bone marrow :
Erythroid hyperplasia
Serum Iron Increased
Decreased MCV,Increased MCHC
Hemosiderosis
Unconjugated bilirubin increased
Osmotic fragility test - hemolysis
Spherocytes
Formed by partial phagocytosis
Decreased deformability
Denser, smaller (in appearance!), round RBC
without central pallor
100
% of hemolysis
75
50
25
80 70 60 50 40
30
% of NaCl
20
10
Molecular studies
Quantification of major proteins using PAGE
Mutation screening/Direct DNA sequencing
Complications
Worsening anemia
Aplastic crisis
Exhaustion of folate reserves
Choilelithiasis
Bilirubin pigment stones
Erythrocyte metabolism
Glucose is the main substrate of red cells
Two pathways
Glycolytic/Energy producing pathway
HMP Shunt/Protective pathway
Glucose-6-Phosphate Dehydrogenase
Deficiency
Basic defect
Inability of red cells to protect themselves
against oxidative injuries
Leading to hemolytic disease
Abnormalities in the hexose monophosphate
shunt or glutathione metabolism
Glucose-6-Phosphate Dehydrogenase
Deficiency
Variants
G6PD B Normal variant
G6PD A- 10% of African Americans
G6PD Mediterranean-clinically significant
hemolytic anemias
G6PD variants
Class I (Severe deficiency,chronic hemolytic
anemia
Class II (Severe def, intermittent hemolysis)
Class III (Moderate def, intermittent
hemolysis)
Class IV (No def)
Class V (Increased activity)
Glucose-6-Phosphate Dehydrogenase
Deficiency
Clinical patterns1. Foods- fava beans (favism),
2. Medications - ***antimalarials (e.g.,
primaquine and chloroquine), sulfonamides,
nitrofurantoins,
3. Infections- viral hepatitis, pneumonia, and
typhoid fever
Hemolysis causes both intravascular and
Extravascular lysis
after exposure to oxidant stress
Glucose-6-Phosphate Dehydrogenase
Deficiency
Why do the red cells die?
Lab diagnosis
Spectrophotometrically measure NADPH
generation (hemolysate+NADP+G6P)
Flourescent spot test
Methemoglobin reduction test using
methylene blue as hydrogen acceptor