Spherocytosis, spectrin ankyrin spherocyte

1. RBC Membrane
Defects

2. Meet The Red Cell
 Shaped like a flattened, bilaterally
indented sphere, a biconcave disc
 In fixed, stained blood smears,
erythrocyte appears circular, with a
diameter of about 7 to 8 μm and an
area of central pallor.
 Average values for the mean cellular
volume in normal subjects range from
80 to 100 fl.
 Highly elastic and deformable.
The normal mature erythrocyte as
visualized by the scanning electron
microscope (×9,800). (Courtesy of Dr.
Wallace N. Jensen.)
The erythrocyte can pass through a vessel of about 3 μm in
maximum diameter

3. Meet The Red Cell
► Durability of Red cell is remarkable
► No nucleus to direct regenerative
processes
► No mitochondria available for
efficient oxidative metabolism
► No ribosomes for regeneration of lost
or damaged protein
► No de novo synthesis of lipid
Images of red blood cells
(top) and a human hair
(bottom) taken with a
confocal microscope
Still survives for 120
days!!!

4. Red Cell Membrane
Structure
Erythrocyte membrane that is normal in structure
and function is essential to survival of red cell
Accounts for the cell's antigenic characteristics
Maintains stability and normal discoid shape of cell
Preserve cell deformability
Retain selective permeability

5. Red Cell Membrane
Structure
►The red cell membrane consists of:
Proteins 52%
Lipids 40%
Carbohydrates: 8%

8. Membrane Proteins

9. Membrane Defects

10. Hereditary Spherocytosis
Haemolytic disorder characterized by
numerous microspherocytic erythrocytes
seen in the blood film.
Most common inherited anaemia in
Northern European descent

11. Micro spherocytes
Small.
 Dark.
Very round.
Hyperchromic cell
With no central pallor.

12. Hereditary Spherocytosis
 75% autosomal dominant fashion
 25% Rarely autosomal recessive
 Loss of membrane surface area relative
to intracellular volume
 spherical shape  decreased deformability 
splenic destruction

13. Hereditary Spherocytosis
ADAR
Defect in 5 possible membrane proteins

14. Pathophysiology
 The anemia is genetically passed down from
one generation to another.
 The basic defect in HS is a membrane
abnormality caused by dysfunctional and/or
deficiencies in one or more of the followings:
 Spectrin, Ankyrin, Band 3, and Protein 4.2,
 all of which are vital components (structural
proteins) of the cell membrane.

17. Specifically, these lead to:
 Reduced cell surface area
 Impaired flexibility, and
 Increased permeability to sodium, which the
cells pump out to stabilize the osmotic
fragility.
- Such process requires a lot of ATP consumption.

18. Pathophysiology
 Despite all of that, the cells life span remains
unaffected until the cells reach the spleen,
where glucose and ATP levels are insufficient.
 Therefore, the cells cannot pump out the
extra sodium leading to an increased
intracellular sodium concentrations and
subsequently, increased water content.

19. Pathophysiology
 This leads to the swelling and rigidity of
the cells which cannot negotiate the
spleen’s microcirculation where they get
trapped and phagocytozed.

20. Pathophysiology of HS
A) Reduced density of membrane skeleton destabilizes overlying lipid
bilayer
B) Loss of Band 3 lipid-stabilizing effect

21. Pathophysiology of HS

22. Laboratory diagnosis
CBC
 Hb: low
 PCV: low
 RBCs count: low
 MCV: low
 MCH: normal
 MCHC: increase in half to two-third of
patients.
Note: HS is the only disease in which
MCHC is elevated.

23. PBP
 As the name indicates, the
characteristic feature of this anemia
is the presence of microcytic
spherocytes in peripheral blood.
• Anisocytosis is prominent:
• mixture of microspherocytes and large
polychromatic cells.
• Poikilocytosis other than spherocytes
is not common.
Reticulocyte count: increase (5-20%)

24. Micro spherocytes
Small.
 Dark.
Very round.
Hyperchromic cell
With no central pallor.

26. Special tests
 Osmotic fragility test: increased
 Autohaemolysis test: increased
 Direct coomb’s test: negative.

28. Biochemical findings:
 Indirect bilirubin: increase
 LDH: increased
 Urobilinogen: increased
 Haptoglobin level: decrease
 Analysis of red cell membrane protein:
determine the exact abnormality of red cell
membrane

29. Differential diagnosisDifferential diagnosis
Other acquired causes of spherocytes in
peripheral blood film:
1.Warm Autoimmune hemolytic anaemias.
2.Hemolytic transfusion reactions.

30. Treatment
Splenectomy (surgical removal of the
spleen) is the treatment of choice for
symptomatic hereditary spherocytosis
and can be done when a child is five
years of age or older.
Treatment before the age of five
consists of daily folic acid
supplementation.

31. Hereditary spherocytosis. A typical Wright-stained peripheral blood smear from a patient with
autosomal dominant hereditary spherocytosis is shown. Small, dense, round, conditioned spherocytes that
lack central pallor are visible throughout

32. Hereditary Elliptocytosis
 The HE syndromes are a family of
genetically determined erythrocyte
disorders characterized by elliptical red
cells on the peripheral blood smear.
 Inheritance of HE is autosomal dominant
(except HPP)
 the HE variants occur with an estimated
frequency of 1:1,000 to 5,000.
 HE has a worldwide distribution, but is
more common in malaria endemic regions
with prevalence approaching 2% in West
Africa.

33.  The mechanistic basis for decreased
membrane mechanical stability in HE is
weakened “horizontal” linkages in membrane
skeleton due either to defective spectrin
dimer-dimer interaction or a defective
spectrin-actin-protein 4.1R junctional complex.
 The mechanism by which these protein
defects result in elliptocyte formation is not
clear.

34. A B
C
A: Common Hereditary elliptocytosis
B: Hereditary pyropoikilocytosis. Red
cell budding and fragmentation.
C: Southeast Asian ovalocytosis