2. Red cell membrane
The red cell membrane is composed of
three major structural elements:
-a lipid bilayer primarily composed of
phospholipids and cholesterol;
- integral proteins embedded in the lipid
bilayer that span the membrane; and
-a membrane skeleton on the internal
side of the red cell membrane
3. The membrane and its skeleton provide the
erythrocyte with the ability to undergo significant
deformation without fragmentation or loss of integrity
during its travel through the microcirculation.
Assembles and organizes the proteins of the lipid
bilayer and the membrane skeleton, allowing the red
cell to participate in a wide range of functions:
-Selectively and reversibly binding and inactivating
glycolytic enzymes, retaining organic phosphates and
other vital compounds, removing metabolic waste,
and sequestering the reductants required to prevent
corrosion by oxygen.
-Responds to EPO during erythropoiesis.
-Imports iron required for erythropoiesis.
4. The lipid bilayer provides an impermeable
barrier between the cytoplasm and the
external environment and helps maintain
a slippery exterior so that erythrocytes do
not adhere to endothelial cells or
aggregate in the microcirculation.
Erythrocyte biogenesis and ageing.
Maintenance of pH homeostasis by
participating in chloride–bicarbonate
exchange.
5. The integrity of the red cell membrane
depends on the molecular interactions
between proteins and protein-lipid
interactions: vertical interactions stabilize
the membrane lipid bilayer, horizontal
interactions provide resistance against
shear stress.
6. HEREDITARY
SPHEROCYTOSIS
Inherited disorders.
Characterized by presence of spheroida
RBCs on the PBF.
Occurs in all racial and ethnic groups.
Whites> blacks.
1 in 2,500 individuals in the US.
7. Etiology and pathogenesis
Loss of membrane surface area relative to
intracellular volume causing spherical shape
and reduced deformability.
Result of increased membrane fragility due to
defects in RBC membrane proteins.
Increased fragility leads to membrane
vesiculation and loss.
Splenic destruction- hemolysis.
Physical entrapment in the splenic
microcirculation and ingestion by
macrophages.
8. Defects in several membrane proteins,
including ankyrin, band 3, α-spectrin, β-
spectrin, and protein 4.2. Combined
spectrin and ankyrin deficiency is the most
common defect observed, followed by
band 3 deficiency, isolated spectrin
deficiency, and protein 4.2 deficiency.
Heterogenous genetic defects.
9. Clinical features
Hemolysis: anemia, jaundice, reticulocytosis,
gallstones and splenomegaly.
Positive family history.
Mild, moderate or severe forms according to
differences in haemoglobin, bilirubin, and reticulocyte
counts correlated with the degree of compensation for
the haemolysis .
Typically presents in childhood but can present at any
age.
Anaemia in 50 %.
Two-thirds to three-quarters of HS patients have
incompletely compensated haemolysis and mild to
moderate anaemia. The anaemia is often
asymptomatic except for fatigue and mild pallor.
10. Jaundice is seen at some time in about 50% of
patients, usually in association with viral infections.
Palpable splenomegaly is detectable in most (75–
95%) older children and adults.
20–30% of HS patients have ‘compensated
haemolysis,’ i.e. erythrocyte production and
destruction are balanced. Although the erythrocyte
lifespan may only be about 20–30 days, these
patients adequately compensate for their haemolysis
with increased marrow erythropoiesis.
5 to 10% of HS patients have moderate to severe
anaemia. Patients with ‘moderately severe’ disease
typically have a Hb of 6 to 8 g/dl, reticulocytes about
10%, bilirubin 2 to 3 mg/dl, and 40 to 80% of the
normal red cell spectrin content.
11. Patients with severe disease have severe
anemia and are transfusion dependent.
Almost always AR HS with most having
isolated severe spectrin deficiency.
They suffer from hemolytic and aplastic
crises.
Inheritance
2/3 – ¾ AD.
Rest AR or de novo mutations.
12. Characteristics of hereditary spherocytosis
Clinical manifestations
◆ Anaemia
◆ Splenomegaly
◆ Intermittent jaundice:
• from haemolysis
• from biliary obstruction
◆ Haemolytic, aplastic, and megaloblastic
crises.
14. ◆ Excellent response to splenectomy
Laboratory characteristics
◆ Reticulocytosis
◆ Spherocytosis
◆ Elevated mean corpuscular haemoglobin
concentration
◆ Increased osmotic fragility
◆ Normal direct antiglobulin test
15. Complications.
Gallbladder disease: bilirubinate stones. Most
between 20 – 30 years. Interval U/S.
Hemolytic crisis: associated with viral
infections and typically in childhood. Mild
jaundice, increased splenimegaly, reduced
hematocrit and reticulocytosis.
Aplastic crisis: after virally induced BM
suppression. Uncommon. P B19. lasts 10 – 14
days.
Megaloblastic crisis: in situations with
increased folate demands.
16. Diagnosis
CBC: anemia, normalMCV ( slightly reduced in
severe cases), increased MCHC due to relative
cellular dehydration> 35 g/dl, increased red cell
distribution width > 14.
PBF: obvious spherocytes lacking central pallor,
anisocytosis, poikilocytosis.
Bilirubin levels.
Osmotic fragility test.
Coomb’s test.
Reticulocyte count.
Increased urinary and fecal urobilinogen.
Reduced haptoglobin levels.
17. Management
Transfusions.
Splenectomy.
- Severe spherocytosis.
- Significant S/S of anemia eg growth
failure, skeletal changes and
extramedullary haematopoietic tumors.
-Older patients with vascular
compromise to vital organs.
18. HEREDITARY ELLIPTOCYTOSIS
(HE) AND PYROPOIKILOCYTOSIS
(HPP)
HE- elliptical or cigar shaped RBCs.
1 in 2,000 to 4,000. Parts of Africa
incidence 1 in 100.
Most patients are asymptomatic.
Common in individuals of African and
Mediterranean ancestry.
Confers some resistance to malaria.
AD inheritance, rare de novo mutations.
19. HPP: rare cause of severe HA.
Erythrocyte morphology resembles that in
severe burns.
Abnormal thermal sensitivity.
Predominantly in Africans.
20. Etiology
Intrinsic mechanical weakness/ fragility of
the RBC membrane due to a defect in
horizontal interactions.
Defects in the red cell membrane proteins
α-spectrin, β-spectrin, protein 4.1, or
glycophorin C. The majority of defects
occur in spectrin, the principal structural
protein of the membrane skeleton.
21. Clinical features
HE: heterogenous asymptomatic to severe
transfusion dependent anemia.
Most are asymptomatic.
Normal RBC lifespan in most patients.
Reduced in 10 %- hemolysis, anaemia,
splenomegaly, intermittent jaundice.
22. Diagnosis
PBF: elliptocytes a few to 100 %. A few
ovalocytes, spherocytes, stomatocytes
and fragmented cells.
Elliptocytes also found in megaloblastic
and iron deficiency anemias, MDS,
myelofibrosis…
HPP: above + bizarre shaped RBCs with
fragmentation and budding.
23. Management
Rarely necessary.
Occasional transfusions.
Splenectomy in severe cases.
Folate supplementation.
U/S- gallstones.
24. SOUTH EAST ASIAN OVALOCYTOSIS (
SAO)
Oval RBCs with a central longitudinal slit
or transverse bar on PBF.
Philippines, Indonesia, New Guinea and
Malaysia.
AD, mutation in critical region of band 3.
SAO RBCs are rigid and resistant to
invasion by malaria.
Asymptomatic with little or no evidence of
hemolysis or anemia.
Normal osmotic fragility.
25. STOMATOCYTOSIS
Heterogenous group of disorders
characterized by mouth shaped RBCs on PBF.
Asymptomatic to hemolysis and anemia.
Increased predisposition to thrombosis or
pulmonary hypertension post splenectomy.
Anaemia is weel compensated in most.
Abnormal membrane permeability to Na+ and
K+ with altered water content: dehydrated
(xerocytosis) to overhydrated (hydrocytosis).
26. ACANTHOCYTOSIS
Acanthocytes are dense contracted RBCs
with irregular thorny projections.
Associated with other syndromes eg:
abetalipoproteinemia, Huntington’s…..
