Red cell Membrane Disorders Hereditary Spherocytosis

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Red cell Membrane DisordersHereditary
Spherocytosis
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• Hemolysis is defined as the premature destruction
  of red blood cells.
• Anemia results when the rate of destruction
  exeeds the capacity of the marrow to produce
  RBCs.
• Normal RBCs survival time is 110-120 days

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• Membrane Disorders
• Inherited red cell membrane defects include
• Hereditary spherocytosis,
• Hereditary elliptocytosis,
• Hereditary stomatocytosis, and
• Pyropoikilocytosis.
• In each abnormalities of the red cell membrane
  result in hemolysis.

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• What is Hereditary Spherocytosis?
• Spherocytosis, is an inherited disease that
  destroys red blood cells. This destruction of the
  red blood cells causes anemia.
• The shape of a normal red blood cell resembles a
  disk. Normal red blood cells easily change shape
  to move effectively through the small blood
  vessels between organs of the body. In
  spherocytosis the red blood cells are very round
  and have difficulty changing this shape. The lack
  of ability to change shapes makes moving through
  the small blood vessels difficult. Therefore, the
  red blood cells stay in the spleen longer than
  normal. This lengthy stay in the spleen damages
  the cell membranes.

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• HS is a common cause of hemolysis and hemolytic
  anemia.
• It is the most common inherited abnormality of
  the RBCs membrane.
• Prevalence approximately 1/5000 people

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• Hereditary spherocytosis, the most frequent of
  the familial anemias, is inherited as an
  autosomal dominant trait it is most common among
  people of northern European . The disease is most
  often identified during childhood or adolescence.

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• Pathophysiology
• Four abnormalities in red cell membrane proteins
  have been identified and include
• spectrin deficiency alone,
• combined spectrin and ankyrin deficiency,
• (3) band 3 deficiency, and
• (4) protein 4.2 defects.
• Spectrin deficiency is the most common defect.
  Each is associated with a variety of mutations
  that result in different protein abnormalities
  and varied clinical expression.

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• A deficiency in spectrin, ankyrin,or protein 3
  results in uncoupling in the vertical
  interactions of the lipid bilayer skeleton and
  the loss of membrane microvesicles.
• The loss of membrane surface area without a
  proportional loss of cell volume causes sphering
  of the RBCs.

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• Defects in vertical stabilization of the
  phospholipid bilayer of the RBC membrane cause
  separation of the spectrin - phospholipid
  bilayer. Portions of the phospholipid bilayer
  form vesicles and are lost from the RBC surface
  resulting in decreased surface area and
  spherocytosis.

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• Symptoms according to age
•  Hydrops fetalis with death in utero can occur in
  the most severe cases . When detected in the
  neonatal period, HS is commonly accompanied by
  jaundice, requiring treatment with phototherapy
  or exchange transfusion .

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• Symptoms of Hereditary spherocytosis
• Anemia, jaundice, and splenomegaly are the
  clinical features of HS.
• Abnormal shaped red cells
• Anemia due to destruction of red blood cells
• Intermittent jaundice
• Enlarged spleen
• Biliary obstruction

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• Diagnosis of HS usually is established from
• 1.Family history
• 2.Blood film
• 3.Splenomegaly

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• Anemia, reticulocytosis, and spherocytosis on
  peripheral blood smear examination provide strong
  hints to suggest the diagnosis of HS.

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• Laboratory Studies
• The classic laboratory features of HS include
• - Minimal anemia,
• -Reticulocytosis,
• -increased mean corpuscular hemoglobin
  concentration (MCHC),
• -Spherocytes on the peripheral blood smear,
  -hyperbilirubinemia,
• -Abnormal results on the Osmotic fragility test.

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• Differential diagnosis
• Other aquired causes of spherocytes in
  peripheral blood film
• 1.Autoimmune hemolytic anaemias.
• 2.Hemolytic transfusion reactions.
• 3.Thermal injury

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• complications
• Gallstones
• Hemolytic crisis
• Aplastic crisis

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• Treatment
• Splenectomy usually is curative
• Red cell survival is improved significantly but
  is not absolutely normal. The MCV usually falls,
  but the MCHC does not change significantly.

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Other Red cell Membrane DisordersHereditary
Elliptoctosis
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HEREDIATRY ELLIPTOCYTOSIS

• Definition
• Heterogeneous disorders with elliptical red
  cells.
• Types
• Common HE with discoidal elliptocytes.
• Silent carriers decrease expression of alpha
  spectrin
• Hereditary pyropoikilocytosis
• Spherocytic HE.
• HF and HPP in neonates

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mode of inheritance

• The mode of inheritance is autosomal dominant,
  except for hereditary pyropoikilocytosis (HPP)
  which is autosomal recessive.

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• Physiology Pathogenesis
• Mutations in ? or ? spectrin (commonest) leading
  to defective spectrin dimer formation.
• Deficiency or dysfunction of protein 4.1.
• Severity of haemolysis depends on the degree of
  spect def.

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• Clinical Features
• Variable, of microcyte reflects severity.
• Asymptomatic carriers (parents or siblings of
  pts HE).
• Transient haemolysis Mild HE infection, renal
  transplant rejection, B12 def., pregnancy.

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• Laboratory features
• Smear diag. depends on of elliptocytes
  
  (N lt 5) HE 25 90 in ve
  family history.
• Elliptocytes oval cells with long diameter gt 2
  times the short diameter.
• Retics, LDH, bil., -ve DAT (Direct
  Antiglobulin Test)
• OF Mild HE normal OF.
• Severe HE OF.
• Autohaemolysis N or (corrected by gl.).

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SPHEROCYTIC ELLIPTOCYTOSIS

• Also called
• HE with spherocytosis.
• Hereditary ovalocytosis.
• Molecular basis unknown.
• Elliptical spherocytes.
• Or round sphero-ovalocytes.
• Clinically Haemolysis.
• OF .

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South East Asian ovalocytosis

• Definition
• Presence of oval elliptocytes and some with
  slit
• RBC with a linear slit like central Pallor
  (N circular)
• genetics
• autosomal dominant.
• Prevalence
• Wide spread in Southeast Asia.

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• Characters
• Oval RBCs with
• 1 2 transverse ridges.
• Or longitudinal slit.
• Red cell rigidity.
• Clinical features
• Variable, jaundice at birth, pallor (variable),
  splenomegaly.

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• Laboratory features
• Anaemia.
• Retics.
• Smear 10 25 stomatocytes.
• OF autohaemolysis.
• Thermal stability.
• Expression of certain red cell antigens.
• Resistance to in vitro invasion by malaria