Membrane Defects Haemolytic Anaemia - H. Spherocytosis, Elliptocytosis Flashcards
In which region if the world is Hereditary spherocytosis the most common Hereditary Haemolytic Anaemia?
Northern European
What is the pathogenesis for Hereditary Spherocytosis?
HS is usually caused by defects in the proteins involved in the vertical interactions between the membrane skeleton and the lipid bilayer of the red cell.
In which disease does red cells lose their membrane and become increasingly spherical (loss of surface area relative to volume) as they circulate through the spleen and the rest of the RE system.
Hereditary Spherocytosis
True or False? Hereditary Spherocytosis is usually Autosomal Dominant with variable expression; rarely, it may be autosomal recessive.
TRUE!!
True or False? Hereditary Spherocytosis only presents in adults.
FALSE!! It can present from infancy to old age.
If Jaundice is particularly marked with patients with Hereditary sphercocytisis it can indicate what?
It can indicate that the patient may also have Gilberts’s disease (a defect of hepatic conjugation of bilirubin). This is because jaundice is normally FLUCTUATING in HS.
What are the molecular abnormalities associated with Hereditary Spherocytosis?
■ Ankyrin deficiency or abnormalities (most common cause – about 50% of patients)
■ α- or β-spectrin deficiency or abnormalities.
■ Band 3 abnormalities
■ Pallidin (protein 4.2) abnormalities
What are the clinical features of Hereditary Spherocytosis?
- Jaundice (fluctuating )
- Splenomegaly
- Pigment Gallstones
- Aplastic crises usually precipitated by parvovirus infection, may cause a sudden increase in the severity of anaemia .
What are the Haematological findings of Hereditary Spherocytosis?
- Anaemia
- Reticulocytes 5-20%
- Microspherocytes
How is diagnosis of Hereditary Spherocytosis confirmed?
A rapid flow cytometric analysis of EMA (eosin-maleimid) bound to erythrocytes is used as a test for HS and membrane protein deficiency
How does the EMA (Eosin - maleimid) testing works?
EMA is a dye that binds specifically to band 3 of the red blood cell cytoskeleton and measures the content of erythrocyte structural proteins, which is altered in HS
True or False? The direct antiglobulin (Coombs’) test is normal in HS excluding an autoimmune cause of spherocytosis and haemolysis.
TRUE!! Test is negative.
What is the principal form of treatment for Hereditary Spherocytosis?
Splenectomy
What are the molecular abnormalities associated with Hereditary Elliptocytosis?
■ α- or β-spectrin mutants leading to defective spectrin dimer formation
■ α- or β-spectrin mutants leading to defective spectrin– ankyrin associations
■ Protein 4.1 deficiency or abnormality
■ South-East Asian ovalocytosis band 3 deletion
The basic defect of Sprectrin dimers is associated with which disease?
Hereditary Elliptocytosis
Fill in the blanks. “Patients with homozygous or doubly heterozygous elliptocytosis present with a severe haemolytic anaemia termed ____________.”
Hereditary pyropoikilocytosis
True or False? Hereditary pyropoikilocytosis is most common in persons of Asian descent.
FALSE!! It is most common in patients of African descent
Red blood cells with ‘ mouth- like slits ‘ are associated with which pathology?
Hereditary Stomatocytosis
True or False? In hereditary Stomatocystosis , the red blood cells release anions into circulation.
FALSE!! They release cations
What is Hereditary Stomatocytosis?
This is a group of rare red cell membrane defects including xerocytosis and overhydrated stomatocytosis
In which countries is South - East Asian Ovalocytosis most common in?
Indonesia
Melanesia
Malaysia
Phillipenes
’ IMMP’
What is the cause of South- East Asian Ovalocytosis ?
It is caused by a 9-amino acid deletion at the junction of the cytoplasmic and transmembrane domains of the band 3 protein.
What types of cells are found in South-East Asian ovalocytosis?
Ovalocytes
Stomatocytes
A protein 4.1 deficiency or abnormality is associated with which disease?
Hereditary Elliptocytosis
A protein 4.2 abnormality is associated with which disease?
Hereditary Spherocytosis
