Membrane Defects Haemolytic Anaemia - H. Spherocytosis, Elliptocytosis

Question 1

In which region if the world is Hereditary spherocytosis the most common Hereditary Haemolytic Anaemia?

Answer 1

Northern European

Question 2

What is the pathogenesis for Hereditary Spherocytosis?

Answer 2

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.

Question 3

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.

Answer 3

Hereditary Spherocytosis

Question 4

True or False? Hereditary Spherocytosis is usually Autosomal Dominant with variable expression; rarely, it may be autosomal recessive.

Answer 4

TRUE!!

Question 5

True or False? Hereditary Spherocytosis only presents in adults.

Answer 5

FALSE!! It can present from infancy to old age.

Question 6

If Jaundice is particularly marked with patients with Hereditary sphercocytisis it can indicate what?

Answer 6

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.

Question 7

What are the molecular abnormalities associated with Hereditary Spherocytosis?

Answer 7

■ 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

Question 8

What are the clinical features of Hereditary Spherocytosis?

Answer 8

• Jaundice (fluctuating )
• Splenomegaly
• Pigment Gallstones
• Aplastic crises usually precipitated by parvovirus infection, may cause a sudden increase in the severity of anaemia .

Question 9

What are the Haematological findings of Hereditary Spherocytosis?

Answer 9

• Anaemia
• Reticulocytes 5-20%
• Microspherocytes

Question 10

How is diagnosis of Hereditary Spherocytosis confirmed?

Answer 10

A rapid flow cytometric analysis of EMA (eosin-maleimid) bound to erythrocytes is used as a test for HS and membrane protein deficiency

Question 11

How does the EMA (Eosin - maleimid) testing works?

Answer 11

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

Question 12

True or False? The direct antiglobulin (Coombs’) test is normal in HS excluding an autoimmune cause of spherocytosis and haemolysis.

Answer 12

TRUE!! Test is negative.

Question 13

What is the principal form of treatment for Hereditary Spherocytosis?

Answer 13

Splenectomy

Question 14

What are the molecular abnormalities associated with Hereditary Elliptocytosis?

Answer 14

■ 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

Question 15

The basic defect of Sprectrin dimers is associated with which disease?

Answer 15

Hereditary Elliptocytosis

Question 16

Fill in the blanks. “Patients with homozygous or doubly heterozygous elliptocytosis present with a severe haemolytic anaemia termed ____________.”

Answer 16

Hereditary pyropoikilocytosis

Question 17

True or False? Hereditary pyropoikilocytosis is most common in persons of Asian descent.

Answer 17

FALSE!! It is most common in patients of African descent

Question 18

Red blood cells with ‘ mouth- like slits ‘ are associated with which pathology?

Answer 18

Hereditary Stomatocytosis

Question 19

True or False? In hereditary Stomatocystosis , the red blood cells release anions into circulation.

Answer 19

FALSE!! They release cations

Question 20

What is Hereditary Stomatocytosis?

Answer 20

This is a group of rare red cell membrane defects including xerocytosis and overhydrated stomatocytosis

Question 21

In which countries is South - East Asian Ovalocytosis most common in?

Answer 21

Indonesia
Melanesia
Malaysia
Phillipenes

’ IMMP’

Question 22

What is the cause of South- East Asian Ovalocytosis ?

Answer 22

It is caused by a 9-amino acid deletion at the junction of the cytoplasmic and transmembrane domains of the band 3 protein.

Question 23

What types of cells are found in South-East Asian ovalocytosis?

Answer 23

Ovalocytes
Stomatocytes

Question 24

A protein 4.1 deficiency or abnormality is associated with which disease?

Answer 24

Hereditary Elliptocytosis

Question 25

A protein 4.2 abnormality is associated with which disease?

Answer 25

Hereditary Spherocytosis