Path Lab - Sickle Cell Anaemia

Question 1

What is pallor and what are 3 common causes?

Answer 1

Pallor is paleness of the skin or mucous membranes. It can may be intrinsic to the blood itself or due to a reduction of blood supply to the skin (i.e. vasoconstriction).

Three possible causes:

• anaemia
• shock
• respiratory failure

Question 2

What is splenomegaly and what are 5 causes of splenomegaly in childhood?

Answer 2

Enlargement of the spleen

Some Causes:

S - Sequestering of red blood cells, i.e. sickle cell anaemia
P - Proliferation - secondary chronic inflammation of infection (EBV, SLE etc)
L - Lipid deposition - various disorders
E - Endowment - congenital disorders such as haemangiomas.
E - Engorgement - splenic trauma, heart failure, sickle cell, portal hypertension.
N - iNvasion - granulomatous, lymphoma, histiocytic of other haematological diseases, i.e. leukaemia.

Question 3

What is dactylitis?

Answer 3

Inflammation of the digits.
It presents acutely as exquisite pain and swelling of the soft tissues in the dorsum of the hands and feet and can last 1-2 weeks.

Question 4

What is a reference interval?

Answer 4

Upper and lower limits of a defined parameter for a defined population in which 95% of the individuals will fall. (incorrect term = ‘normal range’)

Question 5

What do reference intervals vary according to?

Answer 5

Age, sex, pregnancy status, gestation in pregnancy, ethnic background, methodology of test.

Question 6

Why might you see mild leucocytosis (increase in leucocytes) and monocytosis in the blood count of someone with dactylitis?

Answer 6

The mild leucocytosis would be caused by the monocytosis which in turn is secondary to dactylics (reactive monocytosis).

So you would actually expect to see this in someone with dactylitis.

Question 7

What is anaemia?

Answer 7

Anaemia - reduction in RBC mass or concentration of haemoglobin in blood.

Question 8

What are 3 broad pathological mechanisms that can lead to anaemia?

Answer 8

1. Impaired production of RBS (i.e. BM failure, malnutrition, renal failure)
2. Blood loss
3. Excessive RBC destruction (i.e. intrinsic red cell defects, haemaglobinopathies)

Question 9

What would you expect the RBCs on a normal blood film to look like compared to sickle cell anaemia?

Answer 9

Normal: Uniform bioconcave disc with are of central pallor that does not exceed 1/3 o the diameter of the cell.

Sickle Cell: sickle shaped cells and some RBS may have lost area of central pallor. They may also be sparser than normal.
- may see Howell-Jolly bodies (small, round nuclear fragments left in cytoplasm of RBCs), target cells, acanthocytes. If any of these are present, there may be a problem with the spleen.

Question 10

What would you expect the WBCs on a normal blood film to look like compared to sickle cell anaemia?

Answer 10

There may be cytoplasmic vacuolation in the monocytes which is typically reactive.

Question 11

What would you expect the platelets on a normal blood film to look like compared to sickle cell anaemia?

Answer 11

Could be normal on both.

Question 12

What are the 3 types of haemoglobin in a normal adult?

Answer 12

1.HbA - a2β2, The majority

2. HbA2 - α2δ2, 2.5 - 3.4%
3. HbF - α2gamma2,

Question 13

What is haemoglobin switching?

Answer 13

At birth we have mostly HbF (90%) and about 10% HbA. But there is a gradual switching off of HbF and switching on of HbA after birth.

Question 14

Which gene encodes beta globin protein?

What would you see in sanger sequencing in sickle cell anaemia?

Answer 14

HBB Gene

In sanger sequencing, you would expect to see only one peak as a person needs to have both alleles mutated for sickle cell anaemia.

Question 15

What is the mutation nomenclature for sickle cell anaemia?

Answer 15

HbS = haemoglobin sick

Nomenclature:
HBB:c.20A>T
p. Glu7Val

Question 16

What are the hallmarks of sickle cell disease?

Answer 16

• vaso-occlusion ( circulation of blood vessels is obstructed by sickled red blood cells, causing ischemic injuries, often pain is present. Can cause chronic organ dysfunction)
• haemolysis

Question 17

Why do sickle cells cause blockages in microvasculature?

Answer 17

– Loss of deformability
– Loss of membrane asymmetry.
– Expression of other adhesion molecules.

Question 18

What are the factors that promote and prevent sickling?

Answer 18

PROMOTES:
•  Deoxygenation
–  Tissues
–  Fever
–  Acidosis (eg infection,
metabolism)
–  Respiratory compromise

PREVENTS:
• HbF- potent protector.
• maximising HbF prevents “crises”.

Question 19

Why is sickle cell anaemia asymptomatic before 6 months of age?

Answer 19

For the first 6 months of life, infants are protected largely by elevated levels of Hb F.