Hemoglobinopathies L4

Question 1

What causes hemoglobinopathies?

Answer 1

Hereditary disorders with a structural abnormality (replacements, deletion, addition) of amino acids in the globin chains.

Question 2

What causes homozygous HgS?

Answer 2

Glutamic acid replaced by valine, changing the charge the cell.

Question 3

What happens when cell sickles? (cell shape, behaviour, etc)

Answer 3

With the removal of oxygen, polymerization occurs and RBC take a sickled shape.
It is no longer soluble in the blood, not bendable, and can start blocking blood vessels.
Increased viscosity

Question 4

Why are homozygous HgS newborns asymptomatic?

Answer 4

Due to the protective effect of high HgF

Question 5

Progression or symptoms of SS:

Answer 5

Dactylitis in children: pain in fingers and toes
Sequestration crisis: enlargement of spleen with sudden pooling of blood resulting in hypovolemic shock (spleen taking in too much RBC)
Susceptibility to infections

Question 6

What is aplastic crisis and megaloblastic episodes in sickle cell disease?

Answer 6

Aplastic crisis: temporary failure of RBC production (bone marrow shuts down) = fall in Hgb with susceptibility to infections

Megaloblastic episodes: failure of erythropoiesis due to folate depression

Question 7

Blood picture for HgSS

Answer 7

Normocytic, normochromic
Polychromasia
nRBC
Codocytes, Howell-Jolly body
Sickle cells

Question 8

Differentiate SS, SA, CC, CA, SC, S/B+, S/B0 and C/B+ in relation with the quantities of HgA, HgS/HgC

Answer 8

SS: no HgA, high HgS (80%)
(with HgF and A2)

SA: high HgA (50-60%), lower HgS (35-45%)
(N HgF, HgA2)

CC: no HgA, high HgC (90%)
(slight high HgF; 7%)

CA: high HgA (50-60%), lower HgC (30-40%)

SC: HgS and HgC equal in equal amounts, no HgA
(N/high HgF)

S/B+: high HgS (over 50%), lower HgA (15-30%)
(high HgF; 1-20% and HgA2; over 4.5%)

S/B0: no HgA, high HgS (75-95%)
(high HgF; 5-10% and A2; over 4.5%)

C/B+: high HgC, lower HgA (0-20%)
(high HgF; 1-10%)

Question 9

From what are children with SA protected from and why?

Answer 9

Protected from Plasmodium falciparum due to the spleen removing the infected cell. SS patients usually have a splenectomy which cannot remove it.

Question 10

Blood picture of CC

Answer 10

Normocytic, normochromic
Codocytes
HgC crystals

Question 11

Principle of alkaline electrophoresis:

Answer 11

pH of 8.6
Hemoglobin will migrate towards cathode (+)

Equidistant hemoglobin:
\+
I, H, Barts
A, F
S, D
A2, C , E
-

Question 12

Principle of acid electrophoresis:

Answer 12

pH 6.4
Hemoglobin will migrate towards anode (-)
Used to separate C/E and S/D

-
F, Barts
A D E I G Lepore
S
C
\+

Question 13

Principle of Singer-Chernoff - Alkaline denaturation

Answer 13

HgF do not denature in alkaline solution, HgA will.

Question 14

Principle of Kleihauer-Betke - acid elution

Answer 14

In acid solution, HgF do not elute out of the cell (stained), HgA will and results in ghost cells.