Clinical conditions

Question 1

What type of HS is involved in haemolytic transfusion reaction? Describe the pathophysiology of this condition.

Answer 1

T2HS:

i. mismatch between host and donor ABO Ag or rhesus D Ag…
ii. naturally occurring IgM Abs bind… donor RBC lysis (haemolytic anaemia)…
iii. complement activation and DIC

Question 2

Which blood type is the universal donor? Which is the universal recipient? Exlain why.

Answer 2

Type AB = universal recipient as person naturally produces neither anti-A nor anti-B Ab

Type O = universal donor as type O RBs have neither A nor B Ag

Question 3

In which situation does haemolytic disease of the newborn occur? Describe the pathophysiology of this condition.

Answer 3

Occurs when a Rh- mother carries a Rh+ foetus (required Rh+ father).

i. Foetal RBC crosses placental barrier into maternal plasma (foetomaternal haemorrhage (rare) or during placental delivery)… stimulates maternal production of anti-RhD IgG antibodies.
ii. If subsequent pregnancy with another Rh+ foetus… maternal IgG cross placenta… T2HS: foetal RBC lysis by foetal macrophages and lymphocytes (haemolytic anaemia)

Question 4

Describe a possible complication of haemolytic disease of the newborn.

Answer 4

After birth: hyperbilirubinaemia… jaundice… kernicterus.

KERNICTERUS: bilirubin encephalopathy - bilirubin crosses BBB and accumulates in grey matter of brain and spinal cord… neurological damage

Question 5

Name 2 tests by which haemolytic disease of the newborn can be diagnosed.

Answer 5

1. Indirect Coomb’s test (on maternal blood): serum mixed with lab RBCs with Ag on surface and then with Coomb’s reagent. If RBCs agglutinate, suggests presence of Ag in mum’s serum.
2. Direct Coomb’s test (on neonate’s blood) RBCs separated from plasma and mixed with Coomb’s reagent (secondary anti-human globin). If RBCs agglutinate, suggests presence of primary Ab on surface.

Question 6

Why does materno-foetal ABO mismatch rarely cause HDN?

Answer 6

As ABO Ag elicit IgM antibodies which aren’t able to cross placenta.

Question 7

How can HDN be prevented?

Answer 7

RhoGam (anti-D) is a purified polyclonal Ab against Rhesus D Ag, given to Rh- women carrying Rh+ baby within 72hrs of 1st delivery to prevent HDN in subsequent deliveries.

Destroys Rh+ foetal RBCs before the maternal immune response can be mounted to prevent sensitisation (i.e. production of memory B cells).

Question 8

What type of HS reaction is involved in myasthenia gravis? Describe the pathophysiology of this condition.

Answer 8

T2HS:

i. autoimmune production of IgG antibodies agaisnt nAChRs of neuromuscular junctions…
ii. R blockade, preventing ACh binding and muscular contraction…
iii. and complement activation… inflammation and muscle cell destruction… decreased nAChR expression…
iv. muscle weakness, mostly of extra-ocular, facial and swallowing muscles.

Question 9

Why might thymectomy be performed in some MG Ps?

Answer 9

MG Ps often have an enlarged thymus gland, or develop a thymoma (10-20%).

Question 10

What is a myasthenic crisis? How is this treated?

Answer 10

Paralysis of respiratory muscles, requiring assisted ventilation.

Treatment:

• plasmapheresis (remove Ab from circulation)
• intravenous immunoglobulins (bind circulating Ab)

Question 11

Name 2 drug types that can be used in treatment of MG.

Answer 11

1. acetylcholinesterase inhibitors, e.g. pyridostigmine (slow ACh breakdown to improve NMJ transmission)
2. immunosuppressants, e.g. prednisolone, azathioprine (suppress Ab production)