Diseases Of The Blood

Question 1

What is the inheritance pattern of Haemophilia A?

Answer 1

X-linked recessive

Question 2

What is the cause of Haemophilia A?

Answer 2

Deficiency in co-factor VIII (enhances Factor X activation by Factor IX).

Question 3

How is Haemophilia A treated?

Answer 3

Recombinant Factor VIII

Question 4

How does heparin affect blood clotting?

Answer 4

Enhances activity of antithrombin III so inhibits clotting.

Question 5

Suggest a cause of thrombotic disease.

Answer 5

Protein C deficiency

Question 6

Describe the effect of warfarin on blood clotting.

Answer 6

• Inhibits vitamin K (essential co-factor for Gla domain carboxylation) recycling (inhibits vitamin K epoxide reductase).
• So acts as anti-coagulant as no targeting of Factors II, VII, IX and X.

Question 7

Which molecules could be used clinically to break down a blood clot?

Answer 7

Streptokinase and t-PA

Question 8

In which population is SCD more common? Why?

Answer 8

African populations as heterozygotes are resistant to severe malaria.

Question 9

What are the symptoms of SCD?

Answer 9

Anaemia
Fever
Severe pain

Often sudden death

Question 10

What is the mutation in SCD?

Answer 10

A to T point mutation in beta globin gene on chromosome 11. Causes glutamate to valine change.

Question 11

What are the effects of the glutamate to valine change in beta globin gene?

Answer 11

Valine forms hydrophobic pocket on Hb surface - beta subunits polymerise in deoxygenated T state - cells form sickle shape

Question 12

What are the consequences of the sickle cell shape?

Answer 12

1. More prone to lysis - anaemia

2. More rigid and aggregate - block vasculature - ischaemia

Question 13

What are thalassaemias?

Answer 13

Imbalance between number of alpha and beta globin chains

Question 14

What are the symptoms of thalassaemias and when do they appear?

Answer 14

• symptoms of haemolytic anaemia, e.g. Pallor and hepatosplenomegaly.
• at birth in alpha-thalassaemia, several months after birth in beta-thalassaemia

Question 15

What can be the causes of hepatosplenomegaly?

Answer 15

Infectious mononucleosis 
Viral hepatitis
Lysosomal storage disease
Thalassaemias 
Systemic venous hypertension (right sided heart failure)

Question 16

Why are there several levels of severity in alpha thalassaemia?

Answer 16

Multiple copies of alpha gene on chromosome 16 (2 alpha1 and 2 alpha2)

Question 17

What happens to the beta chains in alpha thalassaemia?

Answer 17

Can form stable tetramers (Hb H) with increased affinity for oxygen. Or beta chain precipitates

Question 18

What is the difference between beta thalassaemia minor and major?

Answer 18

Minor = heterozygote
Major = homozygous

Question 19

What happens to the alpha globin chain in beta thalassaemia?

Answer 19

Unable to form stable tetramers, instead form alpha chain precipitates. Can also form Hb F