Lecture 5 bleeding disorders

Question 1

What is a common symptom of a coagulation deficiency?

Answer 1

Most common symptom is easy bruising.

Question 2

What are other symptoms associated with a coagulation deficiency?

Answer 2

• Easy bleeding (for example after brushing your teeth that your gums bleed, or nose bloods etc.)
• Hemathrosis (bleeding into joint cavities)
• Muscle bleeds.

Question 3

Why are coagulation deficiencies so hard to diagnose?

Answer 3

Because it isn’t quite clear whether it’s a platelet disorder or a clotting problem. Both result in easy bruising.

Question 4

What are the different types of hemophilia?

Answer 4

Hemophilia A, B, C and D

Question 5

What factors cause the deficiencies in the different types of hemophilia?

Answer 5

Factor 8 deficieny: is hemophelia A
Factor 9 deficiency: is hemophelia B
Factor 11 deficiency: is hemophilia C (less severe disorder)
Factor 12 deficiency: is Hemophilia D (very rare, also factor 12 is not relevant for haemostasis, so we don’t know the ‘why’ behind the literature)

Question 6

Why are hemophilia A and B the most common coagulation deficiencies compared to hemophilia C and D?

Answer 6

It’s due to the inheritance pattern. X-chromosome genes factor 8 and factor 9 are located on the X-chromosme. So if you have one X-chromosome (male), than you are more likely to have this disease. So half of the popoulation has a mutation on this X-chromosome. If you have a mutation on that gene then you have it immediately when you only have one X-chromosome (so if you’re male). If you have both of the X-alleles then you are most likely a carrier (so if you are a woman).*

*A female with one mutated X chromosome is a carrier. She usually does not show symptoms because the second X chromosome can produce enough Factor VIII or IX to prevent the disorder.
Males, however, do not have a “backup” X chromosome (they have a Y chromosome instead), so they are more likely to exhibit symptoms if their single X chromosome is affected.

Question 7

What is the prevalence of factors VIII, IX and XI?

Answer 7

Factor VIII = 1: 7000 males
Factor IX = 1: 25-30.000 males
Factor XI = 1: 1.000.000 males

Question 8

Why is the prevalence of hemophilia higher in countries where consanquineous marriages are common?

Answer 8

This is because closely related individuals are more likely to carry the same mutations. The prevalence of these deficiencies rises in populations where consanguinity is common and has occurred over multiple generations. This explains why certain coagulation factor deficiencies are geographically and culturally concentrated.

Question 9

What is the most common mutation in hemophilia A?

Answer 9

Intron 22 Inversion Mutation in the Factor VIII Gene.