Haemophilia

Question 1

Where are the genes for FIX and FX found?

Answer 1

X Chromosome

Question 2

What is the deficit in haemophilia? What does lack of the factor lead to?

Answer 2

There is a reduction in thrombin generation

Question 3

What does the classification of haemophilia include?

Answer 3

Severe <1%
Moderate 2-5%
Mild 6-40%

Question 4

What does a severe haemophilic bleeding picture look like?

Answer 4

"spontaneous" bleeds
joints and muscle 
easy bruising
bleeding is often delayed but prolonged
bleeding time is normal

Question 5

What does a moderate picture look like?

Answer 5

prolonged or excessive bleeding after minor trauma

rarely bleeds into joints

Question 6

Mild bleeding picture?

Answer 6

excessive bleeding only after major trauma or surgery

Question 7

How is haemophilia diagnosed?

Answer 7

A prolonged APTT

PT and TT not affected

Question 8

Why is there characteristic bleeding into muscle and joints?

Answer 8

There is reduced thrombin generation, so there is an inability to stabilise the platelet plug
In tissues where TF is low naturally, normally secondary haemostasis is first - intrinsic pathway
So the unstable platelet plug doesn’t hold off the bleeding so they are likely to bleed again after

Question 9

Why is there characteristic bleeding that is delayed?

Answer 9

The primary platelet plug is sufficient to hold off the initial bleed, the inadequate thrombin generation leads to poor fibrin mesh and increased susceptibility to fibrinolysis

Question 10

Why is there no bleeding from superficial cuts?

Answer 10

Primary platelet plug forms via vwf independent of thrombin, this is enough to stop small cuts

Question 11

Describe the clinical presentation of haemarthrosis

Answer 11

Typically begins at approx 1 yr
Bleeds into joint cavities and this causes a rise in pressure which is excruciatingly painful. The pressure stops the bleeding but the blood damages the cartilage as it is pro-inflammatory
There is a predisposition to future bleeds too which leads to a vicious cycle of joint damage
Bleeding -> synovial hypertrophy-> Friable and expanded synovium > bleeding

Question 12

Describe the clinical presentation of muscle bleeds

Answer 12

They are apparently spontaenous and may arise from exertion
The blood fills the muscle capsule and results in compartment syndrome
Psoas muscle is particularly susceptible

Question 13

What are the current treatments for haemophilia?

Answer 13

Currently given factor concentrates which must be given IV

Question 14

What are the limitation s of these treatments?

Answer 14

They are given IV
they have short half lives
need frequent transfusions

Question 15

What are the types of therapy aims?

Answer 15

On demand - given in acute bleed situations

Prophylatic - prevent bleeds allows people to live a near normal life but need to start young

Question 16

What is the pharmocodynamics of the drug?

Answer 16

There are peaks and troughs with the treatment

Question 17

What are the non-concentrate options?

Answer 17

Local measures - pressure and elevate
Tranexamic acid - this is an anti-fibrinolytic and works as a lysine derivative which binds to plasminogen and stops it binding to fibrin and degrading it
DDAVP -vasopressin derivative which acts of V2 receptors and causes as release of FVIII stores from the endothelium

Question 18

What are the potential complications to treatment with blood products?

Answer 18

There is a risk of infection - hep b/c/HIV/prions

There can be immunity development with antibodies

Question 19

Explain the complications of inhibitors

Answer 19

They are antibodies which target foreign FVIII/IX and exist in up to 30% pf haemophiliacs, many of which are persistent and render the drugs useless

Question 20

How can inhibitor effects be mediated?

Answer 20

By-pass agents such as recombinant factor VIIa 
plasma derived activated PT complex
tranexamic acid
and high dose FVIII
combination therapy