The Contact Activation System

Question 1

What is the role of the contact activation system in physological haemostasis?

Answer 1

There is no role
FXII deficiency has no effect on bleeding
FXI deficiency has only mild bleeding issues

Question 2

How is FXII activated? On what kind of surfaces does this occur?

Answer 2

It autoactivates spontaneously on unusual biological/artificial surfaces - it is part of the innate immune system
typically prefers negatively charged surfaces but can occur slower on neutral and positive ones

Question 3

What are some notable negative molecules it can activate on?

Answer 3

Heparan sulphate

platelet polyphosphate - this is an inorganic polymer which is released when platelets activate

Question 4

What is kallikrein and what does it do?

Answer 4

It is a serine protease, it accelerates the rate of activation creating a cycle or positive feedback for FXII

Question 5

What occurs to the contact activation pathway during sepsis?

Answer 5

The pathogen polyphosphates provide the negatively charge surface for activation of FXII
Bacterial proteases can also do this either directly of via prekallikrein
KKS activation can increase inflammation

Question 6

What occurs in the contact activation pathway during thrombosis?

Answer 6

CAS causes thrombosis in cardiopulmonary bypass/catheter thrombosis (foreign surface)
Heparin inhibits FXIIa so helps prevent this

Question 7

What is the Kallikrein/Kinin system?

Answer 7

Kallikrein can digest High molecular weight kininogen to bradykinin which vasoactive effects e.g. increased NO, PGI2 etc
Can occur without CAS activation

Question 8

Draw the contact activation pathway

Answer 8

draw