Fibrin and Fibrinolysis

Question 1

What is the structure of fibrinogen?

Answer 1

Aalpha
Bbeta
gamma
linked by disulphide bonds

Question 2

What are the 3 domains of fibrinogen?

Answer 2

Central E domain flanked by D domains

Question 3

How is fibrin formed?

Answer 3

1. thrombin cleaves the fibrinopeptide A exposing Ea domain
2. Ea interacts with Da and polymerises forming overlapping interactions and branching of fibrils
3. Thrombin then cleaves fibrinopeptin B, which occurs slower than FPA and exposes Eb which polymerises Db
4. The FXIII binding site is exposure and approximates FVIII and thrombin to accelerate FXIIIa activation
5. FXIIIa covalently cross links fibrin fibrils

Question 4

What is the structure of FXIII? What does it do?

Answer 4

it is a transglutaminase and it circulates as a heterodimer

It also approximates FVIII and thrombin accelarating XIIIa activation

Question 5

How does fibrinolysis occur?

Answer 5

Plasminogen and tPA circulate in circulation but do not interact
tPa requires a cofactor to act and plasminogen is a zymogen
the fibrin clot acts as a cofactor, it provides the surface for fibrinolysis to occur
Plasminogen is cleaved to plasmin by tpa

Question 6

What allows plasminogen and tpa to recognise fibrin?

Answer 6

The plasminogen kringle domains recognise the lysine residues leading to approximation

Question 7

What is D-dimer?

Answer 7

It is a soluble degradation product which occurs from breakdown of fibrin clot
Shows evidence of cross link formation