Blood clotting cascade Flashcards
What are the two pathways of the blood clotting cascade?
Intrinsic pathway
Extrinsic pathway
What activates the intrinsic pathway?
Damaged endothelial lining of blood vessel
factor 12 binds
What activates the extrinsic pathway?
Membrane damage exposes tissue factor
tissue factor = factor 3
What do both the intrinsic and extrinsic pathways lead to?
Activation of factor 10
What does activated factor 10 do?
Cleaves prothrombin into thrombin
What does thrombin do?
Cleaves fibrinogen into fibrin
Positively feedbacks on activation of factors in intrinsic pathway and common pathway
What does fibrin do?
Forms cross-links with other fibrin molecules
to form a fibrin clot
What is the structure of prothrombin?
Protease
Kringle domains
Gla domain
What is the function of the kringle domains in prothrombin?
Keep prothrombin in inactive form
What is a Gla residue?
Extra COOH groups attached to glutamate
Which factors have Gla residues?
Factors
- 2
- 7
- 9
- 10
Where in the body are Gla residues formed?
Liver
What is required for the formation of Gla residues?
Vitamin K
What is the function of Gla residues?
Target factor to the site of injury
How do Gla residues target factors to site of injury?
Negatively charged COOH- residues are attracted to calcium ions at site of injury
What is the purpose of Gla residues targeting factors to the site of injury?
So that blood clots form at the site of injury only
What is the structure of fibrinogen?
Two sets of tripeptides
joined by disulphide bond in the middle
Globular domains at middle and exterior ends
What is the structure of fibrin?
Central globular domain is fibrinogen is cleaved off to form fibrin
How does fibrin come together to form fibrin clot?
Exterior globular domains interact with exposed centre of fibrin
How is the blood blotting cascade stopped?
Clotting factors diluted by blood flow
Clotting factors removed by liver
Clotthing factors digested by proteases
Clotting factors are inhibited
What is an example a protease that digests clotting factors?
Protein C
How is protein C activated?
By thrombin
What do defects in protein C cause?
Thrombotic disease
What is an example of an inhibitor of clotting factors?
Antithrombin
What enhances the activity of antithrombin?
Heparin
What is fibrinolysis?
The digestion of the fibrin clot into fibrin fragments
What digests the fibrin clot into fibrin fragments?
Plasmin
What forms active plasmin?
Tissue plasminogen active (tPA)
Streptokinase
What is the inactive form of plasmin?
Plasminogen
