Clotting Cascade

Question 1

Initial Response to Vessel Rupture

Answer 1

A rupture promotes platelets to clump together at the site of the break, forming a plug.

This is due to the reaction of the platelets to collagen, found outside the blood vessel.

Question 2

Extrinsic Pathway

Answer 2

1. At the site of the rupture, Clotting Factor 3 (“Tissue Factor”) from outside the vessel activates CF-7.
2. The activated CF-7 activates CF-10.
3. CF-10 activates prothrombin into CF-2 (Thrombin)

Question 3

Intrinsic Pathway

Answer 3

1. Thrombin activates CF-11, CF-8, and CF-5 (in addition to 7 & 13)

2. CF-12 actiavtes CF-11
3. CF-11 activates CF-9
4. CF-9 and CF-8 activate CF-10
5. CF-10 and CF-5 activate Thrombin

Question 4

Thrombin Activity

Answer 4

• Thrombin is activated by CF-7, CF-10, and CF-5 (cleaved from prothrombin).
• Thrombin activates CF-11, CF-8, CF-7, and CF-5 in the clotting cascades.
• Thrombin also activates CF-1, turning Fibrinogen into Fibrin

Question 5

Fibrin

Answer 5

• Circulates in blood as fibrinogen (soluble) until it is cleaved by thrombin to form fibrin (insoluble).
• Forms a mesh over the platelet plug to reinforce the barrier.
• Crosslinks are formed by CF-13 to strengthen the fibrin mat.

Question 6

Negative Feedback

Answer 6

1. Thrombin activates plasminogen, turning it into plasmin. Plasmin then breaks down the mesh of fibrin over the rupture.
2. Thrombin stimulates production of anti-thrombin, which inhibits the activation of CF-10 as well as thrombin itself.

Question 7

Mechanism of Clotting Amplification

Answer 7

Mainly on the intrinsic pathway; as you progress down the cascade, each susequent CF has a higher concentration than the previous in circulation (with the exception of CF-3, tissue factor, as it is outside of the blood vessel).