Coagulation cascade and Clot Dissolution

What is the end result of the coagulation cascade?

Generation of thrombin (IIa)

Role of thrombin in clot formation (3)

1. Activate platelets

2. Amplify coagulation cascade

3. Activate factor XIII – cross links fibrin

Anticoagulant effects of endothelium first part (2)

1. Endothelium shields coagulation factors from tissue factor

2. Tissue factor pathway inhibitor (TFPI) inactivates tissue factor-VIIa complex

Anticoagulant effects of endothelium second part (4)

1. Antithrombin binds heparin-like molecules on the endothelial cell membrane

2. This causes a conformational change in antithrombin

3. Antithrombin now bind thrombin

4. This inactivates thrombin

Anticoagulant effects of endothelium third part (5)

1. Thrombin binding to thrombomodulin on the surface of epithelial cells

2. Causes thrombin to act as an anticoagulant

3. Thrombin cleaves and activates protein C

4. Activated protein C binds to its cofactor protein

5. This complex inactivates the clotting factors Va and VIIIa

What prevents the clot from continuing to expand and grow outside the site of injury? (2)

1. Flowing blood washes away activated clotting factors

2. Most important – intact endothelium adjacent to the injury site

Clot dissolution or fibrinolysis

1. Tissue-type plasminogen activator is secreted (t-PA)

2. t-PA transfers plasminogen to plasmin

3. Plasmin degrades fibrin

Some disorders or drugs that inhibit the coagulation cascade

1. Liver disease

2. Hemophilia

3. Heparin, Xa inhibitors, or thrombin inhibitors

Liver disease decreases synthesis of

Clotting factors II, VII, IX, and X

Hemophilia causes deficiency in

factor VIII or factor IX