There are three main Anti-Clotting Mechanisms.
1. Non-Specific Mechanisms
- Endothelial Factors
a) Smoothness of Endothelial Lining prevents Platelet, adhesion and Extension of clot into the Blood Vessels. b) Negatively Charged Particles present over the lining of the endothelial repels the clotting factors ( Protein Anions ) i.e Prevents Clotting
- Velocity of Circulation - If Decreased - Leads to clotting
2. Anti-Coagulant System
- Has Enzymetic Pathways (natural anti Coagulants - Antithrombin III , Prtein C , Heparin) - Reduce thrombin Production
- Hence Reduces Fibrin formation
3. Fibrinolytic System
- Dissolves already formed Clots
- Plasmin is the Major Enzyme
- Hence Reduces Blood Clotting
- Anti-Thrombin III is a circulating Protease that binds to Serine Proteases in the coagulation system - Heparin ( a naturally occuring anticoagulant ) increases the effectiveness of antithrombin III by binding to it. - Inhibits the active forms of factors IX , X , XI , XII
- Endothelium of the blood vessels produce Thrombomodulin
- Thrombomodulin is a thrombin binding Protein
- Thrombin is a pro-coagulant that activates factor V & factor VIII - So when thrombomodulin binds to thrombin it forms a Thrombomodulin-Thrombin Complex that activates Protein C - Activated Protein C (APC) along with its Co-factor Protein S ------> Inactivates Factors V and VIII. - APC ( Activated Protein C ) also activates Tissue Plasminogen activator by inactivating an Inhibitor of Tissue Plasminogen activator (t-PA) hence increasing the amount of Plasmin (Fibrinolysin ) Produced.
- Plasmin ( Fibrinolysin) is the active component of the Plasminogen System or otherwise known as the Fibrinolytic System - This Enzyme Lyses Fibrin and Fibrinogen
- Plasmin as mentioned above is formed from its Inactive Precursor Plasminogen by the action of thrombin , (t-PA) tissue type- Plasminogen...
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