Different regulatory controls that prevent clotting of blood in our body.

There are atleast three different mechanisms that oppose clot formation:

• The first anticoagulant mechanism acts during the initiation phase of clotting and utilizes the plasma protein called tissue factor pathway inhibitor (TFPI), which is secreted mainly by endothelial cells. This substance binds to tissue factor- VIIa complexes and inhibits the ability of these complexes to generate factor Xa. This anticoagulant mechanism is the reason that the extrinsic pathway by itself can generate only small amounts of thrombin.
• The second mechanism is triggered by thrombin. Thrombin can bind to an endothelial cell receptor known as thrombomodulin. This binding eliminates all of thrombin's clot producing effects and causes the bound thrombin to bind a particular protein, protein C. The binding to thrombin activates protein C, which in combination with yet another plasma protein, then inactivates factors VIIIa and Va.
• The third naturally occurring anticoagulant mechanism is a plasma protein called antithrombin III, which inactivates thrombin and several other clotting factors. Antithrombin III is activated when it binds to heparin. Antithrombin prevents the spread of a clot by rapidly inactivating clotting factors that are carried away from the immediate site of the clot by the flowing blood.