Probably the most important factors for preventing clotting in the normal vascular system are the following: a protein bound with the endothelial membrane, thrombomodulin, which binds thrombin. Not only does the binding of thrombin with thrombomodulin slow the clotting process by removing thrombin, but the thrombomodulin-thrombin complex also activates a plasma protein, protein C, that acts as an anticoagulant by inactivating activated factors V and VIII. When the endothelial wall is damaged, its smoothness and glycocalyx-thrombomodulin layer are lost, which activates both factor XII and the platelets, thus setting off the intrinsic pathway of clotting. If factor XII and platelets come into contact with the subendothelial collagen, the activation is even more powerful. Intact endothelial cells also produce other substances such a prostacyclin and nitric oxide (NO) that inhibit platelet aggregation and initiation of blood clotting.
