Discuss briefly the processes which prevent blood coagulation within the normal circulatory system.

Outline:

·        Endothelial surface factors

·        Intravascular anticoagulants

·        Lysis of blood clots

Essay:

            When a small blood vessel is damaged, the injury initiates a series of events that leads to the formation of a clot. The in vivo action of the clotting mechanism is balanced by limiting reactions that normally prevent clots from developing in uninjured vessels and maintain the blood in a fluid state. A balance between many complex, interrelated systems must be maintained to prevent hemorrhage while preventing intravascular coagulation. The factors involved include the endothelium of the blood vessels and the collagen underlying it, vascular tone, the platelets, the clotting and fibrinolytic systems and the flow characteristics of blood within the blood vessels.

The endothelial surface of blood capillaries have certain characteristics that prevent blood clotting in the normal vascular system. These are: the smoothness of the endothelium, which prevents contact activation of the intrinsic clotting system and a layer of glycocalyx, a mucopolysaccharide adsorbed to the inner surface of the endothelium, which repels the clotting factors and platelets, thereby preventing activation of clotting.

Thrombomodulin, a protein bound with the endothelial membrane, binds thrombin. The binding of thrombomodulin with thrombin not only slows 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.

            The tendency of blood to clot is balanced in vivo by limiting reactions that tend to prevent clotting inside the blood vessels and to break down any clots that do form. These reactions include removal of some activated clotting factors from the circulation by the liver and reduction in the supply of clotting factors to the degree that they are used up during clotting. Another reaction is the interaction between the platelet-aggregating effect of thromboxane A₂, and the antiaggregating effect of prostacyclin, which causes clots to form at the site when a blood vessel is injured but keeps the vessel lumen free of clot.

            The important intravascular anticoagulants that remove thrombin from blood are the fibrin fibers, antithrombin III, heparin and a-macroglobulin. When a clot is forming, about 85 to 90 per cent of the thrombin formed from the prothrombin becomes adsorbed to the fibrin fibers as they develop. This helps prevent the spread of thrombin into the remaining blood and, therefore, prevents excessive spread of the clot. The thrombin that does not adsorb to the fibrin fibers soon combines with antithrombin III, which blocks the effect of the thrombin on the fibrinogen and then inactivates the bound thrombin during the next 12 to 20 minutes. Heparin is a highly negative charged conjugated polysaccharide abundant in the basophilic mast cells and when it combines with antithrombin III, this increases a hundredfold the effectiveness of antithrombin III in removing thrombin. The complex of heparin and antithrombin III removes several other activated coagulation factors such as Factors XII, XI, IX, and X.  a-macroglobulin is a large globulin molecule having a molecular weight of 360,000 and it function is mainly to act as a binding agent for several of the coagulation factors and prevent their proteolytic actions until they can be destroyed in various ways.

            The plasma protein plasminogen becomes plasmin when activated. Plasmin is a proteolytic enzyme that digests fibrin fibers. When a clot is formed, a large amount of plasminogen is trapped in the clot along with other plasma proteins. The injured tissues and vascular endothelium very slowly release a powerful activator called tissue plasminogen activator (t-PA) that eventually converts plasminogen to plasmin and removes the clot.