Both platelet activation and coagulation are self-perpetuating processes that could potentially continue until an injured vessel is completely occluded. Coagulation inhibitors are present to prevent excessive clotting and to dissolve the clot as tissue repair occurs.

Maintaining adequate blood flow aids in diluting and removing clotting factors and in dispersing aggregated platelets. Partially activated coagulation factors are carried to the liver and the reticuloendothelial system, where they are degraded.¹² Two specific anticoagulation mechanisms also help to prevent excessive clotting: (1) the fibrinolytic system and (2) the antithrombin system.

In the fibrinolytic system, fibrin strands are broken down into progressively smaller fragments by a proteolytic enzyme, plasmin. Although plasmin does not circulate in active form, its precursor, plasminogen, does. Plasminogen is converted into plasmin by several plasminogen activators, among them factor XII, urokinase, and streptokinase. Once activated, plasmin digests fibrin, splits fibrinogen into peptide fragments (fibrin split products [FSP]), and degrades factors V, VIII, and XIII. In addition, the FSP interfere with platelet aggregation, reduce prothrombin, and interfere with conversion of soluble fibrin to insoluble fibrin. Plasma also contains agents that neutralize plasmin itself. Among these are antiplasmin and ₁-antitrypsin. A balance between proplasmin and antiplasmin substances aids in maintaining normal coagulation.¹³

The antithrombin system protects the body from excessive clotting by neutralizing the clotting capability of thrombin.¹⁴ Although various substances inhibit thrombin, the most important one is antithrombin III (AT III), a substance that abolishes the activity of thrombin (activated factor II); activated factors X, XI, and XII; and plasmin. Another name for AT III is heparin cofactor. Heparin augments by approximately 100 times the affinity of AT III and the activated clotting factors on which it acts. A deficiency of AT III, which can be congenital or acquired, makes an individual prone to excessive clotting. Platelet factor 4, which is released when platelets are broken down, inhibits AT III activity.¹⁵