Activation

Factor XIIa, activated Hageman factor, triggers the plasmin fibrinolytic system. As XIIa also triggers the intrinsic pathway of coagulation, this is one means of negative feedback to prevent coagulation progressing indefinitely.

XIIa catalyses the conversion of precursor proteins, circulating in the plasma, into plasminogen activators. Some plasminogen activator is derived directly from local tissue e.g. endothelial cells.

Plasminogen activators are serine enzymes which cleave plasminogen. Plasminogen is a high molecular weight serum beta-globulin which localises to fibrin within a thrombus. Plasminogen is broken down into plasmin and other peptides.

Certain bacteria may produce plasmin directly by secretion of natural streptokinase.

Plasmin is a trypsin-like enzyme which breaks down:

• polymerized fibrin into fibrin degradation products - FDP's - which include D-dimers
• fibrinogen
• factor II
• factor V
• factor VIII
• complement into active components

Many feedback mechanisms exist e.g.:

• local plasmin inhibitors, antiplasmins, which prevent unlimited fibrin degradation
• fibrin fragments, which inhibit the local formation of fibrin by providing binding sites for the plasminogen activator, tPA