Abstract
The physiological and pathophysiological state of tissues determines the exudation
of plasma proteins, hemostasis, and fibrinolysis, i.e., inflammation, injury, and
malignancy. The physiological controls of extravascular fibrinolysis ultimately rest
on a balance between generation of the fibrinolytic enzyme(s), i.e., plasmin, elastase,
cathepsins, etc., and inhibitors of the fibrinolytic enzyme(s), i.e., plasminogen
activator inhibitors, α2-plasmin inhibitor, α2-protease inhibitors, etc. Moreover, it is the structural modification of fibrin that
determines its stability toward proteolytic enzymes and physical duress. The structural
modification of fibrin involves factor XIIIamediated cross-linking of interfibrin
chains and α2-plasmin inhibitor to fibrin. In turn, there are a number of agents that influence
factor XIIIa catalytic activity (e.g., sulfhydryl agents, albumin, erythrocytes).
The two key proenzymes, factor XIII and plasminogen, are tightly bound with the circulating
fibrinogen molecules. Such high selective affinity for fibrin(ogen) provides the reaction
specificity in a complex tissue fluid milieu and governs the kinetics of fibrinolysis.
Any agents that interfere with such binding reactions, e.g., autoantibodies, may also
affect the fibrinolytic reactions. Understanding these unique biochemical controls
of factors involved in fibrinolysis may provide an insight into the complex regulatory
process of extravascular fibrinolysis.
Keywords:
Fibrinolysis - factor XIII - plasminogen - extravascular fibrinolysis - fibrinolytic
inhibitors
