Some Aspects of Fibrin Clot Lysis and Its Inhibition by Human Serum

Abstract

SummaryThe lysis by plasmin of fibrin clots prepared from plasminogen-deficient fibrinogen, and by urokinase of similar clots prepared from plasminogen-rich fibrinogen has been studied. In a simple system containing no plasminogen the clot lysis time is inversely proportional to the concentration of added plasmin, and zero order kinetics are obeyed. The reciprocal of the lysis time is a measure of the fibrinolytic activity in the system, and may be used to study antiplasmins. When serum was included a reduction in reciprocal lysis time resulted, the extent of which varied linearly with the amount of serum added. These relationships persisted whether soluble or insoluble plasmin preparations were used and whether or not chloride ions were present. They indicate that serum antiplasmins behave as irreversible or pseudo-irreversible inhibitors. It was found that sodium chloride exerts a potentiating effect on fibrinolysis by plasmin, but does not influence the extent to which the enzyme is inhibited by serum antiplasmins.When fibrin clots were prepared from plasminogen-rich fibrinogen, and urokinase was included, a direct relationship was found to exist between the concentration of urokinase and the square of the reciprocal clot lysis time. When serum was added, vigorous inhibition of fibrinolysis resulted when sodium chloride was present; no inhibition was observed in its absence. It is proposed that sodium chloride weakens the interaction between plasminogen and fibrin in the clots, and renders the plasmin produced by the action of urokinase more susceptible to inhibition by antiplasmins. Evidence in support of this hypothesis is presented and the kinetics of fibrinolysis by plasmin, and its inhibition, are discussed.