Effect of fibrin structure on plasmin-mediated dissolution of plasma clots

Previous studies in purified systems have demonstrated that fibrin structure influences the rate of conversion of plasminogen to plasmin by t-PA as well as the rate of plasmin-mediated clot digestion. The present study extended these observations to a plasma system in which fibrin structure was altered by varying the thrombin concentration, varying the plasma ionic strength, or by adding dextran 40. The effect of fibrin structure on the rate of fibrinolysis was assessed by adding plasminogen activators (t-PA or urokinase (UK)) either before or after clot formation. Gel formation and dissolution were monitored optically (turbidity) and isotopically (125I-fibrinogen). Clots formed under conditions of high ionic strength and/or high thrombin concentration were composed of thin fibrin fibres that dissolved slowly. Clots formed at lower ionic strengths, at lower thrombin concentrations or in the presence of dextran were composed of thicker fibres and dissolved more rapidly. The difference in fibrinolytic rate between thin and thick fibres was noted when t-PA or UK was added before or after clot formation. These data indicate that even in a plasma milieu fibre diameter is a factor in determining fibrinolytic rate induced by either UK or t-PA. The method by which fibre diameter is altered does not influence the conclusion that fibrinolytic rate is increased with increasing diameter.