EFFECT OF FIBRIN STRUCTURE ON PLASMIN-MEDIATED DISSOLUTION OF PLASMA CLOTS

Previous studies in purified systems have demonstrated that fibrin str ucture influences the rate of conversion of plasminogen to plasmin by t-PA as well as the rate of plasmin-mediated clot digestion. The prese nt study extended these observations to a plasma system in which fibri n structure was altered by varying the thrombin concentration, varying the plasma ionic strength, or by adding dextran 40. The effect of fib rin structure on the rate of fibrinolysis was assessed by adding plasm inogen activators (t-PA or urokinase (UK)) either before or after clot formation, Gel formation and dissolution were monitored optically (tu rbidity) and isotopically (I-125-fibrinogen). Clots formed under condi tions of high ionic strength and/or high thrombin concentration were c omposed of thin fibrin fibres that dissolved slowly. Clots formed at l ower ionic strengths, at lower thrombin concentrations or in the prese nce of dextran were composed of thicker fibres and dissolved more rapi dly. The difference in fibrinolytic rate between thin and thick fibres was noted when t-PA or UK was added before or after clot formation. T hese data indicate that even in a plasma milieu fibre diameter is a fa ctor in determining fibrinolytic rate induced by either UK or t-PA. Th e method by which fibre diameter is altered does not influence the con clusion that fibrinolytic rate is increased with increasing diameter.