The Influence of Fibrin Crosslinking on the Kinetics of Urokinase‐Induced Clot Lysis*

Abstract

S ummary . The effect of fibrin crosslinking on the lysis of plasma clots was investigated with plasma from a patient congenitally deficient in plasma factor XIII (fibrin stabilizing factor). The thrombin‐activated plasma factor XIII was found to render clots more resistant to fibrinolysis when urokinase (UK) was used to induce plasminogen activation. Incorporation of UK in the clot by addition to plasma immediately before clotting resulted in a log‐log relationship when lysis time was plotted against UK concentration, with greater differences between normal and factor‐XIII deficient clots at lower UK concentrations. Addition of UK to the clot externally, after preincubation of the clot, gave linear plots on rectangular coordinates when either plasma or euglobulin fraction was used; and the difference in lysis time between factor‐XIII deficient and normal clots was nearly constant over the range of UK concentrations tested. When the fluorescent amine, dansylcadaverine, was used to measure factor‐XIII activity quantitatively, plasma clot lysis times were found to be directly proportional to amine‐incorporating activity over a wide range of activities at low UK concentrations. The range of proportionality was reduced when UK concentration was increased. Addition of purified factor XIII to the patient's plasma restored the resistance of these clots to within the normal range.