THROMBELASTOGRAPHIC EVALUATION OF THE EFFECT OF ADDED PLASMINOGEN TO PLASMA ON FIBRINOLYSIS USING VARIOUS FIBRINOLYTIC ACTIVATORS

When lysis of peripheral thrombi requires infusion of plasminogen activators for longer than 24 hours duration, slow resolution of an obstructive thrombus can result in tissue injury and loss of limb. This study evaluated the effects of increasing the plasminogen concentration on the kinetics of clot lysis induced by plasminogen activators. By adding varying concentrations of any plasminogen activator to plasma, clot lysis can be continuously monitored using thrombelasto-graphy (TEG). Parameters measured during the lysis portion of the pattern are the final amplitude reached (A_f), various time parameters (T, T’ and T_50% ) and the absolute change in amplitude ( Δ A). By adding different amounts of Lys-Plasminogen (LYS-PLG) to plasma, we were able to measure the effect of added LYS-PLG on the lysis pattern with different activators (streptokinase, the plasminogen-streptokinase complex, or the B-chain-streptokinase complex). Statistical analysis of the plots of T_50%(time for 50% lysis, where the TEG amplitude is reduced to naff that of the maximum amplitude) versus LYS-PLG concentration showed that a second order polynomial regression gave R values of better than 0.969. The addition of a small amount of LYS-PLG (20% of the normal plasma concentration) resulted in a two-fold decrease in T_50% with all activators. Maximum clot-lysis enhancement was reached when 60% excess LYS-PLG was added. This amount caused a 2.9 to 3.9 fold decrease in T_50%. Values above 60% did not significantly reduce clot- lysis time any further when very low levels of plasminogen activator were added to plasma. Plots of clot-lysis (T_50%) versus activator or LYS-PLG concentration showed that tne amount of activator could be decreased by at least two-fold if between 40 to 60% extra LYS-PLG is added

Thus, the addition of LYS-PLG to a plasma clot produced a two- to three-fold increase in the rate of clot lysis (2 to 3 fold decrease in T_50%) or permitted a two-fold lesser amount of activator to produce the same lysis pattern.