Synergy of in vitro thrombolytic action of combinations of recombinant staphylokinase and single-chain urokinase-type plasminogen activator

Kinetics of lysis of human plasma clots immersed in plasma were studied in vitro at 37degreesC under the influence of recombinant staphylokinase, single-chain urokinase-type plasminogen activator (scu-PA), and their simultaneous and consecutive combinations. Staphylokinase and scu-PA caused concentration- and time-dependent lysis of the clots; 32 nM staphylokinase and 75 nM scu-PA separately caused 50516 lysis in 4 h. At these equally effective concentrations staphylokinase in 4 h induced a significantly lesser exhaustion of the plasma plasminogen, alpha(2)-antiplasmin, and fibrinogen than scu-PA. Combinations of staphylokinase (<30 nM) and scu-PA (<75 nM) rendered synergic thrombolytic action on the clots. The synergy of thrombolytic action was more pronounced on the simultaneous addition of the two agents than on their consecutive addition, scu-PA 30 min after staphylokinase. In 4 h after the addition, staphylokinase (25 nM) or scu-PA (15 nM) induced 24% and 2516 lysis, respectively, whereas the simultaneous and consecutive combination of the same concentrations of these agents induced 59516 and 50516 lysis, respectively. The simultaneous combination of 15 nM staphylokinase and 15 nM scu-PA resulted in maximal 3.8-fold increase in the thrombolytic effect as compared to the expected total effect of the individual agents. Synergic combinations of the two agents caused lesser exhaustion of plasma plasminogen, a(2)-antiplasmin, and fibrinogen as compared with the expected total effect of these agents used separately. Thus, simultaneous and consecutive combinations of staphylokinase and scu-PA in a relatively narrow range of their concentrations possessed synergistic fibrin-selective thrombolytic action on the plasma clot in vitro.