THE INFLUENCE OF RECOMBINANT TISSUE-TYPE PLASMINOGEN-ACTIVATOR AND PLASMIN ON PLATELET-AGGREGATION - A QUENCHED-FLOW STUDY

Our study was designed to investigate the influence of human recombina nt tissue-type plasminogen activator (rt-PA) and plasmin on platelet a ggregation kinetics. Quenched-flow aggregometry coupled to single-part icle counting was used with washed human platelets, which were pre-inc ubated for 5 min at 37-degrees-C with physiological and pharmacologica l doses of rt-PA (0. 14-70 nM). Aggregation induced by adenosine dipho sphate (ADP) under physiological flow conditions was followed over 15 s. Depending on donor and reaction time, potentiation (one third of su bjects), inhibition (one third of subjects), and no effect on ADP-indu ced (10 muM) aggregation were noted within the first 5 s, while from 5 .0 to 15.0 s no influence was seen. On the other hand, using 2.5 muM A DP, aggregation was inhibited in all sensitive donors. Pre-incubation of platelets with plasmin (10 nM, 100 nM) for 5 min at 37-degrees-C el icited a biphasic response to ADP. Depending on concentration and reac tion time, plasmin potentiated or inhibited ADP-induced (10 muM) aggre gation. Our data reveal that some individuals are susceptible for pote ntiation of platelet aggregation by both rt-PA and plasmin. Such susce ptibility may contribute to the phenomenon of early reocclusion observ ed during thrombolytic therapy with rt-PA.