STREPTOKINASE AND RT-PA ACTIVATE PLATELETS BY A DIFFERENT WAY - IMPLICATIONS ON THE RETHROMBOSIS RATE AFTER THEIR ADMINISTRATION IN MYOCARDIAL-INFARCTION

The natural history of acute myocardial infarction has been dramatical ly changed by the advent of thrombolytic treatment, with a 30% mortali ty reduction, a better recovery of ventricular function, and a better quality of life. This treatment notwithstanding, failure or delay in a chieving reperfusion, along with reocclusion and bleeding, still worry clinicians and challenge researchers to improve thrombolytic regimens and concomitant antithrombotic treatments. Platelet activation, at le ast in part because of thrombolytic treatment itself, plays a pivotal role in the pathogenesis of resistance to lysis and rethrombosis. The aim of this study was to compare in vitro the effects on platelets of therapeutic concentrations of streptokinase (SK) and recombinant type plasminogen activator (rt-PA). The effects of plasmin and thrombin wer e also studied as a reference. Fluorescence flow cytometry was used to evaluate (1) fibrinogen binding and (2) surface expression of GMP-140 , a sensitive marker of platelet release reaction. Platelet function w as further studied by measuring the release of carbon 14-labeled serot onin, beta-thromboglobulin, plasminogen activator inhibitor-1 (PAI-1) and the generation of thromboxane (TxB(2)). We found that 10 nmol/L SK and 14 nmol/L rt-PA increased fibrinogen binding to platelets by 12 /- 2 and 10 +/- 4 times, respectively (p = not significant). At the sa me concentrations, SK, but not rt-PA, also induced the platelet releas e reaction: surface expression of GMP-140 was increased by 6 +/- 1.5 t imes by SK and 1.3 +/- 0.2 times by rt-PA (p < 0.05). TxB(2) productio n was not modified by plasmin and plasminogen activators. Our data sho wed that plasmin and SK stimulate fibrinogen receptor expression and p latelet degranulation. Conversely, rt-PA, at concentrations up to 14 n mol/L, only promotes fibrinogen binding. These results, coupled with t he less-pronounced lytic state induced by rt-PA, could explain the hig her incidence of reocclusion accompanying rt-PA therapy in comparison with SK that occurs unless effective ''adjunctive'' antithrombotic tre atment is used. Neither of the thrombolytic agents activates the arach idonate pathway. Thus aspirin is probably not an ideal agent to be use d in conjunction with thrombolytic agents. We speculate that newer app roaches, particularly RGD peptides and antibodies against GP IIb/IIIa, might produce better results.