Platelet and vascular function during coronary thrombolysis with tissue-type plasminogen activator

Platelet activation may limit the response to tissue-type plasminogen activator (t-PA) during coronary thrombolysis in humans. As an index of platelet activation, we assessed thromboxane A'2 biosynthesis during coronary thrombolysis with intravenous t-PA in patients with acute myocardial infarction. Urinary 2,3-dinor-thromboxane B₂, a metabolite of thromboxane A₂, was increased to a peak of 3,327 ± 511 pgm/mg creatinine (n = 12) following administration of intravenous t-PA and remained elevated for 48 hours. This increase was abolished by pretreatment with aspirin 325 mg orally (n = 6), indicating de novo biosynthesis of thromboxane A₂ rather than washout of preformed metabolites during reperfusion. Prostacyclin (PGI₂) biosynthesis, determined by excretion of 2,3-dinor-6-keto-PGF(1α), also increased after t-PA administration. However, this increase was less pronounced in patients who reperfused (28 ± 3.3 ng·hr/mg creatinine) than in patients who failed to reperfuse (118 ± 30 ng·hr/mg creatinine, p < 0.05). These data provide evidence of platelet activation during coronary thrombolysis with t-PA. In patients who reperfuse, the reduction in PGI₂ biosynthesis may be a marker of reperfusion injury to the vasculature and may further amplify platelet activation.