Importance of reperfusion on thromboxane A2 metabolite excretion after thrombolysis

Fibrinolytic therapy is a major advance in the treatment of coronary artery disease. A marked elevation in plasma and urinary metabolites of thromboxane A₂ (TXA₂) after administration of thrombolytic therapy has been observed and has been related to a direct effect of thrombolytic drugs on platelets. To test this hypothesis we evaluated the 11-dehydrothromboxane B₂ (11-d-TXB₂) level, as an index of platelet activation, in 20 healthy subjects and in 30 patients with acute myocardial infarction (AMI). Patients with infarction received streptokinase (n = 8), recombinant tissue-type plasminogen activator (rt-PA) (n = 8), or thrombolytic therapy preceded by acetylsalicylic acid (n = 7) or were treated without thrombolytic therapy (n = 7). The urinary 11-d-TXB₂ level in healthy control subjects was 327 ± 126 pg/mg creatinine. A significant increase was observed in patients with AMI with no difference between those who received no thrombolytic therapy (673 ± 283 pg/mg creatinine in the first 12 hours) and those who received streptokinase (833 ± 613 pg/mg creatinine) or rt-PA (836 ± 653 pg/mg creatinine). Patients pretreated with acetylsalicylic acid had urinary 11-d-TXB₂ values ranging between 361 and 155 pg/mg creatinine. A significant difference in 11-d-TXB₂ values was observed only when patients who were reperfused were separated from those who remained occluded according to angiographic criteria (1085 ± 498 vs 391 ± 227 pg/mg creatinine in the first 12 hours, p <0.001). We conclude that reperfusion and not thrombolytic agents per se appears to be the factor that induces platelet activation and consequently facilitates reocclusion.