Marked platelet activation in vivo after intravenous streptokinase in patients with acute myocardial infarction.
We assessed thromboxane biosynthesis as an index of platelet activation in 6 patients with acute myocardial infarction receiving intravenous streptokinase. Urinary 2,3-dinor-thromboxane B2 and plasma 11-dehydro-thromboxane B2, major enzymatic metabolites of thromboxane A2, were markedly increased after intravenous streptokinase (11,063 +/- 2758 pg/mg creatinine and 33 +/- 10 pg/ml, respectively) compared with levels in patients not receiving thrombolytic therapy (502 +/- 89 pg/mg creatinine and 3 +/- 0.7 pg/ml). Prostacyclin biosynthesis also increased markedly after streptokinase coincident with the increase in thromboxane A2 formation. Administration of aspirin between the time of onset of coronary thrombosis and reperfusion both in man and in a canine preparation demonstrated that this reflected thromboxane biosynthesis de novo and not metabolism of preformed inactive thromboxane B2 washed out from the coronary circulation. Since the platelet is the major source of thromboxane A2, these findings suggest that there is marked platelet activation after coronary thrombolysis with streptokinase. Studies in vitro demonstrated that streptokinase enhanced platelet activation in a dose-dependent manner, resulting in the secondary release of thromboxane A2. The increase in platelet activation and thromboxane A2 biosynthesis may limit the therapeutic effect of intravenous streptokinase in acute myocardial infarction.
Fitzgerald
D J
DJ
Divisions of Clinical Pharmacology, Vanderbilt University, Nashville, TN 37232.
Catella
F
F
Roy
L
L
FitzGerald
G A
GA
D001241:Aspirin / Q000627:therapeutic use; D001792:Blood Platelets / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy*; D010974:Platelet Aggregation / Q000187:drug effects*; D013300:Streptokinase / Q000627:therapeutic use*; D013928:Thromboxane A2 / Q000096:biosynthesis*
D013928:Thromboxane A2; D011464:Epoprostenol; D013300:Streptokinase; D001241:Aspirin