Antiplatelet effects of urokinase and their clinical implications.
BACKGROUND
Many angiographers believe that intracoronary urokinase is an unusually effective plasminogen activator in the setting of resistant coronary thrombosis. To determine whether platelet-mediated effects might be associated with this property, we characterized the effects of urokinase on platelets harvested from normal human subjects.


METHODS
Aggregation studies performed in whole blood and plasma, surface labelling of membrane proteins, and sodium dodecylsulfate polyacrylamide gel electrophoresis were used to define the functional and structural properties of platelets exposed to urokinase bound to Sepharose.


RESULTS
Results obtained indicate that urokinase can inhibit platelet aggregation through mechanisms independent of the generation of plasmin. These mechanisms are associated with the elaboration from fibrinogen of a fragment responsible for the decreased platelet aggregation. The observed effect and mechanism appear to be independent of a parallel direct inhibitory effect of platelet aggregation by urokinase that occurs after more prolonged incubations and which is mediated by modification of platelet surface proteins per se.


CONCLUSIONS
The observations obtained indicate that the favorable effect of intracoronary urokinase on refractory coronary thrombi is probably ascribable not only to activation of the fibrinolytic system in blood, but also to the inhibitory effects of urokinase on platelets independent of plasminogen activation.
Torr-Brown
S R
SR
Cardiovascular Diseases Research, Searle, Monearto Company-T1G, St Louis, Missouri, USA.
Sobel
B E
BE
D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D003328:Coronary Thrombosis / Q000097:blood; D004591:Electrophoresis, Polyacrylamide Gel; D005340:Fibrinogen / Q000502:physiology; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D016896:Treatment Outcome; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology*
D010975:Platelet Aggregation Inhibitors; D005340:Fibrinogen; D014568:Urokinase-Type Plasminogen Activator