Influence of thrombolytic agents on human platelet function.
In this study, we have evaluated the effects of four different thrombolytic agents, including Streptokinase from Hoechst and from Kabivitrum, Urokinase from Abbott and tissue plasminogen activator (t-PA) from Genetech, on platelet-rich plasma clots and platelet aggregation. At concentrations lower than 50 ugs/ml, t-PA had no inhibitory effect on clot retraction or platelet aggregation induced by weak or potent agonist. At a higher concentration (greater than 100 ugs/ml), t-PA specifically antagonized the action of thrombin on clot formation and platelet aggregation. Streptokinase (Kabivitrum) potentiated the action of weak agonists on platelet aggregation, but the same agent from Hoechst had no negative or positive influence. None of the drugs tested had an adverse effect on platelet function at suggested therapeutic levels. None of the thrombolytic agents were capable of dissociating preformed clots made from platelet-rich plasma. However, all of them caused lysis of whole blood clots. Also, prior incubation of plasma alone or platelet-rich plasma with any of the agents prevented subsequent clot formation. The studies demonstrate that thrombolytic drugs at therapeutic concentrations do not affect platelet function adversely. They have a potent effect on whole blood clots, but not on clots from platelet-rich plasma. Therefore, platelets may play a critical role in determining the degree of reperfusion and the frequency of reocclusion following treatment with thrombolytic agents in vivo.
Rao
G H
GH
Laboratory Medicine and Pathology, University of Minnesota, Minneapolis 55455.
Wilson
R F
RF
White
C W
CW
White
J G
JG
D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects*; D004357:Drug Synergism; D005340:Fibrinogen / Q000032:analysis; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D010958:Plasminogen / Q000032:analysis; D010974:Platelet Aggregation / Q000187:drug effects; D012016:Reference Values
D005343:Fibrinolytic Agents; D005340:Fibrinogen; D010958:Plasminogen