Interactions between thrombolytic agents and platelets: effects of plasmin on platelet glycoproteins Ib and IIb/IIIa.
The mechanisms by which thrombolytic agents affect platelet function are not yet elucidated. The aim of the present study was to investigate the effects of plasmin, generated by thrombolytic agents in plasma, on platelet glycoproteins (GP) Ib and IIb/IIIa. Platelet-rich plasma was incubated with pharmacological amounts of streptokinase, anistreplase and tissue-type plasminogen activator and the platelet surface GP's were investigated with a panel of monoclonal antibodies using flow cytometry. As assessed from the mean fluorescence intensity of incubated and control platelets, no significant changes in the binding of antibodies to GP Ib and GP IIb/IIIa were found. The functional integrity of these glycoproteins was severely impaired by treatment with the thrombolytic agents, as shown by significant inhibition of ADP- and ristocetin-induced platelet aggregation. Experiments with purified plasmin and washed platelets indicated significant degradation of GP IIb/IIIa and upregulation of GP Ib, which is in agreement with previous findings. In addition, platelet activation by plasmin was shown using two monoclonal antibodies to activation-specific antigens. We conclude that degradation of platelet GP's by plasmin offers no likely explanation for the defect in platelet function, which is induced by thrombolytic agents in platelet-rich plasma.
Hoffmann
J J
JJ
Department of Clinical Laboratories, Catharina Hospital, Eindhoven, The Netherlands.
Janssen
W C
WC
D016255:Anistreplase / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism / Q000494:pharmacology*; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D013300:Streptokinase / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D005343:Fibrinolytic Agents; D010980:Platelet Membrane Glycoproteins; D016255:Anistreplase; D013300:Streptokinase; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin