THROMBOSIS RESEARCH 67; 711-719,1992 0049-3848192 $5.00 + .OOPrinted in the USA. Copyright (c) 1992 Pergamon Press Ltd. All rights reserved.

INTERACTIONS BETWEEN THROMBOLYTIC AGENTS AND PLATELETS: EFFECTS OF PLASMIN ON PLATELET GLYCOPROTEINS lb AND Ilblllla

J.J.M.L. Department

HOFFMANN

and W.C.M.

of Clinical Laboratories, Haematology P.O. Box 1350, 5602 ZA Eindhoven,

JANSSEN Division, Catharina the Netherlands

Hospital,

(Fieceived 6.4.1992; accepted in revised form 22.7.1992 by Editor W. Nieuwenhuizen)

ABSTRACT The mechanisms by which thrombolvtic agents affect platelet function are not vet elucidated. The aim of the present studv was to investigate the effects of plasmin, generated by thrombolytic agents in plasma, on platelet glycoproteins (GP) lb and Ilblllla. 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 ffow cytometry. As assessed from the mean fluorescente intensity of incubated and control platelets, no significant changes in the binding of antibodies to GP lb and GP Ilb/llla were found. The functional integritv of these glycoproteins was severelv 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 Ilblllla and upregulation of GP lb, which is in agreement with previous findings. In addition, platelet activation by plasmin was shown using two monoclonal antibodies activation-specific antigens. We conclude that degradation of platelet GP’s plasmin offers no likely explanation for the defect in platelet function, which induced

bv thrombolvtic

agents

in platelet-rich

to by is

plasma.

INTRODUCTION Plasminogen activators used clinically as thrombolytic drugs will convert plasminogen to plasmin and the dosages used generate so much plasmin that the inhibiting potential of az-antiplas,min and other protease inhibitors is surpassed. This results in the so-called systemic lytic state and platelets are known to be affected by the systemic lytic state. Plasmin can inhibit platelet aggregation in platelet rich plasma (PRP) in vifro (1,2) and recently we have shown that plasimin generated after the administration of anistreplase to patients caused a marked decrease in ex vivo platelet aggregation, which lasted for about 12 hours (3). The mechanism by which platelet function is inhibited is not precisely known. Three possible explanations can be propo$ed: extensive depletion of plasma fibrinogen, competition between fibrin(ogen) degradation prodwcts and intact fibrinogen for binding sites on the platelets and finally, degradation of platelet

I

IIIa.

The mechanisms by which thrombolytic agents affect platelet function are not yet elucidated. The aim of the present study was to investigate the effec...
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