Effects of streptokinase, urokinase, and recombinant tissue plasminogen activator on platelet aggregability and stability of platelet aggregates.
OBJECTIVE
The aim of the study was to evaluate the effects of streptokinase, urokinase and recombinant tissue plasminogen activator (TPA) on platelet aggregability and metabolism and the stability of preformed platelet aggregates.


METHODS
The experiments (n = 15 for each condition) were performed on citrated plasma or on platelet suspensions in phosphate buffered saline, both with a standardised platelet count of 250 x 10(9).litre-1.


METHODS
were healthy volunteers.


RESULTS
With both ADP (1 mumol.litre-1) and collagen (1 mg.litre-1) as aggregating agents, streptokinase at greater than or equal to 10(5) units.litre-1 led to reduction in the rate of platelet aggregation. With collagen and in most instances with ADP, this was associated with a decreased extent of aggregation, though in five out of 30 cases with ADP as aggregating agent, a conversion from reversible to irreversible aggregation occurred with streptokinase. Urokinase inhibited platelet aggregation at greater than or equal to 3 x 10(5) units.litre-1 with both aggregating agents. TPA inhibited aggregation at greater than or equal to 1 mg.litre-1 with ADP and at greater than or equal to 3.3 mg.litre-1 with collagen as aggregating agent. The inhibitory effect was still present when the platelets were suspended in saline. Platelet synthesis of thromboxane on stimulation with collagen, and of c-AMP on stimulation with prostaglandin E1, was markedly reduced by either agent. The stability of platelet aggregates, as assessed photometrically during a 90 min exposure to stirring stress, increased when streptokinase or urokinase was added to platelet rich plasma, but remained uninfluenced with TPA.


CONCLUSIONS
Urokinase and TPA inhibited platelet aggregability uniformly and in a dose dependent manner. Streptokinase inhibited platelet aggregation in most instances, but led to a stimulation of aggregation in a minority of cases. These effects of the thrombolytic agents on platelets might have an influence on the occurrence of bleeding and of reocclusion after thrombolytic therapy.
Terres
W
W
Department of Cardiology, Eppendorf University Hospital, Hamburg, West Germany.
Umnus
S
S
Mathey
D G
DG
Bleifeld
W
W
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors; D000328:Adult; D001792:Blood Platelets / Q000378:metabolism; D003094:Collagen / Q000037:antagonists & inhibitors; D000242:Cyclic AMP / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013300:Streptokinase / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology*
D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D003094:Collagen; D000242:Cyclic AMP; D013300:Streptokinase; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator