Differential effects of low-dose tissue plasminogen activator and streptokinase on platelet aggregation.
Despite increasing success with low-dose intra-arterial thrombolysis, early rethrombosis still occurs. Platelet aggregation is thought to play a major part in this process. We have therefore investigated the effects of recombinant tissue plasminogen activator (rt-PA) and streptokinase on platelet function at doses currently used for peripheral arterial thrombolysis. Platelet-rich plasma was stirred at 37 degrees C, with either streptokinase (100, 300 or 1000 units ml-1) or rt-PA (10 (T10), 30 (T30) and 100 (T100) mg l-1), with immediate addition of an agonist for platelet aggregation (thrombin, collagen, adenosine diphosphate (ADP) or adrenaline) at a predetermined threshold dose. Significant inhibition of collagen-induced and adrenaline-induced platelet aggregation was produced with rt-PA at all doses used (P less than 0.05). With adrenaline as the agonist, T100 produced disaggregation to a mean (s.d.) level of 26 per cent. Thrombin-stimulated platelet aggregation was significantly reduced by T100 (P less than 0.001) and T30 (P less than 0.01) only, disaggregation being dose-dependent and complete with T100. Using ADP as the agonist, T100 produced a significant reduction in maximum platelet aggregation (P less than 0.01), and disaggregation was achieved to a mean (s.d.) level of 48(13) per cent. Streptokinase did not produce any significant changes in any parameter of aggregation.
Berridge
D C
DC
Department of Vascular Surgery, University Hospital, Nottingham, UK.
Burgess-Wilson
M E
ME
Westby
J C
JC
Hopkinson
B R
BR
Makin
G S
GS
D000244:Adenosine Diphosphate / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013300:Streptokinase / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D003094:Collagen; D013300:Streptokinase; D013917:Thrombin; D010959:Tissue Plasminogen Activator; D004837:Epinephrine