A paradox of thrombogenesis by streptokinase and its prevention by iloprost and camonagrel.
Here we report that streptokinase is responsible for forming thrombi both in vitro on blood-superfused endothelial cells of rabbit aorta and in vivo on blood-superfused collagen strips in extracorporal circulation of anesthetized cats. This short-lasting paradoxical thrombogenic phase is followed by the expected long-lasting thrombolysis. The biphasic action of streptokinase occurred in vitro at concentrations of 100-2000 U/ml and in vivo at doses of 1000-3000 U/kg i.v. Both phases are mediated by endogenous plasmin as evidenced by deleting the streptokinase-induced thrombogenesis and thrombolysis following pretreatment with epsilon-aminocaproic acid or aprotinin. On the other hand, selective block of the paradoxical thrombogenesis was achieved after pretreatment with camonagrel, a thromboxane synthase inhibitor which raises plasma levels of endogenous prostacyclin, or with iloprost, a stable analog of prostacyclin. It is suggested that endogenous or exogenous prostacyclin inhibits activation of platelets by plasmin, and hence the thrombogenesis by streptokinase is abolished, while the beneficial thrombolytic action of streptokinase is augmented.
Korbut
R
R
Department of Pharmacology, Medical College of Jagiellonian University, Cracow, Poland.
Gryglewski
R J
RJ
D000818:Animals; D002415:Cats; D004730:Endothelium, Vascular / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000633:toxicity*; D016285:Iloprost / Q000627:therapeutic use*; D007189:Indans; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011817:Rabbits; D013300:Streptokinase / Q000633:toxicity*; D015912:Thrombolytic Therapy; D013927:Thrombosis / Q000139:chemically induced* / Q000517:prevention & control*
D005343:Fibrinolytic Agents; D007189:Indans; D010975:Platelet Aggregation Inhibitors; D013300:Streptokinase; D016285:Iloprost; C103583:camonagrel