Effect of polyamines on in vitro platelet aggregation and in vivo thrombus formation

Introduction: Polyamines are polycations present in all living organisms and have been shown to play an important role in various physiological functions. Previous studies have shown that various amines including polyamines inhibited platelet activation, but there were no definitive studies testing their efficacy in an in vivo thrombosis model. We carried out detailed in vitro platelet aggregation studies using various concentrations of polyamines as well as agonists. Methods: Platelet aggregation was measured by a turbidimetric method. Electric current induced in vivo thrombosis model is used for assessing antithrombotic effect. Incidence of bleeding was evaluated by template bleeding and incisional bleeding. Results: Polyamines inhibited agonist-induced platelet aggregation in a dose-dependent manner. The inhibitory effect of polyamines is inversely proportional to the concentration of the agonist used. Among the polyamines, spermine is the potent inhibitor of platelet aggregation. A partially occlusive thrombus was generated by application of electric current in canine coronary artery. In control animals, the artery was completely occluded in 70±11 min after the current was discontinued. Blood flow remained patent for >240 min when 2 mg/kg spermine was given immediately after stopping the current. The antithrombotic effect of spermine was not associated with increased bleeding tendency. Conclusion: These results indicate that apart from inhibiting in vitro platelet aggregation polyamines can also inhibit in vivo thrombus formation. To our knowledge, this is the first study demonstrating this phenomenon.