calix[4]arene C-145 Effects on Plasma Haemostasis

Background: Calix[4]arene-methylene-bis-phosphonic acid C-192 and its sodium salt C-145 were shown to be efficient inhibitors of fibrin polymerization in vitro. In presented work we analyze the effects of Nalix[4]arene C-145 on haemostasis in vivo. Methods: Parameters of coagulation system of rabbits intravenously injected with C-145 were monitored. We measured thrombin time (TT), ecamulin time (ET) and activated partial thromboplastin time (APTT), determined the levels of fibrinogen, prothrombin, protein C, PAI-1, monitored overall haemostatic potential before and after the injection. Results: C-145 was administrated intravenously in the dose of 7.5 mg/kg of rabbit weight. 4 hours after the injection the thrombin time and activated partial thromboplastin time of rabbit’s blood plasma were prolonged 2 and 1,5 times respectively. Such prolongation was observed after 24 hours as well. However, the total fibrinogen and prothrombin levels did not change. Parameters of fibrinolytic system (PAI-1, clot lysis half-time) and anticoagulant system (protein C) remained unchanged. Conclusions: Therefore we assumed that calix[4]arene C-145’s effects on haemostasis consisted in selective inhibition of fibrin polymerization and formation of three-dimensional fibrin network.