The Corrective Effect of Chitosan on Hemostasis Parameters under Hypocoagulation Conditions Caused by the Antiplatelet Agent Clopidogrel

The effect of chitosan in vitro on the blood plasma of healthy rats and rats with acquired bleeding caused by the use of the antiplatelet agent clopidogrel, which irreversibly inhibits P2Y12 platelet receptors, was studied. It has been shown that the degree of procoagulant activity of chitosan does not depend on the incubation time (5 and 30 min at 37°C) when it is added to the blood plasma pool from healthy animals. However, there was a significant decrease (by 27%) in the fibrin-depolymerization activity of blood plasma, which is even more suppressed (by 42%) with an increase in incubation time. When chitosan was added to hypocoagulation plasma obtained after oral administration of the antiplatelet agent clopidogrel to rats (once, orally at a dose of 5 mg/kg) and incubation for 5 min, a pronounced activation of blood clotting was established. This was evidenced by increased values of fibrinogen concentration (by 38%), fibrin polymerization (by 51%), and platelet aggregation (by 32%), while significantly reducing fibrin depolymerization activity of the blood (by 47%). With an extension of the incubation time of hypocoagulation plasma with chitosan, more pronounced effects of this drug were observed, which manifested itself in a significant increase in the concentration of fibrinogen, platelet aggregation, the degree of polymerization of fibrin, and a decrease in thrombin time, characterizing the general pathway of blood coagulation. Thus, the hemostatic drug chitosan leads to a blockade of bleeding phenomena caused by clopidogrel used in the clinic, which was studied for the first time in this work.