Effects Of Rivaroxaban On Thrombosis And Anticoagulant-relevant Laboratory Markers In Rabbit Jugular Vein Thrombosis Model

Objective:This study investigates the effects of rivaroxaban on thrombosis and evaluates the antithrombotic effects of rivaroxaban by establishing a rabbit jugular vein thrombosis model.We also evaluate the relationship between the antithrombotic effects and anticoagulant-relevant laboratory markers to see if the latter could be used to predict the former and monitor rivaroxaban by detecting laboratory markers including APTT, PT, TT, anti-FXa activity and coagulation factor(FII, FX) activity.Methods:30 healthy rabbits(weighing 1.9~2.4kg) were randomly divided into five groups: control group(vehicle), rivaroxaban 0.3mg/kg group, rivaroxaban 1.0mg/kg group, rivaroxaban 3.0mg/kg group and rivaroxaban 10.0mg/kg group. Jugular vein thrombosis was induced by clipping one section of jugular vein(about 3cm) and injecting thrombin into the section. Blood samples were collected just before and 2h after administration to detect coagulation assays and coagulation factors.At last, thrombus of both sides were removed and weighed after drying. The mean value of the thrombus weights obtained from both right and left vein was used as the thrombus weight of each rabbit.Results: 1.Oral administration of rivaroxaban increased anti-FXa activity in plasma in a dose-dependent manner and anti-FXa activity peaked at 2h after administration. 2.Oral administration of rivaroxaban inhibited thrombus formation in a dose-dependent manner. 3.According to self-comparison before and 2h after administration, anti-FXa activity in all rivaroxaban groups was increased after administration and the difference of anti-FXa activity before and after administration in all groups was statistically significant(P<0.05). PT was prolonged in 3.0mg/kg group and 10.0mg/kg group after administration and the difference of PT before and after administration was statistically significant(P<0.05). APTT and TT wasn’t prolonged after administration and the difference before and after administration wasn’t statistically significant. FII activity and FX activity was inhibited in 1.0mg/kg group, 3.0mg/kg group and 10.0mg/kg group after administration and the difference before and after administration was statistically significant(P<0.05). 4.When comparing the control group and different rivaroxaban groups 2h after administration, it shows anti-FXa activity in all rivaroxaban groups was increased and the difference of anti-FXa activity in different rivaroxaban groups was statistically significant(P<0.05). Compared with the control group, PT was prolonged in 3.0mg/kg group and 10.0 mg/kg group and the difference between these two groups and the other groups was statistically significant(P<0.05). APTT and TT after administration in all groups wasn’t statistically significant. 5.As correlation analysis show, correlation was observed between thrombus mass and anti-FXa activity(r=0.8498,P<0.01). Conclusions: Oral administration of rivaroxaban can inhibit thrombus formation in rabbit jugular vein thrombosis model; Anti-FXa activity is an effective marker to predict the antithrombotic effects of rivaroxaban and monitor rivaroxaban.