Anticoagulants On Ⅱ Factor、Ⅴ Factor、Ⅷ Factor、Ⅹ Factor And Protein C Activity

Objective:By testing the Activated partial thromboplastin time(APTT), Prothrombin time(PT), Thrombin time(TT), Ⅱ factor(FⅡ), Ⅴfactor(FⅤ), Ⅷ factor(FⅧ), factor(FⅩ) and protein C activity of rabbits who take different concentrations of dabigatran etexilate and rivaroxaban, how and why it effect on the coagulation factor activity and protein C activity were analyzed.Methods: 60 New Zealand white rabbits were randomly divided into the dabigatran etexilate experimental group and the rivaroxaban experimental group rivaroxaban. Dabigatran experimental group was divided into control group, 1mg/kg, 5mg/kg, 10mg/kg, 20mg/kg and 40mg/kg group, and each group has six rabbits. Rivaroxaban experimental group was divided into control group, 0.3mg/kg, 1mg/kg and 3mg/kg groups of six. Each animal taked blood 3ml from ear vein before taking, then insert the stomach tube. Dabigatran etexilate experimental groups poured Dabigatran etexilate drugs according to 1mg/kg, 5mg/kg, 10mg/kg, 20mg/kg and 40mg/kg. Rivaroxaban experimental groups poured rivaroxaban drugs according to 0.3mg/kg, 1mg/kg and 3mg/kg. Two control groups were poured into an equal volume of solvent. 2 hours after administration of anesthesia, experimental animals taked 3ml blood in the femoral artery. Blood samples at 2000×g for 15 min. Absorb the upper plasma and stored at-80 °C until assayed. Clotting times(PT and APTT) and Coagulant activity of FII, FV, FVIII, FX,PC in plasma were measured. Changes of above indexes were analysised, and to evaluate the influence of New Oral Anticoagulants on Ⅱ factor、Ⅴ factor、Ⅷfactor、Ⅹfactor and protein C activity.Results:In the dabigatran experiment, APTT and TT in the control group, were not significantly prolonged before and after taking the medication(P>0.05). With increasing concentrations of dabigatran etexilate, APTT and TT time gradually prolonged. From the 5mg/kg group, the APTT and TT prolongation reached statistical difference(P<0.05). From the 10mg/kg group, the APTT was prolonged to more than 2 times(60.18±3.08 VS 132.98±6.72,P<0.01). FII activity in each group was decreased after taking the medicine. From the 10mg/kg group, the difference was statistically significant(22.83±5.78 VS 16.83±3.54,P<0.05). Activity in 20mg/kg and 40 mg groups was significantly decreased(22.00±2.37 VS 15.50±3.39,P<0.01;19.00±2.19 VS 13.17±3.76, P<0.01).We analyzed the change of factor activities before and after taking dabigatran, and found that with dabigatran etexilate concentration increases, the activity factor reduced more and more. F V, F VIII activity after taking were less than baseline activity. With dabigatran etexilate concentration increases, the greater the rate of change and a decrease in activity degree is more and more. We analyze the FX activity, found that activity in 1mg/kg group after taking the medication was slightly increased than before.(39.83±7.08 VS 40.50±14.29,P>0.05). But the rate of change was small, which was-1%. From 5 mg / kg group activity after taking compared with those before taking overall activity was decreased and with dabigatran etexilate concentration increases, rate of change is bigger, decreased to a greater degree. We analyzed the change of PC factor activities before and after taking dabigatran, and found in 5mg/kg and 40mg/kg group after taking activity is slightly higher than baseline activity. In the 10mg/kg and 20mg/kg groups, the activity was lower than that of the former. But the rate of change in all experimental groups was very small, and the mean value did not reach statistical difference(P<0.05). In the 1mg/kg group, the PC activity was lower than that of the pre activity(62.17±12.12 VS 58.00±11.80,P>0.05), and the change rate was 9%. Rivaroxaban of the experimental group, FⅡ、FⅤ、FⅧ、FⅩ activity after medication than before treatment were decrease. And with the increase of the concentration of Rivaroxaban, the greater the degree of factor activity decreased. We analyze the activity of PC in the Rivaroxaban experimental group, and found that there was not significant changes in each group before and after(P>0.05), and the rate of change is very small, between 0.4% and 2%.Conclusion: Dabigatran has obvious inhibitory effect on F II activity. Rivaroxaban has obvious inhibitory effect on F II activity. And with the increase of concentration, the greater the inhibition effect. Novel oral anticoagulant drugs also inhibit FⅤ, FⅧ activity. Low concentration direct thrombin inhibitor dabigatran inhibit the activity of protein C, a high concentration of dabigatran etexilate has no effect on protein C activity. FⅩa inhibitor rivaroxaban had no effect on protein C activity,no matter of concentration.