| OBJECTIVETo explore the correlation between anti-Xa activity and rivaroxaban concentration in plasma,establish the corresponding monitoring range which can be used to clinically evaluate rivaroxaban.By detecting anti-Xa activity,the feasibility of enoxaparin phased anticoagulation regimens was evaluated in patients who underwent diagnostic coronary angiography via the radial artery puncture approach and were likely to undergo or not undergo subsequent PCI.To conduct a comprehensive performance evaluation of fully automated analyzer in testing thrombomodulin(TM),TAT,PIC.and t-PA:PAI-1 complex(tPAI-C).METHODSThe Han nationality deep vein thrombosis patients recruited from the Department of Vascular Surgery,Peking Union Medical College Hospital of the Chinese Academy of Medical Sciences and the inclusion criteria and exclusion criteria were the subjects of this study.At the same time,he instructed rivaroxaban to be served with rice.The patient population used to establish the pharmacokinetic model is limited to patients who have not taken rivaroxaban before,and venous blood samples are collected before(0h)and 1,2,3,8,and 24h after medication;For the population that establishes the anti-Xa activity monitoring range,the selection criteria should be limited to patients taking rivaroxaban for more than 7 days,and collect venous blood samples of patients before and 2 hours after medication.Rivaroxaban blood concentration was measured using the gold standard UPLC-MS/MS method,prothrombin time(full name in English is "prothrombin time",abbreviated as PT),anti-Xa factor activity,and activated partial thromboplastin time(Full name is "activated partial thromboplastin time",abbreviated as "APTT")was measured using a Sysmex CS5100 automatic coagulation analyzer,in which anti-Xa factor activity was also measured using a Stago STA-R EVlution automatic coagulation analyzer.According to the drug dosage,whether subsequent PCI after angiography,the patients were divided into standard-dose group,high-dose group,PCI staged-dose group and PCI single-dose group,drug samples were collected at different time points,and used to detect anti-Xa activity.According to the CLSI EP5-A2,EP6-A,and WS/T 406-2012 specifications,TM,TAT,PIC and t-PAI-C were detected in the apparatus to evaluate the within-run and between-run imprecisions,linear range,carryover rate,reference range,sample stability and interferences.RESULTSCan be clarified by relevant analysis results:the correlation coefficients between PT,APTT,the activity of anti-Xa factor and the plasma concentration of rivaroxaban were r=0.814(P<0.001)、r=0.801(P<0.001)、r=0.980(Stago reagent,P<0.001)、r=0.983(Hyphen reagent,P<0.001),Among them,the correlation between anti-Xa factor activity and blood drug concentration is good,which is better than the correlation between PT,APTT and blood drug concentration.15mg bid,10mg bid,20mg qd,15mg qd,and 10mg qd dose groups of anti-Xa factor activity(Stago reagent example)mean valley values were 168.1,65.5,9.3,28.5,26.2ng/mL,and the average steady-state peak concentration was 262.0,272,1,299.2,326.1,222.2 ng/mL.There was no significant difference in anti-Xa activity between the standard-dose group and the high-dose group before administration(V1-0).After 10min(V1-1)and 90min(V1-2)of administration,the results of anti-Xa activity detection in the high-dose group were higher than that in the standard dose group,and the difference was statistically significant.In the comparison of PCI staged-dose group and PCI single-dose group,there was no statistically significant difference in the anti-Xa activity of the two groups.At 10min after administration(V1-1)and before PCI(V2-0),the detection results of anti-Xa activity in the PCI single-dose group were higher than that in the PCI staged-dose group,and the difference was statistically significant.After the first administration for 90min(V1-2)and 10min(V2-1)after PCI,the anti-Xa results of the PCI staged-dose group were higher than those of PCI single-dose group,with statistically significant differences.After PCI(V2-2),there was no statistically significant difference in anti-Xa activity between the two groups.The within-run and between-run imprecisions of 4 factors were all below 5%,The carryover rates were below1%.Results of liner verification test showed the correlation coefficients were0.998～0.999.The recommended reference ranges of TM,TAT,PIC were appropriate for our laboratory,and the reference of t-PAI·C should be established for the laboratory.The stability data showed that TM can be stable for 2 days in room temperature,but lacked stability in other temperature.TAT can be stable for 5 days in 4℃ and-20℃,but had poor stability in room temperature.PIC and t-PAI·C can be stable for 3 days in all the temperature.TM,TAT,PIC and t-PAI·C can not be interfered by hemoglobin of 510mg/dL,triglyceride of 1490FTU,conjugated bilirubin and free bilirubin of 21.1mg/dL.CONCLUSIONThe detection of anti-Xa activity has a good correlation with rivaroxaban concentration in plasma,which can be used to monitor the anticoagulation effect of rivaroxaban if necessary.Although the linear results of the study showed that the concentrations of PT,APTT and rivaroxaban concentration were less linear,the concentrations of PT and APTT were also prolonged with a certain extent at peak concentrations.For laboratories unable to carry out anti-Xa activity,it is recommended that the laboratories establish their own monitoring ranges of PT and APTT peaks in case of emergency.Analysis of anti-xa activity test results showed that,the standard dose of enoxaparin(0.5 mg/kg)has sufficient anticoagulant effect for patients undergoing contrast surgery only.If patients need to undergo PCI immediately after angiography,then 0.25 mg/kg dose of enoxaparin can be added before PCI to ensure the smooth operation of PCI.TM,TAT,PIC and t-PAI·C which were tested by High sensitivity chemiluminescence analyzer has a good performance in imprecision,carryover rate,linear range,and interference.It is suitable for detection of clinical specimens. |
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