1.Surveillance of bacterial resistance in tertiary hospitals across China:results of CHINET Antimicrobial Resistance Surveillance Program in 2022
Yan GUO ; Fupin HU ; Demei ZHU ; Fu WANG ; Xiaofei JIANG ; Yingchun XU ; Xiaojiang ZHANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Yuling XIAO ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Jingyong SUN ; Qing CHEN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yunmin XU ; Sufang GUO ; Yanyan WANG ; Lianhua WEI ; Keke LI ; Hong ZHANG ; Fen PAN ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Wei LI ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Qian SUN ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanqing ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Wenhui HUANG ; Juan LI ; Quangui SHI ; Juan YANG ; Abulimiti REZIWAGULI ; Lili HUANG ; Xuejun SHAO ; Xiaoyan REN ; Dong LI ; Qun ZHANG ; Xue CHEN ; Rihai LI ; Jieli XU ; Kaijie GAO ; Lu XU ; Lin LIN ; Zhuo ZHANG ; Jianlong LIU ; Min FU ; Yinghui GUO ; Wenchao ZHANG ; Zengguo WANG ; Kai JIA ; Yun XIA ; Shan SUN ; Huimin YANG ; Yan MIAO ; Mingming ZHOU ; Shihai ZHANG ; Hongjuan LIU ; Nan CHEN ; Chan LI ; Jilu SHEN ; Wanqi MEN ; Peng WANG ; Xiaowei ZHANG ; Yanyan LIU ; Yong AN
Chinese Journal of Infection and Chemotherapy 2024;24(3):277-286
Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5%were gram-positive and 70.5%were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3%,76.7%and 77.9%,respectively.Overall,94.0%of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8%of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2%in the isolates from children and 95.7%in the isolates from adults.The resistance rate to carbapenems was lower than 13.1%in most Enterobacterales species except for Klebsiella,21.7%-23.1%of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1%to 13.3%.The prevalence of meropenem-resistant strains decreased from 23.5%in 2019 to 18.0%in 2022 in Pseudomonas aeruginosa,and decreased from 79.0%in 2019 to 72.5%in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.
2.Abnormal elevation of plasma placental derived extracellular vesicles as a warning for adverse pregnancy outcomes in patients with severe preeclampsia
Yuanyuan CHEN ; Jianlong MEN ; Cha HAN
Chinese Journal of Laboratory Medicine 2024;47(5):561-569
Objective:To evaluate the diagnostic performances of plasma placental extracellular vesicles (pcEV) and their clearance protein (Lactadherin) in predicting adverse pregnancy outcomes in patients with severe preeclampsia (sPE).Methods:This is a retrospective case-control study. 60 patients aged 32 (29, 36) years diagnosed with sPE at 27-37 weeks of pregnancy, who underwent prenatal examinations and delivered between January 31 th, 2018 and January 31 th, 2019, were recruited. According to the occurrence of endpoint events (fetal distress and/or fetal growth restriction), sPE patients were further divided into an event group of 34 cases and a non event group of 26 cases. 33 healthy pregnant women of the same gestational age were selected as the control group, aged 31 (29, 36) years old. 25 non pregnant healthy women were selected as the healthy control group, aged 26 (25, 38) years old. Flow cytometry was used to detect placental alkaline phosphatase antibody positivity as pcEV, while membrane surface expression of phosphatidylserine, i.e. membrane associated protein V (AV) positivity as AV +pcEV. ELISA kits were used to detect the level of Lactadherin. Logistic regression was used to perform multiple correlation analysis. The performances of pcEV and Lactadherin in predicting adverse pregnancy outcomes were evaluated by the receiver operating characteristic (ROC) curve. Survival analyses were performed by the Kaplan Meier curve. The hazard ratios (HR) was calculated by the Cox proportional risk regression model. Results:The plasma AV +pcEV levels in sPE patients were 8 260 (4 991, 16 751)/μl, which were higher than 1 088 (784, 1 871)/μl of healthy pregnant women and 206 (116,256)/μl of healthy controls ( H=94.490, P<0.05). The plasma AV +pcEV levels in sPE patients with endpoint events were 11 225 (7 496, 20 599)/μl, which were higher than 5 199 (2 914, 8 347)/μl of patients without endpoint events ( U=178, P<0.05). The plasma levels of Lactadherin in sPE patients were 2 635 (1876, 3 137) pg/ml, which were higher than 1 597 (1 287, 1 818) pg/ml in healthy pregnant woman and 1 123 (749, 1 405) pg/ml in healthy controls ( H=54.307, P<0.05). ROC showed that the critical value of AV +pcEV predicting fetal distress and/or fetal growth restriction events within 77 days in sPE patients was 6 524/μl and area under the curve(AUC) was 0.799 (95% CI 0.680-0.917). The critical value of Lactadherin was 2 336.5 pg/ml and AUC was 0.702 (95% CI 0.564-0.841). Logistic regression analysis showed that there was a significant correlation between AV +pcEV levels in sPE patients and 24-hour urine protein quantification ( OR=9.288, 95% CI 1.993-43.293), as well as the need for combined antihypertensive therapy ( OR=18.690, 95% CI 1.919-182.077) ( P<0.05). Survival analysis showed that the cumulative probability of fetal distress and/or fetal growth restriction events within 77 days were significantly increased in sPE patients with AV +pcEV levels above the critical value (Log-rank χ 2=21.430, P<0.05). The Cox proportional regression model showed that the levels of AV +pcEV can independently identify fetal distress and/or fetal growth restriction events ( HR=7.983, P<0.05). Conclusions:The changes of pcEV in plasma of pregnant women in late pregnancy were related to the development of PE. High concentrations of pcEV suggested an increased risk of fetal distress and fetal growth restriction, and pcEV could serve as an effective marker for early warning of adverse pregnancy outcomes.
3.Plasma thrombin-antithrombin complex evaluates hypercoagulable states and predicts revasenosis after revascularization in patients of atherosclerosis obliterans
Zhubo ZHANG ; Rui MA ; Jing REN ; Jianlong MEN
Chinese Journal of Laboratory Medicine 2022;45(10):1063-1069
Objective:To study the changing characteristics of the levels of plasma thrombin-antithrombin complex (TAT) in atherosclerosis obliterans (ASO) patients with different conditions and the clinical value of predicting luminal restenosis after revascularization.Methods:A total of 386 ASO patients were collected, including 209 males and 177 females, aged 70 (44-97) years old, including 196 patients with intermittent claudication and 190 patients with critical limb ischemia. There were 172 patients with intermittent claudication and 185 patients with critical limb ischemia who received revascularization therapy. During the 30-day follow-up period, 23 patients with intermittent claudication and 49 patients with critical limb ischemia developed restenosis after surgery. Venous blood samples were collected before surgery, on the 3rd day after surgery, and on the 7th day after surgery. Plasma TAT levels were determined by Shine i2900-automatic chemiluminescence immunoassay analyzer; Kruskal-Wallis H test was used for comparison among multiple groups; Mann-Whitney U test was used for data comparison between the two groups; continuous comparison of patient data in the same group was done by using Friedman rank test; multivariate correlation analysis by Logistic regression was conducted to obtain odds ratio( OR). The diagnostic performance of TAT was evaluated by ROC analysis. Kaplan-Meier curve was used to analyze the survival curve, and the hazard ratio (HR) was obtained by Cox proportional hazard regression model. Results:Compared with the healthy control group, the level of plasma TAT in patients with intermittent claudication was significantly higher ( P<0.001); the level of plasma TAT in patients with critical limb ischemia was significantly higher than that in patients with intermittent claudication ( P<0.001). The plasma TAT of patients with Rutherford grade 3 >grade2, grade4 >grade3, and grade6 >grade5 ( P values were 0.038, <0.001, and 0.013, respectively).In the intermittent claudication group, the plasma TAT levels of the patients with restenosis on the 3rd and the 7th day after revascularization were both higher than that of the patients with unobstructed blood flow ( P values were 0.004 and <0.001, respectively); The plasma TAT level of patients with unobstructed blood flow on the 7th day after surgery was lower than that on the 3rd day after surgery and before surgery (both P values <0.001); the plasma TAT level of patients with restenosis on the 7th day after surgery was lower than that on the 3rd day after surgery and higher than before surgery (both P values < 0.001). In the critical limb ischemia group, before surgery, on the 3rd and the 7th day after surgery,the plasma TAT levels of the patients with restenosis were higher than that of the patients with unobstructed blood flow ( P values were 0.001, 0.013, and <0.001, respectively); The plasma TAT level of patients with unobstructed blood flow on the 7th day after surgery was lower than that on the 3rd day after surgery and before surgery (both P values <0.001); the plasma TAT level of patients with restenosis on the 7th day after surgery was lower than that on the 3rd day after surgery ( P<0.001), but was not significantly difference from that before surgery. The ROC analysis showed that the areas under the curve (AUC) of plasma TAT on the 7th day after surgery to predict postoperative restenosis in all the patients, patients with intermittent claudication and those with critical limb ischemia were 0.839, 0.783 and 0.853, respectively. Survival analysis indicated that in the critical limb ischemia group, patients with plasma TAT levels higher than the critical value (≥7.66 ng/ml) on the 7th day after surgery showed significantly higher cumulative risk of restenosis events within 30 days after surgery (Log-rank χ 2=93.674, P<0.001). Cox regression analysis showed that the plasma TAT level on the 7th day after the surgery could be used as an independent indicator to predict the occurrence of restenosis within 30 days after surgery in the critical limb ischemia group ( HR=2.259, P<0.001). Conclusion:Plasma TAT can reflect the hypercoagulable state of ASO patients in different conditions, which is helpful for stratification of disease severity. In addition, TAT is highly sensitive for luminal restenosis after revascularization and can be used as an independent marker for evaluating postoperative restenosis events in patients with critical limb ischemia.
4.Continuous increase of thrombin-antithrombin complex monitoring in patients with traumatic brain injury indicates adverse clinical outcomes
Bowei ZHANG ; Jing REN ; Zhubo ZHANG ; Ye TIAN ; Quanjun DENG ; Jianlong MEN
Chinese Journal of Laboratory Medicine 2021;44(5):402-407
Objective:Study on the feature of thrombin-antithrombin complex (TAT) during traumatic brain injury and the predicting performance with adverse clinical outcomes.Methods:From January 2018 to December 2019, 147 patients with traumatic brain injury(TBI) were enrolled, including 112 males and 35 females, aged 36 (26-48) years old. The plasma levels of TAT were detected on the 0th, 1st, 3rd and 7th day after TBI attack. Kruskal-Wallis H test was used for comparison among multiple groups; Mann-Whitney U test was used for data comparison between the two groups; continuous comparison of patient data in the same group using Friedman rank test; the diagnostic performance of TAT with adverse event risk predicting was evaluated by ROC analysis; Kaplan-Meier curve was used to analyze the survival curve; the risk ratio (HR) was obtained by Cox proportional hazard regression model.Results:Among the patients groups with mild, moderate and severe phenotype, the TAT levels were gradually decreased on the 0th, 1st, 3rd and 7th day after TBI attack(χ 2 values were 95.612, 133.555, and 132.453, respectively, all P values<0.001). The TAT levels on the 0th, 1st, 3rd and 7th day in the adverse event group were higher than in the group of patients with stable condition ( U values were 959.0, 321.0, 36.0 and 1.0 respectively, all P values<0.001). In the stable condition group, the TAT levels on the 0th and 1st day in the severe group were higher than in the mild group ( U values were 0 and 1.0 respectively, both P values<0.001), while there was no statistically significant difference of TAT levels between the 3rd and 7th day in the severe group ( U values were 342.5 and 272.5, P values were 0.486 and 0.065 respectively). The TAT levels of the moderate group on 0th and 1st day were higher than those of the mild group ( U values were 0 and 280.0, respectively, both P<0.001), while there was no significant difference between the TAT levels on the 3rd and 7th day ( U values were 628.0 and 647.0, P values were 0.826 and 0.996, respectively). ROC curves analysis showed that when the TAT diagnostic thresholds were 68.75 ng/ml, 29.05 ng/ml, 17.25 ng/ml and 13.85 ng/ml on the 0th, 1st, 3rd and 7th day, the diagnostic sensitivities of predicting adverse events were 86.8%, 94.3%, 100% and 100%; while the diagnostic specificities were 71.3%, 78.7%, 91.5% and 96.8%, respectively. Survival analysis showed that the cumulative probability of adverse outcomes was significantly higher in patients above the critical value. Cox analysis showed that the HR on the 0th, 1st, 3rd and 7th day to predict adverse clinical outcomes by TAT levels were 1.818, 2.257, 3.526 and 4.813, respectively ( P value<0.001). Conclusion:There was strong relationship between the plasma TAT level and the severity of the patient′s condition, and persistent increasing with TAT level could reflect the risk of adverse events, which could be used as an effective index to comprehensively predicting the development tendency of the TBI patient′s condition.
5.Study on the evaluation of Rivaroxaban′s blood concentration by anti-FX activity assay
Rui MA ; Jing REN ; Yang LI ; Zhenguo ZHAI ; Jianlong MEN
Chinese Journal of Laboratory Medicine 2020;43(3):291-295
Objective:The anti-FⅩa assay can be used to monitor the blood concentration of Rivaroxaban. The aim is to evaluate the critical value and diagnostic performance of this test on bleeding risk assessment.Methods:From September 2017 to June 2019, 368 patients were enrolled for retrospective cohort study, including 201 males and 167 females, aged (62.8±15.7) years old. They were divided into groups by age:≤60 years old group 105 cases,61-70 years old group 135 cases,≥71 years old group 128 cases. Anti-FⅩa was detected on ACL TOP 700 coagulation analyzer using chromogenic substrate method to quantitatively determine the plasma concentration of rivaroxaban. Anti-FⅩa data were expressed as M ( P25- P75);Kruskal-Wallis H test was used for comparison among groups; Mann-Whitney U test was for data comparison between two groups; positive rate comparison was performed by χ 2 test; the diagnostic performance of anti-FⅩa to assess bleeding risk was evaluated by ROC curve;Kaplan-Meier curve was used for the survival analysis;the risk ratio (HR) was obtained by Cox proportional hazard regression model. Results:Both the peak and trough plasma concentrations were higher in patients aged 61-70 years old than ≤60 years old ( U values were 5 618 and 5 725,respectively, P values were 0.006 and 0.011, respectively); higher in patients ≥71 years old than 61-70 years old ( U values were 6 438 and 6 317, respectively, P values were<0.001).The incidence of bleeding events was higher in the 61-70 years old group than ≤60 years old group (χ 2=3.06, P<0.05),while not significantly different in the ≥71 years old group from 61-70 years old group (χ 2=0.35, P>0.05).Both peak and trough blood concentrations were higher in patients with bleeding than without bleeding(U values were 1 429 and 2 185, respectively, P<0.001 and 0.001, respectively).ROC showed that the cut-off values of peak blood concentration in evaluation of the overall and the ≥61 year-old population′s bleeding risk were 200.8 ng/ml and 209.9 ng/ml,respectively, corresponding respectively with the sensitivity of 90.9% and 95.0%; the trough cut-off values were 35.1 ng/ml and 39.1 ng/ml, respectively, corresponding respectively with the sensitivity of 72.7% and 70.0%. However, all the above cut-off values gave a low diagnostic specificity. Survival analysis showed with 35.1 ng/ml as the trough cut-off value, the cumulative risk of bleeding significantly increased in patients above the cut-off value (Log-rank χ 2=4.513, P=0.034). The Cox proportional regression model demonstrated that the hazard ratios for peak and trough blood concentration predictions of bleeding risk were 1.023 (95% CI: 0.834-1.256) and 0.948 (95% CI: 0.773-1.164). respectively. Conclusions:Both the peak and trough values of blood concentration in bleeding patients are higher than non-bleeding patients. The peak blood concentration is highly sensitive to the risk of bleeding, and the elevated trough blood concentration levels indicate that the probability of bleeding risk increases in the short term. However, the specificity of both peak and trough values is relatively low in bleeding risk assessment. When used alone, the prediction of bleeding events does not have direct guiding significance. Dynamic monitoring and joint evaluation are recommended.
6.Genetics research contributes to the etiology exploration of venous thromboembolism
Xiyuan LI ; Yang LI ; Jing REN ; Jianlong MEN ; Zhenguo ZHAI
Chinese Journal of Laboratory Medicine 2020;43(8):768-775
Venous thromboembolism (VTE) is a common multifactorial disease that results from hypercoagulable action of genetic factors and environmental exposures. VTE associated genetic factors include anticoagulant gene loss of function (LOF), procoagulant gene gain of function (GOF), the fibrinolytic system genes dysfunction, variants and epigenetic changes that cause hypercoagulability indirectly. Some VTE follows the pattern of Mendelian inheritance; also, genetic polymorphism is an important aspect of genetic susceptibility to VTE. For patients with suspected VTE associated genetic dysfunctions, polymorphisms test should be performed to those who is supposed to have obvious known polymorphisms genetic susceptibility. In contrast, the individuals who suffer from Mendelian disease or other types of disease with unknown gene variants, NGS test should be a good choice. Further, genetic polygenic risk score (PRS) or epigenetic biomarkers are suitable for VTE recurrence risk assessment.
7.von Willebrand factor and D-dimer to evaluate the thrombosis risk in patients with nonvalvular atrial fibrillation in anti-coagulant therapy
Bowei ZHANG ; Zhubo ZHANG ; Jing REN ; Yang LI ; Jianlong MEN
Chinese Journal of Laboratory Medicine 2020;43(10):1014-1020
Objective:To investigate the performance of von willebrand factor antigen (vWF:Ag) and D-dimer in predicting thrombotic risk in nonvalvular atrial fibrillation (NVAF) patients with anticoagulant therapy.Methods:From March 2017 to March 2019, 256 patients were enrolled, including 152 males and 104 females, aged (57.9±20.4) years old; according to the end-point events during the follow-up period, the patient group was further divided into 227 cases in the no-event group and 29 cases in the thrombotic event group;50 cases in the control group, including 30 males and 20 females, aged (45.0±5.3) years old. vWF:Ag was detected by blood coagulation instrument and determination of D-dimer was done by fluor-euzyme linked immunoassay Analyzer. Mann-Whitney U test was used for data comparison between any two groups, Kruskal-Wallis H test was used for comparison among multiple groups and multivariate correlation analysis was done by Logistic regression to obtain odds ratio ( OR). The prediction performance with thrombotic events of vWF:Ag and D-dimer was evaluated by ROC curve, Kaplan-Meier curve was used to analyze the survival curve and the hazard ratio ( HR) was obtained by Cox proportional hazard regression model. Results:The levels of vWF:Ag and D-dimer in the control group were 103% (86%-131%) and 249 (90-522) μg/L, 234% (102%-623%) and 744 (100-3 352) μg/L in the patient group; in the patient group, of which 225% (102%-623%) and 650 (100-3 281) μg/L in non-event group, 333% (210%-494%) and 1 325 (487-3 352) μg/L in thrombus event group; compared the healthy control, the levels of vWF:Ag and D-dimer were increased in patients group ( P<0.001), of which non-event groups were higher than healthy controls ( P<0.001), and the thrombotic event group was higher than that of the non-event group ( P<0.001). Plasma vWF:Ag level and D-dimer level in NVAF patients were higher than those in the control group ( P<0.001). Plasma vWF:Ag level and D-dimer level in the non-event group were significantly higher than those in the healthy control group ( P<0.001). The plasma vWF:Ag and D-dimer levels of patients in the thrombotic event group were significantly higher than those in the non-event group patients ( P<0.001). The result of ROC showed that the critical value of vWF: Ag for predicting thrombosis within 3 months of NVAF patients was 229% and area under the curve (AUC) was 0.839 (95% CI:0.784-0.894); When the critical value of D-dimer was 588 ng/ml, AUC was 0.803 (95% CI:0.745-0.861).While vWF:Ag combined with D-dimer, AUC was 0.868 (95% CI:0.826-0.909). Logistic regression analysis showed that plasma vWF:Ag level in NVAF patients was significantly correlated with age ( OR=10.240, 95%CI 2.773-37.820), congestive heart failure ( OR=34.779, 95%CI 8.010-151.019), hypertension ( OR=0.068, 95%CI 0.023-0.198) and type 2 diabetes ( OR=6.618, 95%CI 2.469-17.734) ( P<0.001), as well as was significantly correlated with vascular disease ( OR=4.801, 95%CI 1.204-19.145) ( P=0.026). Plasma D-dimer level was significantly correlated with congestive heart failure ( OR=0.146, 95%CI 0.036-0.588) and medication compliance ( OR=0.114, 95%CI 0.016-0.832) ( P value was 0.007 and 0.032). Survival analysis showed that the cumulative probability of thrombosis within 3 months was significantly increased (Log-rank χ2 was 11.394, 17.895 and 32.825 respectively, P value<0.001) in the patients with plasma levels above the critical value of vWF:Ag, D-dimer or vWF:Ag combined with D-dimer. Cox proportional regression model showed that neither vWF:Ag nor D-dimer could independently predict thrombotic events during anticoagulant therapy( HR was 0.866 and 0.834, P-value was 0.253 and 0.152, respectively), but it could improve the prediction performance significantly( HR=0.780, P=0.048) for combined application of both vWF:Ag and D-dimer. Conclusion:The changes with plasma vWF:Ag and D-dimer levels in NVAF patients were associated with a variety of clinicopathological factors and closely related to the risk of thrombosis within 3 months. Combined application could provide the effective basis for clinical prediction of the condition.
8.New progress in laboratory monitoring of the rivaroxaban therapy
Jianlong MEN ; Zhenguo ZHAI ; Jing REN ; Zhubo ZHANG
Chinese Journal of Laboratory Medicine 2019;42(8):710-716
Rivaroxaban is an oral direct factor FXa inhibitor with predictable pharmacokinetics and no routine monitoring, but the laboratory tests can help to assess the safety and effectiveness of rivaroxaban. The laboratory tests for rivaroxaban include liquid chromatography tandem mass spectrometry (LC-MS / MS), prothrombin time(PT), anti factor Xa activity(anti-Xa), thromboelastography(TEG) and rotational thromboelastography(ROTEM). LC-MS / MS can be used to quantitatively detect the blood concentration of rivaroxaban with good specificity and sensitivity, but the instrument is expensive,technologically complex, and lack standardization, so it belongs to the laboratory developed tests(LDTs).Because of insufficient data of TEG and ROTEM, their clinical performance still needs to be verified. PT can detect "treatment concentration" of rivaroxaban, which can be used as a primary screening method to identify the overdose and the risk of severe bleeding, but the sensitivity of different reagents is different;anti-FXa test can sensitively reflect the change of blood concentration of rivaroxaban, and its clinical efficacy is similar to LC-MS/MS, and therefore it can be used as an effective method to guide doctors to use drugs rationally.
9.Study on safety monitoring of rivaroxaban by prothrombin time
Rui MA ; Jing REN ; Zhexiang WANG ; Jianlong MEN
Chinese Journal of Clinical Laboratory Science 2019;37(9):666-670
Objective:
To investigate the safety of rivaroxaban by detecting prothrombin time (PT).
Methods:
105 patients with thrombosis from May 2018 to February 2019 in Tianjin Medical University General Hospital were selected and followed up. 23 patients with hemorrhage were in the bleeding group and 82 others were in the non-bleeding group. PT was detected by IL ACL TOP 700 blood coagulation instrument and its supporting reagents. Data were expressed as M(P 25 ,P 75 ). Mann-Whitney U test was used for data comparison between the bleeding and non-bleeding groups. Kruskal-Wallis H test was used for age data comparison among multiple groups. The diagnostic performance of PT was evaluated by a receiver operating characteristic curve (ROC).
Results::
In the bleeding group, PT changed significantly between before and after treatment of rivaroxaban. On the 1st and 3rd days after treatment, PT peak was significantly higher than the day′s trough level, and on the 3rd day, both the peak value and the trough value were all significantly higher than the levels on the 1st day. There was no significant difference in peak PT between the patients in the non-bleeding group and the bleeding group on the 1st day (P>0.05), while the trough PT level in the bleeding group was significantly higher than that in the non-bleeding group (P<0.001). On the 3rd day, the levels of peak and trough PT in the bleeding group were significantly higher than those in non-bleeding (P<0.001). The diagnostic performance of the trough PT predicting bleeding risk on the day 1 and 3 after treatment was superior to the peak PT level, while the effects of the trough PT predicted on the 1st was similar to the 3rd days. In terms of assessing the risk of bleeding, the trough PT level should be superior to the peak PT, and the 3rd day should be better than the 1st day.
Conclusion
PT could effectively evaluate the bleeding risk of rivaroxaban after sufficient performance verification, and provide a reliable basis for clinical rational use for drug.
10.Evaluation of D-dimer for monitoring venous thromboembolism risk during short-term in hospitalized cancer patients without surgery
Hongyan ZHANG ; Jing REN ; Jianlong MEN
Chinese Journal of Clinical Laboratory Science 2019;37(11):838-841
Objective:
To assess the value of D-dimer for monitoring venous thromboembolism risk in hospitalized non-surgical cancer patients within 15 days.
Methods:
A total of 397 non-surgical cancer patients from January 2018 to December 2018 were enrolled, including 236 males and 161 females in the age of (56±18) years. According to Caprini Thrombosis Risk Scale, the patients were divided into 2 groups: the intermediate-risk group (171 patients, 3 to 4 points) and the high-risk group (226 patients, ≥5 points). The plasma levels of D-dimer were determined by using the Biomerieux Mini Vidas Automated Immunoassay Analyzer and VADIS D-Dimer Exclusion. The enrolled patients were followed up for 15 days with the endpoint event of VTE. The experimental data were expressed by M (P 25 , P 75 ). The Mann-Whitney U test was used to compare the data between the two groups. The Kaplan-Meier curve was used to implement the survival analysis. P<0.05 was considered as statistically significance. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic performance of D-dimer.
Results:
The plasma level of D-dimer in the high-risk group were significantly higher than that in the intermediate risk group (U=13 306, P<0.001). There was no significant difference for the incidence of VTE between the two groups (χ 2 =1.85, P>0.05). When the cut-off point value of D-dimer was defined as 1 579 ng/mL, the sensitivity of VTE risk prediction in cancer patients within 15 days was 69.0%, the specificity was 57.1% and the area under the ROC curve was 0.694 (95% CI: 0.613-0.774). There were significant differences in Caprini scores between the patients with D-dimer ≤1 579 ng/mL and D-dimer>1 579 ng/mL (U=16 104,P=0.002). There was no statistical difference for the incidence of VTE between the two groups (χ 2 =7.36, P>0.05). Among all of the patients, the patients with D-dimer>1 579 ng/mL showed significantly higher cumulative probability of VTE within 15 days, compared with patients with D-dimer≤1 579 ng/mL (Log-rank χ 2 =7.729, P=0.005). In the intermediate-risk group, the cumulative probability of VTE of the patients whose D-dimer plasma level above the cut-off point value within 15 days was significantly higher than that of the patients with D-dimer plasma level below the cut-off point value (Log-rank χ 2 =7.156,P=0.007). In the high-risk group, there was no significant difference in the cumulative probability of VTE between the patients with D-dimer plasma level above the cut-off point value and the patients below the cut-off point value (Log-rank χ 2 =2.009,P=0.156).
Conclusion
According to the Caprini rating scale or D-dimer cut-off point value (1 579 ng/mL), cancer patients could be divided into two groups: VTE intermediate-risk and VTE high-risk. There were no significant differences in the two groups for the incidence of VTE within 15 days. However, the cumulative probability of VTE was significantly increased in total patients of both groups monitored by D-dimer, and the VTE cumulative probability in intermediate-risk group patients was increased.

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