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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.
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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.
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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.
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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.
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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.
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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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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.
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Objective@#Evaluate the diagnostic performance of three methods in testingheparin induced thrombocytopenia antibodies the clinical diagnosis performance of the three heparin induced thrombocytopenia(HIT) antibody testing.@*Methods@#143 patients were collected from the Tianjin Medical university general hospital and China-Japan friendship hospital from the 2017 Sep to 2018 Dec, 67 males and 76 females, with a mean age of (56.1±11.4) years, the pretest probability is estimated to be low (1-3 points) with 24 patients, intermediate (4-5 points) with 79 patients and high(6-8 points) with 40 patients. According to therapeutic regimen, the intermediate and high probability patients were divided into two groups: 31 cases in the heparin discontinuing group and 88 cases in the continuing heparin group. The three methods including:the particle immunofiltration assay to detect the plasma whole HIT antibody; the particle gel immunoassayto detect the plasma whole HIT antibody by ACL TOP 700 coagulation analyzer,; the chemiluminescent immunoassay to detect the plasma IgG-specific HIT antibody by ACL AcuStar chemiluminescent analyzer.@*Results@#There was no significant difference between the high and intermediate probability patients for particle immunofiltration assay, particle gel immunoassay and chemiluminescent immunoassay(χ2 was 3.15, 2.89 and 1.31 respectively, P>0.05). The positive rate with three assays were higher in the heparin discontinuing group than the continuing heparin group(χ2 was 16.09, 43.37 and 26.94 respectively, P<0.01), the positive results of the chemiluminescent immunoassay only in the heparin discontinuing group. All of the patients with three assays positive simultaneousin the heparin discontinuing group(χ2=26.94, P<0.01); more patients in heparin discontinuing group with positive resultsby two assays (particle immunofiltration assay and particle gel immunoassay) than in the continuing heparin group(χ2=10.95, P<0.01); there was no obvious difference(χ2=1.80, P>0.05) between the continuing heparin group and the heparin discontinuing group for positive results with particle immunofiltration assay; all of the patients with there assays negative simultaneous in the continuing heparin group with a significant difference between the two groups(χ2=14.27, P<0.01).@*Conclusions@#Whole HIT antibodies had high sensitivity, and was especially suitable for excluding diagnosis, andthe diagnositic performance withtheparticle gel immunoassay precede the particle immunofiltration assay.For the patients with intermediate or high pretest probability and whole antibodies positive, even if they had been treated with alternative anticoagulant therapy, the IgG specific antibodies(chemiluminescent immunoassay) should be detected for definite diagnosis(if the conditions was appropriate), to verify the rationality of alternative anticoagulant therapy and to avoid overtreatment.
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Objective Evaluate the diagnostic performance of three methods in testingheparin induced thrombocytopenia antibodies the clinical diagnosis performance of the three heparin induced thrombocytopenia(HIT) antibody testing. Methods 143 patients were collected from the Tianjin Medical university general hospital and China-Japan friendship hospital from the 2017 Sep to 2018 Dec, 67 males and 76 females, with a mean age of (56.1 ± 11.4) years, the pretest probability is estimated to be low (1-3 points) with 24 patients, intermediate (4-5 points) with 79 patients and high(6-8 points) with 40 patients. According to therapeutic regimen, the intermediate and high probability patients were divided into two groups:31 cases in the heparin discontinuing group and 88 cases in the continuing heparin group. The three methods including:the particle immunofiltration assay to detect the plasma whole HIT antibody;the particle gel immunoassayto detect the plasma whole HIT antibody by ACL TOP 700 coagulation analyzer,;the chemiluminescent immunoassay to detect the plasma IgG-specific HIT antibody by ACL AcuStar chemiluminescent analyzer.Results There was no significant difference between the high and intermediate probability patients for particle immunofiltration assay, particle gel immunoassay and chemiluminescent immunoassay(χ2 was 3.15, 2.89 and 1.31 respectively, P>0.05). The positive rate with three assays were higher in the heparin discontinuing group than the continuing heparin group(χ2 was 16.09, 43.37 and 26.94 respectively, P<0.01), the positive results of the chemiluminescent immunoassay only in the heparin discontinuing group. All of the patients with three assays positive simultaneousin the heparin discontinuing group(χ2=26.94, P<0.01); more patients in heparin discontinuing group with positive resultsby two assays (particle immunofiltration assay and particle gel immunoassay) than in the continuing heparin group(χ2=10.95, P<0.01);there was no obvious difference(χ2=1.80, P>0.05) between the continuing heparin group and the heparin discontinuing group for positive results with particle immunofiltration assay; all of the patients with there assays negative simultaneous in the continuing heparin group with a significant difference between the two groups(χ2=14.27, P<0.01). Conclusions Whole HIT antibodies had high sensitivity, and was especially suitable for excluding diagnosis, andthe diagnositic performance withtheparticle gel immunoassay precede the particle immunofiltration assay.For the patients with intermediate or high pretest probability and whole antibodies positive, even if they had been treated with alternative anticoagulant therapy, the IgG specific antibodies(chemiluminescent immunoassay) should be detected for definite diagnosis(if the conditions was appropriate), to verify the rationality of alternative anticoagulant therapy and to avoid overtreatment.
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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.
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The P2Y12 receptor antagonist is used widely in prevention and treatment of cardiovascular and cerebrovascular disease. Monitoring changes of platelet function after treatment can improve the prognosis of patients. The platelet function test is the important way to evaluate high residual platelet reactivity after antiplatelet treatment, including light transmission aggregometry (LTA), whole blood impedance aggregometry assay (WBIA), vasodilator- stimulated phosphoprotein (VASP), thrombelastogram (TEG), platelet function analyzer- 100 (PFA-100) and VerifyNow system (VerifyNow). It is very different for the reflecting ability with residual reactivity of platelets among these tests after anti-platelet therapy, and also significant difference for assessment effect. Among them, LTA is a classic method for the curative effect evaluation of anti-platelet agents, which is convenient and cheap, but it is susceptible to the operating and environment interference. The clinical application of WBIA is less, and which lacks threshold value for assessment. VASP is sensitive for the changes of platelet function, but the test is complex and expensive. TEG can monitor the inhibition ratio of drugs on anti-platelets, but it needs to verify the safety of treatment. It is not clear for sensitivity and specificity with monitoring anti-platelet agent by PFA-100. VerifyNow is effective and reliable, but the cost is high. The evidence of clinical study shows that LTA, VASP and VerifyNow can reflect the effect of platelet inhibition of P2Y12 receptor antagonists sensitively, and is associated with the risk of major adverse cardiac events (MACE) in patients with cadiovascular diseases.
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The clinical application of the laboratory examination with thrombosis can be divided into four categories,including risk assessment,diagnosis by exclusion,auxiliary diagnosis and therapic monitoring.Theevidence based parameters which subsumed into the international guidelines of thrombosis related clinical management,included the prothrombin time,activited partial thomboplastin time,anti-factor X a activity,D-dimer,coagulation factor Ⅷ,naturally occurring anticoagulants,antiphospholipid syndromeassociative parameters,heparin induced thrombocytopenia antibodies and platelet aggregation test,which provided the important evidence for clinical intervention and establishment of antithrombotic strategy.Theother thrombosis tests are still lack of sufficient evidence,therefore we need to participate in multicentric clinical randomized controlled study actively,and implementing the systematic review and meta-analysis forwardly,solving clinical questions based on PICO (Patients,Intervention,Comparision,Outcome),promoting the clinical application of laboratory parameters.
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Objective To investigate the effect of perioperative period D-dimer and tissue factor (TF)-1208 D/I gene polymorphism on the long-term prognosis of patients with off-pump coronary artery bypass grafting (OPCABG). Methods Retrospective analysis of the case data of the first OPCABG patients admitted to Tianjin Medical University General Hospital from May 2015 to May 2016 were enrolled. The general data, operation time, bypass number, left ventricular ejection fraction (LVEF), flow rate of 24-hour pleural effusion, intraoperative heparin dosage, combined anticoagulant and antiplatelet time, and the time of postoperative ventilator were measured. The blood biochemical indexes of 1, 4, 7, 14 days and 1, 2, 3 months after operation, perioperative complications, the level of D-dimer in the patients with different TF-1208 D/I gene polymorphism, and prognosis of 1-year follow-up were recorded. The risk factors of recurrent angina 1 year after operation was analyzed by Logistic regression analysis. Results The level of plasma D-dimer was increased continuously after OPCABG, and reached a peak at 1 month after operation [1.94 (1.07, 2.70) mg/L], then decreased, and decreased to preoperative level 3 months after operation [0.20 (0.10, 0.45) mg/L]. The level of D-dimer in TF-1208 I I genotype was significantly higher than that in TF-1208 DD genotype and TF-1208 D/I genotype group at 14 days and 1 month after operation [mg/L: 4.17 (1.54, 5.09) vs. 1.91 (1.07, 2.26), 1.02 (0.91, 1.88) at 14 days; 5.12 (2.41, 6.32) vs. 1.94 (1.18, 2.70), 1.62 (0.22,1.88) at 1 month, all P < 0.05]. The results of 1-year follow-up showed that 25 patients with recurrent angina pectoris without the occurrence of myocardial infarction. The proportion of recurrent angina pectoris in TF-1208 I I genotype was significantly higher than that in TF-1208 DD genotype and TF-1208 D/I genotype group (χ2= 0.197, P = 0.004). Logistic regression analysis showed that LVEF< 0.50 [odds ratio (OR) = 6.482, 95% confidence interval (95%CI) = 1.365-18.763, P = 0.015] and TF-1208 I I genotype (OR = 8.864, 95%CI = 1.613-46.743, P = 0.012) were independent risk factors for recurrent angina pectoris at 1 year after OPCABG. Conclusions After OPCABG, the body was in a hypercoagulable state and lasted for a long time, and almost recovered 3 months after operation. LVEF < 0.50 and TF-1208 I I genotype were independent risk factors of angina pectoris at 1 year after surgery.
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Heparin induced thrombocytopenia ( HIT ) is a severe side effect of heparin with antibody-mediation.Laboratory assays can be divided into two major categories, about functional assays and HIT antibodiesdetection.Thefunctional assays, such as the serotonin release assay ( SRA ) and heparin-induced platelet activationassay( HIPA) , are sensitive and specific for HIT.They arethe reference standard assays generally, but have thedeficiencies of complicated operation and time-consuming, and cannot be used as a routine examination. TheHIT antibodiesdetections, such as ELISA, immune turbidimetry assay, chemiluminescent assay and lateral flow immunoassay, have high diagnostic sensitivityandareavailable at routine laboratories.They can exclude the diagnosis of HIT or beused to diagnose HIT effectively combined with the pre-test probability score(4Ts score) of HIT.
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Platelets is the important hemostatic component in the blood and the critical participants in inflammation. It is an important promoting factor during inflammation and can recruit leukocytes and aggregate in sepsis. Decreasing plate?let count was correlated with reverse clinical outcome. Therefore, the value of the platelets examination in clinical monitor was studied by many researchers. Under circumstance of fungal infections, platelets mediate antimicrobial activity and assist dissemination of the fungi synchronously. Regulating interaction between platelets and fungi is difficult. In allergic inflamma?tion patients, the excessive activating of platelets aggravates airway obstruction and worsen pulmonary function. We reviewed current research in activating platelets during inflammation.
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Objective To study the variation characteristics of plasma von Willebrand factor antigen (vWF Ag) after the off-pump coronary artery bypass graft (OPCAB) and its predictive value on the assessment of cardiovascular ischemia events in the postoperative patients.Methods A total of 338 patients with non-ST-segment elevation myocardial infarction were selected from 2010 to 2012 in this retrospective cohort study,with 249 males and 89 females and a mean age of (69.2 ± 4.5) years.The level of vWF Ag was assayed by the IL ACL-TOP 700 blood coagulation instrument.Receiver-operator curve (ROC) analysis of vWF Ag levels in the prediction of risk of ischemic events was performed.x2 test and Logistic regression were conducted to analyze the relevance between vWF Ag and clinical pathological factors.Cox regression analysis model were used to evaluate the effect on prognosis.Results There was significant difference in vWF Ag level at different time point between the poor recovery group and the stable disease group (x2 =129.53 and 101.48 respectively,both P＜0.01).And the vWF Ag level was higher in the poor recovery group on the 14th,30th,60th,90th day after OPCAB than in the stable disease group at the same time points respectively (all P＜0.05).The optimum cut-off point of vWF Ag (the 30th day after OPCAB) for prediction of ischemic events was 251 ％ within the 31-90th day after OPCAB,the area under ROC curve was 0.839 (95％ confidence interval:0.776-0.902).The Logistic regression analysis showed that the vWF Ag level on 30th day after OPCAB was affected by age,left ventricular ejection fraction,left main artery disease,serum creatinine level,vascular number of bypass grafts,history of myocardial infarction and hypertension (all P＜0.01).The Cox analysis showed that the cut-off value of vWF Ag (on the 30th day after OPCAB) was the independent prognostic assessment parameter for ischemic events in patients with cardiovascular diseases within one year.Conclusions The variation of serum vWF Ag level can reflect the integrated influence of multiple pathological factors on vascular endothelial function after the OPCAB,it can become the effective predictor for disease progression within 90 days and the long-term prognosis after OPCAB.
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Objective To compare the mRNA expressions of interleukin (IL)-17 and IL-23 in peripheral blood of patients with psoriasis vulgaris versus healthy individuals,assess the relationship of these parameters with psoriasis area and severity index (PASI) score,and to investigate the therapeutic mechanisms of total glucosides of peony (TGP) for psoriasis vulgaris.Methods Fifty patients with psoriasis vulgaris and 40 healthy individuals were enrolled in this study.Of these patients,42 were treated with TGP of 600-900 mg twice a day for 8 weeks.Blood samples were obtained from all the healthy individuals,50 patients before treatment,42 patients after 4-week treatment,and 23 patients after 8-week treatment.Real-time fluorescence-based quantitative reverse transcription PCR (RT-PCR) was used to determine the mRNA expression levels of IL-17 and IL-23 in the blood samples.The severity of psoriasis was evaluated using PASI score before and after the treatment.Statistical analysis was done by t test,rank sum test,and Pearson correlation analysis using the SPSS16.0 software.Results The IL-17 and IL-23 mRNA expression levels (given in △Ct value) in the patients before treatment were significantly higher than those in the healthy controls (IL-17,-5.32 ± 0.80 vs.2.79 ± 0.76,t =47.71,P ＜ 0.05; IL-23,-5.43 ± 0.68 vs.-3.77 ± 0.86,t =10.38,P ＜ 0.05),and positively correlated with the PASI score (r =0.61,0.52 respectively,both P ＜ 0.05).A significant decrease was observed in the mRNA expression levels of IL-17 and IL-23 as well as PASI score in the 42 patients after 4-week treatment with TGP compared with those before treatment(IL-17,-2.24 ± 0.61 vs.-5.30 ± 0.78,t =20.40,P ＜ 0.05; IL-23,-1.97 ± 0.74 vs.-5.44 ± 0.68,t =21.69,P ＜ 0.05; PASI,5.8 ± 2.7 vs.9.4 ± 4.2,t =4.68,P ＜ 0.05),and in the 23 patients after 8-week treatment compared with those after 4-wek treatment(IL-17,-1.51 ± 0.78 vs.-2.21 ± 0.59,t =3.50,P ＜ 0.05; IL-23,-1.27 ± 0.81 vs.-1.89 ± 0.72,t =2.70,P＜ 0.05; PASI,3.8 ± 1.8 vs.7.3 ± 2.5,t =5.47,P＜ 0.05).Conclusions It seems that both IL-17 and IL-23 are involved in the pathogenesis of psoriasis vulgaris,and TGP treatment can reduce the mRNA expression levels of IL-17 and IL-23 as well as PASI score in patients with psoriasis vulgaris.
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Objective To study the assessment value of serum protein C activity ( PC∶A) test in the patient′s condition and prognosis in bronchial asthma.Methods 202 bronchial asthma patients were selected from the Tianjin medical university general hospital from 2010 to 2012 for this retrospective cohort study, 77 males and 125 females with a mean age of 41.2 ±11.4 years.the level of PC∶A were analysed by IL ACL TOP 700 coagulation analyzer.Receiver operating characteristic curve ( ROC) was used to analyze the diagnosis performance of PC∶A, χ2 test was used to analyze the relevance between PC∶A and clinical pathological factors , Cox regression analysis model was used to evaluate the effect on prognosis , Kaplan-Meier curve to implement survival analysis.Results The elevels of PC∶A were:control group ( 102.2 ± 13.6)%, intermittent attack group (104.8 ±11.9)%, mild persistent group (136.3 ±15.8)%, moderate persistent group ( 129.0 ±13.5 )% and severe persistent ( 126.8 ±14.7 )% respectively , and there was significantly difference among the all groups ( F =7.15, P <0.01 ).Compared the control group and intermittent attack group with other groups , the PC∶A level was higher in mild persistent group ( q=16.83, q=15.54, P<0.05), moderate persistent group (q=19.94,q=12.15, P<0.05), and severe persistent group(q=11.37,q=10.66, P<0.05).The PC∶A level was lower in moderate and severe persistent group than mild persistent group ( q =3.82, q =4.30, P <0.05 ).After undergoing regular treatment for six months, the PC∶A level was higher in partly controlled group and uncontrolled group than complete controlled group (q=12.45, q=9.91,P<0.05).The optimum cut-off point of PC∶A (after undergoing regular treatment for six months ) for asthma condition with uncontrolled was 118.0%, the area under ROC curve was 0.892 ( 95% confidence interval:0.851-0.936 ).The χ2 test results showed that there was the relevance between the serum PC∶A level and the eosinocyte , total serum IgE , complicated allergic rhinitis and lung function ( FEV1%) ( P<0.01 ).The Cox analysis and survival analysis showed that the serum PC∶A level ( after undergoing regular treatment for six months ) was the independent assessment parameter for asthma acute attack in 7th-12th month, the cumulative probability of acute attack was increased obviously in the patients who with PC∶A level over the cut-off value.Conclusions The serum PC∶A level was increased obviously in asthma patients , and was related to patient′s condition, level of asthma control and severe attacks risk , which could be used as an effective indicator for assessment of disease progression and asthma control in asthma patients.
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Objective To study the variation of D-dimer after the off-pump coronary artery bypass grafting(OPCAB),and to evaluate its value for the assessment of postoperative cardiovascular ischemia events.Methods This is a retrospective cohort study.203 patients with non-ST-segment elevation myocardial infarction(NSTEMI) were random selected from the Tianjin medical university general hospital from 2010 to 2012,including 151 males and 52 females with a mean age of (66.9 ±8.4) years.The level of D-dimer was analysed by using the Biomerieux VIDAS fluor-euzymelinked immunoassay Analyzer assay.Receiver operating characteristic curve (ROC) was used to evaluate the sensitivity and specificity,the relevance between D-dimer and clinical pathological factors was analysed by x2 test,the effect on prognosis was evaluated by using cox regression analysis model.Results Compared the group with stable disease,the level of D-dimer was increased remarkable in the group with poor recovery on the 14th day after surgery,(U =75.09,P ＜0.01).The optimum cut-off point with D-dimer(the 14th day after surgery) for the diagnosis of ischemic events within the 31th-90th day after surgery was 2 590μg/L,the area under ROC curve was 0.867(95％ confidence interval:0.791-0.943).The logistic analysis showed that the D-dimer was influenced by the sex,age,left ventricular ejection fraction,left main coronary artery disease,the number of vascular with bypass grafts,using internal mammary artery,hypertension and other factors,OR value was 0.495(95％ CI:0.327-0.694),0.527(95％ CI:0.370-0.812),0.564(95％ CI:0.419-0.638),0.331(95％ CI:0.278-0.426),0.592(95％ CI:0.440-0.785),2.093(95％ CI:1.533-2.856),0.580 (95 ％ CI:O.451-0.709) respectively (P ＜ 0.01).The Cox analysis showed that the level of Ddimer on the 14th day after surgery was not the independent assessment parameter for long-term prognosis.Conclusion The serum D-dimer was influenced by multiple pathological factors after the OPCAB,the level of serum D-dimer(on the 14th day after surgery) could be used as effective estimate parameter for the adverse events within the 31 th-90th after OPCAB.
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Objective To investigate the reasonable time limit for stopping the aspirin treatment in preoperative pa-tients with general surgery and the effects on platelet function in postoperative patients with recovering the therapy of aspirin. Methods A total of 121 patients undergoing elective general surgery were divided into stopping aspirin treatment 5 d group (n=59) and stopping aspirin treatment 7 d group (n=62). Fifty healthy volunteers were used as the control group. The arachi-donic acid (AA)-induced platelet aggregation test was used to detect the platelet agglutination rate in all groups. Aspirin was reused 24~48 h after surgery. The level of urinary 11-dehydro-thromboxane B2 (11-DH-TXB2) was assayed by ELISA 7 and 10 d after retreatment. Results The levels of the PAgT (5 min, 8 min and 10 min) were decreased significantly in pa-tients with stopping aspirin treatment 5 d group compared with those of patients with stopping aspirin treatment 7 d group and control group (P0.05). Conclusion The platelet aggregative function returned to normal level in patients with 7-d preoperative stopping aspirin. The laboratory moni-toring of aspirin therapy should be more than 7 d after postoperative reusing aspirin.