ABSTRACT
OBJECTIVE@#To explore the predictive value of four items of new thrombus markers combined with conventional coagulation tests for thrombosis in antiphospholipid syndrome.@*METHODS@#A total of 121 antiphospholipid syndrome (APS) patients who hospitalized at Peking University People's Hospital from March 2022 to January 2023 were selected and divided into thrombus group (50 cases) and nonthrombus group (71 cases) according to whether thrombosis occurred. The differences of laboratory characteristics including antiphospholipid antibodies were compared between the thrombotic and non-thrombotic groups. Chemiluminescent immunoassay was used to detect thrombomodulin (TM), thrombin-antithrombin complex (TAT), Plasmin-α2 plasmin inhibitor complex (PIC), and tissue plasminogen activator inhibitor complex (t-PAIC) in plasma from venous. The independent risk factors of thrombosis in patients with APS were determined using binary Logistic regression. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the efficacy of each index on the prediction of thrombosis.@*RESULTS@#Compared with the patients without thrombosis, the patients with thrombosis were older [49 (32, 64) years vs. 36 (32, 39) years, P < 0.05]. The percentages of male, smoking, hypertension, and global antiphospholipid syndrome score (GAPSS)≥10 in the patients with thrombosis were significantly higher than those in the patients without thrombosis (P < 0.05). The positive rates of anticardiolipin antibody (aCL) and lupus anticoagulant (LA) in the thrombotic group were significantly higher than those in the non-thrombotic group (P < 0.05), and the levels of prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin degradation product in the thrombotic group were significantly higher than those in the non-thrombotic group (P < 0.05).Among the thrombosis group, venous thrombosis accounted for 19 (38.00%), including deep vein thrombosis (16, 84.21%) and pulmonary embolism accounted (5, 26.32%); Arterial thrombosis accounted for 35 (70.00%), including myocardial infarction (6, 17.14%) cerebral infarction (30, 85.71%). The patients in the thrombotic group had significantly greater TM levels than those in the non-thrombotic group (P < 0.05).There were no significant dif-ferences between the two groups in TAT (Z=-1.420, P=0.156), PIC (Z=-0.064, P=0.949), and t-PAIC (Z=-1.487, P=0.137). Univariate and binary Logistic regression analysis of relevant variables showed that advanced age [OR=1.126, P=0.002], elevated TM [OR=1.325, P=0.048], prolonged prothrombin time (PT) [OR=4.127, P=0.008] were independent risk factors for thrombosis in the patients with APS. ROC curve analysis of the above three independent risk factors showed that the combined detection of age, PT and TM had the highest Yoden index (0.727) and sensitivity (83.0%), with a specificity of 89.7%.@*CONCLUSION@#TAT, PIC, TM, and t-PAIC may reflect thrombus formation from the coagulation system, fibrinolysis system, and endothelial system. The combined of age TM and PT is superior to the application of a single marker, which has diagnostic value for the early identification of APS thrombosis.
Subject(s)
Humans , Male , Antiphospholipid Syndrome/diagnosis , Tissue Plasminogen Activator , Thrombosis/etiology , Antibodies, Antiphospholipid/analysis , Blood Coagulation Tests/adverse effectsABSTRACT
【Objective】 To analyze the value of plasmin-α2-plasmin inhibitor complex (PIC) and thrombin-antithrombin complex (TAT) for risk stratification of massive transfusion (MT) in patients with postpartum hemorrhage (PPH). 【Methods】 Clinical data and blood samples of patients with PPH in our hospital from January 2019 to December 2022 were retrospectively analyzed. MT (MT group, n=60) was defined as transfusion of red blood cells≥10 U within 24 h after delivery, and 3.25 ng/mL and PIC level>1.04 μg/mL were independent risk factors for MT after PPH. 【Conclusion】 Elevated TAT and PIC levels are independent predictors of MT in patients with PPH, and their combined predictive efficacy is better.
ABSTRACT
OBJECTIVES@#There is a high coagulation state in pregnant women, which is prone to coagulation and fibrinolysis system dysfunction. This study aims to explore the latest coagulation markers-thrombomodulin (TM), thrombin-antithrombin complex (TAT), plasmin-α2 plasmin inhibitor complex (PIC), and tissue plasminogen activator/plasminogen activator inhibitor compound (tPAI-C) in different stages of pregnancy, establish reference intervals (RIs) for healthy pregnant women of Chinese population, and to provide an effective and reliable reference for clinicians.@*METHODS@#A total of 492 healthy pregnant women, who underwent pregnancy examination and delivery in the Department of Obstetrics, Second Xiangya Hospital of Central South University from October 2019 to October 2020, were enrolled for this study. They were assigned into the first trimester group, the second trimester group, the third trimester group, and the puerperium group according to the pregnancy period, and 123 healthy non-pregnant women were selected as the controls. Plasma levels of TM, TAT, PIC and tPAI-C were analyzed by automatic chemiluminescence immunoassay analyzer. The RIs for TM, TAT, PIC, and tPAI-C were defined using non-parametric 95% intervals, determined following Clinical and Laboratory Standards Institute Document C28-A3c (CLSI C28-A3c), and Formulation of Reference Intervals for the Clinical Laboratory Test Items (WS/T402-2012).@*RESULTS@#TM and TAT levels increased gradually in the first, second, and third trimester women and decreased in the puerperium women (P<0.05 or P<0.01). PIC level of healthy non-pregnant women was lower than that of pregnant women (P<0.05 or P<0.01), but PIC level of pregnant and puerperium women did not differ significantly (P>0.05). tPAI-C level in healthy non-pregnant women was lower than that of pregnant women (P<0.05 or P<0.01), and tPAI-C level was significantly decreases in the puerperium women (P<0.01). The RIs for TM were as follows: Healthy non-pregnant women at 3.20-4.60 TU/mL, the first and second trimester at 3.12-7.90 TU/mL, the third trimester at 3.42-8.29 TU/mL, puerperium at 2.70-6.40 TU/mL. The RIs for TAT were as follows: Healthy non-pregnant women at 0.50-1.64 ng/mL, the first and second trimester at 0.52-6.91 ng/mL, the third trimester at 0.96-12.92 ng/mL, puerperium at 0.82-3.75 ng/mL. The RIs for PIC were as follows: Healthy non-pregnant women at 0.160-0.519 ng/mL, pregnant women at 0.162-0.770 μg/mL. The RIs for tPAI-C were as follows: Healthy non-pregnant women at 1.90-4.80 ng/mL, the first and second trimester at 2.03-9.33 ng/mL, the third trimester at 2.80-14.20 ng/mL, puerperium at 1.10-8.40 ng/mL.@*CONCLUSIONS@#The levels of 4 new coagulation markers TM, TAT, PIC, and tPAI-C in pregnant women are increased significantly during pregnancy and gradually return to normal after delivery. The RIs for TM, TAT, PIC, and tPAI-C in pregnant women by trimester are established according to CLSI C28-A3c, thus providing a clinical reference for clinician in judgement of thrombotic risk.
Subject(s)
Female , Humans , Pregnancy , Biomarkers/blood , Blood Coagulation , Postpartum Period , Reference ValuesABSTRACT
Objective:To investigate the clinical significance of plasma thrombin-antithrombin complex (TAT) levels in patients with sepsis-induced cardiomyopathy(SIC).Methods:One hundred and seven sepsis patients who were admitted to intensive care units (ICU) of the 908th Hospital of Chinese PLA Logistical Support Force were enrolled in the study. Patients were divided into sepsis group ( n=79) and the sepsis-induced cardiomyopathy group ( n=28) according to whether the cardiac ultrasound examination in 2 hours after admission, and the differences of each indicators between the two groups were compared including acute physiological and chronic health score (APACHEⅡ), lactate, blood routine, liver and kidney function, cardiac troponin I, N-terminal?pro-brain?natriuretic?peptide (NT-pro BNP), conventional coagulation tests and molecular markers of coagulation [tissue plasminogen activator-inhibitor complex (t-PAIC), thrombomodulin (TM), TAT, plasmin-α2-plasmin inhibitor complex (PIC)].Logistical?regression?was?used?to analyze the?risk?factors?for sepsis-induced cardiomyopathy and the receiver operating characteristic (ROC) curve was to analyze their cut-off values. The effect of low-molecular-weight heparin anticoagulation therapy on sepsis patients with TAT>8.26 ng/ml was evaluated by Kaplan-Meier analysis. Results:Compared with the cardiac troponin I[0.02(0.01, 0.09) ng/ml], NT-proBNP [1 118.09 (333.25, 2687.00) pg/ml], lactate[1.35(0.90, 2.60) mmol/L], TAT[6.50(3.94, 12.14) ng/ml], PIC[1.256 (0.668, 2.045) μg/ml] and t-PAIC[10.50 (6.70, 21.30) ng/ml] in sepsis group, the cardiac troponin I [0.75(0.01, 6.02) ng/ml], NT-proBNP[12 125.14(4 185.89, 33 611.62) pg/ml], lactate[2.35(1.43, 4.34) mmol/L], TAT[19.85 (9.08, 45.78) ng/ml], PIC[2.115 (0.878, 4.114) μg/ml] and t-PAIC [22.03(15.61,33.20) ng/ml] levels in the sepsis-induced cardiomyopathy group were significantly increased ( P<0.05). Logistical regression showed that positive NT-pro BNP and elevated TAT levels were independent risk factors for sepsis-induced cardiomyopathy. ROC curve analysis showed that the area under the curve of plasma TAT level for predicting sepsis-induced cardiomyopathy was 0.78. The sensitivity and specificity at the cut-off value of plasma TAT level with 8.26 ng/ml were 0.82 and 0.63, respectively. Conclusions:The elevated TAT level was an independent risk factor for the development of sepsis-induced cardiomyopathy. Low-molecular-weight heparin anticoagulation therapy can improve the 28-day survival rate of sepsis patients with TAT>8.26 ng/ml.
ABSTRACT
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.
ABSTRACT
[Abstract] Objective To determine the prognostic value of thrombomodulin (TM) combined with thrombin-antithrombin complex (TAT) in patients with sepsis. Methods A retrospective analysis of the clinical data from 80 patients with sepsis who met the inclusion and exclusion criteria admitted to the 908th Hospital of Chinese PLA Logistical Support Force from May 2018 to July 2019. The conventional coagulation tests, thromboelastographic (TEG) parameters, TM, TAT, α2-plasmin inhibitor-plasmin complex (PIC, namely plasmin/alpha 2-antiplasmin complex, PAP) and tissue plasminogen activator-inhibitor-1 complex (t-PAIC) were collected within 2 hours at admission. According to the prognosis of 90 days, the patients were divided into survival group and death group and statistical analysis were performed. Results Compared with TM [11.7(8.8, 15.9) TU/ml] and TAT [11.3(7.0, 20.5) ng/ml] in the survival group, TM [20.2(14.1, 23.8) TU/ml] and TAT [17.7(11.8, 54.6) ng/ml] were significantly increased in the death group (P16.95 TU/ml combined with TAT>10.55 ng/ml. Conclusion TM combined with TAT can effectively judge the prognosis of sepsis patients and early identify sepsis related coagulation disorders.
ABSTRACT
Objective@#To evaluate the clinical value of four items of thrombosis detection, including thrombin-antithrombin complex (TAT), α2-plasmin inhibitor-plasmin complex (PIC), thrombomodulin (TM) and tissue plasminogen activator-inhibitor complex (t-PAIC), combined with D-dimer (D-D) and fibrin degradation products (FDP) in venous thrombosis in patients with malignant tumor.@*Methods@#A total of 904 patients with malignant tumor from October 2017 to March 2019 in General Hospital of Heilongjiang Province Land Reclamation Bureau were selected (malignant tumor group), and 200 healthy physical examination patients were selected as healthy control group. Among 904 patients with malignant tumor, 92 patients had venous thrombosis (thrombosis group), and 812 patients had not venous thrombosis (non-thrombosis group). The TAT, PIC, TM, t-PAIC, FDP and D-D were detected. The relationship between TAT, PIC, TM, t-PAIC, D-D, FDP and venous thrombosis was analyzed by binary Logistic regression. The receiver operating characteristic (ROC) curve was used to determine the diagnostic performance of each index, and the maximum value of the Youden index was the optimal cut-off value.@*Results@#The TAT, PIC, TM, t-PAIC, D-D and FDP in malignant tumor group were significantly higher than those in healthy control group, and there were statistical differences (P<0.01). The TAT, PIC, TM, t-PAIC, D-D and FDP in thrombosis group were significantly higher than those in non-thrombosis group: 20.20 (12.30, 59.45) μg/L vs. 8.60 (4.87, 15.15) μg/L, 1.23 (0.69, 2.84) mg/L vs. 0.70 (0.37, 1.45) mg/L, 14.55 (8.12, 21.10) kU/L vs. 10.05 (7.975, 13.90) kU/L, 10.20 (7.30, 15.17) μg/L vs. 7.40 (5.20, 12.65) μg/L, 3.42 (1.38, 7.07) μg/L vs. 1.69 (0.53, 4.64) μg/L, 6.41 (3.21, 17.05) mg/L vs. 5.15 (2.26, 10.01) mg/L, and there were statistical differences (P<0.01 or <0.05). Binary Logistic regression analysis result showed that TAT, PIC, TM, t-PAIC, D-D and FDP were correlated with venous thrombosis in patients with malignant tumor (OR = 1.277, 1.209, 1.107, 1.089, 1.260, 1.078 and 0.002; P<0.01 or <0.05). ROC curve result showed that the optimal cut-off values of TAT, PIC, TM, t-PAIC, D-D and FDP in the diagnosis of venous thrombosis in patients with malignant tumor were 24.450 μg/L, 2.624 mg/L, 17.750 kU/L, 13.250 μg/L, 5.290 μg/L and 22.435 mg/L; and the area under curve (AUC) were 0.788, 0.659, 0.621, 0.597, 0.626 and 0.598, respectively. The AUC of TAT + PIC + TM + t-PAIC and TAT + PIC + TM + t-PAIC + D-D + FDP in the diagnosis of venous thrombosis in patients with malignant tumor were significantly higher than D-D + FDP (0.808 and 0.796 vs. 0.633). Ninety patients with TAT>24.450 μg/L or PIC>2.624 mg/L were selected. Fourty-five cases of them were injected with low molecular weight heparin (experimental group) for 6 weeks, and another 45 cases were not treated with low molecular weight heparin (control group). Both groups were followed up for 1 year. The incidence of venous thrombosis in the experimental group was significantly lower than that in control group: 2.22% (1/45) vs. 15.56% (7/45), the survival time was significantly longer than that in control group: (10.6 ± 3.1) months vs. (8.5 ± 2.8) months, and there were statistical differences (P<0.05), and no bleeding occurred in experimental group.@*Conclusions@#Four items of thrombosis detection combined with D-D and FDP is better than single detection. It is the best non-invasive method to detect venous thrombosis. It can predict the possibility of venous thrombosis in patients with malignant tumor at an early stage, and help patients actively use preventing drug, determine the best and most reasonable treatment time, improve the prognosis of patients, and prolong survival time.
ABSTRACT
Objective According to the cell-based coagulation theory, antithrombin complex (TAT) reflecting the activation of coagulation system, plasmin-α2 anti-plasmin complex (PIC) reflecting the activation of fibrinolytic system, thrombomodulin (TM) and tissue plasminogen activator-plasminogen activator inhibitor-1 complex (t-PAIC) reflecting vascular endothelial function were selected to explore their diagnostic values for disseminated intravascular coagulation. Methods A prospective study was conducted on 154 patients in the Department of Critical Care Medicine of the 908th Hospital from May to December 2018. The subjects were divided into non-overt DIC group (n=134) and overt DIC group (n=20) according to the diagnostic criteria of International Thrombus and Hemostatic Association. The differences among groups of TM, t-PAIC, TAT and PIC were compared along with statistical analysis. Results Compared with TM [10.5 (8.0~14.3) TU/mL], TAT [9.6 (4.9~21.8) ng/mL], PIC [1.253 (0.789~2.802) μg/mL] and t-PAIC [ 11.2 (7.1~22.1) ng/mL] in non-overt DIC group, TM [16.8 (11.8~21.5) TU/mL], TAT [33.6 (10.3~120.0) ng/mL], PIC [4.080 (0.814~8.651) μg/mL] and t-PAIC [19.4 (10.0~30.1)ng/mL] ) in overt DIC group were significantly increased (P<0.05). The area under the curve of TM>14.85 TU/mL combined with TAT>23.05 ng/mL as the standard diagnostic overt DIC was 0.835 (P=0.000), and the sensitivity, specificity, positive predictive value and negative predictive value were 0.85, 0.761, 0.592, 0.925 respectively. Conclusion TM combined with TAT has a higher diagnostic efficacy for overt DIC.
ABSTRACT
To clarify the role of TAFI in hypertensive disorders in pregnancy, 22 subjects, including 10 with pre-eclampsia (PE) and 12 with gestational hypertension were examined for the levels of TAFI and thrombin-antithrombin (TAT) complex. Thirty normal pregnant women served as controls. ELISA was employed for the detection. The results showed that the TAFI antigen levels in normal pregnancy group, gestational hypertension group and PE group were (85.35±24.69)%, (99.65±18.27)%, (110.12±23.36)%; (97.06±21.40)%, (114.08±27.76)%, (125.49±24.70)%; (106.6±19.21)%, (129.2±25.07)%, (139.1±30.12)%, in the 1st, 2nd and 3rd trimester respectively. No significant differences were found between the normal pregnancy group and gestational hypertension group but significant difference existed between normal pregnancy group and PE group in each tri- mester (P<0.05). TAT complexes were significantly higher in patients with PE than that in controls (P<0.05), but no correlation was found between TAT and TAFI. It is concluded that TAFI may con- tributed to the impairment of fibrinolysis in the patients with PE and may serves as a sensitive indi- cator for PE, but it may not help in the diagnosis of the gestational hypertension.
ABSTRACT
Objective To observe the effects of recombinant staphylokinase (r-SAK) on platelet activation parameters in patients with acute myocardial infarction(AMI) by intravenous thrombolysis in order to investigate the clinical thrombolytic efficacy of r-SAK therapy in AMI comparing with recombinant tissue-type plasminogen activator(rt-PA) therapy.Methods Thirty-three patients with AMI within 12 h after the onset were selected and divided randomly into the r-SAK therapy group(n=17) and rt-PA therapy group(n=16).Coronary artery angiography(CAG) was performed 90 min after thrombolytic therapy in patients.Thrombin-antithrombin complex(TAT) and alpha granule membrane protein(GMP-140) were measured by similar commercial enzyme-linked immunosorbent assay(ELISA).Results In r-SAK group and rt-PA group,the plasma contents of GMP-140 2 h after thrombolytic therapy were significantly higher than before therapy(P0.05).In rt-PA group,the plasma content of TAT 2 h after thrombolytic therapy increased significantly(P0.05).) Conclusion r-SAK has similar effect with rt-PA and it will become available for highly fibrin-selective thrombolytic therapy of AMI.Thrombolytic treatment with r-SAK can improve the injury of myocardial microperfusion.
ABSTRACT
BACKGROUND: The anticoagulant efficacy of low molecular weight heparin (LMWH) as an alternative substitute for standard heparin (SH) was evaluated by measuring thrombin-antithrombin complex (TAT) and tissue factor pathway inhibitor (TFPI). METHODS: Twenty-two patients with coronary artery disease (CAD) were divided into three groups and plasma heparin concentration, platelet count, aPTT, TAT and TFPI before and after injection of SH and LMWH were measured. RESULTS: Plasma heparin concentrations were well correlated after the injection of heparin in group B (LMWH 200 U/kg) and C (LMWH 240 U/kg), but not in group A (SH). Platelet counts were not decreased in most patients and life-threatened bleeding was not observed in any patients. APTT prolongations were observed in all patients of SH group, but not in any patients of B and C. TAT levels were not significantly different between groups. TFPI levels were not significantly different between groups. Heparin levels were well correlated with TFPI levels, but not with TAT levels. CONCLUSION: The anticoagulant effect of LMWH up to 240 U/kg/D was not superior over SH in CAD patients, although it has several merits such as no requirement of aPTT monitoring or better predictability.