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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 12 antithrombins (AT) gene mutations that cause AT deficiency and discuss the relationship between the SERPINC1 gene. mutations and venous thrombotic events.Methods:This study belongs to case series of observational studies. Collected the clinical data of 12 AT deficiency cases in the First Affiliated Hospital of Wenzhou Medical University from April 2014 to April 2021 and collected the blood samples before treatment. The AT activity (AT: A) and AT antigen (AT: Ag) was detected by chromogenic substrate and immunoturbidimetry, respectively. The 7 exons and flanking sequences of the SERPINC1 gene were sequenced directly by PCR, the suspected mutations were validated by reverse sequencing. Analyzed the correlation between the SERPINC1 gene. mutations and venous thrombotic events and figured out the proportion.Results:The AT: A of the 12 patients all decreased significantly, ranging from 30% to 66%, and the AT: Ag of the 7 patients decreased accordingly, showing type Ⅰ AT deficiency, and the AT: Ag of the other 5 patients were normal, presented type Ⅱ AT deficiency. 12 mutations were found including 6 heterozygous mutations which were discovered for the first time: c.456_458delCTT(p.phe121del), c.318_319insT(p.Asn75stop), c.922G>T(p.Gly276Cys), c.938T>C (p.Met281Thr), c.1346T>A(p.Leu417Gln)and c.851T>C(p.Met252Thr). All 12 patients had venous thrombosis, and 3 cases including 2 compound heterozygotes and 1 single heterozygote all suffered from deep venous thrombosis (DVT) when they were younger without obvious triggers. The other 9 patients all combined with the other thrombotic factors including old age, hypertensive, smoking, pregnancy, and prolonged immobilization.Conclusion:Patients with AT deficiency caused by SERPINC1 gene defects are prone to venous thrombosis, especially combined with other thrombotic factors.
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【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.
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Abstract Marfan syndrome classically presents with aortic root aneurysms. Aortic ectasia causes diverse blood flow alterations, influencing the behavior of coagulation factors and platelet activity. Heparin resistance has also been reported associated with Marfan Syndrome in a small number of patients, probably due to antithrombin III (ATIII) deficiency or various mutations. The ascending aorta and the aortic valve are replaced with prosthetic material during Bentall- de Bonno procedures. Resistance to anticoagulation during extracorporeal circulation, represents a significant challenge for both anesthesiologists and the surgical team. Resistance to heparin was observed in a patient with Marfan syndrome undergoing a Bentall procedure. ATIII concentrate was not available, and Activated Coagulation Time did not increase despite high doses of heparin. An alternate anticoagulation approach was used successfully.
Resumen El síndrome de Marfan clásicamente se presenta con aneurismas de la raíz de la aorta. La ectasia aórtica produce alteraciones en el flujo sanguíneo que influyen sobre el comportamiento de los factores de la coagulación y la actividad de las plaquetas. También se ha reportado resistencia a la heparina asociada al Síndrome de Marfan en un menor número de pacientes, probablemente debido a deficiencia de antitrombina III (ATIII) o a diversas mutaciones. La aorta ascendente y la válvula aórtica se reemplazan con material prostético en los procedimientos Bentall- de Bonno. La resistencia a la anticoagulación durante circulación extracorpórea significa un enorme desafío tanto para los anestesiólogos, como para el equipo quirúrgico. Se observó resistencia a la heparina en un paciente con Síndrome de Marfan sometido a un procedimiento de Bentall. No había disponibilidad de concentrado ATIII y no aumentó el Tiempo de Coagulación Activada a pesar de las elevadas dosis de heparina. Se utilizó exitosamente un abordaje alterno de anticoagulación.
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Objective To evaluate the effect of coagulation function changes on the incidence of acute kidney injury (AKI) after liver transplantation. Methods Clinical data of 245 liver transplant recipients who met the inclusion and exclusion criteria were retrospectively analyzed. According to the incidence of AKI after liver transplantation, all recipients were divided into the AKI group (n=99) and non-AKI group (n=146). The incidence of AKI after liver transplantation was summarized. Perioperative parameters of the recipients were collected. The risk factors of AKI after liver transplantation were assessed by univariate and multivariate analysis. Results Among 245 recipients undergoing liver transplantation, 99 cases developed AKI after operation with an incidence rate of 40.4%. Preoperative serum creatinine levels of the recipients and the in-hospital fatality were relatively high in the AKI group (all P < 0.05). Compared with the recipients in the non-AKI group, those in the AKI group presented with significantly higher liver function parameters within postoperative 24 h, significantly decreased levels of stage Ⅱ coagulation parameters including coagulation factorsⅤ, Ⅶ, Ⅸ, Ⅹ, Ⅻ and protein S, protein C and antithrombin Ⅲ, evidently elevated prothrombin time international normalized ratio (PT-INR), remarkably increased stage Ⅲ coagulation parameters including D-dimer and fibrin degradation product (FDP) levels and considerably decreased fibrinogen (FIB) level (all P < 0.05). Thrombelastogram showed that the R value was increased, the α angle was decreased and the coagulation time was prolonged in the AKI group (all P < 0.05). Logistic regression analysis demonstrated that the increased R value of postoperative thrombelastogram [odd ratio (OR) 1.116, 95% confidence interval (CI) 1.018-1.223, P=0.019], and decreased levels of antithrombin Ⅲ (OR 0.974, 95%CI 0.955-0.993, P=0.007) were the independent risk factors of incidence of AKI after liver transplantation. Conclusions The incidence of AKI after liver transplantation is high, which is associated with the coagulation function changes of the recipients. Decreased coagulation factor activity (increased R value) and declined antithrombin Ⅲ level are the independent risk factors of AKI in liver transplantat recipients.
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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.
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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:To investigate the value of antithrombin Ⅲ (AT-Ⅲ) in evaluating patients with decompensated hepatitis B liver cirrhosis and complicated with esophagogastric variceal bleeding (EVB).Methods:From January 1, 2018 to December 31, 2021, clinical data of 193 hospitalized patients with hepatitis B liver cirrhosis diagnosed in the Second Hospital of Shanxi Medical University were retrospectively analyzed, which included coagulation indicator (AT-Ⅲ), liver function indicators (total bilirubin, etc.), abdominal ultrasound results (portal vein diameter, portal vein blood flow velocity), and the occurrence of esophagogastric varices. According to the presence or absence of main complications, 193 patients with hepatitis B liver cirrhosis were divided into compensated group (60 cases) and decompensated group (133 cases). According to the presence or absence of EVB, 133 patients of decompensated group were divided into non-bleeding subgroup (96 cases) and bleeding subgroup (37 cases). The above indicators were compared among compensated group, decompensated group and their subgroups. The independent related factors of decompensated hepatitis B liver cirrhosis and EVB were analyzed. The level of AT-Ⅲ of each group were compared, and the relationship between AT-Ⅲ and Child-Pugh score was analyzed. The diagnostic capability of AT-Ⅲ in decompensated hepatitis B liver cirrhosis and complicated with EVB were analyzed. Mann-Whitney U test, independent sample t test, chi-square test, multiple logistic regression analysis, Pearson correlation analysis and receiver operating characteristic curve (ROC) analysis were used for statistical analysis. Results:The total bilirubin level of the decompensated group was higher than that of the compensated group, the portal vein diameter was larger than that of the compensated group, and the portal vein blood flow velocity was lower than that of the compensated group (31.50 μmol/L (21.90 μmol/L, 48.80 μmol/L) vs. 19.40 μmol/L (15.00 μmol/L, 25.50 μmol/L); (14.31±3.53) mm vs. (12.57±3.83) mm; (13.39±3.49) cm/s vs. (15.08±4.28) cm/s), and the differences were statistically significant ( Z=-5.76, t=-2.78 and 2.40; P<0.001, =0.006 and 0.018). The incidence of esophagogastric varices of the compensated group and the decompensated group was compared (40.0%, 24/60 vs. 87.2%, 116/133), and the difference was statistically significant ( χ2=64.06, P<0.001). The diameter of portal vein of the bleeding subgroup was larger than that of the non-bleeding subgroup, and the portal vein blood flow velocity was lower than that of the non-bleeding subgroup ((15.54±4.23) mm vs. (13.87±3.16) mm; (12.05±3.12) cm/s vs. (13.85±3.51) cm/s), and the differences were statistically significant ( t=-2.15 and 2.23, P=0.034 and 0.028). The AT-Ⅲ levels gradually decreased in the non-bleeding subgroup and bleeding subgroup of the compensated group and decompensated group, which were (79.52±16.02)%, (63.91±19.96)% and (35.92±13.69)%, respectively, the difference was statistically significant ( F=5.71, P=0.018). The AT-Ⅲ level of the compensated group was higher than that of the non-bleeding subgroup and the bleeding subgroup of the decompensated group, and the AT-Ⅲ level of the non-bleeding subgroup of the decompensated group was higher than that of the bleeding subgroup, and the differences were statistically significant ( t=5.11, 13.74 and 7.84, all P<0.001). The results of multivariate logistic regression analysis showed that total bilirubin and AT-Ⅲ were independent related factors of decompensation of hepatitis B liver cirrhosis ( OR (95% confidence interval (95% CI) 1.060 (1.018 to 1.104) and 0.945 (0.922 to 0.970), P=0.005 and <0.001). AT-Ⅲ was an independent related factor of decompensation of hepatitis B liver cirrhosis and complicated with EVB ( OR(95% CI) 0.902 (0.856 to 0.950, P<0.001). AT-Ⅲ was negatively correlated with Child-Pugh score ( r=-0.559, P<0.001). ROC analysis showed that the cut-off values of AT-Ⅲ in the diagnosis of decompensated stage of hepatitis B liver cirrhosis and complicated with EVB were 62.5% and 61.5%, the sensitivity was 88.3% and 89.2%, the specificity was 70.7% and 61.5%, and the area under the curve (95% CI) was 0.815 (0.755 to 0.874, P<0.001) and 0.899 (0.828 to 0.971, P<0.001), respectively. Conclusion:AT-Ⅲ is an important indicator in evaluating the severity of disease progression in patients with hepatitis B liver cirrhosis, and it has a certain clinical value in evaluating the bleeding tendency of patients with decompensated hepatitis B liver cirrhosis and complicated with esophagogastric varices.
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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.
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Female , Humans , Pregnancy , Biomarkers/blood , Blood Coagulation , Postpartum Period , Reference ValuesABSTRACT
OBJECTIVE@#To explore the changes of Ⅻ antithrombin (FⅫa-AT), thrombospondin-1 (TSP-1), and lupus anticoagulant (LA) ratio in the peripheral blood factor of patients with systemic lupus erythematosus (SLE) and the clinical value of combined diagnosis of thrombotic events.@*METHODS@#A total of 133 SLE patients treated in Xingtai People's Hospital were selected and divided into simple SLE group (105 cases) and SLE complicated with thrombosis group (28 cases) according to whether thrombotic events occurred, and 102 cases of healthy people in the same period were selected as control. The clinical data of the 3 groups, the level of peripheral blood FⅫa-AT, TSP-1, and LA ratio were compared, the relationship between each peripheral blood index and SLE disease activity index (SLEDAI) score were analyzed. The influencing factors of thrombotic events in SLE patients were analyzed, and the value of each peripheral blood index in the diagnosis of SLE complicated with thrombotic events were evaluated.@*RESULTS@#The proportion of the patients with age ≥60 year, hypertension, and smoking history in SLE complicated with thrombosis group was higher than those in simple SLE group and control group (P＜0.05). The SLEDAI score, peripheral blood FⅫa-AT, TSP-1, LA ratio levels of the patients in SLE complicated with thrombosis group were significantly higher than those in simple SLE group and control group, and the simple SLE group was significantly higher than the control group (P＜0.05). FⅫa-AT, TSP-1, LA ratio in peripheral blood of SLE patients were positively correlated with SLEDAI score (r=0.663, 0.578 and 0.625). Age, blood pressure, smoking history, peripheral blood FⅫa-AT, TSP-1, LA ratio were the important influencing factors of thrombotic events in SLE patients (P＜0.05). The AUC diagnosed by the FⅫa-AT, TSP-1, and LA ratio in peripheral blood was 0.881, the 95% CI was 0.813-0.931, the sensitivity was 82.14%, and the specificity was 91.43%, which was superior to each index alone (P＜0.05).@*CONCLUSION@#Peripheral blood FⅫa-AT, TSP-1, LA ratio level changes in SLE patients are significantly related to disease activity, and the combined diagnosis of thrombotic events is more reliable.
Subject(s)
Humans , Lupus Erythematosus, Systemic/complications , Risk Factors , Thrombosis/etiology , Thrombospondin 1ABSTRACT
【Objective】 To investigate the relationship between the level of thrombin-antithrombin complex (TAT)/α2-plasmin inhibitor-plasmin complex (PIC) and the utilization rate of mechanical ventilation (MV) in critically ill patients. 【Methods】 For the cross-sectional study, adult patients who had been admitted to the intensive care unit (ICU) for one day or longer and had a record of the first four tests for thrombosis were enrolled. Age, gender, the results of TAT and PIC, disseminated intravascular coagulation score, treatment, and diagnostic information were retrospectively collected from the hospital information system and laboratory information system. Logistic regression model was used to explore the relationship between TAT/PIC and the MV utilization rate. Interaction analysis and subgroup analysis were conducted to explore whether there was any difference between patients with different age and gender, patients with/without DIC, and with/without infection. 【Results】 A total of 1 176 patients were enrolled in this study. The median of the first TAT/PIC was 15.84 (8.13-33.11) in all the patients. The multivariable Logistic regression model results showed that for every 5 increase in TAT/PIC, the possibility of using MV increased by 2.9% (OR=1.029, 95% CI: 1.008-1.050), and the possibility of using MV in Q3 patients was 1.566 times than that in Q1 patients (OR=1.566, 95% CI: 1.095-2.239); the possibility of using MV in Q4 patients was 2.457 times than that in Q1 patients (OR=2.457, 95% CI: 1.694-3.563). Interaction results showed that the relationship between the level of TAT/PIC and MV usage was different in patients with and without infection (Pinteraction=0.02). Further subgroup analysis showed that in the infected patients (674 cases), the possibility of using MV increased by 5.9% for every 5 increase in TAT/PIC (OR=1.059, 95% CI: 1.022-1.097, P=0.001), while there was no significant difference between different TAT/PIC and MV usage in non-infected patients (502 cases) (OR=1.012, 95% CI: 0.984-1.040, P=0.405). 【Conclusion】 There is a correlation between the level of TAT/PIC and mechanical ventilation in patients with infection in the ICU.
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Plasma protein products, essential drugs for various clinical diseases, are therapeutic biological products extracted from healthy human plasma. The research and development of new plasma protein products, led by United States and European, has been widely deepened and enhanced. Therefore, accelerating the development of new plasma protein products in China is of great significance. This review summarizes the research and development of plasma protein products that have been marketed abroad but have not produced in China, as well as analyzes the difficulties and prospects of the development of plasma protein products in China.
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【Objective】 To study the effect of different concentrations of heparin, ATⅢ or a mixture of heparin and antithrombin Ⅲ (ATⅢ) (1∶1)on the activity of human coagulation factor Ⅸ (FⅨ). 【Methods】 The heparin or heparin/ATⅢ with different concentrations were added into human coagulation Ⅸ products or human prothrombin complex (PCC) to prepare heparin or heparin/ATⅢ samples, containing 0, 0.1, 0.3, 0.5, 0.8, 1, 2 and 4 IU per unit. ATⅢ with different concentrations were added into FⅨ or PCC to prepare ATⅢ samples containing ATⅢ 0, 0.1, 0.5 and 1 IU per unit. The FⅨ activity of the samples prepared was tested by one-stage coagulation method. Then corresponding amount of protamine sulfate were added to neutralize heparin or heparin/ATⅢ to detect the FⅨ activity again. Their influence of heparin, ATⅢ and heparin/ATⅢ with different concentrations on the activity of FⅨ were analyzed. 【Results】 When the content of heparin or heparin/ATⅢ was 0, 0.1, 0.3 and 0.5 IU per unit of FⅨ, the detection results of FⅨ titer in samples were consistent. When the content of heparin or heparin/ATⅢ per unit of FⅨ was 0.8, 1, 2 and 4 IU, the detection results of FⅨ titer were all lower than those of samples without heparin. When the ATⅢ content was 0, 0.1, 0.5 and 1 IU, the FⅨ titer of the samples was consistent. 【Conclution】 When the content of heparin or heparin/ATⅢ in the product is less than or equal to 0.5 IU per IU of FⅨ, the step of protamine sulfate adding could be omitted as it has little effect on FⅨ activity. When >0.5 IU per IU of FⅨ, however, protamine sulfate adding, to neutralize heparin, is necessary before FⅨ activity testing.
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Objective:To assess the predictors of outcomes for different subtypes of liver failure, and the effectiveness of artificial liver support systems in the treatment of liver failure.Methods:The clinical data of 112 patients with hepatitis B virus (HBV)- and non-HBV-related liver failure admitted to the intensive care unit (ICU) of the Fifth People's Hospital of Wuxi were collected from January to December 2020. The relevant etiologies of acute, subacute, acute-on-chronic, subacute-on-chronic, chronic subtype liver failure were analyzed. The efficacies of artificial liver support systems in the treatment of various subtypes of liver failure were also compared. The correlation of various indicators was analyzed by Spearman correlation analysis, the risk factors affecting the prognosis of patients with liver failure were analyzed by multivariate Logistic regression equation, and receiver operator characteristic curve (ROC curve) of subjects was plotted to evaluate the predictive value of each risk factor for the prognosis of patients with liver failure.Results:Among the 112 liver failure patients, 63 were caused by hepatitis B and 49 were caused by non-hepatitis B. The liver failure caused by hepatitis B was 6 times higher than for men than for women, which was higher than that of non-HBV liver failure group (1.33 times). Antithrombin Ⅲ (AT Ⅲ) and total bilirubin (TBil) levels of subacute liver failure were higher than those of pre-liver failure in the HBV liver failure group [AT Ⅲ: (59.33±14.57)% vs. (35.66±20.72)%, TBil (μmol/L): 399.21±112.94 vs. 206.08±126.96, both P < 0.05]. The levels of AT Ⅲ in patients with pre-liver failure and chronic liver failure in the non-HBV liver failure group were significantly higher than those with acute liver failure [(58.33±15.28%), (44.00±19.10)% vs. (31.33±7.57)%, both P < 0.05], patients with acute liver failure had significantly lower level of TBil than pre-liver failure (μmol/L: 107.83±49.73 vs. 286.20±128.92, P < 0.05), the TBil levels in patients with subacute and acute-on-chronic liver failure were also significantly higher than that in pre-liver failure group (μmol/L: 417.27±118.60, 373.00±187.00 vs. 286.20±128.92, both P < 0.05). Patients with subacute liver failure, subacute-on-chronic liver failure and chronic liver failure in the non-HBV failure group were significantly longer than those in acute liver failure (days: 36.00±8.31, 27.52±11.71, 27.72±22.71 vs. 11.00±1.41, all P < 0.05). There was no statistically significant difference in the case fatality rate of using the artificial liver support system between the HBV failure group and the non-HBV failure group (55.6% vs. 50.0%, P < 0.05), the levels of AT Ⅲ in the two groups of surviving patients were significantly higher than that of the dead [HBV liver failure group: (36.20±6.26)% vs. (27.33±8.87)%, non-HBV liver failure group: (41.06±4.16)% vs. (28.71±12.35)%, both P < 0.01]. Correlation analysis showed that there was a clear positive correlation between AT Ⅲ and TBil in the dead patients of HBV liver failure group and the survival and death patients of non-HBV liver failure group ( r values were 0.069, 0.341, 0.064, and P values were 0.723, 1.196 and 0.761, respectively); there was a significant inverse correlation between AT Ⅲ and TBil in the HBV liver failure group ( r = -0.105, P = 0.745). Multivariate Logistic regression analysis showed that AT Ⅲ was an independent risk factor affecting the prognosis of patients with non-HBV liver failure [odd ratio ( OR) = 1.023, 95% confidence interval (95% CI) was -0.001 to 0.001, P = 0.007]. TBil was an independent risk factor affecting prognosis of patients with HBV liver failure ( OR = 1.005, 95% CI was -0.002 to -7.543, P = 0.033). The analysis of ROC curve showed that AT Ⅲ had a predictive value for the prognosis of patients with non-HBV liver failure, the area under the ROC curve (AUC) = 0.747, the 95% CI was 0.592-0.902, P = 0.009. When the optimal truncation value was 39.5%, its sensitivity and specificity were 83.33% and 56.25%, respectively. Conclusions:Artificial liver support system treatment of liver failure was difficult to effectively reduce the mortality of patients with end-stage liver failure. In addition to AT Ⅲ, TBil also could be used as an indicator to assess liver compensatency and predict prognosis in liver failure patients.
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Resumen: La coexistencia entre el fracaso fibrinolítico y la presencia de infección es más frecuente de lo que parece; desafortunadamente muchas veces pasa por alto y es concebido como algo incidental, generando consigo catástrofes vasculares y serias disfunciones endoteliales. Presentamos el caso de un adulto joven quien debuta con choque obstructivo de acuerdo con la cardioscopia invasiva y a la información gasométrica requiere terapias tempranas dirigidas por objetivos en el contexto de sepsis severa con aislamientos de Enterococcus faecalis y púrpura fulminans postinfecciosa aguda en el escenario clínico de deficiencia de antitrombina III. De acuerdo con el perfil hemodinámico referido y manifestaciones eléctricas presentadas se documentaron marcadores de actividad fibrinolítica, por lo cual fue llevado a perfusión pulmonar documentándose enfermedad pulmonar tromboembólica. Evoluciona favorablemente y es trasladado a piso para continuar atención médica en salud por los servicios de neumología y hematología.
Abstract: Coexistence between fibrinolytic failure and the presence of infection is more common than it seems; unfortunately it often is not recognized and is conceived as incidental; leading to vascular catastrophes and serious endothelial dysfunctions. We present the case of a young adult who debuts with purpura fulminans related to Enterococcus faecalis isolation in the clinical setting of antithrombin III deficiency and thromboembolic pulmonary disease. According to the hemodynamic profile referred and electrical manifestations presented, markers of fibrinolytic activity were documented, for which it was taken to pulmonary perfusion documenting thromboembolic lung disease. He evolves favorably and is transferred to continue medical health care by the services of pulmonology and hematology.
Resumo: A coexistência entre falência fibrinolítica e presença de infecção é mais frequente do que parece; Infelizmente, muitas vezes é negligenciado e concebido como algo incidental, gerando catástrofes vasculares e graves disfunções endoteliais. Apresentamos o caso de um adulto jovem que apresenta choque obstrutivo de acordo com cardioscopia invasiva e informações gasométricas, requer terapias precoces direcionadas por objetivos no contexto de sepse grave com isolamento de Enterococcus fecalis e púrpura fulminante pós-infecciosa aguda no cenário clínico de deficiência de antitrombina III. De acordo com o perfil hemodinâmico referido e manifestações elétricas apresentadas, foram documentados marcadores de atividade fibrinolítica, para o qual foi encaminhado para perfusão pulmonar, documentando doença pulmonar tromboembólica. O paciente progride favoravelmente e é transferido para o leito para continuar o atendimento médico nos serviços de pneumologia e hematologia.
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Objective To investigate the detection and clinical significance of thrombus molecular markers in diffuse large B-cell lymphoma (DLBCL). Methods We collected the blood specimens of 60 patients with DLBCL, involving 23 cases in the initial treatment group, 24 cases in the remission group and 13 cases in the non-remission group, 23 cases in the thrombus group and 37 cases in the non-thrombus group. We selected 46 healthy people in the same period as the control group. The levels of thrombomodulin (TM), plasmin-α2 plasmin inhibitor complex (PIC), tissue plasminogen activator-plasminogen activator inhibitor-1 complex (t-PAIC) and thrombin-antithrombin Ⅲ complex (TAT) in plasma were detected by chemical immunoassay, and the levels of lactate dehydrogenase (LDH) in serum was detected by automatic biochemical analyzer. We analyzed the differences of thrombus molecular markers among groups and prognostic factors. Results The levels of TM and PIC in plasma of lymphoma patients were higher than those in health control group (P < 0.05). The levels of TM and PIC in the initial treatment and non-remission groups were significantly higher than those in the remission group (P < 0.05). The levels of TM, PIC and TAT in thrombus group were higher than those in non-thrombus group (P < 0.05). TM and PIC levels in plasma were closely related to the prognosis of DLBCL patients. PIC was an independent prognostic factor (P < 0.001). TM and PIC levels were correlated with LDH prognostic indicators in lymphoma patients. Conclusion TM and PIC levels in plasma are significantly increased in DLBCL patients. They are expected to be the indicators for effectiveness and prognosis of DLBCL patients.
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[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.
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Antithrombin Ⅲ (AT-Ⅲ) is a single chain glycoprotein secreted by liver and vascular endothelial cells with a half-life of 2.69 days and is one of the important members of the broad-spectrum serine protein inhibitor family.AT-Ⅲ plays an important role in anticoagulant regulation in the human body,accounting for about 70％-80％ of the total activity of the plasma anticoagulant system.It is involved in maintaining the homeostasis of the coagulation system and anticoagulant system in the body.In recent years,pediatricians have found that the AT-Ⅲ index has important clinical value in evaluating children's thrombosis,sepsis and nephrotic syndrome.This article mainly reviews the factors influencing the detection of antithrombin Ⅲ in children.
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To explore diagnostic value of platelet count (PLT) ,plasma D– dimer (D‐D) , antithrombin Ⅲ(AT‐III) levels and UACR for microvascular disease (MVD) in type 2 diabetes mellitus (T2DM).Methods : A total of 284 T2DM patients treated in our hospital were divided into no MVD group (n＝144) and MVD group (n＝140) according to MVD condition .Another 120 healthy people were enrolled as healthy contrrol group .Levels of PLT ,plasma D‐D and AT‐Ⅲ,unine microalbuminuria (UMA) and creatinine (UCr) and UMA／UCr ratio (UACR) were measured and compared a‐mong all groups .The diagnostic value of combined detection of PLT ,plasma D‐D and AT‐Ⅲ levels and above triple detec‐tion combined UACR for MVD in T2DM were analyzed.Results : Compared with healthy control group ,there were signif‐icant reductions in levels of PLT [ (212.34 ± 51.23)×109／L vs.(116.46 ± 46.43)×109／L vs.(98.48 ± 35.66)× 109／L] and plasma AT‐III [(103.54 ± 7.23)% vs.(99.52 ± 4.24)% vs.(75.34 ± 5.31)%] ,and significant rise in levels of plasma D‐D [ (0.31 ± 0.16) mg／L FEU vs.(0.85 ± 0.33) mg／L FEU vs.(1.08 ± 0.52) mg／L FEU] and UCr [ (3.36 ± 1.56) mmol／L vs.(4.51 ± 1.79) mmol／L vs.(12.31 ± 5.12) mmol／L] in no MVD group and MVD group . And levels of PLT and plasma AT‐III of MVD group were significantly lower than those of no MVD group ,plasma D‐D and UCr levels of MVD group were significantly higher than those of no MVD group ( P＜ 0.01 all).Compared with healthy control group ,no MVD group ,there were significant rise in levels of UACR [ (11.25 ± 5.02) mg／mmol vs. (10.01 ± 4.39) mg／mmol vs.(59.89 ± 16.32) mg／mmol] , UMA [ (38.25 ± 17.22) mg／mmol vs.(41.11 ± 18.53) mg／L vs.(722.32 ± 101.54) mg／L] in MVD group ,and UACR of no MVD group was significantly lower than that of health control group (P＜0.05 or 0.01).Compared with single UACR detection and triple combined detection of PLT ,plasma D‐D and AT‐Ⅲ levels ,there were significant rise in sensitivity (85.51% vs.87.82% vs.90.33%) ,specificity (90.54%vs.85.32% vs.94.32%) and accuracy (82.33% vs.84.56% vs.90.21%) in triple detection combined UACR ( P＝0.001 all).Conclusion :Combined detection of PLT ,plasma D‐D and AT‐Ⅲ levels with UACR are significanly superior to combined detection for screening MVD in T2DM.
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Objective@#To evaluate the changes of molecular markers of thrombosis in patients with deep venous thrombosis of lower extremities and analyze their value in the detection of venous thrombosis and evaluate the therapeutic effects. @*Methods@#In case-control study, we selected traumatic patients after surgery from Beijing Jishuitan Hospital during December 2018 to May 2019. A total of 64 patients with thrombosis were in DVT group, 39 patients without thrombosis were in non-DVT group, and 28 healthy subjects in the same period were in healthy control group. Venous blood samples were taken from all these people. Coagulation parameters thrombin-antithrombin complexes (TAT), plasmin-α2-plasmin inhibitor complexes (PIC) and tissue-type plasminogen activator-inhibitor complexes (t-PAIC) were detected at first diagnosis and one month after rivaroxaban anticoagulation therapy beginning. The differences of the markers between these groups were compared. @*Results@#The coagulation markers of the patients with lower extremity deep venous thrombosis increased significantly at diagnosis. The levels of plasma TAT, PIC, t-PAIC and sTM in DVT group were significantly higher than those in non-DVT group (P＜0.05). The levels of plasma TAT, PIC and t-PAIC in DVT group were higher than those in healthy control group (P＜0.05). There was no significant difference in sTM level between DVT group and healthy control group (P＞0.05). The results and changes of TAT, PIC, t-PAIC in the patients before and after one month of anticoagulation therapy were statistically different (P＜0.05) in comparison. @*Conclusion@#The molecular markers of thrombosis, TAT, PIC and t-PAIC, could effectively detect deep venous thrombosis of lower extremities and showed significant efficacy in evaluating the efficacy of anticoagulation therapy.