Plasmin-α2-plasmin inhibitor complex and thrombin-antithrombin complex in risk stratification of massive transfusion in patients with postpartum hemorrhage / 中国输血杂志

【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.

Optimization of the formulation of a porcine fibrin patch / 中国药房

OBJECTIVE To optimize the formulation of a porcine fibrin patch （abbreviated as “DBT”）. METHODS Based on single-factor tests， with the contents of fibrinogen， thrombin and collagen before freeze-drying as the factors， with the overall desirability （OD） value of adhesion strength， holding viscosity and water absorption as response value， the formulation of DBT was optimized by Box-Behnken-response surface methodology， and the verification tests were conducted. RESULTS According to the results of the single factor tests and Box-Behnken-response surface methodology， combined with the actual production， the optimal formulation of DBT was 6.5 mg/cm2 of fibrinogen， 8.0 IU/cm2 of thrombin and 5.6 mg/mL of collagen. The average OD value of 3 validation tests was 0.726 6 （RSD＝0.58%， n＝3）， and the relative error of which with the predicted value （0.733 0） was －0.87%. CONCLUSIONS The optimal formulation of DBT is stable and feasible.

Performance and reference intervals of thrombin generation test: results from the Brazilian longitudinal study of adult health (ELSA-Brasil). A cross-sectional study

ABSTRACT BACKGROUND: The thrombin generation test (TGT) has shown promise for investigation of hemorrhagic and thrombotic diseases. However, despite its potential, it still needs standardization. Moreover, few studies have established reference values for TGT parameters. In Brazil, these values have not yet been established. OBJECTIVE: To determine TGT performance and reference intervals for TGT parameters in healthy individuals. DESIGN AND SETTING: Cross-sectional study conducted among participants in the Brazilian Longitudinal Study of Adult Health (Estudo Longitudinal de Saúde do Adulto, ELSA-Brasil). METHODS: The reference sample consisted of 620 healthy individuals. The calibrated automated thrombogram (CAT) method, under low and high tissue factor (TF) conditions, was used to assess thrombin generation. Test performance was analyzed using intra and interassay coefficients of variation (CV) and reference intervals were calculated using the nonparametric method proposed by the International Federation of Clinical Chemistry and the Clinical and Laboratory Standards Institute. RESULTS: The intraassay CV ranged from 1.4% to 2.2% and the interassay CV, 6.8% to 14.7%. The reference intervals for TGT parameters under low and high TF conditions were, respectively: lagtime: 3.0-10.3 and 1.4-3.7 min; endogenous thrombin potential (ETP): 1134.6-2517.9 and 1413.6-2658.0 nM.min; normalized ETP: 0.6-1.3 and 0.7-1.4; peak: 103.2-397.7 and 256.4-479.0 nM; normalized peak: 0.3-1.3 and 0.7-1.2; and time-to-peak: 5.6-16.0 and 3.4-6.7 min. These parameters were categorized relative to sex. Conclusion: TGT performance was adequate and the proposed reference intervals were similar to those of other studies. Our findings may be useful for consolidating the TGT, through contributing to its standardization and validation.

Changes of new coagulation markers in healthy pregnant women and establishment of reference intervals in Changsha / 中南大学学报(医学版)

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.

Clinical significance of plasma thrombin-antithrombin complex levels in patients with sepsis-induced cardiomyopathy / 中华检验医学杂志

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.

Plasma thrombin-antithrombin complex evaluates hypercoagulable states and predicts revasenosis after revascularization in patients of atherosclerosis obliterans / 中华检验医学杂志

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.

Comparison of four-coagulation-tests values in normal pregnant women during early and late pregnancy and the influence of age / 中华妇产科杂志

Objective:To explore and compare the reference ranges of four coagulation tests in normal pregnant women during early and late pregnancy and the influence of age.Methods:Values of four coagulation tests from 4 974 pregnant women, who gave single birth at Peking University First Hospital, Obstetrics and Gynecology Hospital of Fudan University, West China Second University Hospital, Peking University Third Hospital and Shengjing Hospital of China Medical University from February 2017 to July 2020, were measured and analyzed in this study, including prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and thrombin time (TT). The four normal reference ranges of coagulation during early and late pregnancy phases were expressed as P2.5- P97.5. The difference of two pregnancy phases was compared by non-parametric test of two related samples. And the difference between pregnant women of advanced and non-advanced age in the same pregnancy phase was compared by independent sample non-parametric test. Chi-square test was used to compare the incidence of pregnancy complications in different coagulation reference ranges. Results:The reference ranges of PT of normal pregnant women′s early and late pregnancy were 10.0-13.9 s and 9.6-12.3 s, the reference ranges of APTT were 22.6-35.3 s and 22.4-30.9 s, the reference ranges of Fib were 2.4-5.0 g/L and 3.0-5.7 g/L, the reference ranges of TT were 12.0-19.0 s and 11.5-18.4 s. Compared with early pregnancy, PT, APTT and TT shortened significantly, while the Fib significantly increased in late pregnancy (all P<0.001). PT, APTT and TT of advanced and non-advanced age pregnant women were significantly different (all P<0.01). Compared with the ranges of non-pregnant population, more pregnant women were included in the normal pregnant reference ranges of PT in early pregnancy and APTT in the early and late pregnancy, while the incidence of pregnancy complications had no significant differences (all P>0.05). The incidence of fetal distress was higher and the incidence of preterm birth was lower in the reference range of PT in late pregnancy. The incidence of gestational diabetes mellitus was higher in the early and late gestational Fib reference ranges, and the incidence of hypertensive disorders in pregnancy was higher in the late gestational Fib reference range (all P<0.05). Conclusions:The coagulation function of pregnant women increases significantly with the growth of pregnancy, and there is a significant difference between advanced significantly and non-advanced age pregnant women. The recommended ranges of normal pregnant women′s early and late pregnancy PT are 10.0-13.9 s and 9.6-12.3 s, the recommended ranges of APTT are 22.6-35.3 s and 22.4-30.9 s, the recommended ranges of TT are 12.0-19.0 s and 11.5-18.4 s. The appropriate ranges of normal pregnant women′s early and late pregnancy Fib still need further exploration.

Disfunción en la plasminogénesis en paciente críticamente enfermo con infección polimicrobiana asociado a deficiencia de glicoproteínas / Plasminogenesis disfunction in critical ilness patient with polimicrobial infection associated glycoproteins deficiency / Disfunção da plasminogênese em paciente crítico com infecção polimicrobiana associada a deficiência de glicoproteínas

Resumen: Presentamos el caso clínico de una paciente de 59 años de edad con sepsis por neumonía polimicrobiana con aislamientos virales condicionantes de sobreinfección bacteriana y trombosis. Su escanografía de tórax reportó colapsos posterobasales con atelectasias e infiltrados intersticiales reticulares; evolucionó con deterioro cognitivo relacionado con enfermedad cerebro vascular multiinfarto documentado por tomografía cerebral con emisión de fotón único por medicina nuclear debido a estudios de cráneo normales; ante la evolución neurológica se realizaron estudios de extensión con ecocardiograma Doppler dúplex color transtorácico, el cual fue normal, así como estudio contrastado de cuatro vasos de cuello, Holter de ritmo eléctrico y perfil metabólico completo también normales. Realizamos una revisión en la literatura con miras a brindar entendimiento y evidenciar la relación directa entre síndromes sépticos e infecciones virales con diferentes estados de hipercoagulabilidad, inflamación y apoptosis.

Abstract: We present the clinical case of a 59-year-old patient with sepsis due to polymicrobial pneumonia with viral isolates conditioning bacterial infection and thrombosis. His chest scannography reported basals collapses with atelectasis and reticular interstitial infiltrates; Evolved with cognitive impairment related to multi-infarction vascular brain disease documented by single-photon emission brain tomography by nuclear medicine due to normal scannographies studies; Given the neurological evolution, extension studies were carried with transthoracic duplex Doppler echocardiogram which was normal, as well as a contrasted study of four neck vessels, electrical rhythm holter and complete metabolic profile also normal. We conducted a review in the literature with a view to providing understanding and evidence of the direct relationship between septic syndromes and viral infections with different states of hypercoagulability, inflammation and apoptosis.

Resumo: Apresentamos o caso clínico de um paciente de 59 anos com sepse por pneumonia polimicrobiana com isolados virais condicionando superinfecção bacteriana e trombose. Sua cintilografia de tórax relatou colapsos póstero-basais com atelectasia e infiltrados intersticiais reticulares; Evoluiu com deterioração cognitiva relacionada à doença cerebrovascular multi-infarto documentada por tomografia cerebral com emissão de fóton único pela medicina nuclear devido a estudos de crânio normais; dada a evolução neurológica, realizaram-se estudos de extensão com ecocardiograma Doppler colorido transtorácico duplex, que foi normal, bem como estudo contrastado de quatro vasos do pescoço, Holter de ritmo elétrico e perfil metabólico completo, também normais. Realizamos uma revisão da literatura com o objetivo de compreender e evidenciar a relação direta entre síndromes sépticas e infecções virais com diferentes estados de hipercoagulabilidade, inflamação e apoptose.

Comparación del potencial de generación de trombina en puerperios de parto con puerperios de cesárea. Resultados preliminares

Resumen: Introducción: El embarazo es un estado asociado con profundos cambios en el sistema hemostático determinando un estado de hipercoagulabilidad relacionado con un aumento en generación de trombina, y como tal, un factor de riesgo bien establecido de Enfermedad Tromboembólica Venosa. El objetivo del presente trabajo es determinar y comparar la generación de trombina en los puerperios de parto con puerperios cesáreas. Evaluar el potencial de generación de trombina como un factor de riesgo adicional para decidir la indicación tromboprofilaxis. Metodología: Estudio analítico observacional prospectivo realizado en el Hospital Pereira Rossell, octubre de 2018 a agosto del 2019. La medición del potencial endógeno de trombina se realizó en el analizador de coagulación BCS® XP automatizado en el Hospital de Clínicas. Resultados: 220 embarazadas, 70 cesáreas (C) y 150 partos (P). El potencial endogeno de trombina (ETP AUC2) fue menor estadísticamente en el grupo P, valor p < 0,001.La concentración máxima de generación de trombina calculado (ETPB AUC2) fue estadísticamente menor en el grupo P valor p = 0,010. Discusión: Hay una diferencia estadísticamente significativa cuando comparamos los parámetros de ETP AUC2 y ETPB AUC2 de los grupos de partos vs cesárea, siendo menor para partos. Conclusión: Las cesáreas presentan un ETP AUC2, ETPB AUC2 mayor que los partos. Esto permitiría seleccionar pacientes con mayor riesgo de enfermedad tromboembólica venosa. La cesárea se identificó como un evento generador de trombina probablemente asociado al mayor daño endotelial que produce.

Abstract: Introduction: Pregnancy is a state associated with profound changes in the hemostatic system, determining a state of hypercoagulability related to an increase in thrombin generation, and as such, a well-established risk factor for Venous Thromboembolic Disease. The objective of this work is to determine and compare the generation of thrombin in postpartum delivery with postpartum cesarean section. Evaluate the potential for thrombin generation as an additional risk factor to decide the thromboprophylaxis indication. Methodology: Prospective observational analytical study carried out at the Pereira Rossell Hospital, from October 2018 to August 2019. The measurement of the endogenous potential of thrombin was carried out in the automated BCS® XP coagulation analyzer at the Hospital de Clínicas. Results: 220 pregnant women, 70 cesarean sections (C) and 150 deliveries (P). The endogenous thrombin potential (ETP AUC2) was statistically lower in group P, p-value < 0.001. The maximum concentration of thrombin generation calculated (ETPB AUC2) was statistically lower in group P, p-value = 0.010. Discussion: There is a statistically significant difference when we compare the ETP AUC2 and ETPB AUC2 parameters of the delivery vs. cesarean section groups, being lower for deliveries. Conclusion: Caesarean sections have a higher ETP AUC2, ETPB AUC2 than deliveries. This would allow selecting patients with a higher risk of venous thromboembolic disease. Cesarean section was identified as a thrombin-generating event probably associated with the greater endothelial damage it produces.

Resumo: Introdução: A gravidez é um estado associado a profundas alterações no sistema hemostático, determinando um estado de hipercoagulabilidade relacionado ao aumento da geração de trombina e, como tal, um fator de risco bem estabelecido para Doença Tromboembólica Venosa. O objetivo deste trabalho é determinar e comparar a geração de trombina no pós-parto com a cesariana pós-parto. Avaliar o potencial de geração de trombina como fator de risco adicional para decidir a indicação de tromboprofilaxia. Metodologia: Estudo analítico observacional prospectivo realizado no Hospital Pereira Rossell, de outubro de 2018 a agosto de 2019. A medição do potencial endógeno da trombina foi realizada no analisador de coagulação automatizado BCS® XP do Hospital de Clínicas. Resultados: 220 gestantes, 70 cesarianas (C) e 150 partos (P). O potencial endógeno da trombina (ETP AUC2) foi estatisticamente menor no grupo P, valor p < 0,001. A concentração máxima de geração de trombina calculada (ETPB AUC2) foi estatisticamente menor no grupo P, valor p = 0,010. Discussão: Há diferença estatisticamente significativa quando comparamos os parâmetros ETP AUC2 e ETPB AUC2 dos grupos de parto vs. cesariana, sendo menor para partos. Conclusão: As cesarianas têm uma ETP AUC2, ETPB AUC2 mais alta do que os partos. Isso permitiria selecionar pacientes com maior risco de doença tromboembólica venosa. A cesariana foi identificada como evento gerador de trombina, provavelmente associado ao maior dano endotelial que produz.

Correlation between protein C -1641A/-1654C haplotype and coagulation disorder in sepsis / 中华急诊医学杂志

Objective:To investigate the correlation between protein C -1641A/-1654C haplotype and coagulation disorder in Chinese Han septic patients.Methods:The genotypes of protein C gene -1641A>G (rs1799809) and -1654C>T (RS1799808) in septic patients were detected by direct sequencing, and their haplotypes were analyzed and divided into two groups according to the haplotype, -1641A/-1654C (AC) carriers and non-AC haplotype carriers. At the same time, unpaired t test or Mann-Whitney U test was used to compare the differences in coagulation/fibrinolytic parameters, including partial activated thrombin time, prothrombin time, internationally standardized ratio of prothrombin time, thrombin time, fibrinogen and D-dimer levels, as well as APC levels between the two groups. Results:A total of 174 septic patients were included in this study, including 60 AC haplotype carriers and 114 non-AC haplotype carriers. Compared with non-AC haplotype carriers, AC haplotype carriers had significantly lower platelet counts, significantly longer partial activated thrombin time, and significantly decreased activated protein C levels. Other coagulation/fibrinolytic parameters including prothrombin time, internationally standardized ratio of prothrombin time, thrombin time, fibrinogen and D-dimer were not significantly different between the two groups.Conclusions:In this study, the protein C-1641A/-1654C haplotype was found to lead to decreased circulating activated protein C levels decreased platelet counts, and prolonged partial activated thrombin time in septic patients. These results suggest that the protein C-1641A/-1654C haplotype may directly affect the APC level and consequently influence the coagulation disorder of sepsis.

Functional and binding studies of gallic acid showing platelet aggregation inhibitory effect as a thrombin inhibitor / 中草药·英文版

Objective: This study was devoted to identifying natural thrombin inhibitors from traditional Chinese medicine (TCM) and evaluating its biological activity in vitro and binding characteristics. Methods: A combination strategy containing molecular docking, thrombin inhibition assay, surface plasmon resonance (SPR) and molecular dynamics simulation were applied to verify the study result. Results: Gallic acid was confirmed as a direct thrombin inhibitor with IC

Abnormal coagulation activity and the related clinical significance in patients with novel bunyavirus infection / 中华检验医学杂志

Objective:To explore the related indexes of coagulation and thrombosis and their clinical significance in patients with severe fever with thrombocytopenia symptoms (SFTS) during the onset and recovery period after novel bunyavirus infection.Methods:A total of 36 patients diagnosed with SFTS (SFTS onset group) and 18 convalescent SFTS patients, who were hospitalized in the First Affiliated Hospital of Anhui Medical University from April 12, 2020, to October 12, 2020 were recruited in this study. Thirty-six healthy controls were recruited from volunteers. Plasma was collected and prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time(TT), antithrombin-Ⅲ (AT-Ⅲ), fibrin degradation product (FDP) and D-dimer (D-D) were determined by automatic blood coagulation analyzer. Thrombomodulin (TM), thrombin-antithrombin complex (TAT), plasminase-α2 plasminase inhibitor complex (PIC) and tissue plasminogen activator-plasminogen activator inhibitor 1 complex (t-PAIC) were determined by an automatic chemiluminescence analyzer.Results:Compared with the healthy control group, PT was significantly prolonged (12.5 [12.1, 13.6] s, vs 10.8 [10.5, 11.5] s, P<0.05) in SFTS onset group, but was still within the reference range (14.0-21.0 s), and APTT (49.1 [42.0, 58.2]s vs 28.5 [26.6, 30.4]s, P<0.05) was also significantly prolonged in SFTS onset group. Compared with healthy control group, FDP (6.07 [2.67, 8.64] μg/ml vs 1.00 [0.80, 1.87] μg/ml, P<0.001), D-D (2.27 [1.04, 2.98] μg/ml vs 0.30 [0.21, 0.47] μg/ml, P<0.001), TAT (16.05 [8.05, 26.58] ng/ml vs 3.55 [2.60, 4.85] ng/ml, P<0.001), PIC (4.44 [2.52, 5.54] μg/ml vs 0.84 [0.60, 1.35] μg/ml, P<0.001), TM ([19.41±8.29] TU/ml vs [9.33±1.89] TU/ml, P<0.001), and t-PAIC ([37.52±21.10] ng/ml vs [7.06±3.37] ng/ml, P<0.001) values were all significantly higher in the SFTS onset group (all P<0.001). The level of TAT in the SFTS recovery group (9.10 [3.95, 18.40] ng/ml) was still out of the reference range (<4 ng/ml), while the level of PIC in the SFTS recovery group was lower than in SFTS onset group (1.91 [1.45, 2.93] μg/ml vs 4.44 [2.52, 5.54] μg/ml, P<0.05). Compared with SFTS onset group, the levels of TM and t-PAIC were lower in the SFTS recovery group ( P<0.05). Conclusions:Coagulation system activation and vascular endothelial injury are evidenced in SFTS patients. In the convalescence period, the vascular endothelial injury is recovered, however, there is still a certain degree of coagulation dysfunction, therefore, it is necessary to monitor the coagulation indicator of discharged patients post SFTS.

Study on the relationship between the expression of TSP-1, VEGF, and plasma inflammatory factors and early acute lung injury in COPD / 公共卫生与预防医学

Objective To analyze the relationship between the expression of TSP-1, VEGF, and Th17-related inflammatory factors and early acute lung injury (ALI) in COPD. Methods The clinical data of 140 randomly selected patients with COPD in our hospital from May 2016 to June 2018 were retrospectively analyzed. According to the condition of the disease, they were divided into control group (n = 70) and observation group (n = 70). The related indicators were determined by flow cytometry and enzyme-linked immunosorbent assay (ELISA). Statistical analysis of data was carried out by Pearson linear correlation analysis and logistic regression analysis. Results Compared with the control group, the levels of FEV1 and FEV1/FVC in the patients with COPD complicated with early ALI were significantly lower, while the ratio of Th17/Treg in peripheral blood was significantly higher in the observation group. The plasma levels of TSP-1, VEGF and related inflammatory factors were significantly higher in the observation group than those in the control group. Pearson correlation analysis showed that TSP-1 and VEGF were positively correlated with CD4+Th17 cell ratio. Logistic regression analysis showed that IL-17 was an independent risk factor for early acute lung injury in COPD. Conclusion The increased release of Th17-related inflammatory cytokines will aggravate the airway inflammatory response, cause abnormal expression of TSP-1 and VEGF, and lead to vascular endothelial dysfunction, which will further aggravate the condition of patients, and increase the risk of acute lung injury in patients with COPD.

Effect of thrombin concentration on the prevention of postoperative cerebrospinal leakage by fibrin glue / 中国组织工程研究

BACKGROUND: Fibrin glue is commonly used to prevent postoperative cerebrospinal fluid leakage from dural injuries. However, fibrin glue with standard-concentration thrombin coagulates too fast, resulting in poor adhesion of dural mater. Effect of low-concentration thrombin fibrin glue on sealing dural injuries to prevent cerebrospinal fluid leakage is unclear. OBJECTIVE: To compare the effect of low-concentration thrombin and standard-concentration thrombin on the prevention of cerebrospinal fluid leakage from dural injuries by fibrin glue. METHODS: Forty patients including 25 males and 15 females with dural injuries admitted at Fifth People’s Hospital of Chengdu from May 2017 to December 2019 were enrolled. Patients were randomly divided into two groups, 20 patients in each group. In low-concentration thrombin group, dural injuries were sealed with fibrin glue prepared with low-concentration thrombin solution (100 IU/mL). In standard-concentration thrombin group, dural injuries were sealed with fibrin glue prepared with standard-concentration thrombin solution (500 IU/mL). All patients were followed up for 2 months. The incidence of cerebrospinal fluid leakage, cumulative drainage flow, drainage duration and incision complications were compared between the two groups. The study was approved by Ethics Committee of Fifth People’s Hospital of Chengdu. RESULTS AND CONCLUSION: (1) The incidence of cerebrospinal leakage, accumulative volume and duration of drainage in the low-concentration thrombin group were lower than those of standard-concentration thrombin group (P 0.05). (3) These results indicate that fibrin glue prepared with low-concentration thrombin solution decreases the rate of cerebrospinal leakage, reduces the drainage volume and shortens the duration of drainage, which is demonstrated to be an effective strategy for sealing dural injuries.

Detection and Clinical Significance of Thrombus Molecular Markers in Diffuse Large B-cell Lymphoma / 肿瘤防治研究

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.

Hemostatic evaluation of rabbits envenomed with Bothrops alternatus treated with anti-bothropic serum, desmopressin and tranexamin acid / Avaliação hemostática de coelhos envenenados com Bothrops alternatus e tratados com soro antibotrópico, desmopressina e ácido tranexâmico

In Brazil, snakes from the Bothrops genus are responsible for thousands of accidents, and their venoms are mainly composed of proteolytic enzymes. Although the antibothropic serum produced by the Brazilian Institutes is remarkably efficient, more studies are necessary, especially in veterinary medicine. The venom contain enzymes and non-enzymatic proteins that interfere with hemostasis leading to hemorrhage or even thrombosis. Possible treatment associations with known bothropic antivenom were the reason for the development of the present study. The aim of this study was to evaluate hemostasis alterations caused by Bothrops alternatus venom in rabbits followed by treatments with anti-bothropic serum, tranexamic acid and desmopressin. Twenty New Zealand rabbits were distributed into five groups (n=4) that were experimentally envenomed with 150mcg/kg of B. alternatus venom via intramuscular injection and treated as follow: Group 1 (G1) was the positive control and received venom and PBS/BSA; Group 2 (G2) was treated with tranexamic acid; Group 3 (G3) with desmopressin; Group 4 (G4) with tranexamic acid and anti-bothropic serum; and Group 5 (G5) with anti-bothropic serum and desmopressin. Blood samples were collected before venom administration, and one, four, eight and 12 hours after, for Partial activated partial thromboplastin time, Prothrombin Time, Thrombin Time and fibrinogen evaluation. Thrombin generation (TG) test was carried out with a pool of samples from final times (8 and 12h). At the end of 12h, all animals were euthanized and necropsy was conducted. Samples from muscle tissue, heart, lungs and kidney were analyzed. Classic coagulation tests showed no significant differences amongst groups and times. However, TG indicated that the venom causes a hypocoagulability state, which was not reversed by proposed treatments. Histology showed muscle inflammation, hemorrhage and necrosis, as well as hemorrhage in other tissues with no differences amongst groups. B. alternatus envenomation causes hypocoagulability detected by TG assay, but not through classical coagulation tests. The use of tranexamic acid and desmopressin for hemostasis stabilization after inoculation of the venom did not show advantage in coagulation restoration.(AU)

No Brasil, as serpentes do gênero Bothrops são responsáveis por milhares de acidentes, e seus venenos são compostos principalmente de enzimas proteolíticas. Embora o soro antiofídico produzido pelos institutos brasileiros seja notavelmente eficiente, mais estudos são necessários, especialmente na medicina veterinária. O veneno contem enzimas e proteínas não-enzimáticas que interferem com a hemostasia levando a hemorragias ou trombose. A associação de outros tratamentos ao soro antibotrópico foi a razão para o desenvolvimento do presente estudo. O objetivo deste estudo foi avaliar as alterações da hemostasia causadas pelo veneno de Bothrops alternatus em coelhos, após tratamento com soro antibotrópico, ácido tranexâmico e desmopressina. Vinte coelhos da Nova Zelândia foram distribuídos em cinco grupos (n = 4) que foram submetidos a experimentos com 150mcg/kg de veneno de B. alternatus por injeção intramuscular. O Grupo 1 (G1) foi o controle positivo e recebeu veneno e PBS / BSA, enquanto o Grupo 2 (G2) foi tratado com ácido tranexâmico, o Grupo 3 (G3) com desmopressina, o Grupo 4 (G4) com ácido tranexâmico e soro antibotrópico, e o Grupo 5 (G5) com soro antibotrópico e desmopressina. As amostras de sangue foram coletadas antes da administração do veneno, e uma, quatro, oito e 12 horas após os tratamentos para realização de tempo de tromboplastina parcial ativada parcial (TTPa), tempo de protrombina (TP), tempo de trombina (TT) e mensuração de fibrinogênio. Para o ensaio de geração de trombina (TG) foi realizado com um pool de amostras nos tempos finais (8 e 12h). Ao final das 12h, todos os animais foram sacrificados e a necropsia foi realizada. Amostras de tecido muscular, coração, pulmões e rins foram analisadas. Os testes TTPa, TP, TT e fibrinogênio não mostraram diferenças significativas entre os grupos e os tempos. No entanto, o TG indicou que o veneno causa um estado de hipocoagulabilidade, que não foi revertido pelos tratamentos propostos. Na histologia, foram observadas inflamação muscular, hemorragia e necrose, além de hemorragia em outros tecidos, sem diferenças entre os grupos. O envenenamento por B. alternatus causa hipocoagulabilidade detectada mais precocemente pelo teste de geração de trombina. O uso de ácido tranexâmico e desmopressina para estabilização da hemostasia após a inoculação do veneno não mostrou vantagem na restauração da coagulação.(AU)

Effects of adjuvant therapy with low molecular weight heparin on nephrotic syndrome in 32 cases / 中国基层医药

Objective:To investigate the clinical efficacy of adjuvant therapy with low molecular weight heparin on nephrotic syndrome.Methods:Sixty-four patients with nephrotic syndrome who received treatment in Linyi People's Hospital between January 2018 and January 2020 were included in this study. They were randomly assigned to receive either conventional treatment combined with low molecular weight heparin treatment (observation group, n = 32) or conventional treatment (control group, n = 32) for 28 successive days. Before and after treatment, renal function indexes, blood lipid, coagulation function indexes, clinical efficacy, and adverse reactions were compared between the two groups. Results:After treatment, serum creatinine, urea nitrogen, 24-hour urinary protein, total cholesterol and triacylglycerol levels in the observation group were (109.21 ± 9.81) μmol/L, (5.35 ± 1.01) mmol/L, (1.12 ± 0.25) g/L, (5.12 ± 1.09) mmol/L, (1.52 ± 0.18) mmol/L, respectively, which were significantly lower than those in the control group [(120.54 ± 9.72) μmol/L, (6.05 ± 0.95) mmol/L, (1.42 ± 0.28) g/L, (6.92 ± 1.15) mmol/L, (1.96 ± 0.22) mmol/L, t = 4.641, 2.855, 4.521, 6.426, 8.756, all P < 0.05]. The activated partial thromboplastin time and prothrombin time in the observation group were (1.52 ± 0.18) seconds and (14.57 ± 1.70) seconds, respectively, which were significantly longer than those in the control group [(31.02 ± 4.59) seconds, (12.62 ± 1.67) seconds, t = -4.388, -4.628, both P < 0.05]. Total effective rate in the observation group was significantly higher than that in the control group [96.88% (31/32) vs. 75.00% (24/32), χ2 = 6.335, P < 0.05]. The time to relief of symptom in the observation group was significantly shorter than that in the control group [(3.12 ± 1.42) weeks vs. (5.04 ± 1.24) weeks, t = -5.761, P < 0.05). The incidence of adverse reactions in the observation group was significantly lower than that in the control group [3.13% (1/32) vs. 21.88% (7/32), χ2 = 5.143, P < 0.05]. Conclusion:Based on conventional treatment, adjuvant therapy with low molecular weight heparin for nephrotic syndrome can greatly improve clinical symptoms, increase clinical efficacy, and decrease the incidence of adverse reactions.

Coagulación intravascular diseminada / Disseminated intravascular coagulation

Resumen La coagulación intravascular diseminada es un estado alterado de la coagulación secundario a cuadros inflamatorios locales o sistémicos. Se caracteriza por un aumento de la coagulación y una inadecuada fibrinólisis endógena que da como resultado la formación de fibrina intravascular, trombosis microvascular multiorgánica y un excesivo consumo de los factores de coagulación sanguínea, esto desencadena sangrados severos y trombosis, los cuales conducen a falla orgánica y circulatoria como principal manifestación clínica. Este artículo tiene como objetivo realizar una revisión del estado del arte describiendo su definición, etiología, fisiopatología, manifestaciones clínicas y actualidades en su diagnóstico y tratamiento. Para esto, se realizó una búsqueda bibliográfica en PubMed utilizando el término MeSH "Disseminated Intravascular Coagulation", seleccionándose 63 artículos por la relevancia y pertinencia de su información al objetivo de la investigación. De esta manera, se espera brindar al clínico las herramientas necesarias para responder adecuadamente frente a esta patología. MÉD.UIS.2020;33(2):75-84.

Abstract Disseminated Intravascular Coagulation is an altered state of coagulation secondary to local or systemic inflammatory symptoms. It is characterized by increased coagulation and inadequate endogenous fibrinolysis resulting in intravascular fibrin formation, multi-organ microvascular thrombosis, and excessive consumption of blood coagulation factors, this triggers severe bleeding and thrombosis, which lead to organic and circulatory failure as the main clinical manifestation.This article aims to review the state of the art describing its definition, etiology, pathophysiology, clinical manifestations and news in its diagnosis and treatment. Accordingly, a bibliographic search was carried out in PubMed using the MeSH term "Disseminated Intravascular Coagulation", selecting 63 articles for the relevance and pertinence of their information to the objective of the investigation. Therefore, it is expected to provide the clinician with the necessary tools to adequately respond to this pathology. MÉD.UIS.2020;33(2):75-84.

Thrombin generation and thromboelastometry tests in dogs with chronic kidney disease / Testes de geração de trombina e tromboelastometria em cães com doença renal crônica

Patients with chronic kidney disease (CKD) have paradoxical hemostatic potential because they have bleeding episodes but are also prone to thrombosis. Few studies have evaluated blood viscoelastic properties in dogs with kidney disease; on the other hand, hypercoagulability has been observed in these patients. It is also emphasized that the platelet function and its participation in this process have not yet been fully understood. The objective of this study was to evaluate and compare the Thrombin Generation Test (TGT) and also viscoelastic properties of the blood measured by thromboelastometry (TEM) in dogs with proteinuria in CKD. Twenty healthy dogs (Control Group) and 19 dogs with CKD in stage III or IV, classified according to International Renal Interest Society - IRIS, were selected, and the reference test of urine protein:creatinine ratio (UPCR) should be greater than one (CKD group). Blood samples for TEM, thrombin generation, Prothrombin Time (PT), activated Partial Thromboplastin Time (aPTT), and fibrinogen concentration was collected at a single time for both groups after inclusion criteria being confirmed. Statistical analysis was performed according to the distribution of variables at 5% significance level. Differences were observed between healthy dogs and those with proteinuria in CKD noted in TEM. The TGT was unable to differentiate between sick and healthy groups. However, when the nephropathy was stratified, increases in TTP and peak thrombin concentration by TGT were observed in females and dogs over 30 days of diagnosis of CKD. Both tests signaled a discrete state of hypercoagulability. In fact, TEM is more sensitive to detect hypercoagulability in dogs with CKD. However, the TGT has potential clinical application by allowing long-term sample storage.(AU)

Os pacientes com doença renal crônica (DRC) apresentam um potencial hemostático paradoxal, pois apresentam episódios de sangramento, mas também são propensos à trombose. Poucos estudos avaliaram as propriedades viscoelásticas sanguíneas em cães com doenças renais, entretanto, a hipercoagulabilidade já foi observada nestes pacientes. Ressalta-se ainda que a função plaquetária e sua participação neste processo ainda não foram totalmente esclarecidas. O objetivo foi avaliar e comparar o teste de geração de trombina (TGT) e as propriedades viscoelásticas sanguíneas medidas pela tromboelastometria (TEM) em cães com DRC proteinúrica. Foram selecionados 20 cães saudáveis (grupo controle) e 19 cães com DRC em estágios III ou IV classificados segundo o IRIS e a relação proteína/creatinina urinária maior que um (grupo DRC). As amostras de sangue para a realização da tromboelastometria (TEM), geração de trombina, tempo de protrombina (TP), tempo de tromboplastina parcial ativada (TTPA) e concentração de fibrinogênio foram colhidas em momento único para ambos os grupos após os critérios de inclusão confirmados. A análise estatística foi realizada de acordo com a distribuição das variáveis, ao nível de 5% de significância. Foi observada diferença entre os cães saudáveis e os com DRC proteinúrica observados na TEM. O teste de geração de trombina não foi capaz de diferenciar os grupos doente e saudável. Entretanto, quando os nefropatas foram analisados de forma estratificada, foram observados aumentos do ETP e da concentração máxima de trombina (peak) pelo TGT em fêmeas e em cães com mais de 30 dias de diagnóstico da DRC. Ambos os testes sinalizando para um discreto estado de hipercoagulabiliade. A tromboelastometria é mais sensível para detectar a hipercoagulabilidade em cães com DRC. Entretanto, o teste de geração de trombina tem melhor aplicabilidade por permitir o armazenamento da amostra em longo prazo.(AU)

Determination of glycine in human thrombin by HPLC / 药学实践杂志

Objective To establish a HPLC method for glycine assay in the human thrombin. Methods The sample was derivatized with 2,4-dinitrofluorobenzene (DNFB). HPLC was performed on an ODS-C18 column with 50% acetonitrile –0.05mol/L sodium acetate buffer (35:65) as the mobile phase. The flow rate was 1.0 ml/min and detection wavelength at 360 nm. Results The linear range of glycine was 0.006-0.030 mg/ml (r=0.999 6). The average recovery was 100.4%, with RSD 0.44% (n=9). Conclusion This method is simple, accurate and specific. It is suitable for glycine assay in human thrombin.