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BACKGROUND: Hantaan virus (HTNV), Seoul virus (SEOV) and Puumala virus (PUUV) are major serotypes of the Hantavirus, which can cause hemorrhagic fever with renal syndrome (HFRS). The pathophysiology of HFRS in humans is complex and the determinants associated with mortality, especially the coagulation and fibrinolysis disorders, are still not been fully elucidated. Severe patients usually manifest multiple complications except for acute kidney injury (AKI). The aim of this study was to observe the levels of peripheral blood routine, biochemical and coagulation parameters during the early stage, so as to find independent risk factors closely related to the prognosis, which may provide theoretical basis for targeted treatment and evaluation. METHODS: A total of 395 HFRS patients from December 2015 to December 2018 were retrospectively enrolled. According to prognosis, they were divided into a survival group (n = 368) and a death group (n = 27). The peripheral blood routine, biochemical and coagulation parameters were compared between the two groups on admission. The relationship between the parameters mentioned above and prognosis was analyzed, and the dynamic changes of the coagulation and fibrinolysis parameters during the first week after admission were further observed. RESULTS: In addition to AKI, liver injury was also common among the enrolled patients. Patients in the death group manifested higher levels of white blood cell counts (WBC) on admission. 27.30% (107/392) of the patients enrolled presented with disseminated intravascular coagulation (DIC) on admission and DIC is more common in the death group; The death patients manifested longer prothrombin time (PT) and activated partial thromboplastin time (APTT), higher D-dimer and fibrinogen degradation product (FDP), and lower levels of platelets (PLT) and fibrinogen (Fib) compared with those of the survival patients. The proportion of D-dimer and FDP abnormalities are higher than PT, APTT and Fib. Prolonged PT, low level of Fib and elevated total bilirubin (TBIL) on admission were considered as independent risk factors for prognosis (death). CONCLUSIONS: Detection of PT, Fib and TBIL on admission is necessary, which might be benefit to early predicting prognosis. It is also important to pay attention to the dynamic coagulation disorders and hyperfibrinolysis during the early stage in the severe HFRS patients.
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Injúria Renal Aguda , Coagulação Intravascular Disseminada , Febre Hemorrágica com Síndrome Renal , Humanos , Estudos Retrospectivos , Testes de Coagulação Sanguínea , Prognóstico , Fibrinogênio , Coagulação Intravascular Disseminada/etiologiaRESUMO
Purpose: We aimed to investigate the impact of Omicron variant infection on the perioperative organ function in patients undergoing elective surgery. Methods: A total of 5029 patients who underwent elective surgery between October 2022 and January 2023 at our hospital were enrolled. Among them, the patients who underwent elective surgery between October 2022 and November 2022 composed Group 1 (not infected with the Omicron variant) the control group; those who underwent elective surgery between December 2022 and January 2023 composed Group 2 (one month after Omicron variant infection) the experimental group. We further divided the patients into two subgroups for analysis: the tumor subgroup and the nontumor subgroup. Data on organ system function indicators, including coagulation parameters, liver function, complete blood count (CBC), and kidney function, were collected before and after surgery. Differences between the two groups were subsequently analyzed via binary logistic regression analysis. Results: Compared with those in the uninfected patient group, the following changes were observed in patients with Omicron variant infection who underwent elective surgery one month after infection: prothrombin activity (PTa), prothrombin time (PT), fibrinogen, albumin/globulin, alanine aminotransferase (ALT), mean corpuscular hemoglobin concentration (MCHC), platelet (PLT), and anemia were increased AST/ALT, indirect bilirubin (IBILI), eosinophils, and uric acid were decreased before surgery; and lung infection/pneumonia and fibrinogen were increased, while AST/ALT, globulin, total bilirubin (TBIL), white blood cell count (WBC), and uric acid were decreased after surgery. There was no significant difference in the mortality rate or length of hospital stay (LOS) between the two groups. Subgroup analysis revealed elevated monocyte, PLT, and fibrinogen classification, levels and decreased globulin, prealbumin (PBA), eosinophil, and uric acid levels in the tumor subgroup of patients who underwent elective surgery one month after Omicron infection compared with those in the uninfected patients. Compared with the nontumor subgroup, fibrinogen levels, lung infection/pneumonia, TBIL, and PLT count were increased in the uninfected patients, while the globulin and eosinophil levels were decreased. Conclusion: Compared with uninfected patients, patients who underwent elective surgery one month after Omicron variant infection exhibited minimal changes in perioperative coagulation parameters, liver function, CBC counts, and kidney function. Additionally, no significant differences in postoperative mortality or LOS were observed between the two groups.
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Globulinas , Neoplasias , Pneumonia , Humanos , Estudos Retrospectivos , Estudos de Casos e Controles , Ácido Úrico , Fígado/cirurgia , Fígado/patologia , Rim/cirurgia , Fibrinogênio , Bilirrubina , Neoplasias/patologiaRESUMO
BACKGROUND: Preeclampsia (PE), an obstetric disorder, remains one of the leading causes of maternal and infant mortality worldwide. In individuals with PE, the coagulation-fibrinolytic system is believed to be among the most significantly impacted systems due to maternal inflammatory responses and immune dysfunction. Therefore, this systematic review and meta-analysis aimed to assess the association of prothrombin time (PT), thrombin time (TT) and activated partial thromboplastin time (APTT) levels with preeclampsia. METHODS: This systematic review and meta-analysis was conducted in accordance with the PRISMA guidelines. Articles relevant to the study, published from July 26, 2013, to July 26, 2023, were systematically searched across various databases including PubMed, Scopus, Embase, and Hinari. The methodological quality of the articles was evaluated using the Joanna Briggs Institute critical appraisal checklist. Utilizing Stata version 14.0, a random-effects model was employed to estimate the pooled standardized mean difference (SMD) along with the respective 95% CIs. The I2 statistics and Cochrane Q test were utilized to assess heterogeneity, while subgroup analyses were performed to explore its sources. Furthermore, Egger's regression test and funnel plot were employed to assess publication bias among the included studies. RESULTS: A total of 30 articles, involving 5,964 individuals (2,883 with PE and 3,081 as normotensive pregnant mothers), were included in this study. The overall pooled SMD for PT, APTT, and TT between PE and normotensive pregnant mothers were 0.97 (95% CI: 0.65-1.29, p < 0.001), 1.05 (95% CI: 0.74-1.36, p < 0.001), and 0.30 (95% CI: -0.08-0.69, p = 0.11), respectively. The pooled SMD indicates a significant increase in PT and APTT levels among PE patients compared to normotensive pregnant mothers, while the increase in TT levels among PE patients was not statistically significant. CONCLUSIONS: The meta-analysis underscores the association between PE and prolonged PT and APTT. This suggests that evaluating coagulation parameters like PT, APTT, and TT in pregnant women could offer easily accessible and cost-effective clinical indicators for assessing PE. However, multicenter longitudinal studies are needed to evaluate their effectiveness across various gestational weeks of pregnancy.
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Pré-Eclâmpsia , Tempo de Protrombina , Humanos , Gravidez , Feminino , Pré-Eclâmpsia/sangue , Tempo de Tromboplastina Parcial , Tempo de Trombina , Coagulação SanguíneaRESUMO
BACKGROUND: Experimental studies have shown that disinfection byproducts (DBPs) induce coagulotoxicity, but human evidence is scarce. OBJECTIVE: This study aimed to explore the relationships of DBP exposures with blood coagulation parameters. METHODS: Among 858 women from the Tongji Reproductive and Environmental (TREE) study, urinary dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were detected as internal biomarkers of DBP exposures. We measured activated partial thromboplastin time (APTT), fibrinogen (Fbg), international normalized ratio (INR), prothrombin time (PT), and thrombin time (TT) as blood coagulation parameters. Multivariable linear regression models were utilized to estimate the relationships between urinary DCAA and TCAA and blood coagulation parameters. The effect modifications by demographic and lifestyle characteristics were further explored. RESULTS: Elevated tertiles of urinary DCAA concentrations were associated with increased PT and INR (11.29%, 95% CI: 1.66%, 20.92% and 0.99%, 95% CI: 0.08%, 1.90% for the third vs. first tertile, respectively; both P for trends < 0.05). Stratification analysis showed that the positive associations were only observed among younger (< 30 years), leaner (body mass index < 24.0 kg/m2), and non-passive smoking women. Moreover, elevated tertiles of urinary TCAA concentrations in positive associations with PT and INR were observed among younger women (17.89%, 95% CI: 2.50%, 33.29% and 1.82%, 95% CI: 0.34%, 3.30% for the third vs. first tertile, respectively; both P for trends < 0.05) but not among older women (both P for interactions < 0.05). CONCLUSION: Higher levels of urinary DCAA and TCAA are associated with prolonged clotting time among women.
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Desinfecção , Reprodução , Humanos , Feminino , Idoso , Desinfecção/métodos , Coagulação Sanguínea , Ácido Tricloroacético/urina , Biomarcadores/urina , Ácido Dicloroacético/urinaRESUMO
BACKGROUND: Thromboelastography (TEG) is a viscoelastic test that may be used to evaluate the hemostatic function of whole blood, and it may be useful for burn patients with multiple hemostatic defects. METHODS: We retrospectively recruited patients with burns between January 2019 and July 2021. Blood samples were drawn on admission and subjected to coagulation parameter assessment, including conventional coagulation tests and TEG assessment. Receiver operating characteristic (ROC) analysis was performed to predict the occurrence of complications in patients with early burns. RESULTS: Ninety-three patients with early burns met the inclusion criteria. Patients with minor, moderate, severe, and extremely severe burns accounted for 19.4 %, 36.6 %, 16.1 %, and 27.9 % of all patients, respectively. Compared with the healthy controls, patients with early burns showed significant reductions in the R and K values, and significant elevation in the maximum amplitude (MA), coagulation index (CI), and alpha angle. Compared with minor and moderate burn patients, patients with severe and extremely severe burns had lower K values and thrombin time and higher alpha angle, CI, prothrombin time, international normalized ratio, D-dimer, and fibrin degradation products. Patients with hypercoagulation had lower R and K values, longer MA, longer CI, and greater alpha angle. After ROC analysis, the areas under the ROC curve for acute lung injury, acute kidney injury, and bleeding were 0.789, 0.802, and 0.900, respectively. CONCLUSION: TEG provides insight into the hemostatic state of patients with early burns, and can predict complications in early burn patients when combined with conventional coagulation tests.
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Queimaduras , Hemostáticos , Trombose , Humanos , Tromboelastografia , Estudos Retrospectivos , Coagulação Sanguínea , Testes de Coagulação SanguíneaRESUMO
BACKGROUND: Multiple etiologies contribute to recurrent pregnancy loss (RPL) including immunological, endocrine, anatomical, genetic and infection but more than 50% of cases remain unexplained. Evidences of thrombotic and inflammatory processes were observed at maternal-fetal interface and considered pathological findings in most RPL cases including unexplained cases. This study aimed to evaluate the association between RPL and several risk factors: platelet parameters, coagulation factors, antiphospholipid syndrome, and thyroid function. METHODS: This is an unmatched case-control study that included 100 RPL and 100 control women. Anthropometric and health data were collected and a gynecologist examined participants to assure fitting the inclusion criteria. Platelet parameters [including Mean Platelet Mass (MPM), Concentration (MPC) and Volume (MPV)] and ratios (MPV/Platelet, MPC/Platelet, MPM/Platelet, Platelet/Mononuclear cells), coagulation markers [Protein C (PC), Protein S (PS), Antithrombin III, D-dimer], antiphospholipid antibodies [Anti-phospholipid (APA), Anti-cardiolipin (ACA) and anti-B2-glycoprotein 1], Lupus anticoagulant, Antinuclear antibodies, and thyroid function (Thyroid stimulating hormone and anti-thyroid peroxidase) were measured. RESULTS: Mean ages of cases and controls at marriage were 22.5 years for both, and their current ages were 29.4 and 33.0, respectively. 92% of cases and 99% of controls aged blow 30 years at marriage. 75% of cases have 3-4 miscarriages and 9% have ≥ 7 miscarriages. Our results indicated significantly lower male/female age ratio (p = .019), PC (p = .036) and PS (p = .025) in cases compared to controls. Plasma D-dimer (p = .020) and antiphospholipid antibodies [ACA (IgM and IgG), APA (IgM)] were significantly higher in cases compared to controls. No significant differences were observed between cases and controls concerning APA (IgG), anti-B2-glycoprotein 1 (IgM and IgG), Lupus anticoagulant, Antinuclear antibodies, platelet parameters, thyroid markers, family history of miscarriage, consanguineous marriage, and other health data. CONCLUSIONS: This is the first study that investigated the association between platelet, coagulation, antiphospholipid, autoimmune and thyroid parameters, and RPL in Palestinian women. Significant associations between male/female age ratio, PC, PS, D-dimer, ACA (IgM, IgG), APA (IgM) and RPL were observed. These markers could be used in evaluating RPL. These findings confirm the heterogeneous nature of RPL and emphasize the need for further studies to find out risk factors for RPL.
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Aborto Habitual , Síndrome Antifosfolipídica , Gravidez , Feminino , Humanos , Masculino , Idoso , Adulto Jovem , Adulto , Síndrome Antifosfolipídica/complicações , Inibidor de Coagulação do Lúpus , Estudos de Casos e Controles , Anticorpos Antinucleares , Árabes , Anticorpos Antifosfolipídeos , Aborto Habitual/etiologia , Glicoproteínas , Imunoglobulina G , Imunoglobulina MRESUMO
OBJECTIVE: To investigate the correlation between obstructive sleep apnea (OSA) and coagulation status and to speculate on the underlying mechanism in children with OSA. METHODS: We divided 345 children with OSA (age 2-14 years) into four groups according to the apnea-hypopnea index (AHI). We compared platelet (PLT) and coagulation parameters among groups. Correlations between the polysomnography parameters and coagulation parameters were investigated. RESULTS: Children with OSA had higher PLT counts than those without OSA (P < 0.001), while no significant difference was observed in prothrombin time, international normalized ratio, activated partial thromboplastin time, thrombin time, or fibrinogen among children with/without OSA. In linear regression analysis, the AHI and oxygen desaturation index (ODI) presented positive correlation with the PLT count (R2 = 0.155, beta = 0.307, P < 0.001 and R2 = 0.113, beta = 0.262, P < 0.001), and there was no correlation among the AHI, ODI, and other coagulation parameters. The minimum and mean oxygen saturation of arterial blood manifested negative correlation with the PLT count (R2 = 0.076, beta = - 0.116, P = 0.034 and R2 = 0.083, beta = - 0.140, P = 0.008, respectively). CONCLUSIONS: Children with OSA have a higher PLT count, positively correlated with OSA severity, and no evidence of coagulation disorder.
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Apneia Obstrutiva do Sono , Adolescente , Criança , Pré-Escolar , Humanos , Oxigênio , Contagem de Plaquetas , Polissonografia , Apneia Obstrutiva do Sono/diagnósticoRESUMO
PURPOSE: It has been shown that abnormalities of coagulation and fibrinolysis system are involved in the pathogenesis of necrotizing enterocolitis (NEC), but not well studied challenge in the context of early detection of disease progression. The present study mainly explores the predictive significance of coagulation parameters at the time of NEC diagnosis in identifying the patients who eventually received surgery and/or NEC-related deaths. METHODS: The retrospective study of 114 neonates with NEC was conducted with assessments of demographic data, laboratory results at the time of NEC diagnosis, treatment methods and prognosis. According to treatment methods, patients were divided into surgical intervention group and medical treatment group. Predictive factors were put forward and determined by receiver operating characteristic (ROC) curve analysis. An analysis of the surgical intervention and prognosis was performed. RESULTS: Of 114 patients, 46 (40.4%) cases received surgical intervention and 14 (12.3%) deaths. prothrombin time (PT), PT international normalized ratio, activated partial thromboplastin time (APTT), fibrinogen and platelet count at the time of NEC diagnosis were independently associated with surgical NEC. The APTT could identify patients at high risk for surgical NEC, with 67.39% sensitivity, 86.76% specificity, better than that of other serological parameters. Coagulopathy was found in 38.6% of all patients. For surgical intervention, the area under the ROC curve (AUC) of coagulopathy was 0.869 (95% confidence interval [CI]: 0.794 ~ 0.944, P < 0.001), with 82.61% sensitivity and 91.18% specificity, outperformed APTT (95% CI: 0.236 ~ 0.173, P = 0.001). Furthermore, the AUC for coagulopathy to predict mortality was 0.809 (95% CI: 0.725 ~ 0.877, P < 0.001), with 92.86% sensitivity and 69.0% specificity. CONCLUSION: Coagulation parameters at the time of NEC diagnosis were conducive to early prediction of surgical NEC and -related deaths, which should be closely monitored in neonates at high risk of NEC and validated as a clinical decision-making tool.
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Enterocolite Necrosante , Doenças Fetais , Doenças do Recém-Nascido , Enterocolite Necrosante/diagnóstico , Enterocolite Necrosante/cirurgia , Feminino , Humanos , Recém-Nascido , Prognóstico , Curva ROC , Estudos RetrospectivosRESUMO
OBJECTIVES: Coagulation factors participates in the inflammatory cascade, known to play a crucial role in the development of acute kidney injury (AKI). Thus, it's likely that some factors may be associated with AKI. Among them, low levels of fibrinogen and antithrombin III (ATIII) activity have been proved to increase mortality in patients with sepsis. Moreover, they are also reported to be associated with higher incidence of AKI. However, the association between coagulation parameters, especially fibrinogen and ATIII, and prognosis of AKI has not been examined. METHODS: Data were acquired from Multiparameter Intelligent Monitoring in Intensive Care Database IV (MIMIC-IV) version 1.0. Cox proportional hazards regression model was used to estimate the relationship between coagulation parameters and in-hospital mortality in critically ill patients with AKI. Subgroup analysis was also conducted to assess the robustness of the association. Restricted cubic spline (RCS) curve was utilized to examine the nonlinear relationships between fibrinogen or ATIII and in-hospital mortality. Kaplan-Meier method was used to estimate cumulative incidence of mortality by fibrinogen or ATIII levels. Receiver-operating characteristic (ROC) curve was plotted and area under curve was calculated to evaluate predictive ability of fibrinogen or ATIII. RESULTS: A total of 5914 eligible patients were enrolled in fibrinogen cohort study and 115 patients were eligible for ATIII cohort study. The baseline of low fibrinogen (<150 mg/dL) or ATIII (<80%) activity was associated with significantly higher in-hospital mortality (fibrinogen HR [95% CIs] 2.01 [1.79, 2.27]; ATIII 3.73 [1.11, 12.54]). The HR [95% CIs] of low fibrinogen remained significant 1.29 (1.13, 1.48) in multivariate analysis. The RCS curve showed nearly linear relationship. Subgroup analysis also proved the robustness of the association between fibrinogen and in-hospital mortality. Kaplan-Meier survival curve and ROC demonstrated the predictive capability of fibrinogen and ATIII. CONCLUSION: Low fibrinogen is an independent predictor of in-hospital mortality in critically ill patients with AKI. Low ATIII activity is also likely to impact the risk of in-hospital death.
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Injúria Renal Aguda , Estado Terminal , Humanos , Mortalidade Hospitalar , Antitrombina III , Fibrinogênio , Estudos de Coortes , Injúria Renal Aguda/etiologia , Prognóstico , Anticoagulantes , Estudos RetrospectivosRESUMO
Background and Aims: The hypercoagulability occurring in COVID-19 patients is detected only by Rotational thromboelastometry (ROTEM). However, the benefit of performing ROTEM in the management of disease and predicting the outcome of COVID-19 patients is yet to be established. Material and Methods: The data of 23 critically ill and 11 stable COVID-19 adult patients were extracted from the hospital information system admitted between July and August 2020 and patient charts and analyzed retrospectively. The critically ill patients were divided as a survivor and non-survivor groups. The Intrinsic pathway part of ROTEM (INTEM) and Fibrinogen part of ROTEM (FIBTEM) were performed on day 0 for both critically ill and stable patients, and on day 10 for critically ill patients. The statistical package for social science (SPSS) version 26 was used for statistical analysis. Results: The median FIBTEM amplitude at 5 min (A5) and maximum clot firmness (MCF) were elevated in both stable and critically ill patients (24 vs 27 mm, P = 0.46 and 27.5 vs 40 mm, P = 0.011) with a significant difference in FIBTEM MCF. But there was no significant difference between number of survivors and non-survivors with FIBTEM MCF >25 at day 0 and day 10. Conclusion: The Hypercoagulability state as detected by ROTEM parameters at day 0 and day 10 had no association with the outcome (mortality) of critically ill COVID-19 patients. Hence it cannot be used as a prognostic test. The increasing age, comorbidities and D-dimer values were associated with a poor prognosis in COVID-19 patients.
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BACKGROUND: This article is to explore changes in levels of coagulation parameters in different trimesters among healthy pregnant women in China. METHODS: A total of 760 eligible women were enrolled (first-trimester group: n = 183, second-trimester group: n = 183, third-trimester group: n = 263, non-pregnant group: n = 131). Seven parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), D-dimer (DD), fibrinogen degradation products (FDP), and antithrombin III (ATIII), of all participants were collected. The non-parametric 2.5th-97.5th percentiles reference intervals were calculated for each parameter. RESULTS: The reference intervals for FIB, PT, APTT, TT, FDP, DD, and ATIII at first trimester were 2.11-4.32 g/L, 10.90-13.85 s, 24.60-39.28 s, 12.95-15.88 s, 0.04-2.55 µg/mL, 0.03-1.15 µg/mL, and 75.57%-125.31%, respectively. The reference intervals at second trimester were 2.31-4.77 g/L, 9.70-12.64 s, 24.16-35.43 s, 12.95-15.88 s, 0.15-7.40 µg/mL, 0.08-2.13 µg/mL, and 74.35%-119.28%, respectively. For the third-trimester, the intervals were 2.39-4.96 g/L, 9.20-11.95 s, 23.90-35.51 s, 13.41-18.00 s, 0.55-13.43 µg/mL, 0.15-3.60 µg/mL, and 71.61%-118.29%, respectively. The third-trimester group showed decreased PT, APTT, and ATIII and increased FIB, TT, DD and FDP as compared with the other groups. CONCLUSION: In this study, level changes of coagulation parameters in different trimesters were observed. And the ranges for coagulation parameters were presented, which may provide some reference for clinicians to more accurately monitor the coagulation and fibrinolytic system in pregnant women.
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Povo Asiático , Coagulação Sanguínea , Trimestres da Gravidez/sangue , Gestantes , Adulto , Feminino , Humanos , Gravidez , Valores de ReferênciaRESUMO
The timely and accurate diagnosis of infection with severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), remains the cornerstone of efforts to provide appropriated treatment for patients, to limit further spread of the virus and ultimately to eliminate the virus from the human society. We focus this article on (a) developments for improvement of diagnosis of specific SARS-CoV-2 virus, (b) laboratory changes in the immunologic and coagulation system, (c) therapeutic options for anticoagulant treatment of seriously affected patients and (d) on the perspectives through improvement of diagnostic and therapeutic medical procedures.
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Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Anticorpos Antivirais/sangue , Betacoronavirus/metabolismo , Betacoronavirus/patogenicidade , COVID-19 , Coronavirus/imunologia , Progressão da Doença , Humanos , Pandemias , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/imunologia , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Carga ViralRESUMO
The coagulation cascade is the process of the conversion of soluble fibrinogen to insoluble fibrin that terminates in production of a clot. Factor Xa (FXa) is a serine protease involved in the blood coagulation cascade. Moreover, FXa plays a vital role in the enzymatic sequence which ends with the thrombus production. Thrombosis is a common causal pathology for three widespread cardiovascular syndromes: acute coronary syndrome (ACS), venous thromboembolism (VTE), and strokes. In this research a series of N-propargyltetrahydroquinoline and 1,2,3-triazole derivatives as a potential factor Xa (FXa) inhibitor were designed, synthesized, and evaluated for their FXa inhibitor activity, cytotoxicity activity and coagulation parameters. Rational design for the desired novel molecules was performed through protein-ligand complexes selection and ligand clustering. The microwave-assisted synthetic strategy of selected compounds was carried out by using Ullmann-Goldberg, N-propargylation, Mannich addition, Friedel-Crafts, and 1,3-dipolar cycloaddition type reactions under microwave irradiation. The microwave methodology proved to be an efficient way to obtain all novel compounds in high yields (73-93%). Furthermore, a thermochemical analysis, optimization and reactivity indexes such as electronic chemical potential (µ), chemical hardness (η), and electrophilicity (ω) were performed to understand the relationship between the structure and the energetic behavior of all the series. Then, in vitro analysis showed that compounds 27, 29-31, and 34 exhibited inhibitory activity against FXa and the corresponding half maximal inhibitory concentration (IC50) values were calculated. Next, a cell viability assay in HEK293 and HepG2 cell lines, and coagulation parameters (anti FXa, Prothrombin time (PT), activated Partial Thromboplastin Time (aPTT)) of the most active novel molecules were performed to determine the corresponding cytotoxicity and possible action on clotting pathways. The obtained results suggest that compounds 27 and 29 inhibited FXa targeting through coagulation factors in the intrinsic and extrinsic pathways. However, compound 34 may target coagulation FXa mainly by the extrinsic and common pathway. Interestingly, the most active compounds in relation to the inhibition activity against FXa and coagulation parameters did not show toxicity at the performed coagulation assay concentrations. Finally, docking studies confirmed the preferential binding mode of N-propargyltetrahydroquinoline and 1,2,3-triazole derivatives inside the active site of FXa.
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Coagulação Sanguínea/efeitos dos fármacos , Inibidores do Fator Xa/síntese química , Inibidores do Fator Xa/farmacologia , Fator Xa/química , Quinolinas/química , Triazóis/química , Compostos de Anilina/síntese química , Compostos de Anilina/química , Azidas/síntese química , Azidas/química , Testes de Coagulação Sanguínea , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Desenho de Fármacos , Fator Xa/metabolismo , Inibidores do Fator Xa/química , Humanos , Concentração Inibidora 50 , Ligantes , Micro-Ondas , Simulação de Acoplamento Molecular , Quinolinas/síntese química , Triazóis/síntese químicaRESUMO
BACKGROUND & AIMS: Patients with chronic HCV infection besides hepatitis often present cardiovascular damage, the pathogenesis of which is not defined. In chronic liver diseases, including NAFLD and cirrhosis, a procoagulant imbalance, potentially responsible for atherosclerosis has been reported. We aimed at evaluating whether a procoagulant imbalance is present also in non-cirrhotic patients with HCV infection and whether the procoagulant imbalance correlates with cardiovascular damage. The correlation between the procoagulant imbalance, coexisting steatosis, and liver fibrosis was analysed. METHODS: From 2014 to 2018, 393 subjects (205 patients with chronic HCV infection from two liver units and 188 controls) were enrolled. Metabolic, cardiovascular, liver assessment and coagulation parameters-procoagulants (FII and FVIII) and anticoagulants (antithrombin and protein C [PC]), endogenous thrombin potential (ETP), peak-thrombin and their ratios (with/without thrombomodulin)-were determined. RESULTS: The procoagulant imbalance (defined as high FVIII, FVIII/PC ratio, ETP-ratio and peak-thrombin-ratio (with/without thrombomodulin)) was significantly higher in patients with chronic HCV than controls. Steatosis was detected in 87 patients (42%). No difference in coagulation imbalance, carotid and cardiac parameters and severity of liver fibrosis was observed in patients with or without steatosis, despite the latter had less severe metabolic alterations. The FVIII/PC ratio was independently associated with carotid intima-media thickness (coefficient 0.04, 95% CI 0.002-0.07, P = .04) and liver fibrosis (coefficient 0.64, 95% CI 0.37-0.92, P < .0001). CONCLUSION: Patients with HCV infection, even in the absence of cirrhosis have a procoagulant-imbalance that possibly plays a role in increasing the risk of cardiovascular disease and progression of fibrosis.
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Coagulação Sanguínea , Hepatite C Crônica/sangue , Trombina/metabolismo , Adulto , Idoso , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , Fígado Gorduroso/etiologia , Feminino , Hepatite C Crônica/complicações , Humanos , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The view that 2 l of crystalloid and 1.5 l of colloid can be infused while awaiting compatible blood for patients with major postpartum haemorrhage is based on expert opinion documents. We describe real-world changes in levels of coagulation parameters after the administration of different volumes of clear fluids to women suffering from major postpartum haemorrhage. METHODS: We performed a nationwide retrospective cohort study in the Netherlands among 1038 women experiencing severe postpartum haemorrhage who had received at least four units of red cells or fresh frozen plasma or platelets in addition to red cells. The volume of clear fluids administered before the time of blood sampling was classified into three fluid administration strategies, based on the RCOG guideline: < 2 L, 2-3.5 L and > 3.5 L. Outcomes included haemoglobin, haematocrit, platelet count, fibrinogen, aPTT and PT levels. RESULTS: Haemoglobin, haematocrit, platelet count, fibrinogen and aPTT were associated with volumes of clear fluids, which was most pronounced early during the course of postpartum haemorrhage. During the earliest phases of postpartum haemorrhage median haemoglobin level was 10.1 g/dl (IQR 8.5-11.6) among the women who received < 2 L clear fluids and 8.1 g/dl (IQR 7.1-8.4) among women who received > 3.5 L of clear fluids; similarly median platelet counts were 181 × 109/litre (IQR 131-239) and 89 × 109/litre (IQR 84-135), aPTT 29 s (IQR 27-33) and 38 s (IQR 35-55) and fibrinogen 3.9 g/L (IQR 2.5-5.2) and 1.6 g/L (IQR 1.3-2.1). CONCLUSIONS: In this large cohort of women with severe postpartum haemorrhage, administration of larger volumes of clear fluids was associated with more severe deterioration of coagulation parameters corresponding to dilution. Our findings provide thus far the best available evidence to support expert opinion-based guidelines recommending restrictive fluid resuscitation in women experiencing postpartum haemorrhage. TRIAL REGISTRATION: Netherlands Trial Register ( NTR4079 ), registration date July 17, 2013.
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Transtornos da Coagulação Sanguínea/sangue , Coloides/administração & dosagem , Soluções Cristaloides/administração & dosagem , Hidratação/métodos , Hemorragia Pós-Parto/terapia , Adulto , Coagulação Sanguínea , Transtornos da Coagulação Sanguínea/etiologia , Volume Sanguíneo , Feminino , Fibrinogênio/metabolismo , Hidratação/efeitos adversos , Hematócrito , Hemoglobinas/metabolismo , Humanos , Países Baixos , Tempo de Tromboplastina Parcial , Contagem de Plaquetas , Gravidez , Tempo de Protrombina , Estudos RetrospectivosRESUMO
INTRODUCTION AND AIM: Patients with acute on chronic liver failure (ACLF) have abnormal conventional coagulation tests- platelet count and international normalized ratio (INR). Thromboelastography (TEG) is a rapid, point-of-care assay, more comprehensive than platelet count and INR as it assesses for platelet adequacy (number and function), coagulation factors and clot retraction. The aim of the study was to evaluate the TEG parameters in patients with ACLF, chronic liver disease having acute decompensation (AD) and healthy subjects (HC). MATERIAL AND METHODS: TEG parameters were assessed in patients with ACLF and AD within 24 h of admission. Consecutive patients were included in the study over 12 months. Healthy subjects were recruited as controls. RESULTS: 179 patients were included- 68 ACLF, 53 AD and 58 HC. The mean values of INR in ACLF, AD and HC groups were 2.9 ± 1.4, 1.6 ± 0.4 and 1.1 ± 0.2; P < 0.001. Among TEG parameters - maximum amplitude (MA) was low in ACLF and AD patients as compared with HC (53.8 ± 15, 58.3 ± 13.9 mm and 67.2 ± 12.1 mm, respectively; P < 0.001). Lysis at 30 min (LY30) was high in ACLF patients, as compared to AD and HC (8.6 ± 14.1%, 5.0 ± 9.5% and 4.9 ± 9.8%, respectively; P = 0.060). There were no differences in r time, k time, and alpha angle between groups; normal in >90% patients. There was no difference in TEG parameters between different ACLF grades, whereas CCTs were more deranged with increasing grades of ACLF. CONCLUSION: Despite abnormal conventional coagulation tests, TEG parameters in ACLF patients are essentially normal, except reduced maximum amplitude. Future studies are needed to explore the utility of TEG in clinical management of ACLF patients.
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Insuficiência Hepática Crônica Agudizada/diagnóstico por imagem , Insuficiência Hepática Crônica Agudizada/patologia , Tromboelastografia/métodos , Insuficiência Hepática Crônica Agudizada/mortalidade , Adulto , Idoso , Análise de Variância , Coagulação Sanguínea/fisiologia , Estudos de Casos e Controles , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Índia , Coeficiente Internacional Normatizado/métodos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Prognóstico , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença , Taxa de SobrevidaRESUMO
WHAT IS KNOWN AND OBJECTIVE: Little is known regarding changes in blood coagulation parameters associated with tetracycline antibiotics. We report a possible case of elevated PT, APPT and PT/INR associated with doxycycline and cefoperazone co-administration. CASE SUMMARY: An 83-year-old Chinese male inpatient with severe pneumonia, chronic renal insufficiency and malnutrition experienced elevated PT, APPT and PT/INR which occurred within a few days of doxycycline added to his cefoperazone treatment and returned to normal after removal of it. WHAT IS NEW AND CONCLUSION: Very close monitoring of coagulation parameters might be advisable in those subjects when administering doxycycline and cefoperazone concomitantly.
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Antibacterianos/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , Cefoperazona/uso terapêutico , Doxiciclina/efeitos adversos , Idoso de 80 Anos ou mais , Interações Medicamentosas , Humanos , MasculinoRESUMO
BACKGROUND: Postoperative drainage autologous blood re-transfusion (ABT) is an important treatment method that maintains a high haemoglobin (HGB) content and obviates the need for allogeneic blood transfusion in patients after surgery. However, the safety of ABT remains controversial. OBJECTIVES AND METHODS: This study aimed to investigate the safety of postoperative drainage ABT in primary total hip arthroplasty (THA). In this randomized, controlled study, patients undergoing THA were selected and randomly divided into two groups. A device for postoperative ABT was used for the 49 patients in the ABT group, whereas conventional postoperative vacuum drainage was used for the 42 patients in the drainage blood (Drain) group without ABT. The coagulation parameters and D-dimer (DD) levels of the two groups of patients were recorded before surgery (T0) and on postoperative days one (T1), three (T2), seven (T3), and 14 (T4). RESULTS: A within-group comparison after THA showed that the postoperative fibrinogen (FIB) and DD levels were higher than those before surgery in both groups (P < 0.01). A between-group comparison showed that, at different time points, the postoperative drainage blood amount and the coagulation parameters were not significantly different between the two groups. Compared with the Drain group, the DD levels in the ABT group were significantly higher at T1, T2, and T3 (P < 0.05). CONCLUSION: Postoperative drainage ABT did not significantly impact the coagulation parameters of patients after THA. However, the DD levels after ABT significantly increased, which may affect the risk of thrombosis.
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Artroplastia de Quadril , Coagulação Sanguínea , Transfusão de Sangue Autóloga , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Cuidados Pós-Operatórios , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: Trauma-induced coagulopathy (TIC) in multiple trauma patients is a potentially lethal complication. Whether quickly available laboratory parameters using point-of-care (POC) blood gas analysis (BGA) may serve as surrogate parameters for standard coagulation parameters is unknown. The present study evaluated TraumaRegister DGU® of the German Trauma Society for correlations between POC BGA parameters and standard coagulation parameters. METHODS: In the setting of 197 trauma centres (172 in Germany), 86,442 patients were analysed between 2005 and 2012. Of these, 40,129 (72% men) with a mean age 46 ± 21 years underwent further analysis presenting with direct admission from the scene of the accident to a trauma centre, injury severity score (ISS) ≥ 9, complete data available for the calculation of revised injury severity classification prognosis, and blood samples with valid haemoglobin (Hb) measurements taken immediately after emergency department (ED) admission. Correlations between standard coagulation parameters and POC BGA parameters (Hb, base excess [BE], lactate) were tested using Pearson's test with a two-tailed significance level of p < 0.05. A subgroup analysis including patients with ISS > 16, ISS > 25, ISS > 16 and shock at ED admission, and patients with massive transfusion was likewise carried out. RESULTS: Correlations were found between Hb and prothrombin time (r = 0.497; p < 0.01), Hb and activated partial thromboplastin time (aPTT; r = -0.414; p < 0.01), and Hb and platelet count (PLT; r = 0.301; p < 0.01). Patients presenting with ISS ≥ 16 and shock (systolic blood pressure < 90 mmHg) at ED admission (n = 4,329) revealed the strongest correlations between Hb and prothrombin time (r = 0.570; p < 0.01), Hb and aPTT (r = -0.457; p < 0.01), and Hb and PLT (r = 0.412; p < 0.01). Significant correlations were also found between BE and prothrombin time (r = -0.365; p < 0.01), and BE and aPTT (r = 0.327, p < 0.01). No correlations were found between Hb, BE and lactate lactate. CONCLUSIONS: POC BGA parameters Hb and BE of multiple trauma patients correlated with standard coagulation parameters in a large database analysis. These correlations were particularly strong in multiple trauma patients presenting with ISS > 16 and shock at ED admission. This may be relevant for hospitals with delayed availability of coagulation studies and those without viscoelastic POC devices. Future studies may determine whether clinical presentation/BGA-oriented coagulation therapy is an appropriate tool for improving outcomes after major trauma.
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Anticoagulantes/uso terapêutico , Serviços Médicos de Emergência/métodos , Serviço Hospitalar de Emergência , Traumatismo Múltiplo/sangue , Acidentes , Adulto , Idoso , Coagulação Sanguínea , Gasometria , Feminino , Hemoglobinas/análise , Humanos , Escala de Gravidade do Ferimento , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Sistemas Automatizados de Assistência Junto ao Leito , Valor Preditivo dos TestesRESUMO
Background: Severe coagulation abnormalities are common in patients with COVID-19 infection. We aimed to investigate the relationship between pro-inflammatory cytokines and coagulation parameters concerning socio-demographic, clinical, and laboratory characteristics. Methods: Our study included patients hospitalized during the second wave of COVID-19 in the Republic of Serbia. We collected socio-demographic, clinical, and blood-sample data for all patients. Cytokine levels were measured using flow cytometry. Results: We analyzed data from 113 COVID-19 patients with an average age of 58.15 years, of whom 79 (69.9%) were male. Longer duration of COVID-19 symptoms before hospitalization (B = 69.672; p = 0.002) and use of meropenem (B = 1237.220; p = 0.014) were predictive of higher D-dimer values. Among cytokines, higher IL-5 values significantly predicted higher INR values (B = 0.152; p = 0.040) and longer prothrombin times (B = 0.412; p = 0.043), and higher IL-6 (B = 0.137; p = 0.003) predicted longer prothrombin times. Lower IL-17F concentrations at admission (B = 0.024; p = 0.050) were predictive of higher INR values, and lower IFN-γ values (B = -0.306; p = 0.017) were predictive of higher aPTT values. Conclusions: Our findings indicate a significant correlation between pro-inflammatory cytokines and coagulation-related parameters. Factors such as the patient's level of education, gender, oxygen-therapy use, symptom duration before hospitalization, meropenem use, and serum concentrations of IL-5, IL-6, IL-17F, and IFN-γ were associated with worse coagulation-related parameters.