RESUMEN
OBJECTIVE: To investigate the characteristic of circulating microparticle in patients with acute myocardial infarction (AMI) and its possible mechanism of promoting coagulation. METHODS: A prospective case-control study was conducted. The patients with coronary heart disease admitted to the second department of cardiology in Harbin First Hospital from June to November 2023 were enrolled, and they were grouped according to whether the patients occurred AMI or not. On the day of admission, disseminated intravascular coagulation (DIC) score was calculated. At the same time, fasting venous blood was collected, and the levels of D-dimer, fibrin degradation product (FDP) and the activities of major coagulation factors were detected. The level of circulating microparticle was determined by microparticle trapping method. The microparticle carrying tissue factor (TF+MP) level was detected by tissue factor (TF) dependent F Xa production assay. Spearman correlation method was used to analyze the correlation among the indicators. RESULTS: A total of 52 patients with coronary heart disease were enrolled, including 26 patients in AMI group and 26 patients in non-AMI group. There was no significant difference in gender, age, body mass index (BMI), underlying diseases, smoking history, and pre-admission treatment of patients between the two groups, indicating that the baseline data of the two groups were balanced and comparable. Compared with the non-AMI group, the DIC score and D-dimer, FDP levels in the AMI group were significantly increased [DIC score: 3 (3, 4) vs. 3 (2, 3), D-dimer (mg/L): 8.80 (6.84, 15.66) vs. 2.13 (1.64, 3.86), FDP (mg/L): 30.13 (19.30, 52.54) vs. 20.00 (13.51, 28.37), all P < 0.01], indicating that the degree of coagulation activation in AMI patients was more severe. The consumption of major coagulation factors in the coagulation pathway in the AMI group was heavier than that in the non-AMI group [F II: 59.45% (49.65%, 71.25%) vs. 63.65% (49.98%, 73.22%), F V: 96.95% (73.50%, 112.78%) vs. 105.05% (73.48%, 131.48%), F VII: 42.30% (36.98%, 51.98%) vs. 53.40% (46.58%, 69.88%), F X: 60.90% (48.22%, 80.82%) vs. 73.50% (56.80%, 85.98%), F XI: 82.45% (62.90%, 99.10%) vs. 92.40% (73.90%, 114.25%), F XII: 29.90% (12.42%, 42.38%) vs. 34.65% (16.32%, 48.20%), all P < 0.05]. The circulating TF+MP level in the AMI group was significantly higher than that in the non-AMI group [nmol/L: 0.13 (0.06, 0.20) vs. 0.08 (0.04, 0.15), P < 0.05]. There was no significant difference in the level of circulating microparticle between AMI group and non-AMI group [nmol/L: 1.24 (0.71, 3.77) vs. 1.35 (0.73, 2.14), P > 0.05]. Correlation analysis showed that circulating TF+MP level in the patients with coronary heart disease was significantly positively correlated with coagulation indicator DIC score (r = 0.307, P = 0.027), D-dimer (r = 0.696, P < 0.001) and FDP (r = 0.582, P < 0.001), and there was a strong negative correlation with exogenous pathway factor F VII (r = -0.521, P < 0.001) and common pathway factor F X (r = -0.332, P = 0.016). CONCLUSIONS: The circulating TF+MP level in AMI patients was significantly higher than that in the non-AMI patients. TF+MP may play an important role in activating the extrinsic coagulation pathway, exacerbating coagulation factor consumption, and promoting clot formation during AMI occurrence.
Asunto(s)
Coagulación Sanguínea , Micropartículas Derivadas de Células , Productos de Degradación de Fibrina-Fibrinógeno , Infarto del Miocardio , Tromboplastina , Humanos , Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico , Estudios Prospectivos , Estudios de Casos y Controles , Micropartículas Derivadas de Células/metabolismo , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Tromboplastina/metabolismo , Factores de Coagulación Sanguínea/metabolismo , Factores de Coagulación Sanguínea/análisis , Femenino , Masculino , Coagulación Intravascular Diseminada/sangre , Persona de Mediana Edad , Enfermedad Coronaria/sangreRESUMEN
The role of blood clots in tissue repair has been identified for a long time; however, its participation in the integration between implants and host tissues has attracted attention only in recent years. In this work, a mesoporous silica thin film (MSTF) with either vertical or parallel orientation was deposited on titania nanotubes surface, resulting in superhydrophilic nanoporous surfaces. A proteomic analysis of blood plasma adsorption revealed that the MSTF coating could significantly increase the abundance of acidic proteins and the adsorption of coagulation factors (XII and XI), with the help of cations (Na+, Ca2+) binding. As a result, both the activation of platelets and the formation of blood clots were significantly enhanced on the MSTF surface with more condensed fibrin networks. The two classical growth factors of platelets-derived growth factors-AB and transformed growth factors-ßwere enriched in blood clots from the MSTF surface, which accounted for robust osteogenesis bothin vitroandin vivo. This study demonstrates that MSTF may be a promising coating to enhance osteogenesis by modulating blood clot formation.
Asunto(s)
Coagulación Sanguínea , Materiales Biocompatibles Revestidos , Osteogénesis , Dióxido de Silicio , Titanio , Adsorción , Dióxido de Silicio/química , Coagulación Sanguínea/efectos de los fármacos , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Animales , Osteogénesis/efectos de los fármacos , Titanio/química , Porosidad , Propiedades de Superficie , Humanos , Plaquetas/metabolismo , Proteómica/métodos , Proteínas Sanguíneas/química , Proteínas Sanguíneas/metabolismo , Nanotubos/química , Ratones , Masculino , Ensayo de Materiales , Factores de Coagulación Sanguínea/metabolismo , Factores de Coagulación Sanguínea/químicaRESUMEN
Objective: To explore the causal association between coagulation function, including von Willebrand factor (vWF), a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13), activated partial thromboplastin time (aPTT), coagulation factor â § (Fâ §), coagulation factor â ª (Fâ ª), coagulation factor â ¦ (Fâ ¦), coagulation factor â © (Fâ ©), endogenous thrombin potential (ETP), plasminogen activator inhibitor-1 (PAI-1), protein C, and plasmin, and gestational diabetes mellitus (GDM) using two-sample two-way Mendelian randomization (MR), and to provide genetic evidence for the association between coagulation function and the pathogenesis of GDM. Methods: The IEU OpenGWAS database was accessed using the R package TwoSampleMR (v 0.5.6) to obtain the statistical data of the genome-wide association study (GWAS) summary of GDM. MR analysis of the causal association between 11 coagulation function and GDM was performed by the inverse-variance weighted method (IVW), the MR-Egger method, and the weighted median method (WM). Results: In this study, the GWAS summary statistics of GDM (covering 5 687 cases and 117 892 controls) were used for MR analysis. It was found that there was a causal relationship between the predicted plasma Fâ § level and the risk for GDM (IVW: [odds ratio, OR]=0.28, 95% confidence interval [CI]: 0.10-0.75, P<0.001; WM: OR=0.30, 95% CI: 0.09-0.98, P<0.001). There was no causal relationship between other coagulation function and the risk for GDM (P>0.05). Conclusion: There is a significant causal relationship between the plasma Fâ § level and the risk for GDM. This finding highlights the complex interaction between coagulation function and glucose metabolism during pregnancy, but further research on this finding is warranted.
Asunto(s)
Coagulación Sanguínea , Diabetes Gestacional , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Humanos , Diabetes Gestacional/genética , Diabetes Gestacional/sangre , Femenino , Embarazo , Coagulación Sanguínea/genética , Polimorfismo de Nucleótido Simple , Factor de von Willebrand/genética , Factor de von Willebrand/metabolismo , Factores de Coagulación Sanguínea/genética , Factores de Coagulación Sanguínea/metabolismoRESUMEN
BACKGROUND: Metabolic clusters can stratify subgroups of individuals at risk for type 2 diabetes mellitus and related complications. Since obesity and insulin resistance are closely linked to alterations in hemostasis, we investigated the association between plasmatic coagulation and metabolic clusters including the impact on survival. METHODS: Utilizing data from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, we assigned 917 participants without diabetes to prediabetes clusters, using oGTT-derived glucose and insulin, high-density lipoprotein cholesterol, triglycerides, and anthropometric data. We performed a comprehensive analysis of plasmatic coagulation parameters and analyzed their associations with mortality using proportional hazards models. Mediation analysis was performed to assess the effect of coagulation factors on all-cause mortality in prediabetes clusters. RESULTS: Prediabetes clusters were assigned using published tools, and grouped into low-risk (clusters 1,2,4; n = 643) and high-risk (clusters 3,5,6; n = 274) clusters. Individuals in the high-risk clusters had a significantly increased risk of death (HR = 1.30; CI: 1.01 to 1.67) and showed significantly elevated levels of procoagulant factors (fibrinogen, FVII/VIII/IX), D-dimers, von-Willebrand factor, and PAI-1, compared to individuals in the low-risk clusters. In proportional hazards models adjusted for relevant confounders, elevated levels of fibrinogen, D-dimers, FVIII, and vWF were found to be associated with an increased risk of death. Multiple mediation analysis indicated that vWF significantly mediates the cluster-specific risk of death. CONCLUSIONS: High-risk prediabetes clusters are associated with prothrombotic changes in the coagulation system that likely contribute to the increased mortality in those individuals at cardiometabolic risk. The hypercoagulable state observed in the high-risk clusters indicates an increased risk for cardiovascular and thrombotic diseases that should be considered in future risk stratification and therapeutic strategies.
Asunto(s)
Biomarcadores , Factores de Coagulación Sanguínea , Coagulación Sanguínea , Causas de Muerte , Angiografía Coronaria , Estado Prediabético , Humanos , Estado Prediabético/sangre , Estado Prediabético/mortalidad , Estado Prediabético/diagnóstico , Masculino , Persona de Mediana Edad , Femenino , Medición de Riesgo , Anciano , Biomarcadores/sangre , Factores de Coagulación Sanguínea/metabolismo , Factores de Coagulación Sanguínea/análisis , Pronóstico , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Glucemia/metabolismo , Factores de Riesgo , Análisis de Mediación , Valor Predictivo de las Pruebas , Diabetes Mellitus Tipo 2/mortalidad , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnósticoRESUMEN
Aim: This retrospective clinical study was designed to examine the predictive value of thromboelastography (TEG) combined with coagulation function for venous thromboembolism (VTE) in hospitalized patients with cancer. Materials & methods: Among 215 patients admitted between May 2020 and January 2022, 39 (18.14%) were diagnosed with VTE during hospitalization. Results: Significant differences were found in D-dimer, ATIII and TEG parameters (maximum amplitude and coagulation index) between VTE-positive and VTE-negative patients (p < 0.05). Multivariate analysis revealed tumor node metastasis stage, concomitant infection, smoking history and D-dimer as independently associated with VTE. The constructed model and D-dimer areas under the curve were 0.809 and 0.764, respectively. Conclusion: TEG parameters were not significantly predictive indicators for VTE, with D-dimer remaining a key predictor.
[Box: see text].
Asunto(s)
Productos de Degradación de Fibrina-Fibrinógeno , Neoplasias , Tromboelastografía , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/sangre , Tromboembolia Venosa/etiología , Tromboembolia Venosa/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Neoplasias/complicaciones , Neoplasias/sangre , Estudios Retrospectivos , Anciano , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Factores de Riesgo , Factores de Coagulación Sanguínea/metabolismo , Factores de Coagulación Sanguínea/análisis , AdultoRESUMEN
Migrasomes are organelles that are generated by migrating cells. Here we report the key role of neutrophil-derived migrasomes in haemostasis. We found that a large number of neutrophil-derived migrasomes exist in the blood of mice and humans. Compared with neutrophil cell bodies and platelets, these migrasomes adsorb and enrich coagulation factors on the surface. Moreover, they are highly enriched with adhesion molecules, which enable them to preferentially accumulate at sites of injury, where they trigger platelet activation and clot formation. Depletion of neutrophils, or genetic reduction of the number of these migrasomes, significantly decreases platelet plug formation and impairs coagulation. These defects can be rescued by intravenous injection of purified neutrophil-derived migrasomes. Our study reveals neutrophil-derived migrasomes as a previously unrecognized essential component of the haemostasis system, which may shed light on the cause of various coagulation disorders and open therapeutic possibilities.
Asunto(s)
Coagulación Sanguínea , Plaquetas , Ratones Endogámicos C57BL , Neutrófilos , Neutrófilos/metabolismo , Animales , Humanos , Plaquetas/metabolismo , Ratones , Hemostasis , Movimiento Celular , Activación Plaquetaria , Masculino , Factores de Coagulación Sanguínea/metabolismo , Factores de Coagulación Sanguínea/genéticaRESUMEN
BACKGROUND: Intracerebral hemorrhage (ICH) of undetermined etiology occurs infrequently in young and middle-aged adults. We hypothesized that slight decreases in coagulation factors and formation of less compact fibrin clots prone to faster lysis predispose to this type of ICH. METHODS: We recruited 44 consecutive patients aged <50 years following ICH of unknown cause at least 3 months since the event. Subjects free of ICH (n = 47) matched for age, sex, BMI, and hypertension served as the control group. We assessed plasma fibrin clot permeability, turbidity and fibrinolytic capacity, along with thrombin generation, coagulation factors (F) II, FV, FVII, FVIII, FIX, FX, FXI, antithrombin, and fibrinolysis proteins. RESULTS: ICH patients (median age 41 years, 45.5 % women) had 8.4 % lower FII (p = 0.0001) and 10.1 % lower FVII activity (p = 0.0003), 9.4 % higher antithrombin activity (p = 0.0004) and 13.5 % lower platelet count (p = 0.02). Other factors and thrombin generation did not differ between the two groups. The ICH survivors were characterized by impaired fibrin polymerization reflected by 10.1 % longer lag phase of the turbidimetry curve (p = 0.0002), decreased fiber density indicated by 11.8 % lower maximum absorbance (p = 0.004), as well as 11.1 % shorter clot lysis time (p = 0.014) and 10.0 % faster increase of maximal D-Dimer levels (p = 0.000001). CONCLUSIONS: We demonstrated a prohemorrhagic fibrin clot phenotype, along with lower FII, FVII and higher antithrombin activity in adults below 50 years of age who suffered from ICH of unknown cause, which might indicate novel mechanisms contributing to ICH in younger individuals.
Asunto(s)
Hemorragia Cerebral , Fibrina , Humanos , Femenino , Masculino , Adulto , Hemorragia Cerebral/sangre , Estudios de Casos y Controles , Fibrina/metabolismo , Persona de Mediana Edad , Fenotipo , Coagulación Sanguínea , Fibrinólisis , Factores de Coagulación Sanguínea/metabolismo , Factores de Coagulación Sanguínea/análisis , Adulto JovenRESUMEN
Pro- and anticoagulant factors are core components of hemostasis [...].
Asunto(s)
Factores de Coagulación Sanguínea , Humanos , Factores de Coagulación Sanguínea/metabolismo , Factores de Coagulación Sanguínea/genética , Anticoagulantes/uso terapéutico , Anticoagulantes/farmacología , Coagulación Sanguínea , Hemostasis , AnimalesRESUMEN
OBJECTIVE: To investigate the intervention effect and mechanism of regulating miR-155 on young rats with dysfunction of blood coagulation. METHODS: Twenty-six healthy and clean SD male rats were selected to establish the coagulopathy models. Twenty-four rats successfully established models and were randomly divided into three groups: model group, up-regulated miR-155 group and down-regulated miR-155 group, with 8 rats in each group. The expression of miR-155 was detected by real-time fluorescence quantitative polymerase chain reaction. The changes of coagulation factors and coagulation indicators were observed. Liver pathological tissues were observed by HE staining. The expressions of HMGB1-RAGE/TLRs-NF-κB signaling pathway related proteins were detected by Western blot. RESULTS: Compared with model group, the expressions of HMGB1, RAGE, TLR2, TLR4 and NF-κB were significantly increased in up-regulated miR-155 group (all P < 0.05), while decreased in down-regulated miR-155 group (all P < 0.05). Compared with model group, the expressions of coagulation factor â ¡, â ¦, â ¨, and â © were significantly decreased in up-regulated miR-155 group (all P < 0.05), while increased in down-regulated miR-155 group (P < 0.05). There was no significant difference in the expression of coagulation factor â ª among the three groups (P >0.05). Compared with model group, the levels of prothrombin time (PT) and activated partial thromboplastin time (APTT) were lower and fibrinogen (FIB) was higher in up-regulated miR-155 group (all P < 0.05), while in the down-regulated miR-155 group they were opposite. CONCLUSION: Down-regulation of miR-155 can effectively improve coagulation factors and coagulation indexes and inhibit inflammation in young rats with dysfunction of blood coagulopathy, and the mechanism may be related to HMGB1-RAGE/TLRs-NF-κB signaling pathway.
Asunto(s)
Coagulación Sanguínea , Proteína HMGB1 , MicroARNs , FN-kappa B , Ratas Sprague-Dawley , Transducción de Señal , Animales , Ratas , Masculino , FN-kappa B/metabolismo , Proteína HMGB1/metabolismo , Trastornos de la Coagulación Sanguínea , Regulación hacia Abajo , Receptor Toll-Like 4/metabolismo , Factores de Coagulación Sanguínea/metabolismo , Receptor Toll-Like 2/metabolismoRESUMEN
PURPOSE OF REVIEW: This article summarizes the role of coagulation factors in the pathophysiology of heart failure including D-dimer, fibrinogen and fibrin, prothrombin, p-selectin, tissue factor, tissue plasminogen activator, von Willebrand factor, ß-thromboglobulin, Factor XI, tissue thromboplastin, plasminogen activator inhibitor-1 (PAI-1), thrombomodulin, soluble urokinase-type plasminogen activator receptor (suPAR) and stuart-prower factor. RECENT FINDINGS: The D-dimer, P-selectin, prothrombin, von Willebrand factor, tissue plasminogen activator, fibrinogen, suPAR, tissue factor, thrombomodulin and Factor XI play significant roles the pathophysiology of heart failure. However, no associations were found between ß-thromboglobulin, tissue thromboplastin, PAI-1 and stuart-prower factor in the context of heart failure. Coagulation factors play significant role in the pathophysiology of heart failure. Consequently, the underlying pathophysiological mechanisms that explain changes in the cascade are closely related to the diagnostic, prognostic and therapeutic roles of coagulation cascade factors, which help physicians identify and treat heart failure.
Asunto(s)
Factores de Coagulación Sanguínea , Coagulación Sanguínea , Insuficiencia Cardíaca , Humanos , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/sangre , Coagulación Sanguínea/fisiología , Factores de Coagulación Sanguínea/metabolismo , PronósticoRESUMEN
BACKGROUND: Thromboelastography (TEG) is a widely utilized clinical testing method for real-time monitoring of platelet function and the thrombosis process. Lipid metabolism disorders are crucial risk factors for thrombosis. The lipid metabolism characteristics of hamsters resemble those of humans more closely than mice and rats, and their relatively large blood volume makes them suitable for studying the mechanisms of thrombosis related to plasma lipid mechanisms. Whole blood samples from golden Syrian hamsters and healthy humans were obtained following standard clinical procedures. TEG was employed to evaluate coagulation factor function, fibrinogen (Fib) function, platelet function, and the fibrinolytic system. METHODS: The whole blood from hamster or healthy human was isolated following the clinical procedure, and TEG was employed to evaluate the coagulation factor function, Fib function, platelet function, and fibrinolytic system. Coagulation analysis used ACLTOP750 automatic coagulation analysis pipeline. Blood routine testing used XN-2000 automatic blood analyzer. RESULTS: TEG parameters revealed that hamsters exhibited stronger coagulation factor function than humans (reaction time [R], p = 0.0117), with stronger Fib function (alpha angle, p < 0.0001; K-time [K], p < 0.0001). Platelet function did not differ significantly (maximum amplitude [MA], p = 0.077). Hamsters displayed higher coagulation status than humans (coagulation index [CI], p = 0.0023), and the rate of blood clot dissolution in hamsters differed from that in humans (percentage lysis 30 min after MA, p = 0.02). Coagulation analysis parameters indicated that prothrombin time (PT) and activated partial thromboplastin time (APTT) were faster in hamsters than in humans (PT, p = 0.0014; APTT, p = 0.03), whereas the Fib content was significantly lower in hamsters than in humans (p < 0.0001). No significant difference was observed in thrombin time (p = 0.1949). CONCLUSIONS: In summary, TEG could be used to evaluate thrombosis and bleeding parameters in whole blood samples from hamsters. The platelet function of hamsters closely resembled that of humans, whereas their coagulation function was significantly stronger.
Asunto(s)
Mesocricetus , Tromboelastografía , Animales , Tromboelastografía/métodos , Humanos , Masculino , Cricetinae , Coagulación Sanguínea/fisiología , Femenino , Adulto , Fibrinógeno/metabolismo , Fibrinógeno/análisis , Plaquetas/metabolismo , Factores de Coagulación Sanguínea/metabolismo , Factores de Coagulación Sanguínea/análisis , Pruebas de Coagulación SanguíneaRESUMEN
INTRODUCTION: Recent research has shown that blood coagulation and the extrinsic coagulation cascade are involved in the pathogenesis of chronic spontaneous urticaria (CSU), but little is known about the coagulation factors in angioedema. METHODS: This study included 58 participants: 29 patients with chronic angioedema (14 with isolated angioedema and 15 with angioedema with wheals) and 29 healthy controls (HCs). We compared the values of coagulation factors in patients with isolated angioedema to those with wheals. Plasma levels of D-dimer, fibrinogen, and factor VII were measured by enzyme-linked immunosorbent assay (ELISA) for all participants. RESULTS: Significantly higher D-dimer (p = 0.016; ε² = 0.381) and fibrinogen (p = 0.044; ε² = 0.331) levels were recorded in patients with angioedema (both groups) than in the HCs, with higher levels for angioedema with wheals. Factor VII and fibrinogen levels did not differ significantly between the groups with angioedema, but coagulation factors were more often elevated in both angioedema groups than in HCs. CONCLUSIONS: One characteristic of angioedema is an elevated blood coagulation potential, which may help produce fibrin and may be important in controlling angioedema attacks.
Asunto(s)
Angioedema , Productos de Degradación de Fibrina-Fibrinógeno , Fibrinógeno , Femenino , Humanos , Masculino , Angioedema/sangre , Factores de Coagulación Sanguínea/análisis , Factores de Coagulación Sanguínea/metabolismo , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Fibrinógeno/análisis , Fibrinógeno/metabolismo , Urticaria/sangreRESUMEN
Chemical and UV light-based pathogen reduction technologies are currently in use for human platelet concentrates (PCs) to enhance safety from transfusion-transmitted infections. Relative to UV light, 405 nm violet-blue light in the visible spectrum is known to be less harmful. Hence, in this report for the first time, we have assessed the global hemostasis activity of PCs stored in plasma and the activities of six plasma coagulation factors (CFs) as a measure of in vitro hemostatic activity following exposure to the microbicidal 405 nm light. Apheresis PC samples collected from each screened human donor (n = 22) were used for testing of PCs and platelet poor plasma (PPP). Both PCs and PPPs were treated for 5 h with 405 nm light to achieve a previously established microbicidal light dose of 270 J/cm2. Activated partial thromboplastin time and prothrombin time-based potency assays using a coagulation analyzer and hemostatic capacity via Thromboelastography were analyzed. Thromboelastography analysis of the light-treated PCs and plasma present in the PCs showed little difference between the treated and untreated samples. Further, plasma present in the PCs during the light treatment demonstrated a better stability in potency assays for several coagulation factors compared to the plasma alone prepared from PCs first and subjected to the light treatment separately. Overall, PCs stored in plasma treated with 405 nm violet-blue light retain activity for hemostasis.
Asunto(s)
Plaquetas , Hemostasis , Rayos Ultravioleta , Humanos , Plaquetas/efectos de la radiación , Hemostasis/efectos de la radiación , Tromboelastografía , Luz , Tiempo de Tromboplastina Parcial , Tiempo de Protrombina , Coagulación Sanguínea/efectos de la radiación , Coagulación Sanguínea/efectos de los fármacos , Factores de Coagulación Sanguínea/metabolismoRESUMEN
Reactive oxygen species (ROS) are constantly generated in a living organism. An imbalance between the amount of generated reactive species in the body and their destruction leads to the development of oxidative stress. Proteins are extremely vulnerable targets for ROS molecules, which can cause oxidative modifications of amino acid residues, thus altering structure and function of intra- and extracellular proteins. The current review considers the effect of oxidation on the structural rearrangements and functional activity of hemostasis proteins: coagulation system proteins such as fibrinogen, prothrombin/thrombin, factor VII/VIIa; anticoagulant proteins - thrombomodulin and protein C; proteins of the fibrinolytic system such as plasminogen, tissue plasminogen activator and plasminogen activator inhibitor-1. Structure and function of the proteins, oxidative modifications, and their detrimental consequences resulting from the induced oxidation or oxidative stress in vivo are described. Possible effects of oxidative modifications of proteins in vitro and in vivo leading to disruption of the coagulation and fibrinolysis processes are summarized and systematized, and the possibility of a compensatory mechanism in maintaining hemostasis under oxidative stress is analyzed.
Asunto(s)
Hemostasis , Activador de Tejido Plasminógeno , Activador de Tejido Plasminógeno/metabolismo , Especies Reactivas de Oxígeno , Coagulación Sanguínea , Factores de Coagulación Sanguínea/metabolismo , Estrés OxidativoRESUMEN
BACKGROUND: Until recently, the treatment of hemophilia A relied on factor (F)VIII replacement. However, up to one-third of patients with severe hemophilia A develop neutralizing alloantibodies that render replacement therapies ineffective. The development of emicizumab, a bispecific antibody that partially mimics FVIIIa, has revolutionized the treatment of these patients. However, the use of an activated prothrombin complex concentrate [FEIBA (Takeda)] to treat breakthrough bleeding in patients on emicizumab has been associated with thrombotic complications including a unique microangiopathy. OBJECTIVES: We hypothesized that the thrombotic complications observed with the combination of emicizumab and FEIBA might be due to excessive expression of procoagulant activity on the surface of endothelial cells. METHODS: We examined the ability of emicizumab to promote FX activation on endothelial cells using 2 cell culture models. RESULTS: We found that endothelial cells readily support emicizumab-mediated activation of FX by FIXa. The level of FXa generation depends on the concentration of available FIXa. The addition of FEIBA to emicizumab increased FXa generation in a dose-dependent manner on endothelial cells in both models. The rate of FXa generation was further enhanced by endothelial cell activation. However, unlike emicizumab, we found limited FXa generation in the presence of FVIII(a), which followed a significant lag time and was not dependent on FIXa concentration under these conditions. CONCLUSION: Emicizumab promotes FXa generation on the surface of endothelial cells, which is markedly enhanced in the presence of FEIBA. These findings demonstrate a potential mechanism for the thrombotic complications seen with the combined use of emicizumab and FEIBA.
Asunto(s)
Anticuerpos Biespecíficos , Anticuerpos Monoclonales Humanizados , Factores de Coagulación Sanguínea , Células Endoteliales , Factor Xa , Humanos , Anticuerpos Biespecíficos/farmacología , Anticuerpos Monoclonales Humanizados/farmacología , Factor Xa/metabolismo , Factores de Coagulación Sanguínea/metabolismo , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Coagulación Sanguínea/efectos de los fármacos , Hemofilia A/tratamiento farmacológico , Hemofilia A/sangre , Factor IX/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Cultivadas , Coagulantes/farmacologíaRESUMEN
INTRODUCTION: Negative symptoms impact the quality of life of individuals with psychosis and current treatment options for negative symptoms have limited effectiveness. Previous studies have demonstrated that complement and coagulation pathway protein levels are related to later psychotic experiences, psychotic disorder, and functioning. However, the prognostic relationship between complement and coagulation proteins and negative symptoms is poorly characterised. METHODS: In the North American Prodrome Longitudinal Studies 2 and 3, negative symptoms in 431 individuals at clinical high-risk for psychosis (mean age: 18.2, SD 3.6; 42.5 % female) were measured at multiple visits over 2 years using the Scale of Psychosis-Risk Symptoms. Plasma proteins were quantified at baseline using mass spectrometry. Four factors were derived to represent levels of proteins involved in the activation or regulation of the complement or coagulation systems. The relationships between standardised protein group factors and serial measurements of negative symptoms over time were modelled using generalised least squares regression. Analyses were adjusted for baseline candidate prognostic factors: negative symptoms, positive symptoms, functioning, depressive symptoms, suicidal ideation, cannabis use, tobacco use, antipsychotic use, antidepressant use, age, and sex. RESULTS: Clinical and demographic prognostic factors of follow-up negative symptoms included negative, positive, and depressive symptoms, functioning, and age. Adjusting for all candidate prognostic factors, the complement regulators group and the coagulation regulators group were identified as prognostic factors of follow-up negative symptoms (ß: 0.501, 95 % CI: 0.160, 0.842; ß: 0.430, 95 % CI: 0.080, 0.780 respectively. The relationship between complement regulator levels and negative symptoms was also observed in NAPLS2 alone (ß: 0.501, 95 % CI: -0.037, 1.039) and NAPLS3 alone, additionally adjusting for BMI (ß: 0.442, 95 % CI: 0.127, 0.757). CONCLUSION: The results indicate that plasma complement and coagulation regulator levels are prognostic factors of negative symptoms, independent of clinical and demographic prognostic factors. These results suggest complement and coagulation regulator levels could have potential utility in informing treatment decisions for negative symptoms in individuals at risk.
Asunto(s)
Proteínas del Sistema Complemento , Trastornos Psicóticos , Humanos , Femenino , Masculino , Pronóstico , Adolescente , Adulto Joven , Proteínas del Sistema Complemento/metabolismo , Proteínas del Sistema Complemento/análisis , Trastornos Psicóticos/sangre , Adulto , Factores de Coagulación Sanguínea/metabolismo , Factores de Coagulación Sanguínea/análisis , Estudios LongitudinalesRESUMEN
BACKGROUND: Mathematical models of coagulation have been developed to mirror thrombin generation in plasma, with the aim of investigating how variation in coagulation factor levels regulates hemostasis. However, current models vary in the reactions they capture and the reaction rates used, and their validation is restricted by a lack of large coherent datasets, resulting in questioning of their utility. OBJECTIVES: To address this debate, we systematically assessed current models against a large dataset, using plasma coagulation factor levels from 348 individuals with normal hemostasis to identify the causes of these variations. METHODS: We compared model predictions with measured thrombin generation, quantifying and comparing the ability of each model to predict thrombin generation, the contributions of the individual reactions, and their dependence on reaction rates. RESULTS: We found that no current model predicted the hemostatic response across the whole cohort and all produced thrombin generation curves that did not resemble those obtained experimentally. Our analysis has identified the key reactions that lead to differential model predictions, where experimental uncertainty leads to variability in predictions, and we determined reactions that have a high influence on measured thrombin generation, such as the contribution of factor XI. CONCLUSION: This systematic assessment of models of coagulation, using large dataset inputs, points to ways in which these models can be improved. A model that accurately reflects the effects of the multiple subtle variations in an individual's hemostatic profile could be used for assessing antithrombotics or as a tool for precision medicine.
Asunto(s)
Coagulación Sanguínea , Trombina , Humanos , Trombina/metabolismo , Pruebas de Coagulación Sanguínea , Hemostasis , Reproducibilidad de los Resultados , Factores de Coagulación Sanguínea/metabolismo , Modelos Biológicos , Masculino , Femenino , Adulto , Persona de Mediana EdadRESUMEN
Hemostasis is a sophisticated sequence of events aimed at repairing vessel injury. This process occurs in combination with angiogenesis, which leads to new blood vessel formation, helping in wound repair and facilitating tissue healing. The fine mechanisms that regulate hemostasis and angiogenesis are well described, but for a long time, coagulation factors (CF) have been considered merely players in the coagulation cascade. However, evidence from several experiments highlights the crucial functions of these CF in regulating endothelial functionality, especially in the angiogenic process. Some of these CF (e.g., thrombin and tissue factor) have been widely investigated and have been described as triggering intracellular signaling related to endothelial cell (EC) functionality. For others (e.g., factor VIII and thrombomodulin), potential receptors and molecular mechanisms have not been fully elucidated but some data show their potential to induce EC response. This review focuses on the emerging roles of selected CF in regulating EC functions, highlighting in particular their ability to activate signaling pathways involved in angiogenesis, migration, proliferation and endothelial barrier stability.
Asunto(s)
Factores de Coagulación Sanguínea , Células Endoteliales , Hemostasis , Transducción de Señal , Humanos , Factores de Coagulación Sanguínea/metabolismo , Células Endoteliales/metabolismo , Animales , Neovascularización Fisiológica , Coagulación Sanguínea , Endotelio Vascular/metabolismoRESUMEN
BACKGROUND: The mechanism of livedoid vasculopathy (LV) remains unknown. OBJECTIVES: To investigate the association between coagulation factors and LV and to assess the efficacy and safety of rivaroxaban in the treatment of patients with LV. METHODS: From May 2019 to July 2022, 89 patients with LV and 35 healthy controls were included in a cross-sectional cohort to measure the levels of coagulation factors. In addition, 55 patients with LV treated with rivaroxaban were included in a treatment cohort to assess the complete remission rate of ulcers (n = 44) and retiform purpura (n = 11) within 12 weeks. RESULTS: In the cross-sectional cohort, the activities of coagulation factor X in patients with LV were significantly higher than those in healthy controls: median 110.5% [interquartile range (IQR) 97.5-127.0%] vs. 101.3% (IQR 91.6-115.6); P = 0.05. In addition, coagulation factor X activities in the progressive stage were higher than at the stable stage: median 111.6% (IQR 102.3-132.5) vs. 105.4% (IQR 92.9-118.8); P = 0.04. Moreover, coagulation factor X activities were higher at the progressive stage than at the stable stage in a subgroup of 20 patients with LV (P = 0.04). In the treatment cohort taking rivaroxaban, 91% (40/44) of patients with ulcers achieved complete remission within 12 weeks, and 73% (8/11) of patients with retiform purpura achieved complete remission within 12 weeks. Mild side-effects occurred in 25% of patients (14/55), including menorrhagia (n = 10), gingival bleeding (n = 3) and haemorrhage (n = 1). CONCLUSIONS: Coagulation factor X was associated with the incidence and severity of LV in this study. In addition, rivaroxaban was an effective and safe treatment for ulcers and retiform purpura in people with LV.
Asunto(s)
Inhibidores del Factor Xa , Rivaroxabán , Humanos , Rivaroxabán/uso terapéutico , Rivaroxabán/efectos adversos , Femenino , Masculino , Estudios Retrospectivos , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/efectos adversos , Persona de Mediana Edad , Adulto , Estudios Transversales , Resultado del Tratamiento , Factores de Coagulación Sanguínea/metabolismo , Livedo Reticularis/tratamiento farmacológico , Factor X , AncianoRESUMEN
The August 2023 article in Science Signaling, "TGF-ß uncouples glycolysis and inflammation in macrophages and controls survival during sepsis," challenges the traditional M1/M2 macrophage classification by investigating the impact of transforming growth factor ß on macrophage metabolism and function. Despite its conventional anti-inflammatory role, transforming growth factor ß-treated macrophages exhibit a distinct phenotype marked by heightened glycolysis, suppressed proinflammatory cytokines, and increased coagulation factor expression. The study identifies phosphofructokinase, liver type as a crucial glycolytic enzyme regulated by transforming growth factor ß via the mTOR-c-MYC pathway. Epigenetic changes induced by transforming growth factor ß, such as increased Smad3 activation and reduced proinflammatory transcription factor motif enrichment, contribute to the anti-inflammatory profile. The research extends its implications to sepsis, revealing the role of transforming growth factor ß in exacerbating coagulation and reducing survival in mouse models. This effect involves upregulation of coagulation factor F13A1, dependent on phosphofructokinase, liver type activity and glycolysis in macrophages. Connections to COVID-19 pathology are drawn, as transforming growth factor ß-treated macrophages and SARS-CoV-2 E protein-exposed cells display similar metabolic profiles. Bioinformatic analysis of COVID-19 patient data suggests correlations between myeloid expression of TGFßR1, PFKL, and F13A1 with disease severity. The study challenges the M1/M2 classification, emphasizing the complexity of macrophage responses influenced by transforming growth factor ß, proposing transforming growth factor ß as a potential therapeutic target for conditions like sepsis and COVID-19 where dysregulated coagulation is significant. Overall, the research provides valuable insights into transforming growth factor ß-mediated immunometabolic regulation, paving the way for future investigations and potential therapeutic interventions.