RESUMEN
Uncontrolled non-compressible hemorrhage, which is often accompanied by coagulopathy, is a major cause of mortality following traumatic injuries in civilian and military populations. In this study, coagulopathy-independent injectable catechol-modified chitosan (CS-HCA) hemostatic materials featuring rapid shape recovery were fabricated by combining controlled sodium tripolyphosphate-crosslinking with hydrocaffeic acid (HCA) grafting. CS-HCA exhibited robust mechanical strength and rapid blood-triggered shape recovery. Furthermore, CS-HCA demonstrated superior blood-clotting ability, enhanced blood cell adhesion and activation, and greater protein adsorption than commercial hemostatic gauze and Celox. CS-HCA showed enhanced procoagulant and hemostatic capacities in a lethal liver-perforation wound model in rabbits, particularly in heparinized rabbits. CS-HCA is suitable for mass manufacturing and shows promise as a clinically translatable hemostat.
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Catecoles , Quitosano , Hemorragia , Hemostáticos , Quitosano/química , Quitosano/farmacología , Animales , Conejos , Catecoles/química , Catecoles/farmacología , Hemorragia/tratamiento farmacológico , Hemostáticos/química , Hemostáticos/farmacología , Coagulación Sanguínea/efectos de los fármacos , Ácidos Cafeicos/química , Ácidos Cafeicos/farmacología , Masculino , Materiales Inteligentes/química , InyeccionesRESUMEN
Antiplatelet and anticoagulant therapies are cornerstones of secondary prevention in high-risk cardiovascular patients. Whereas in former days the focus was set on effective antithrombotic effects, more recent trials and guidelines placed emphasis on a more balanced approach, thus including the bleeding risk for an individualized therapy. Type, strength, combination, and duration are important components to modify the individual bleeding risk. Novel antiplatelet and anticoagulant agents have shown promising results that might offer safer options in the future for high-risk cardiovascular patients. This review aims to give an overview about established drug target and pharmacologic approaches that are currently in the pipeline.
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Anticoagulantes , Coagulación Sanguínea , Activación Plaquetaria , Inhibidores de Agregación Plaquetaria , Humanos , Activación Plaquetaria/efectos de los fármacos , Activación Plaquetaria/fisiología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/farmacología , Coagulación Sanguínea/efectos de los fármacos , Coagulación Sanguínea/fisiología , Anticoagulantes/uso terapéutico , Anticoagulantes/farmacología , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/sangre , Plaquetas/efectos de los fármacos , Plaquetas/fisiologíaRESUMEN
BACKGROUND: The purpose of the study is to examine if prolonged thromboprophylaxis decreases the risk of thrombosis after intended curative surgery for oesophageal cancer. Study results are expected to inform a guideline for thromboprophylaxis after oesophageal cancer surgery. The perspective is to reduce morbidity and mortality in this critically ill patient group. Thrombosis is the second-most common cause of cancer death after the cancer itself. The risk of thrombosis depends on the cancer type, and upper gastrointestinal cancers are considered high risk. This risk is further increased when patients undergo surgery. However, only few studies have investigated the peri- and postoperative coagulation profile in oesophageal cancer patients. Due to this lack of knowledge, prophylaxis is currently restricted to 5000 IU (international units) low-molecular weight heparin daily from surgery until discharge from hospital (approximately 10 days), whereas patients with gastric cancer receive 30 days of treatment. The present study examines whether a 30-day treatment is superior and safe, compared with the current standard treatment. METHODS: The study is a randomised controlled trial. Inclusion is ongoing, and we aim to include 100 patients. Blood samples are drawn before and after surgery, and the coagulation is extensively examined. The primary endpoint is the difference in plasma levels of prothrombin fragment 1 + 2 (F1 + 2) 30 days after surgery between the intervention and the standard group. Furthermore, patients are examined with ultrasound to screen for asymptomatic venous thrombotic events (VTE). Secondary endpoints are incidence of bleeding, symptomatic and asymptomatic VTE and mortality 30 days 1 one year after surgery. DISCUSSION: The study will provide valuable information on the perioperative coagulation profile and VTE risk of oesophageal cancer patients. The study seeks to aid in optimising the postoperative thromboprophylaxis, and the perspective is to reduce morbidity and mortality in this at-risk patient population. TRIALS REGISTRATION: The trial was prospectively registered at the EU Clinical Trials Register with ID 2021-001335-24 on 30 June 2021 and at ClinicalTrials.gov with study identifier NCT05067153.
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Anticoagulantes , Neoplasias Esofágicas , Protrombina , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/mortalidad , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Esofagectomía/efectos adversos , Factores de Tiempo , Heparina de Bajo-Peso-Molecular/uso terapéutico , Heparina de Bajo-Peso-Molecular/administración & dosificación , Fragmentos de Péptidos/sangre , Resultado del Tratamiento , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/etiología , Coagulación Sanguínea/efectos de los fármacos , Factores de Riesgo , Esquema de MedicaciónRESUMEN
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.
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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 survival and proliferation of pathogenic Leptospira within a host are complex phenomena that require careful consideration. The ErpY-like lipoprotein, found on the outer membrane surface of Leptospira, plays a crucial role in enhancing the bacterium's pathogenicity. The rErpY-like protein, in its recombinant form, contributes significantly to spirochete virulence by interacting with various host factors, including host complement regulators. This interaction facilitates the bacterium's evasion of the host complement system, thereby augmenting its overall pathogenicity. The rErpY-like protein exhibits a robust binding affinity to soluble fibrinogen, a vital component of the host coagulation system. In this study, we demonstrate that the rErpY-like protein intervenes in the clotting process of the platelet-poor citrated plasma of bovines and humans in a concentration-dependent manner. It significantly reduces clot density, alters the viscoelastic properties of the clot, and diminishes the average clotting rate in plasma. Furthermore, the ErpY-like protein inhibits thrombin-catalyzed fibrin formation in a dose-dependent manner and exhibits saturable binding to thrombin, suggesting its significant role in leptospiral infection. These findings provide compelling evidence for the anticoagulant effect of the ErpY-like lipoprotein and its significant role in leptospiral infection.
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Coagulación Sanguínea , Fibrinógeno , Trombina , Fibrinógeno/metabolismo , Fibrinógeno/química , Humanos , Trombina/metabolismo , Animales , Bovinos , Unión Proteica , Leptospira/metabolismo , Leptospirosis/microbiología , Proteínas de la Membrana Bacteriana Externa/metabolismo , Lipoproteínas/metabolismo , Interacciones Huésped-PatógenoRESUMEN
BACKGROUND: Due to similar symptoms of abdominal pain, acute pancreatitis (AP) is often difficult to differentiate from acute aortic dissection (AAD) in clinical practice. It is unknown whether serum amylase and coagulation function indices can be used to distinguish AP from AAD. METHODS: In this retrospective study, 114 AP patients (AP group) and 48 cases with AAD (AAD group) admitted for acute abdominal pain were enrolled for a final analysis. The levels of serum amylase and coagulation function indices, including prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (FIB), and D-dimer (DD), were tested before or on admission and compared between the two groups. Student's t-test was adopted for comparing the mean. Model discrimination was evaluated by using the area under the receiver operating characteristic curve (AUC). Comparison of AUC was performed by using the Z-test. RESULTS: Compared with the AAD group, amylase and FIB were both significantly increased, while DD was significantly lower in the AP group (all p < 0.01). There were no statistically significant differences of PT, INR, and APTT between AP and AAD (all p > 0.05). The AUCs in distinguishing AP from AAD were 0.913, 0.854, and 0.837 for amylase, FIB, and DD, respectively, but there were no significant differences observed among amylase, FIB, and DD (all p > 0.05). Finally, the cutoff values (specificity, sensitivity, and Youden index) in distinguishing between AP and AAD were 114 µ/L (80.70%, 95.83%, 0.765) for amylase, 2.62 g/L (76.32%, 85.42%, 0.617) for FIB, and 2.74 mg/L (95.61%, 62.50%, 0.581) for DD, respectively. CONCLUSIONS: Amylase, FIB, and DD can demonstrate accurate and reliable diagnostic values, suggesting that they are useful and potential biomarkers in distinguishing AP from AAD.
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Amilasas , Disección Aórtica , Pancreatitis , Humanos , Disección Aórtica/diagnóstico , Disección Aórtica/sangre , Masculino , Amilasas/sangre , Femenino , Pancreatitis/diagnóstico , Pancreatitis/sangre , Persona de Mediana Edad , Estudios Retrospectivos , Diagnóstico Diferencial , Anciano , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Adulto , Coagulación Sanguínea/fisiología , Enfermedad Aguda , Biomarcadores/sangre , Curva ROC , Fibrinógeno/análisis , Fibrinógeno/metabolismo , Pruebas de Coagulación Sanguínea/métodos , Tiempo de Protrombina , Tiempo de Tromboplastina ParcialRESUMEN
Activated partial thromboplastin time (aPTT)-based clot waveform analysis (CWA) is a plasma-based global haemostatic assay. Elevated CWA parameters have been associated with hypercoagulability in venous thromboembolism, but its role in arterial thrombotic disease is uncertain. This study aims to explore the relationship between aPTT-based CWA and acute myocardial infarction (AMI) and its complications. In a retrospective cohort study of patients with AMI who underwent emergency cardiac catheterisation, pre-procedural aPTT and CWA parameters-min1, min2 and max2 were measured. These were compared against a control group of patients, consisting of patients who underwent elective orthopaedic and urological procedures. Within the AMI cohort, we also compared aPTT and CWA parameters of those with and without clinical complications of AMI. Results: Compared to controls (N = 109), patients with AMI (N = 214) had shorter aPTT (26.7 ± 3.3 s vs 27.9 ± 1.7 s, P < 0.001) and higher CWA parameters (min1: 6.11 ± 1.40%/s vs 5.58 ± 1.14%/s; min2: 0.98 ± 0.23%/s2 vs 0.90 ± 0.19%/s2; max2: 0.81 ± 0.20%/s2 vs 0.74 ± 0.16%/s2, all P ≤ 0.001). There was an increased incidence of elevated CWA parameters, in the AMI group, with odds ratio (OR) of 2.06 [95% CI 1.10-3.86], 2.23 (95% CI 1.18-4.24) and 2.01 (95% CI 1.07-3.77) for min1, min2 and max2, respectively. Similarly, elevated min1 and min2 were both individually associated with the presence of adverse outcomes of AMI, both with ORs of 2.63 (95% CI 1.24-5.59). Elevated aPTT-based CWA parameters are significantly associated with the occurrence of AMI and its complications. These findings identify the potential utility of CWA as risk and prognostic markers for AMI and warrants future works.
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Infarto del Miocardio , Humanos , Tiempo de Tromboplastina Parcial , Infarto del Miocardio/sangre , Masculino , Femenino , Anciano , Estudios Retrospectivos , Persona de Mediana Edad , Coagulación SanguíneaRESUMEN
Reducing unnecessary blood loss in hemostasis is a major challenge for traditional hemostatic materials due to uncontrolled blood absorption. Tuning the hydrophilic and hydrophobic properties of hemostatic materials provides a road to reduce blood loss. Here, we developed a superhydrophobic aerogel that enabled remarkably reduced blood loss. The aerogel was fabricated with polydopamine-coated and fluoroalkyl chain-modified bacterial cellulose via a directional freeze-drying method. Primarily, the hydrophobic feature prevented blood from uncontrolled absorption by the material and overflowing laterally. Additionally, the aerogel had a dense network of channels that allowed it to absorb water from blood due to the capillary effect, and fluoroalkyl chains trapped the blood cells entering the channels to form a compact barrier via hydrophobic interaction at the bottom of the aerogel, causing quick fibrin generation and blood coagulation. The animal experiments reveal that the aerogel reduced the hemostatic time by 68% and blood loss by 87 wt % compared with QuikClot combat gauze. The study demonstrates the superiority of superhydrophobic aerogels for hemostasis and provides new insights into the development of hemostatic materials.
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Celulosa , Hemostasis , Hemostáticos , Interacciones Hidrofóbicas e Hidrofílicas , Nanofibras , Celulosa/química , Celulosa/farmacología , Animales , Nanofibras/química , Hemostáticos/química , Hemostáticos/farmacología , Hemostasis/efectos de los fármacos , Geles/química , Polímeros/química , Polímeros/farmacología , Ratones , Humanos , Coagulación Sanguínea/efectos de los fármacos , Indoles/químicaRESUMEN
Abnormalities in coagulation and fibrinolytic status have been demonstrated to be relevant to inflammatory bowel disease. Nevertheless, there is no study to methodically examine the role of the coagulation and fibrinolysis-related genes in the diagnosis of ulcerative colitis (UC). UC-related datasets (GSE169568 and GSE94648) were originated from the Gene Expression Omnibus database. The biomarkers related to coagulation and fibrinolysis were identified through combining differentially expressed analysis and machine learning algorithms. Moreover, Gene Set Enrichment Analysis and immune analysis were carried out. A total of 4 biomarkers (MAP2K1, CREBBP, TAF1, and HP) were identified, and biomarkers were markedly enriched in pathways related to immunity, such as T-cell receptor signaling pathway, primary immunodeficiency, chemokine signaling pathway, etc. In total, the infiltrating abundance of 4 immune cells between UC and control was markedly different, namely eosinophils, macrophage M0, resting mast cells, and regulatory T cells. And all biomarkers were significantly relevant to eosinophils. Our findings detected 4 coagulation and fibrinolysis-related biomarkers (MAP2K1, CREBBP, TAF1, and HP) for UC, which contributed to the advancement of UC for further clinical investigation.
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Biomarcadores , Proteína de Unión a CREB , Colitis Ulcerosa , Biología Computacional , Fibrinólisis , Humanos , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/sangre , Colitis Ulcerosa/genética , Biomarcadores/sangre , Proteína de Unión a CREB/genética , Proteína de Unión a CREB/sangre , Coagulación Sanguínea , Factor de Transcripción TFIID/genética , Factor de Transcripción TFIID/sangre , Aprendizaje Automático , Carboxipeptidasa B2/sangre , Carboxipeptidasa B2/genéticaRESUMEN
BACKGROUND: This study aimed to evaluate the application value and safety of Warfarin, Rivaroxaban, and Dabigatran in elderly patients with atrial fibrillation. METHODS: A total of 180 elderly patients with atrial fibrillation admitted to our hospital were retrospectively analyzed. According to their anticoagulant treatment regimen, patients were divided into three groups: Warfarin (57 cases), Rivaroxaban (61 cases), and Dabigatran (62 cases). General demographic information was collected, and coagulation function indicators-including fibrinogen (FIB), thrombin time (PT), activated partial thrombin time (APTT), and D-dimer (D-D)-as well as liver function indexes-including total bilirubin (TbiL), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine transferase (ALT)-were compared before and after 4 weeks of treatment. RESULTS: There were no significant differences in demographic characteristics such as gender, age, body mass index, or disease course among the three groups. The total effective rate in the Warfarin group (84.21%) was significantly lower than in the Rivaroxaban (98.36%) and Dabigatran (96.77%) groups (p < 0.05). However, there was no significant difference in the total effective rate between the Rivaroxaban and Dabigatran groups (p > 0.05). Additionally, no significant differences were found in the effects of the three drugs on coagulation function, liver function, or the incidence of bleeding (p = 0.052). CONCLUSION: Warfarin, Rivaroxaban, and Dabigatran can effectively prevent thrombosis in elderly patients with atrial fibrillation, with Rivaroxaban and Dabigatran showing superior effectiveness. All three drugs demonstrated similar low rates of bleeding events and had no significant impact on coagulation and liver function.
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Anticoagulantes , Fibrilación Atrial , Coagulación Sanguínea , Dabigatrán , Rivaroxabán , Warfarina , Humanos , Dabigatrán/efectos adversos , Dabigatrán/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Rivaroxabán/efectos adversos , Rivaroxabán/uso terapéutico , Masculino , Femenino , Anciano , Estudios Retrospectivos , Warfarina/efectos adversos , Warfarina/uso terapéutico , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Coagulación Sanguínea/efectos de los fármacos , Resultado del Tratamiento , Anciano de 80 o más Años , Antitrombinas/efectos adversos , Antitrombinas/uso terapéutico , Hemorragia/inducido químicamente , Hemorragia/epidemiologíaRESUMEN
Sepsis is a life-threatening condition that has the potential to multiple organ dysfunction and mortality. One of its frequent complications is disseminated intravascular coagulation (DIC), characterized by hyperactive clotting mechanisms that cause widespread clot formation and tissue damage. This study aimed to investigate early diagnostic markers of sepsis-associated DIC by comparing inflammatory factor levels, 28-day survival rates, coagulation function, and markers between patients with sepsis (non-DIC group) and those with sepsis-induced DIC (DIC group). The study analyzed the diagnostic efficacy of coagulation function and markers in predicting the occurrence and prognosis of sepsis-associated DIC, presenting survival curves. Results indicated significantly increased levels of APTT, TAT, tPAIC, PIC, and sTM in the DIC group compared to the non-DIC group. Sequential Organ Failure Assessment (SOFA) scores on days 1, 3, and 7 were notably lower in the non-DIC group. Correlation analysis revealed positive associations between PT, APTT, TAT, tPAIC, PIC, sTM levels, and SOFA scores, as well as negative associations with Fib and SOFA scores. Survival curves showed substantially lower mortality rates in the non-DIC group, highlighting significant survival disparities between groups. Combining all four coagulation indicators (TAT+ tPAIC + PIC + sTM) showed promising diagnostic value in evaluating disease severity, early DIC diagnosis, and sepsis prognosis.
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Biomarcadores , Coagulación Sanguínea , Coagulación Intravascular Diseminada , Sepsis , Humanos , Sepsis/diagnóstico , Sepsis/mortalidad , Sepsis/sangre , Coagulación Intravascular Diseminada/diagnóstico , Coagulación Intravascular Diseminada/sangre , Coagulación Intravascular Diseminada/mortalidad , Coagulación Intravascular Diseminada/etiología , Biomarcadores/sangre , Pronóstico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Puntuaciones en la Disfunción de Órganos , Adulto , Pruebas de Coagulación SanguíneaRESUMEN
Psoriasis is a chronic inflammatory skin condition associated with systemic inflammation and a higher risk of cardiovascular comorbidities. This study retrospectively evaluates coagulation parameters in psoriasis vulgaris patients treated with IL-17 inhibitors (secukinumab, ixekizumab) and IL-23 inhibitors (risankizumab, guselkumab), compared to those untreated systemically. The study reviewed records from 177 patients treated between January 2019 and March 2023. Patients were grouped into control (n = 77), secukinumab (n = 36), ixekizumab (n = 19), guselkumab (n = 24), and risankizumab (n = 21). Coagulation parameters, including PT, aPTT, PLT, MPV, INR, fibrinogen, D-dimer, and B12 levels, were analyzed. The primary endpoint was the comparison of coagulation parameters between groups. Significant differences were found in PT, with secukinumab-treated patients showing a significantly shorter PT compared to controls (p = 0.002). No significant differences were observed in other coagulation parameters across the groups. The study highlights a potential effect of secukinumab on coagulation pathways, possibly related to IL-17's role in inflammation and endothelial function. Despite current literature suggest a risk of cerebrovascular events with risankizumab, this study did not show any significant changes in coagulation parameters with risankizumab, indicating no hypercoagulability risk associated with this IL-23 inhibitor. Our findings suggest IL-17 and IL-23 inhibitors are generally safe concerning coagulation parameters, but regular monitoring may be warranted for patients on secukinumab due to its effect on PT. Further long-term studies are needed to fully understand the cardiovascular risks associated with these therapies.
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Anticuerpos Monoclonales Humanizados , Coagulación Sanguínea , Interleucina-17 , Interleucina-23 , Psoriasis , Humanos , Psoriasis/tratamiento farmacológico , Psoriasis/sangre , Psoriasis/inmunología , Estudios Retrospectivos , Masculino , Interleucina-17/antagonistas & inhibidores , Interleucina-17/sangre , Femenino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Persona de Mediana Edad , Interleucina-23/antagonistas & inhibidores , Interleucina-23/sangre , Adulto , Coagulación Sanguínea/efectos de los fármacos , Anciano , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/efectos adversosRESUMEN
Sepsis and atherosclerotic cardiovascular disease (ASCVD) are major health challenges involving complex processes like inflammation, renin-angiotensin system (RAS) dysregulation, and thrombosis. Despite distinct clinical symptoms, both conditions share mechanisms mediated by bradykinin. This review explores bradykinin's role in inflammation, RAS modulation, and thrombosis in sepsis and ASCVD. In sepsis, variable kininogen-bradykinin levels may correlate with disease severity and progression, though the effect of bradykinin receptor modulation on inflammation remains uncertain. RAS activation is present in both diseases, with sepsis showing variable or low levels of Ang II, ACE, and ACE2, while ASCVD consistently exhibits elevated levels. Bradykinin may act as a mediator for ACE2 and AT2 receptor effects in RAS regulation. It may influence clotting and fibrinolysis in sepsis-associated coagulopathy, but evidence for an antithrombotic effect in ASCVD is insufficient. Understanding bradykinin's role in these shared pathologies could guide therapeutic and monitoring strategies and inform future research.
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Aterosclerosis , Coagulación Sanguínea , Bradiquinina , Sistema Renina-Angiotensina , Sepsis , Transducción de Señal , Humanos , Bradiquinina/metabolismo , Sepsis/fisiopatología , Sepsis/metabolismo , Sepsis/sangre , Aterosclerosis/fisiopatología , Aterosclerosis/metabolismo , Aterosclerosis/sangre , Animales , Coagulación Sanguínea/efectos de los fármacos , Receptores de Bradiquinina/metabolismo , Trombosis/fisiopatología , Trombosis/sangre , Trombosis/metabolismoRESUMEN
Purpose: This study aimed to examine the quality of life of patients receiving warfarin therapy at Dr. Hasan Sadikin Central General Hospital, and its relationship with demographic factors. Patients and Methods: The procedures started with the submission of a study permit, followed by validation of the Duke Anticoagulation Satisfaction Scale (DASS) questionnaire. In addition, the validated questionnaire was completed by the participants, and significant variables were analyzed using the chi-square method for multivariate analysis. Results: The results showed that the questionnaire was valid and could be used for further analyses. Among the 88 selected participants, 52 and 36 had scoring categories <56.266 and 56.266 ≤ x ≤ 143.734, respectively, with no patients having a scoring category > 143.734. In addition, participants with low education and aged ≥ 52 years were 4.916 and 3.161 times more at risk of having quality of life score of 56.266 ≤ x ≤ 143.734, respectively. Based on the results, the average quality of life score of patients was 59.66. Participants with low educational levels and those aged ≥ 52 years were at a higher risk of having quality of life score of 56.266 ≤ x ≤ 143.734. Conclusion: In summary, a lower quality of life score was linked to increased comfort and satisfaction among patients receiving warfarin treatment. Additionally, these patients experienced fewer feelings of limitations and inconveniences related to their treatment plans.
Asunto(s)
Anticoagulantes , Satisfacción del Paciente , Calidad de Vida , Centros de Atención Terciaria , Warfarina , Humanos , Warfarina/uso terapéutico , Warfarina/efectos adversos , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Persona de Mediana Edad , Masculino , Femenino , Encuestas y Cuestionarios , Indonesia/epidemiología , Adulto , Anciano , Reproducibilidad de los Resultados , Resultado del Tratamiento , Escolaridad , Factores de Riesgo , Estudios Transversales , Factores de Edad , Coagulación Sanguínea/efectos de los fármacosRESUMEN
Patients on left ventricular assist devices (LVAD) are prone to excessive hemostasis disturbances due to permanent contact of artificial pump surfaces with blood components. We aimed to investigate if fibrin clot permeability is altered in patients on long-term continuous-flow LVAD therapy and if the clot permeability is associated with clinical characteristics and adverse events. We investigated 85 end-stage heart failure patients (90.6% men, age 48.6-63.8 years) scheduled for continuous flow long-term LVAD support according to current clinical indications. The patients were assessed periodically: prior to LVAD implantation (T1), 3-6 months (T2) after LVAD implantation, 6-12 months after (T3) and then every 6 months. We tested the first three blood samples (T1-T3) and the last available blood sample (T4), but no longer than 5 years after LVAD implantation. We assessed hemostasis parameters (Activated Partial Thromboplastin Time (APTT) Prothrombin Time, Activated Partial Thromboplastin Time, Fibrinogen, D-dimer, Antithrombin, Thrombin Time, Factor VIII, and von Willebrand Factor, aspirin-induced platelet inhibition, adenosine-diphosphate test) changes during the study period. Fibrin Clot Permeability was evaluated using a pressure system and Permeability Coefficient (Ks) was calculated. We observed a decrease in fibrin clot permeability (Ks) between T1, T2, T3 and T4 time periods; P < 0.01 for each comparison. Fibrin clot permeability was negatively correlated with fibrinogen concentration: r = - 0.51, P < 0.001, factor VIII activity r = - 0.42, P < 0.001. There was no association of Ks with age, Left Ventricular Ejection Fraction (LVEF) and medications P > 0.001, however cumulative measurements in patients on aspirin showed shortening of Ks in this group P = 0.0123. Major adverse cardiac and cerebrovascular events (MACCE) occurred in 36.5% patients, bleeding events in 25.9%, Net Adverse Clinical Events (NACE) in 62.4%; 31.7% patients died, and 17.6% underwent transplantation. The transplantation was considered as the endpoint. Discrepancies in Ks were observed between patients with MACCE, bleeding, and NACE, and patients without adverse events. Ks showed a constant trend towards normalization (P < 0.01) only in patients without adverse events. Patients with advanced heart failure have disturbed clot structure. A trend towards normalization of the Ks values is associated with fewer thromboembolic and bleeding complications in this group of patients.
Asunto(s)
Fibrina , Insuficiencia Cardíaca , Corazón Auxiliar , Humanos , Corazón Auxiliar/efectos adversos , Persona de Mediana Edad , Masculino , Femenino , Fibrina/metabolismo , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/metabolismo , Permeabilidad , Coagulación Sanguínea , HemostasisAsunto(s)
Factor XII , Unión Proteica , Humanos , Factor XII/metabolismo , Factor XII/genética , Coagulación Sanguínea , Animales , Sitios de UniónRESUMEN
Aiming to improve the retrieval rate of retrievable vena cava filters (RVCF) and extend its dwelling time in vivo, a novel hydrogel coating loaded with 10 mg/mL heparin and 30 mg/mL cyclodextrin/paclitaxel (PTX) inclusion complex (IC) was prepared. The drug-release behavior in the phosphate buffer solution demonstrated both heparin and PTX could be sustainably released over approximately two weeks. Furthermore, it was shown that the hydrogel-coated RVCF (HRVCF) with 10 mg/mL heparin and 30 mg/mL PTX IC effectively extended the blood clotting time to above the detection limit and inhibited EA.hy926 and CCC-SMC-1 cells' proliferation in vitro compared to the commercially available bare RVCF. Both the HRVCF and the bare RVCF were implanted into the vena cava of sheep and retrieved at at 2nd and 4th week after implantation, revealing that the HRVCF had a significantly higher retrieval rate of 67 % than the bare RVCF (0 %) at 4th week. Comprehensive analyses, including histological, immunohistological, and immunofluorescent assessments of the explanted veins demonstrated the HRVCF exhibited anti-hyperplasia and anticoagulation properties in vivo, attributable to the hydrogel coating, thereby improving the retrieval rate in sheep. Consequently, the as-prepared HRVCF shows promising potential for clinical application to enhance the retrieval rates of RVCFs.
Asunto(s)
Ciclodextrinas , Heparina , Hidrogeles , Paclitaxel , Filtros de Vena Cava , Ciclodextrinas/química , Ciclodextrinas/farmacología , Paclitaxel/farmacología , Paclitaxel/química , Heparina/química , Heparina/farmacología , Animales , Hidrogeles/química , Hidrogeles/farmacología , Humanos , Ovinos , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Coagulación Sanguínea/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Liberación de FármacosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Every year, cardiovascular diseases (CVDs) account for about 17.9 million deaths, making them the primary cause of both morbidity and mortality. Conventional drugs, which are often prescribed to treat cardiovascular diseases, are costly and have adverse effects. Consequently, dietary modifications and other medications are needed. Traditional use of Solanum indicum as cardiotonic to treat hypertension and anticoagulant potency has been reported but poorly evaluated scientifically. AIM OF THE STUDY: This study investigated the in vivo anticoagulant activity and mechanism of anticoagulation of quercetin (QC), a bioactive compound isolated from S. indicum (SI) hydroethanolic fruit extract. MATERIALS AND METHODS: Bioassay-guided fractionation (anticoagulant activity) extracted QC from hydroethanolic SI extract. QC was extensively characterized biochemically and pharmacologically. The interaction between QC and thrombin was investigated using spectrofluorometric and isothermal calorimetric methods. Cytotoxicity, antiplatelet, and thrombolytic studies were carried out in vitro. The Swiss albino mice were used to assess the in vivo, anticoagulant, and antithrombotic activities of QC. RESULTS: QC exhibits anticoagulant activity via (i) uncompetitive inhibition of thrombin but not FXa with a Ki value of 33.11 ± 4.2 µM and (ii) a partial inhibition of thrombin-catalyzed platelet aggregation with an IC50 value of 13.2 ± 1.2 µM. The experimental validation of the in silico study's prediction of QC's binding to thrombin was confirmed by spectrofluorometric and isothermal calorimetric analyses. QC was nontoxic to mammalian, non-hemolytic cells and demonstrated thrombolytic activity by activating plasminogen. QC demonstrated in vivo anticoagulant efficacy, preventing k-carrageen-induced thrombus formation in mice's tails. In the acute circulatory stasis paradigm in mice, QC reduces thromboxane B2 (TXB2) and endothelin-1 (ET-1) while increasing nitric oxide synthase (eNOS) and 6-keto prostaglandin F1α (6-keto-PGF1 α). CONCLUSION: Effective in vivo anticoagulant and antithrombotic properties of S. indicum's bioactive component QC point to the plant's potential use as a herbal anticoagulant medication for preventing and treating cardiovascular diseases linked to thrombosis.
Asunto(s)
Anticoagulantes , Fibrinolíticos , Extractos Vegetales , Agregación Plaquetaria , Quercetina , Solanum , Animales , Quercetina/farmacología , Quercetina/aislamiento & purificación , Ratones , Fibrinolíticos/farmacología , Fibrinolíticos/aislamiento & purificación , Solanum/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Anticoagulantes/farmacología , Anticoagulantes/aislamiento & purificación , Humanos , Agregación Plaquetaria/efectos de los fármacos , Masculino , Plantas Medicinales/química , Trombosis/tratamiento farmacológico , Trombosis/prevención & control , Frutas/química , Trombina , Simulación del Acoplamiento Molecular , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/aislamiento & purificación , Coagulación Sanguínea/efectos de los fármacosRESUMEN
OBJECTIVE: To explore the key factors affecting plasma clot retraction and optimize the experimental method of plasma clot retraction, in order to study the regulation of platelet function and evaluate the modulatory effects of drugs on plasma clot retraction. METHODS: The effects of different concentrations of thrombin, Ca2 + and platelets on plasma clot retraction were studied, and the detection system of plasma clot retraction was optimized. The availability of the detection system was then validated by analyzing the regulatory effects of multiple signaling pathway inhibitors on plasma clot retraction. RESULTS: Through the optimization study of multiple factors, platelet rich plasma (PRP) containing 0.5 mmol/L Ca2 + and 40×109/L platelets was treated with 0.2 U/ml thrombin to perform plasma clot retraction analysis. After treatment with thrombin for 15 min, plasma clot retracted significantly. After treatment with thrombin for 30 min, the percentage of plasma clot retraction was more than 50%. The regulatory effects of multiple signaling pathway inhibitors on plasma clot retraction were studied in this detection system. PKC inhibitor Go 6983 exhibited a significant inhibitory effect on plasma clot retraction, while PI3K inhibitor Ly294002 and p38 MAPK inhibitor SB203580 slightly suppressed plasma clot retraction. CONCLUSION: PRP containing 0.5 mmol/L Ca2 + and 40×109/L platelets can be induced with 0.2 U/ml thrombin to conduct plasma clot retraction analysis, which can be used to study the regulation of platelet function and evaluate the modulatory effects of drugs on plasma clot retraction.