ABSTRACT
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.
Subject(s)
Blood Coagulation , Cell-Derived Microparticles , Fibrin Fibrinogen Degradation Products , Myocardial Infarction , Thromboplastin , Humans , Myocardial Infarction/blood , Myocardial Infarction/diagnosis , Prospective Studies , Case-Control Studies , Cell-Derived Microparticles/metabolism , Fibrin Fibrinogen Degradation Products/metabolism , Thromboplastin/metabolism , Blood Coagulation Factors/metabolism , Blood Coagulation Factors/analysis , Female , Male , Disseminated Intravascular Coagulation/blood , Middle Aged , Coronary Disease/bloodABSTRACT
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.
Subject(s)
Anticoagulants , Esophageal Neoplasms , Prothrombin , Randomized Controlled Trials as Topic , Humans , Esophageal Neoplasms/surgery , Esophageal Neoplasms/mortality , Anticoagulants/therapeutic use , Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Esophagectomy/adverse effects , Time Factors , Heparin, Low-Molecular-Weight/therapeutic use , Heparin, Low-Molecular-Weight/administration & dosage , Peptide Fragments/blood , Treatment Outcome , Venous Thromboembolism/prevention & control , Venous Thromboembolism/etiology , Blood Coagulation/drug effects , Risk Factors , Drug Administration ScheduleABSTRACT
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.
Subject(s)
Catechols , Chitosan , Hemorrhage , Hemostatics , Chitosan/chemistry , Chitosan/pharmacology , Animals , Rabbits , Catechols/chemistry , Catechols/pharmacology , Hemorrhage/drug therapy , Hemostatics/chemistry , Hemostatics/pharmacology , Blood Coagulation/drug effects , Caffeic Acids/chemistry , Caffeic Acids/pharmacology , Male , Smart Materials/chemistry , InjectionsABSTRACT
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.
Subject(s)
Anticoagulants , Blood Coagulation , Platelet Activation , Platelet Aggregation Inhibitors , Humans , Platelet Activation/drug effects , Platelet Activation/physiology , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/pharmacology , Blood Coagulation/drug effects , Blood Coagulation/physiology , Anticoagulants/therapeutic use , Anticoagulants/pharmacology , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/blood , Blood Platelets/drug effects , Blood Platelets/physiologyABSTRACT
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.
Subject(s)
Anticoagulants , Atrial Fibrillation , Blood Coagulation , Dabigatran , Rivaroxaban , Warfarin , Humans , Dabigatran/adverse effects , Dabigatran/therapeutic use , Atrial Fibrillation/drug therapy , Atrial Fibrillation/complications , Rivaroxaban/adverse effects , Rivaroxaban/therapeutic use , Male , Female , Aged , Retrospective Studies , Warfarin/adverse effects , Warfarin/therapeutic use , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Blood Coagulation/drug effects , Treatment Outcome , Aged, 80 and over , Antithrombins/adverse effects , Antithrombins/therapeutic use , Hemorrhage/chemically induced , Hemorrhage/epidemiologyABSTRACT
The advanced-PRF+ (A-PRF+) is a platelet concentrate, showing a higher concentration of growth factors, an increased number of cells and looser structure of the fibrin clot than leukocyte-PRF. A high variability in the size of PRF associated with patients, haematological features and centrifugation protocols was reported. The aims of this study were to evaluate the feasibility of A-PRF+ production in the field and the correlation between haematological parameters, macroscopic and microscopic features in equine A-PRF+. Samples from twenty Standardbred horses (3-7 years) were harvested with glass tubes without anticoagulants, previously heated at 37 °C. Blood samples were centrifugated at 1300 rpm for 8 min with a fixed-angle centrifuge and a horizontal centrifuge in the field, at a temperature of 15-17 °C. Clots were measured and placed on the Wound Box® for a 2-min compression. Membranes were measured and fixed in 10% formalin for histological examination. Clot and membrane surface did not differ between sex and centrifuge. Haematological parameters did not show a significant correlation to clot and membrane size. Membranes obtained from both centrifugation protocols showed a loose fibrin structure and cells evenly distributed throughout the clot. Tubes' warming was effective to obtain A-PRF+ clots from all samples, regardless the environmental temperature. Further studies are needed to evaluate the influence of other blood molecules on the A-PRF+ structure and size.
Subject(s)
Platelet-Rich Fibrin , Animals , Horses/blood , Male , Female , Blood Platelets , Centrifugation/veterinary , Blood Coagulation/physiologySubject(s)
Factor VIII , Hemophilia A , Humans , Factor VIII/immunology , Factor VIII/antagonists & inhibitors , Hemophilia A/drug therapy , Hemophilia A/blood , Hemophilia A/immunology , Blood Coagulation/drug effects , Animals , Blood Coagulation Factor Inhibitors/blood , Blood Coagulation Factor Inhibitors/immunologyABSTRACT
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.
Subject(s)
Blood Coagulation , Diabetes, Gestational , Genome-Wide Association Study , Mendelian Randomization Analysis , Humans , Diabetes, Gestational/genetics , Diabetes, Gestational/blood , Female , Pregnancy , Blood Coagulation/genetics , Polymorphism, Single Nucleotide , von Willebrand Factor/genetics , von Willebrand Factor/metabolism , Blood Coagulation Factors/genetics , Blood Coagulation Factors/metabolismABSTRACT
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.
Subject(s)
Blood Coagulation , Coated Materials, Biocompatible , Osteogenesis , Silicon Dioxide , Titanium , Adsorption , Silicon Dioxide/chemistry , Blood Coagulation/drug effects , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Animals , Osteogenesis/drug effects , Titanium/chemistry , Porosity , Surface Properties , Humans , Blood Platelets/metabolism , Proteomics/methods , Blood Proteins/chemistry , Blood Proteins/metabolism , Nanotubes/chemistry , Mice , Male , Materials Testing , Blood Coagulation Factors/metabolism , Blood Coagulation Factors/chemistryABSTRACT
The development of efficient hemostatic materials is crucial for achieving rapid hemorrhage control and effective wound healing. Inorganic polyphosphate (polyP) is recognized as an effective modulator of the blood coagulation process. However, the specific effect of polyP chain length on coagulation is not yet fully understood. Furthermore, calcium ions (Ca2+) are essential for the coagulation process, promoting multiple enzyme-catalyzed reactions within the coagulation cascade. Hence, calcium ion-coupled polyphosphate powders with three different degrees of polymerization (CaPP-n, n = 20, 50, and 1500) are synthesized by an ion-exchange reaction. CaPP exhibits a crystalline phase at a low polymerization degree and transitions to an amorphous phase as the polymerization degree increases. Notably, the addition of Ca2+ enhances the wettability of polyP, and CaPP promotes hemostasis, with varying degrees of effectiveness related to chain length. CaPP-50 exhibits the most promising hemostatic performance, with the lowest blood clotting index (BCI, 12.1 ± 0.7%) and the shortest clotting time (302.0 ± 10.5 s). By combining Ca2+ with polyP of medium-chain length, CaPP-50 demonstrates an enhanced ability to accelerate the adhesion and activation of blood cells, initiate the intrinsic coagulation cascade, and form a stable blood clot, outperforming both CaPP-20 and CaPP-1500. The hemostatic efficacy of CaPP-50 is further validated using rat liver bleeding and femoral artery puncture models. CaPP-50 is proven to possess hemostatic properties comparable to those of commercial calcium-based zeolite hemostatic powder and superior to kaolin. In addition, CaPP-50 exhibits excellent biocompatibility and long-term storage stability. These results suggest that CaPP-50 has significant clinical and commercial potential as an active inorganic hemostatic agent for rapid control of bleeding.
Subject(s)
Calcium , Hemorrhage , Polymerization , Polyphosphates , Animals , Polyphosphates/chemistry , Polyphosphates/pharmacology , Calcium/chemistry , Rats , Hemorrhage/prevention & control , Hemorrhage/drug therapy , Hemostatics/chemistry , Hemostatics/pharmacology , Blood Coagulation/drug effects , Rats, Sprague-Dawley , Male , Hemostasis/drug effects , Ions/chemistryABSTRACT
The term 'routine coagulation' typically applies to hemostasis tests routinely performed in hematology laboratories, often available 24/7, and potentially ordered urgently. These tests would comprise of the prothrombin time (PT), the PT converted to an international normalized ratio, the activated partial thromboplastin time (often called partial thromboplastin time in North American laboratories) and potentially the thrombin time, the D-dimer assay, and fibrinogen assays. Although other tests could feasibly be offered (testing feasible), there are good reasons for not including all of these other tests in all routine coagulation laboratories.
Subject(s)
Prothrombin Time , Humans , Blood Coagulation Tests , Blood Coagulation , Partial Thromboplastin Time , Blood Coagulation Disorders/diagnosis , Blood Coagulation Disorders/blood , Fibrin Fibrinogen Degradation Products/analysisABSTRACT
Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by progressive motoneuron degeneration, and effective clinical treatments are lacking. In this study, we evaluated whether intranasal delivery of mesenchymal stem cell-derived small extracellular vesicles (sEVs) is a strategy for ALS therapy using SOD1G93A mice. In vivo tracing showed that intranasally-delivered sEVs entered the central nervous system and were extensively taken up by spinal neurons and some microglia. SOD1G93A mice that intranasally received sEV administration showed significant improvements in motor performances and survival time. After sEV administration, pathological changes, including spinal motoneuron death and synaptic denervation, axon demyelination, neuromuscular junction degeneration and electrophysiological defects, and mitochondrial vacuolization were remarkably alleviated. sEV administration attenuated the elevation of proinflammatory cytokines and glial responses. Proteomics and transcriptomics analysis revealed upregulation of the complement and coagulation cascade and NF-ĸB signaling pathway in SOD1G93A mouse spinal cords, which was significantly inhibited by sEV administration. The changes were further confirmed by detecting C1q and NF-ĸB expression using Western blots. In conclusion, intranasal administration of sEVs effectively delays the progression of ALS by inhibiting neuroinflammation and overactivation of the complement and coagulation cascades and NF-ĸB signaling pathway and is a potential option for ALS therapy.
Subject(s)
Amyotrophic Lateral Sclerosis , Extracellular Vesicles , NF-kappa B , Signal Transduction , Animals , Male , Mice , Administration, Intranasal , Amyotrophic Lateral Sclerosis/metabolism , Blood Coagulation , Disease Models, Animal , Extracellular Vesicles/metabolism , Mesenchymal Stem Cells/metabolism , Mice, Inbred C57BL , Mice, Transgenic , Motor Neurons/metabolism , NF-kappa B/metabolism , Spinal Cord/metabolism , Spinal Cord/pathology , Superoxide Dismutase-1/genetics , Superoxide Dismutase-1/metabolismABSTRACT
OBJECTIVE: Several pathological conditions trigger the formation of microvesicles (MVs), including infectious diseases such as COVID-19. The shedding of MVs increases the levels of inflammatory factors (e.g., interleukin-6; IL-6) and ultimately leads to an inflammatory cascade response, while also increasing the procoagulant response. The current study aimed to evaluate the level of circulating MVs and their procoagulant activity as well as the serum level of IL-6 in patients with COVID-19 and healthy controls. In this case-control study, 65 patients with COVID-19 and 30 healthy individuals were sampled after obtaining written informed consent. MVs counting was measured using conjugated CD61, CD45, CD235a, and Annexin-V antibodies. Additionally, the procoagulant activity of MVs and the IL-6 level were estimated using enzyme-linked immunosorbent assay (ELISA). RESULTS: The majority of MVs were platelet-derived MVs (PMVs). Patients with COVID-19 had significantly higher levels of MVs, procoagulant MVs, and IL-6 compared to healthy controls (p < 0.001). MVs were significantly correlated with procoagulant MVs, D-Dimer levels, fibrinogen, and IL-6, but not with platelet, lymphocyte, and neutrophil counts. CONCLUSION: Elevated levels of procoagulant MVs and their association with inflammatory and coagulation markers in patients with COVID-19 are suggested as a novel circulatory biomarker to evaluate and predict the procoagulant activity and severity of COVID-19.
Subject(s)
COVID-19 , Cell-Derived Microparticles , Interleukin-6 , SARS-CoV-2 , Humans , COVID-19/blood , Cell-Derived Microparticles/metabolism , Male , Female , Case-Control Studies , Middle Aged , Interleukin-6/blood , Adult , Blood Coagulation , Blood Platelets/metabolism , Fibrin Fibrinogen Degradation Products/analysis , Fibrin Fibrinogen Degradation Products/metabolism , AgedABSTRACT
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.
Subject(s)
Biomarkers , Blood Coagulation Factors , Blood Coagulation , Cause of Death , Coronary Angiography , Prediabetic State , Humans , Prediabetic State/blood , Prediabetic State/mortality , Prediabetic State/diagnosis , Male , Middle Aged , Female , Risk Assessment , Aged , Biomarkers/blood , Blood Coagulation Factors/metabolism , Blood Coagulation Factors/analysis , Prognosis , Coronary Artery Disease/mortality , Coronary Artery Disease/blood , Coronary Artery Disease/diagnostic imaging , Blood Glucose/metabolism , Risk Factors , Mediation Analysis , Predictive Value of Tests , Diabetes Mellitus, Type 2/mortality , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosisABSTRACT
BACKGROUND: To explore the feasibility and effectiveness of a segmented sodium citrate solution anticoagulation strategy in patients receiving CRRT. METHODS: A prospective, randomized controlled study was conducted. RESULTS: According to the inclusion and exclusion criteria, 80 patients were included and randomly divided into two groups. Moreover, coagulation indices, liver function indices, renal function indices, and SOFA and APACHE II scores did not significantly differ between the two groups (P > 0.05). The coagulation grade of the venous ports in the experimental group was lower than that in the control group and the two groups of filters, but the difference was not statistically significant (P = 0.337). Both sodium citrate solution infusion methods maintained a low blood calcium concentration (0.25-0.45 mmol/L) in the peripheral circulation pathway, and no patient developed hypocalcaemia (< 1.0 mmol/L). The lifespans of the extracorporeal circulation tube in the experimental group and the control group were 69.43 ± 1.49 h and 49.39 ± 2.44 h, respectively (t = 13.316, P = 0.001). CONCLUSION: The segmented citrate solution anticoagulation strategy could extend the lifespan of the extracorporeal circulation tube and improve CRRT efficacy. TRIAL REGISTRATION: The Chinese Clinical Trial Registry number is ChiCTR2200057272. Registered on March 5, 2022.
Subject(s)
Anticoagulants , Critical Illness , Sodium Citrate , Humans , Prospective Studies , Anticoagulants/administration & dosage , Sodium Citrate/administration & dosage , Male , Middle Aged , Female , Aged , Blood Coagulation/drug effects , Treatment Outcome , Continuous Renal Replacement Therapy/methods , Feasibility Studies , China , Renal Replacement Therapy/methodsABSTRACT
Examining the critical role of anticoagulants in medical practice, particularly their central function in preventing abnormal blood clotting, is of the utmost importance. However, the study of interactions between blood proteins and alternative anticoagulant nano-surfaces is still understood poorly. In this study, novel approach involving direct functionalisation of magnetic iron oxide nanoparticles (MNPs) as carriers with sulphated dextran (s-dext) is presented, with the aim of evaluating the potential of magnetically-responsive MNPs@s-dext as anticoagulants. The physicochemical characterisation of the synthesised MNPs@s-dext includes crystal structure analysis, morphology study, surface and electrokinetic properties, thermogravimetric analysis and magnetic properties` evaluation, which confirms the successful preparation of the nanocomposite with sulfonate groups. The anticoagulant potential of MNPs@s-dext was investigated using a standardised activated partial thromboplastin time (APTT) test and a modified APTT test with a quartz crystal microbalance with dissipation (QCM-D) which confirmed the anticoagulant effect. Time-resolved solid-liquid interactions between the MNPs@s-dext and model blood proteins bovine serum albumin and fibrinogen were also investigated, to gain insight into their hemocompatibility, and revealed protein-repellence of MNPs@s-dext against blood proteins. The study also addressed comprehensive cytotoxicity studies of prepared nanocomposites, and provided valuable insights into potential applicability of MNPs@s-dext as a promising magnetic anticoagulant in biomedical contexts.
Subject(s)
Anticoagulants , Dextran Sulfate , Nanocomposites , Anticoagulants/pharmacology , Anticoagulants/chemistry , Humans , Nanocomposites/chemistry , Nanocomposites/toxicity , Dextran Sulfate/chemistry , Serum Albumin, Bovine/chemistry , Blood Coagulation/drug effects , Magnetic Iron Oxide Nanoparticles/chemistry , Magnetic Iron Oxide Nanoparticles/toxicity , Animals , Ferric Compounds/chemistry , Ferric Compounds/pharmacology , Fibrinogen/chemistry , Cell Survival/drug effects , Partial Thromboplastin Time , Magnetite Nanoparticles/chemistry , Magnetite Nanoparticles/toxicityABSTRACT
Background: Thyroid hormones significantly influence cardiovascular pathophysiology, yet their prognostic role in acute aortic dissection (AAD) remains inadequately explored. This study assesses the prognostic value of thyroid hormone levels in AAD, focusing on the mediating roles of renal function and coagulation. Methods: We included 964 AAD patients in this retrospective cohort study. Utilizing logistic regression, restricted cubic splines, and causal mediation analysis, we investigated the association between thyroid hormones and in-hospital mortality and major adverse cardiovascular events (MACEs). Results: In AAD patients overall, an increase of one standard deviation in FT4 levels was associated with a 31.9% increased risk of MACEs (OR 1.319; 95% CI 1.098-1.584) and a 36.1% increase in in-hospital mortality (OR 1.361; 95% CI 1.095-1.690). Conversely, a higher FT3/FT4 ratio was correlated with a 20.2% reduction in risk of MACEs (OR 0.798; 95% CI 0.637-0.999). This correlation was statistically significant predominantly in Type A AAD, while it did not hold statistical significance in Type B AAD. Key renal and coagulation biomarkers, including blood urea nitrogen, creatinine, cystatin C, prothrombin time ratio, prothrombin time, and prothrombin time international normalized ratio, were identified as significant mediators in the interplay between thyroid hormones and MACEs. The FT3/FT4 ratio exerted its prognostic influence primarily through the mediation of renal functions and coagulation, while FT4 levels predominantly impacted outcomes via a partial mediation effect on coagulation. Conclusion: FT4 levels and the FT3/FT4 ratio are crucial prognostic biomarkers in AAD patients. Renal function and coagulation mediate the association between the thyroid hormones and MACEs.
Subject(s)
Aortic Dissection , Blood Coagulation , Thyroid Hormones , Humans , Male , Female , Prognosis , Retrospective Studies , Middle Aged , Thyroid Hormones/blood , Blood Coagulation/physiology , Aortic Dissection/blood , Aortic Dissection/physiopathology , Kidney/physiopathology , Aged , Biomarkers/blood , Hospital Mortality , Adult , Acute DiseaseABSTRACT
COVID-19 is a highly contagious virus that uses Angiotensin-converting enzyme 2 (ACE2) as a receptor to enter human cells. The virus leads to an increase in inflammatory cytokines (i.e. IL-6) and an impaired coagulation system, which can cause serious complications during and after the disease. Physical exercise has been shown to improve COVID-19 complications through various mechanisms, such as modulation of the immune and coagulation systems. Therefore, this study investigated the effects of 8 weeks of training on inflammatory, coagulation, and physical factors in patients with COVID-19 during the recovery phase. Twenty-seven male and female volunteers (age 20-45 years) who recently recovered from COVID-19 were assigned to the control (n = 13) or the training group (n = 14). Blood samples, aerobic capacity and muscle endurance were collected 24 h before the start of the interventions and 24 h after the final training session in week 4 and 48 h after the final training session in week 8. IL-6, ACE2, fibrinogen, and D-dimer were measured using ELISA. The training group showed a significant increase in muscle endurance (p = 0.004) and aerobic capacity (p = 0.009) compared to the control group. Serum levels of IL-6 and fibrinogen decreased in the training group but this decrease was not statistically significant (p > 0.05). Despite a slight increase in the quality of life and sleep in the training group, no statistically significant difference was observed between the training and the control group. It appears that physical training has beneficial effects on the coagulation system, inflammatory factors, and sleep quality and can facilitate the recovery of COVID-19 patients.
Subject(s)
Angiotensin-Converting Enzyme 2 , Blood Coagulation , COVID-19 , Exercise , Interleukin-6 , SARS-CoV-2 , Humans , COVID-19/blood , Male , Female , Angiotensin-Converting Enzyme 2/metabolism , Adult , Interleukin-6/blood , Middle Aged , Exercise/physiology , Young Adult , Fibrin Fibrinogen Degradation Products/metabolism , Fibrin Fibrinogen Degradation Products/analysis , Survivors , Fibrinogen/metabolism , Exercise Therapy/methodsABSTRACT
Coagulation disorders are common in Kawasaki disease (KD). The main objectives of the present study were to probe the associations of coagulation profiles with clinical classification, IVIG responsiveness, coronary artery abnormalities (CAAs) in the acute episode of KD. A total of 313 KD children were recruited and divided into six subgroups, including complete KD (n = 217), incomplete KD (n = 96), IVIG-responsive KD (n = 293), IVIG-nonresponsive KD (n = 20), coronary artery noninvolvement KD (n = 284) and coronary artery involvement KD (n = 29). Blood samples were collected within 24-h pre-IVIG therapy and 48-h post-IVIG therapy. Coagulation profiles, conventional inflammatory mediators and blood cell counts were detected. Echocardiography was performed during the period from 2- to 14-day post-IVIG infusion. In addition, 315 sex- and age-matched healthy children were enrolled as the controls. (1) Before IVIG therapy, coagulation disorders were more prone to appear in KD patients than in healthy controls, and could be overcome by IVIG therapy. FIB and DD significantly increased in the acute phase of KD, whereas reduced to normal levels after IVIG therapy. (2) PT and APTT were significantly longer in patients with complete KD when compared with their incomplete counterparts after IVIG therapy. (3) The larger δDD, δFDP and the smaller δPT, δINR predicted IVIG nonresponsiveness. (4) The higher δDD and δFDP correlated with a higher risk for CAAs (DD: r = -0.72, FDP: r = -0.54). Coagulation disorders are correlated with complete phenotype, IVIG nonresponsiveness and CAA occurrence in the acute episode of KD, and can be rectified by synergistic effects of IVIG and aspirin.