vWF Levels Research Articles

Altered fibrin clot properties and elevated von Willebrand Factors level are associated with progression to permanent atrial fibrillation during follow-up: a cohort study

Abstract Introduction Little is known about association of prothrombotic markers and atrial fibrillation (AF) progression to permanent arrythmia (PerAF). Formation of denser and poorly lysable fibrin clots have been observed in AF including patients with sinus rhythm in association with stroke and bleeding risk. We investigated whether altered fibrin clot properties and other prothrombotic state markers may contribute to AF transition to PerAF. Methods In the cohort study, in 226 anticoagulated AF patients (median age 69 years, median CHA2DS2-VASc of 3)with paroxysmal (n=83, 36.7%) or persistent (n=143, 63.3%) arrythmia we assessed at baseline plasma clot permeability (Ks), lysis time (CLT), and fibrinolysis involved proteins, including plasminogen activator inhibitor type 1 (PAI-1) along with von Willebrand factor (vWF) antigen. We recorded patients with PerAF during a median follow-up of 58 months. Results PerAF was documented in 62 (27.4%, 5.7%/year) subjects. These patients were older, with larger prevalence of heart failure (HF), higher body mass index by 9.6%, more often presented persistent AF and had longer history of arrythmia by 60%. We observed by 25.7% longer CLT and similar Ks, compared with the remainders, along with higher levels of vWF by 29% and PAI-1 by 21.3%. By multivariable analysis CLT, vWF and HF were independently associated with PerAF (R2=0.697, P<0.001). A cut-off CLT value of ≥105 min had a sensitivity of 88.7% and specificity of 78.7% in prediction of PerAF (area under curve 0.892, 95% confidence interval 0.848-0.935, P<0.001). Conclusion Impaired global fibrinolysis and elevated vWF levels are independently associated with faster progression to PerAF despite anticoagulation.Figure1

α9β1 integrin & its ligands as new potential biomarkers in FMF.

Background & objectives Familial Mediterranean Fever (FMF) manifests as a hereditary condition characterized by repeated bouts of fever, abdominal, chest, and joint discomfort, and swelling. Colchicine is the most common form of treatment, but it does not eliminate the disease. The underlying causes of the inflammatory mechanism are still not fully known. Methods A total of 20 healthy controls, 16 individuals with FMF in the attack period, and 14 in the remission period participated in the study. ITGA9, ITGB1, OPN, TNC, VEGF, VCAM-1, TGM2, TSP-1, Emilin-1, and vWF levels were measured by ELISA by obtaining serum from blood samples of individuals. In addition, gene expressions of α9β1 (ITGA9, ITGB1) and its best known ligands (TNC, SPP1) were analyzed by quantitative real-time PCR (qPCR). Results The findings of this study showed that serum levels of α9β1 and its ligands were higher in individuals with FMF in the attack period than in the healthy controls and the FMF group in the remission period (P<0.05). The marker levels of the healthy group were also higher than those in the remission period (p<0.05). In addition, when the gene expressions were compared between the healthy controls and FMF group, no significant difference was found for ITGA9, ITGB1, TNC, and SPP1 genes. Interpretation & conclusions The function of α9β1 and its ligands in FMF disease was investigated for the first time in this study as per our knowledge. Serum levels of these biomarkers may help identify potential new targets for FMF disease diagnosis and treatment approaches.

Predictive indicators in peripheral blood and left atrium blood for left atrial spontaneous echo contrast in atrial fibrillation patients

ObjectivesThe purpose of this study was to demonstrate the discriminating predictive indicators in peripheral blood and left atrium blood for predicting the risk of left atrial spontaneous echo contrast (LASEC) in atrial fibrillation patients underwent catheter ablation.MethodsA total of 108 consecutive AF patients treated with radiofrequency ablation between July 2022 and July 2023 were enrolled and divided into two groups based on preprocedural transesophageal echocardiography: the non LASEC group (n = 71) and the LASEC group (n = 37). Circulating platelet and endothelial- derived MPs (PMPs and EMPs) in peripheral blood and left atrial blood were detected. Plasma soluble P-selectin (sP-selectin) and von Willebrand factor (vWF) were observed. Diagnostic efficiency was measured using receiver operating characteristic (ROC) curve.ResultsPeripheral sP-selectin, vWF and EMPs expressions elevated in all subjects when compared to those in left atrium blood. Levels of sP-selectin and vWF were significantly higher in peripheral blood of LASEC group than those of non LASEC group (p = 0.0018,p = 0.0271). Significant accumulations of peripheral PMPs and EMPs were documented in LASEC group by comparison with non LASEC group (p = 0.0395,p = 0.018). The area under curve(AUC) of combined PMPs and sP-selectin in predicting LASEC was 0.769 (95%CI: 0.678–0.845, sensitivity: 86.49%, specificity: 59.15%), significantly larger than PMPs or sP-selectin alone.ConclusionsExpressions of PMPs, sP-selectin, EMPs and vWF Increased in NVAF patients with LASEC and that might be potential biomarkers for LASEC prediction.

Flexible inner surface of polysulfone membranes prevents platelet adhesive protein adsorption and improves antithrombogenicity in vitro.

We investigated whether the condition of the inner surface of hollow fibers affects the blood compatibility of hemodialyzers. We used scanning probe microscope/atomic force microscopy (SPM/AFM) to investigate the height of the swelling and flexible layers (thickness and softness) on the inner surfaces of the hollow fibers. Next, we tested the blood compatibility between dialyzers comprising a hollow fiber membrane, in which the other dialyzers, except for PVP, were additionally coated using PS membranes coated with other materials. After blood was injected into the dialyzer and plugged, dynamic stimulation was performed by slightly rotating the dialyzer for 4 h, although there was no blood circulation. The vitamin E-coated polysulfone (PS) membrane showed a higher thickness and softness of the flexible layer than the asymmetric cellulose triacetate membrane without polyvinylpyrrolidone (PVP) and the PS membranes with PVP. We found that the dialyzer with vitamin E coating significantly suppressed the decrease in platelets, increase in β-TG, and increase in PF4 compared to those coated with NV polymer. Additionally, as the adsorbed protein on the inner surface, the total protein, fibronectin, and vWF levels were significantly lower in the vitamin E-coated dialyzer. The thickness and softness of the flexible layer of the inner surface of the hollow fiber membrane in vitro affect differences in blood coagulation performance in clinical research. Future clinical trials are required to confirm our results.

Exploring the roles and therapeutic implications of melatonin-mediated KLF6 in the development of intracranial aneurysm

Background Intracranial aneurysm (IA) is a cerebrovascular disease with a high mortality rate due to ruptured subarachnoid hemorrhage. While Krüppel-like factor 6 (KLF6) dysregulation has been implicated in cancer and cardiovascular diseases, its role in IA remains unclear. Materials and methods The GSE122897 and GSE15629 datasets were downloaded from the Gene Expression Omnibus database. Immune cell infiltration and hypoxia analysis were performed to explore the effects of KLF6 on IA. Weighted gene co-expression network analysis was used to identify hub genes related to KLF6 expression for subsequent analyses. Hypoxia-related genes were identified. Drug prediction was performed for IA. Samples from healthy individuals and patients with IA were collected to detect the expression of endothelin-1 (ET-1), vascular hematoma factor (vWF), and KLF6. A model of H2O2-induced human brain vascular smooth muscle cells (HBVSMC) injury was constructed to explore the effects of KLF6 and melatonin to treat IA. Results T cells CD4 memory resting and monocytes were significantly different in the KLF6 high and low expression groups. Four hypoxia-related gene sets were significantly enriched in the KLF6 high-expression group. Six hypoxia-related hub genes were obtained, which were significantly associated with KLF6. Drug prediction showed that melatonin may be a potential drug for IA. The levels of ET-1, vWF, and KLF6 were significantly upregulated in patients with IA. KLF6 exacerbates H2O2-induced injury in HBVSMC, ameliorated by melatonin. Conclusion KLF6 may be a potential target for IA treatment, with melatonin-mediated KLF6 effects playing a crucial role in the development of IA.

Poly (β-amino esters)/Mobil Composition of Matter 41-mediated delivery of siIL-1β alleviates deep vein thrombosis in rat hind limbs.

Introduction: Deep vein thrombosis (DVT) is a major cause of cardiovascular disease-related deaths worldwide and is considered a thrombotic inflammatory disorder. IL-1β, as a key promoter of venous thrombus inflammation, is a potential target for DVT treatment. Constructing a nanocarrier system for intracellular delivery of siIL-1β to silence IL-1β may be an effective strategy for alleviating DVT. Methods: ELISA was used to detect the expression levels of IL-1β and t-PA in the serum of DVT patients and healthy individuals. In vitro, HUVEC cells were treated with IL-1β, and changes in VWF and t-PA expression levels were assessed. PBAE/MCM-41@siIL-1β (PM@siIL-1β) nano-complexes were synthesized, the characterization and biocompatibility of PM@siIL-1β were evaluated. A rat hind limb DVT model was established, and PM@siIL-1β was used to treat DVT rats. Morphology of the inferior vena cava, endothelial cell count, IL-1β, vWF, and t-PA levels, as well as changes in the p38 MAPK and NF-κB pathways, were examined in the different groups. Results: IL-1β and t-PA were highly expressed in DVT patients, and IL-1β treatment induced a decrease in VWF levels and an increase in t-PA levels in HUVEC cells. The synthesized PM@siIL-1β exhibited spherical shape, good stability, high encapsulation efficiency, and high drug loading capacity, with excellent biocompatibility. In the DVT model rats, the inferior vena cava was filled with blood clots, endothelial cells increased, IL-1β and VWF levels significantly increased, while t-PA levels were significantly downregulated. Treatment with PM@siIL-1β resulted in reduced thrombus formation, decreased endothelial cell count, and reversal of IL-1β, VWF, and t-PA levels. Furthermore, PM@siIL-1β treatment significantly inhibited p38 phosphorylation and upregulation of NF-κB expression in the DVT model group. Conclusion: IL-1β can be considered a therapeutic target for suppressing DVT inflammation. The synthesized PM@siIL-1β achieved efficient delivery and gene silencing of siIL-1β, demonstrating good therapeutic effects on rat hind limb DVT, including anti-thrombotic and anti-inflammatory effects, potentially mediated through the p38 MAPK and NF-κB pathways.

Association of periodontitis with cardiometabolic and haemostatic parameters

ObjectiveTo investigate the association between periodontitis and cardiometabolic and haemostatic parameters.Materials and methodsBetween 2014 and 2019, 54 individuals needing full mouth extraction, and 50 control individuals, were recruited for a combined cross-sectional (individuals versus controls) and longitudinal (individuals before and after extraction) study. Periodontitis severity was measured using the periodontal inflamed surface area (PISA). Blood was drawn to measure the haemostatic (Factor VIII, von Willebrand factor [VWF], endogenous thrombin potential, d-dimer, clot lysis time) and cardiovascular risk (C-reactive protein [CRP], lipid profile) parameters, prior to and 12 weeks post-extraction. The results were analysed group-wise.ResultsThe mean VWF and CRP levels were higher and the high-density lipoprotein levels were lower in the individuals prior to extraction compared to the controls. The VWF was significantly correlated with the PISA (a 21% unit increase in VWF per 1000 mm2 increase in PISA, 95%CI: 6–36%, p = 0.01). The other analyses were comparable between the individuals and controls, and did not change in the individuals after the extraction.ConclusionVWF levels are associated with periodontitis severity; they do not improve after full-mouth extraction. Severe periodontitis in control individuals does not induce substantial changes in their haemostatic or inflammatory systems.Clinical relevanceTreatment of periodontitis has been shown to improve the cardiometabolic blood profile of patients with established cardiometabolic disease. However, whether periodontitis treatment improves cardiometabolic and haemostatic profiles in people without cardiometabolic disease is uncertain.

Blood coagulation in Prediabetes clusters–impact on all-cause mortality in individuals undergoing coronary angiography

BackgroundMetabolic 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.MethodsUtilizing 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.ResultsPrediabetes 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.ConclusionsHigh-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.Graphical

The Phenomenon of Thrombotic Microangiopathy in Cancer Patients.

Thrombotic microangiopathy (TMA) encompasses a range of disorders characterized by blood clotting in small blood vessels, leading to organ damage. It can manifest as various syndromes, including thrombotic thrombocytopenic purpura (TTP), hemolytic-uremic syndrome (HUS), and others, each with distinct causes and pathophysiology. Thrombo-inflammation plays a significant role in TMA pathogenesis: inflammatory mediators induce endothelial injury and activation of platelet and coagulation cascade, contributing to microvascular thrombosis. Primary TMA, such as TTP, is primarily caused by deficient ADAMTS13 metalloproteinase activity, either due to antibody-mediated inhibition or intrinsic enzyme synthesis defects. In cancer patients, a significant reduction in ADAMTS13 levels and a corresponding increase in VWF levels is observed. Chemotherapy further decreased ADAMTS13 levels and increased VWF levels, leading to an elevated VWF/ADAMTS13 ratio and increased thrombotic risk. Drug-induced TMA (DITMA) can result from immune-mediated or non-immune-mediated mechanisms. Severe cases of COVID-19 may lead to a convergence of syndromes, including disseminated intravascular coagulation (DIC), systemic inflammatory response syndrome (SIRS), and TMA. Treatment of TMA involves identifying the underlying cause, implementing therapies to inhibit complement activation, and providing supportive care to manage complications. Plasmapheresis may be beneficial in conditions like TTP. Prompt diagnosis and treatment are crucial to prevent serious complications and improve outcomes.

The Significance of von Willebrand Factor Antigen Levels in Predicting the Severity of Coronary Artery Disease in Patients with ST-Segment Elevation Myocardial Infarction

Background When the endothelium of the coronary artery is damaged, it exposes the underlying structure to a series of events that can cause complete blockage and a myocardial infarction with ST-segment elevation (STEMI). One of the key factors in this process is a protein called von Willebrand factor (vWF) that helps platelets adhere to the damaged area. Our objective was to investigate the importance of measuring vWF levels in patients with STEMI to determine the severity of their coronary artery disease (CAD) on angiography. Methods The study included 30 patients who experienced their first STEMI. Patients with a history of CAD, cardiomyopathies, valvular heart disease, atrial fibrillation, anticoagulants, coagulation disorders, and pregnancy were not included in the study. After informed consent, all patients were subjected to routine blood investigations, electrocardiography, echocardiography, and coronary angiography. Blood samples were collected for vWF Ag within 24 hours of the patients’ arrival at the hospital. After the angiography, the coronary arteries were evaluated for stenosis and quantified using the modified Gensini score (mGS). The score was then correlated with vWF Ag levels using the Spearman rank correlation. Additionally, the receiver operating characteristic (ROC) curve was plotted for the value of vWF Ag levels to detect significant CAD. Results The average age of the group was (49.77 ± 10.79) years. The average levels of vWF Ag were (204.17% ± 51.99%). Patients with an mGS score of over 150 had higher levels of vWF Ag than those with a score of under 100 ( P &lt; .001). There was a positive correlation ( r2: 0.67) between the parameters. On the ROC curve, vWF Ag levels higher than 186% predicted the presence of CAD, with an area under curve indicating sensitivity and specificity. Conclusion: In patients with STEMI, higher levels of vWF Ag were found to be associated with a greater severity of CAD.

Obesity is associated with higher levels of circulating cytokines involved in the development of cardiovascular disease in people living with HIV.

Obesity is increasingly described in people living with HIV (PLWH), but its impact on immune activation and inflammation in HIV is still poorly characterised. We aimed to analyse the difference in circulating cytokines involved in pathways associated with co-morbidities in PLWH according to the presence or absence of obesity. Age and sex matched PLWH with and without obesity (BMI ≥30 kg/m2) from a multicentre, prospective cohort were recruited with a 1:2 ratio. Twenty-three biomarkers covering pathways associated with systemic inflammation (hsCRP, IL-2, IL-6, TNFR1, TNFR2, TNF-α, IFN-γ, IL-18), coagulation (vWF, D-dimer, sCD40L), endothelial function (E-selectin, P-selectin, sICAM-1, sVCAM-1), atherosclerosis (MPO, Lp-PLA2), immune regulation (IL-1RA), innate immune activation (MIP-1, MCP-1, sCD163, sCD14) and microbial translocation (LBP) were measured in the two groups. Between-group difference in biomarkers were assessed using Mann-Whitney test. Associations between obesity and biomarkers were assessed using logistic regression adjusted for age, gender, ethnicity, smoking status, and antiretroviral therapy (ART). Ninety-nine ART-treated PLWH were included in the analysis (33 with obesity, 66 without obesity). PLWH with obesity had higher levels of hsCRP, IL-6, vWF, D-dimer, E-selectin, MPO, IL-1RA, and LBP. Six markers (hsCRP, IL-6, vWF, E-selectin, MPO, IL-1RA), reflecting systemic inflammation, coagulation and atherosclerosis pathways were associated with increased odds of obesity in the adjusted logistic regression model: hsCRP (aOR 2.7, 95% CI [1.7, 4.29]), IL-6 (3.77 [1.43, 9.93]), vWF (5.33 [1.51, 18.75]), E-selectin (6.28 [1.36, 29.04]), MPO (6.85 [1.87, 25.04]), IL-1RA (6.45 [2.28, 18.2]). No association was observed between obesity and markers of innate immune activation and gut microbial translocation. Obesity in PLWH was associated with activation of systemic inflammatory, endothelial, atherosclerosis and coagulation pathways, rather than those associated with innate immune activation and gut microbial translocation. These pathways point towards an unfavourable cardiovascular profile in PLWH with obesity, which will have to be further explored in future studies on long-term outcomes.

Aerobic Training and Ointment Effect on range of motion, von Willebrand factor, vascular endothelial factor and Femoral Artery Hemodynamics in Joint Contracture: A Rat Model.

Using a rat model, we investigated the effect of multidisciplinary rehabilitation, including aerobic training and ointment, on the ROM, vWF, VEGF content, and femoral artery hemodynamics in rats with joint contracture. A total of 44 Wistar rats were divided into the normal control group (NC, eight rats) and the experimental group (EG). A joint contracture model was established for the rats in the EG group by an external fixator. After fixator removal, 32 rats are further divided into the MC, SC, RE, and SR groups (n = 8). Before and after the 42day intervention, the ROM, vWF, VEGF, PS, ED, and RI were measured using X-ray imaging, ELISA, and color Doppler ultrasound, respectively. After fixator removal, ROM for EG group was lower than that of the NC group (p < .01). After the intervention, ROM for the SR, RE, and SC groups was improved. The ROM for the SR group reached a similar value for NC group. vWF and VEGF levels in SR group were lower than in the MC, SC, and RE groups (p < .05), and had a similar value to the NC groups. PS value for SR and RE groups was higher than the MC and SC groups. The RI value for SR group was higher than that of NC and MC groups. Multidisciplinary rehabilitation used in this study can treat joint contracture synergistically. It improves the ROM of the joint, reduces the content of vWF and VEGF, and improves the femoral artery hemodynamics.

Combined Intracoronary Prourokinase Thrombolysis on Myocardial Perfusion and Vascular Endothelial Function in STEMI.

This study aimed to investigate the effects of intracoronary prourokinase thrombolysis combined with emergency percutaneous coronary intervention (PCI) on myocardial perfusion and vascular endothelial function in patients with acute ST-segment elevation myocardial infarction (STEMI). A total of 104 patients with STEMI were collected from August 2020 to August 2022, and were divided into control group and observation group in a random manner. The control group received PCI directly, and the observation group received intracoronary prourokinase thrombolytic therapy before PCI. The treatment effects were evaluated by measuring the cardiac function indexes, including left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), and left ventricular ejection fraction (LVEF), the TIMI myocardial perfusion grade, the vascular endothelial indexes, including soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1), the von Willebrand factor (vWF), the myocardial injury indexes, including cardiac troponin I (cTnI), creatine kinase isoenzyme MB (CK-MB), and lactate dehydrogenase (LDH), and the inflammatory factors, including myeloperoxidase (MPO), C-reactive protein (CRP), and interleukin-6 (IL-6). Furthermore, the treatment safety was assessed by recording the incidence of major MACE events, 6 months after the operation. After treatment, LVEDD and LVESD were lower in the observation group than in the control group, and LVEF was higher (p < 0.05). The TIMI myocardial perfusion grade in the observation group was higher than in the control group, after treatment (p < 0.05). The levels of sICAM-1, sVCAM-1, and vWF were higher in the observation group than in the control group (p < 0.05). The levels of cTnI, CK-MB, and LDH in the observation group were lower than those in the control group, 24 hours after surgery. At 3 days after surgery, MPO was lower in the observation group than in the control group, and CRP and IL-6 were higher (p < 0.05). The incidence of major MACE events in the observation group was lower than that in the control group, 6 months after surgery (p < 0.05). There was 1 case of puncture site bleeding in the observation group, 1 case of puncture site bleeding and 1 case of subcutaneous ecchymosis in the control group, but no serious bleeding events, such as internal bleeding or cerebral hemorrhage, in the two groups. Intracoronary prourokinase thrombolytic therapy combined with emergency PCI can promote the recovery of cardiac function, improve myocardial perfusion and vascular endothelial function, and reduce inflammation and the incidence of major postoperative MACE events in acute STEMI patients.

COVID-19 impact on thrombotic complications in cancer patients

Aim: to study the features of thrombotic complications in cancer patients during COVID-19 infection, and identify the most significant diagnostic and prognostic criteria.Materials and Methods. Within the framework of cohort non-randomized study, there were analyzed the course of coronavirus infection in 72 hospitalized patients with uterine cancer (n = 22), cervical cancer (n = 19), ovarian cancer (n = 24) as well as vaginal and vulvar cancer (n = 7). All patients hospitalized for COVID-19 were examined and treated in accordance with the Interim guidelines “Prevention, diagnosis and treatment of novel coronavirus infection (COVID-19)” effective at the time of therapy. Additionally, on days 3–7 after hospitalization, a blood test was performed once to determine the level of metalloproteinase ADAMTS-13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13), ADAMTS-13 activity, ADAMTS-13 inhibitor and von Willebrand factor (vWF) level.Results. It was shown that the average age of the patients was 56.96 ± 7.55 years, the length of hospitalization ranged from 7 to 19 (13.0 ± 3.79) days. The disease severity was assessed by the degree of lung tissue damage based on computed tomography (CT), respiratory failure and development of systemic inflammatory response syndrome (SIRS). During hospitalization, CT-2 was detected in 46 (63.9 %) patients, CT-3 – in 26 (36.1 %) patients; 37 (51.4 %) patients were transferred to the intensive care unit (ICU). Clinically significant deep vein thrombosis (DVT) was diagnosed in 9 (12.5 %) patients, and pulmonary embolism (PE) – in 4 (5.6 %) patients. Of these, 6 cases of DVT and 3 cases of PE were fatal. A total of 14 (19.44 %) patients deceased due to developing acute cardiopulmonary failure. A vWF/ADAMTS-13 ratio greater than 2.1 was found in all ICU patients. Despite anticoagulant therapy, patients with DVT and PE had this ratio higher than 3.3 (4.00 ± 0.48), whereas in all 14 deceased patients it exceeded 2.98.Conclusion. Venous thromboembolism, including PE and DVT, has been identified as а serious complication of COVID-19. An opportunity to predict them early is of special importance because they may lead to serious complications such as disseminated intravascular coagulation, SIRS, cardiopulmonary failure, and death. In patients suffering from cancer infected with COVID-19, not only a decline in ADAMTS-13 activity and level was detected, but also a parallel increase in vWF level. A vWF/ADAMTS-13 ratio may be an early indicator of COVID-19 severity in such patients: a vWF/ADAMTS-13 ratio exceeding 2.1 was common for all ICU patients. Hence, it evidences about a potential for using this parameter to early identify such risk patients who may require more intensive care and medical intervention.

Rare VPS33B gene mutation combined with GP1BA mutation causes severe decrease in plasma VWF levels: a case report and literature review

A 28-year-old woman was found to have coagulation factor Ⅷ activity (FⅧ∶C) <1% and von Willebrand factor antigen (VWF∶Ag) <1% during routine prenatal examinations. No pathogenic variation was found in the exon region of the VWF gene using next-generation sequencing. The clinical presentation of this patient does not match the clinical characteristics of type Ⅲ hemophilia [von Willebrand disease (VWD) ]; therefore, third-generation sequencing technology was used to perform whole-genome sequencing on the patient and her family members. Multiple members of the patient's paternal family carried a heterozygous variant of VPS33B, c.869G>C. The family members carrying this variant all had varying degrees of reduced VWF levels (39% -56% ). Moreover, the proband was detected with the heterozygous variant c.1474dupA in GP1BA. The ACMG and Clinvar databases determined that this variation was associated with platelet-type pseudo VWD. The decrease in VWF levels caused by heterozygous variations in VPS33B in families is the first international report, and no previous studies have reported cases of severe decrease in plasma VWF levels caused by double heterozygous variations in VPS33B and GP1BA.

Proteomic profiling of extracellular vesicles derived from human serum for the discovery of biomarkers in Avascular necrosis

BackgroundAvascular necrosis (AVN) is a medical condition characterized by the destruction of bone tissue due to a diminished blood supply. When the rate of tissue destruction surpasses the rate of regeneration, effective treatment becomes challenging, leading to escalating pain, arthritis, and bone fragility as the disease advances. A timely diagnosis is imperative to prevent and initiate proactive treatment for osteonecrosis. We explored the potential of differentially expressed proteins in serum-derived extracellular vesicles (EVs) as biomarkers for AVN of the femoral head in humans. We analyzed the genetic material contained in serum-derived exosomes from patients for early diagnosis, treatment, and prognosis of avascular necrosis.MethodsEVs were isolated from the serum of both patients with AVN and a control group of healthy individuals. Proteomic analyses were conducted to compare the expression patterns of these proteins by proteomic analysis using LC-MS/MS.ResultsOur results show that the levels of IGHV3-23, FN1, VWF, FGB, PRG4, FCGBP, and ZSWIM9 were upregulated in the EVs of patients with AVN compared with those of healthy controls. ELISA results showed that VWF and PRG4 were significantly upregulated in the patients with AVN.ConclusionsThese findings suggest that these EV proteins could serve as promising biomarkers for the early detection and diagnosis of AVN. Early diagnosis is paramount for effective treatment, and the identification of new osteonecrosis biomarkers is essential to facilitate swift diagnosis and proactive intervention. Our study provides novel insights into the identification of AVN-related biomarkers that can enhance clinical management and treatment outcomes.

Relationship between thrombus vWF and NETs with clinical severity and peripheral blood immunocytes' indicators in patients with acute ischemic stroke.

To investigate the association between von Willebrand factor (vWF) and neutrophil extracellular traps (NETs) in thrombus with clinical severity and peripheral blood immunocytes' indicators in patients with early-stage acute ischemic stroke (AIS). A retrospective study was conducted using the clinical data of 66 patients with AIS who underwent endovascular mechanical thrombectomy and had their thrombus samples collected. The concentrations of vWF and NETs in the thrombus samples were quantitatively assessed. Peripheral blood samples taken in the early stages of the disease were analyzed for total white blood cell counts (WBC), ratios of neutrophils (NEU%), lymphocytes (LYM%), eosinophils (EOS%), and monocytes (MONO%). The severity of clinical symptoms in these patients was evaluated using the modified Rankin Scale (mRS), Essen Stroke Risk Score (ESRS), Barthel Index (BI), and National Institute of Health Stroke Scale (NIHSS). Higher vWF levels in thrombus were associated with lower NIHSS scores, while higher NETs levels were associated with higher initial NIHSS scores. In the early stages of AIS, WBC count and vWF levels were negatively correlated, as well as NEU%. LYM% was positively correlated with vWF level; however, it was negatively correlated with NETs. EOS% was positively correlated with vWF levels. In the early stages of AIS, a higher peripheral WBC count and NEU%, combined with decreased EOS% and LYM%, were significantly correlated with a lower vWF level in the thrombus, potentially indicating more severe symptoms. Consequently, the timely administration of vWF-targeted medications is recommended for such patients. Reduced LYM% is indicative of elevated NETs levels and correlated with more severe clinical symptoms. Therefore, the prompt initiation of NETs-targeted medication is warranted for these patients.

Exploration on the effect of anserine on the alleviation of DVT and its molecular mechanism

BackgroundThis study aimed to explore the regulatory effect of anserine on HUVEC cell injury and thrombosis in deep venous thrombosis (DVT) rats, and to elucidate the underlying molecular mechanisms.MethodsNon-targeted metabolomics data analyses were conducted using an ultra-performance liquid chromatography system Vanquish UHPLC and mass spectrometer to detect plasma metabolism profiles. The transcriptome sequencing and gene intervention experiments were performed to verify the regulatory effect. Further in vivo and in vitro experiments were performed. Enzyme-linked immunosorbent assay was used to detect the levels of P-selectin, E-selectin, and vWF, hematoxylin-eosin (HE) staining was performed to observe thrombotic and inflammatory cell infiltration, flow cytometry and TUNEL assays were performed to detect apoptosis, and qPCR and WB assays were conducted to determine the gene and protein expression.ResultsAnserine alleviated HUVECs injury, reduced adhesion molecule expression, and inflammation. It decreased P-selectin, E-selectin, vWF, THBD, TFPI levels, and apoptosis while promoting NOS3, ET-1, and NO release in HUVECs. In DVT rats, anserine reduced P-selectin, E-selectin, vWF, thrombosis, cell infiltration, apoptosis, and promoted NO release. Transcriptome sequencing and gene intervention confirmed anserine’s regulation of the PI3K-Akt pathway and coagulation via MYB. CARNMT1, a regulatory enzyme for anserine metabolism, increased anserine content, inhibiting coagulation, thrombosis, cell infiltration, and promoting NO release in rats.ConclusionThis study confirmed anserine could alleviate DVT by improving the inflammatory response, inhibiting blood agglutination, and promoting vasodilation, providing new potential therapeutic targets, important scientific evidence for the development of DVT management, and new clues for an in-depth understanding of its molecular mechanisms.

Role of Von Willebrand factor level as a biomarker in acute ischemic stroke

BackgroundVon Willebrand factor (VWF) is a large, multimeric glycoprotein that plays a role in thrombus formation; it is also an important mediator of inflammation. Our study aims to determine the association of VWF plasma level and acute ischemic stroke and determine plasma level of VWF in different subtypes of acute ischemic stroke. This case–control study was conducted on 90 subjects: 30 acute ischemic atherosclerotic stroke patients, 30 acute cardioembolic stroke patients and 30 healthy age and sex-matched control subjects. Stroke patients were recruited within the first week of stroke onset with an age range from 18 to 75 years. All subjects underwent complete neurological examination, duplex ultrasonography (U/S), CT brain, routine laboratory work-up and serum level of VWF.ResultsVWF serum levels were significantly elevated in patients of acute ischemic stroke, compared to control subjects. Higher plasma levels of VWF were observed in patients with acute ischemic atherosclerotic stroke.ConclusionSerum level of VWF can be used as a marker for acute ischemic stroke, especially the atherosclerotic subtype.

Clinical value of coagulation parameters in predicting the severity of severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus infection with a high lethality rate. The purpose of this study was to investigate the changes in coagulation parameters in patients with SFTS, aiming to provide clinical evidence for early diagnosis, treatment, and disease analysis. A total of 40 patients with SFTS attended from April 1, 2020 to May 21, 2022 in Nanjing Drum Tower Hospital were selected and grouped according to the duration of the disease, mild and severe disease, cure and death, with 50 healthy physical examiners as controls, and the risk of severe and death disease was predicted using ROC curves. Comparison between the healthy, mild and severe groups revealed that PT, INR, APTT, TT, D-D and vWF levels were higher than those in the healthy control group, and FII, FIX, FX, FXI, FXII, PC and PS levels were lower than those in the healthy control group, the differences were statistically significant (p < 0.05). Comparing the results of SFTS patients with different course times, the results of Fib, FV, FVII, FVIII, FIX, FX, FXI were statistically significant (p < 0.05). Among the survived and deceased patients, the PT, INR, DD and PS results of the deceased patients were higher than those of the survived patients, and the FVIII, FIX, FXI, FXII and PC were lower than those of the survived patients. The area under the ROC curve showed that D-D had higher predictive ability for the risk of severe disease (AUROC 0.93, sensitivity and specificity at a Cut-off value of 1.50 mg/L were 90.0 and 86.5%, respectively) and the risk of death occurring (AUROC 0.84, sensitivity and specificity at a Cut-off value of 3.39 mg/L were 87.5 and 80.0%, respectively). The monitoring of the coagulation parameters in patients with SFTS is great significance for identifying the severity and death of the patient's condition, and it is of great clinical value to provide early attention, timely intervention and maximum reduction of the mortality rate for patients at risk of severe disease.