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Severe deficiency of ADAMTS13 (<10 iu/dL) is diagnostic of thrombotic thrombocytopenic purpura (TTP) and leads to accumulation of ultra-large vWF multimers, platelet aggregation, and widespread microthrombi, which can be life-threatening. However, the clinical implications of a low ADAMTS13 activity level are not only important in an acute episode of TTP. In this article, we discuss the effects of low ADAMTS13 activity in congenital and immune-mediated TTP patients not only at presentation but once in a clinical remission. Evidence is emerging of the clinical effects of low ADAMTS13 activity in other disease areas outside of TTP, and here, we explore the wider impact of low ADAMTS13 activity on the vascular endothelium and the potential for recombinant ADAMTS13 therapy in other thrombotic disease states. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Von Willebrand factor (VWF) is a critical glycoprotein in hemostasis and is an important factor in diagnosing bleeding disorders. Albeit the analysis of VWF is often compromised by inconsistent methodologies and challenges quantifying multimeric size. Current VWF multimer analysis methods are costly, time‐consuming, and often inconsistent; thus, demanding skilled professionals. This study aimed to streamline and optimize the VWF multimer analysis technique, making it more efficient and reproducible, particularly for identifying or predicting mechanical circulatory support (MCS) induced bleeding disorders.Blood samples from healthy volunteers were exposed to high shear forces via a Medtronic HeartWare ventricular assist device. VWF multimers were analyzed using vertical‐gel agarose electrophoresis and Western blotting. Differences in VWF distribution were determined using densitometry, and two methods of densitometric analysis were compared: proprietary software against open‐source software.Using the developed method: (i) protocol duration was accelerated from three days (in classical methods) to ~ eight hours; (ii) the resolution of the high molecular weight (HMW) VWF multimers were substantially improved; and (iii) densitometric analysis tools were validated. Additionally, the densitometry analysis using two software types showed a strong correlation between results, with the proprietary software reporting slightly higher HMW VWF percentages.This methodology is recommended for affordable, accurate, and reproducible VWF multimer evaluations during MCS use and testing. Further research comparing this method with semi‐automated methods would provide additional insight and improve inter‐laboratory comparisons. [ABSTRACT FROM AUTHOR]

Yifei Zhu,1,&ast; Jiayi Gu,1,&ast; Yuxin Lu,1 Qianying Tao,1 Xinliang Cao,1 Yanqing Zhu,1 Mu-qing Yang,2 Xin Liang1 1Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People’s Republic of China; 2Department of Hepatobiliary Surgical Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Liang; Mu-qing Yang, Email xin.liang@ecust.edu.cn; andyymq@tongji.edu.cnPurpose: The crosstalk between hepatocellular carcinoma (HCC) cells and hepatic stellate cells (HSCs) is one of the important mechanisms of liver cancer metastasis. The relationship between liver cancer metastasis and glycolysis has been extensively studied recently. However, the role of von Willebrand factor (vWF) mediated glycolysis mechanism in liver cancer metastasis is currently unknown.Methods: Western blot was used to verify the expression of vWF in HCC cells. PAS staining, glycogen and L-lactate content assays were used to reflect cellular glycolysis levels. The ability of cell migration was explored by Wound-healing and Transwell assays. Besides, the effect of vWF on the progression of HCC in vivo was also studied using subcutaneous xenograft model.Results: vWF derived from HCC cells promoted tumor migration by mediating glycolysis. Besides, vWF participated in the crosstalk between HCC cells and HSCs. HCC cells activated HSCs through vWF-mediated TGFB1 expression and secretion, and activated HSCs upregulated vWF expression in HCC cells through IL-6 secretion feedback. Further, in vitro and in vivo experiments also confirmed the importance of the JAK1/vWF/TGFB1 axis in regulating HSCs-derived IL-6 mediated HCC migration and growth.Conclusion: In summary, this article demonstrated that IL-6 released from hepatic stellate cells enhanced glycolysis and migration ability of liver cancer cells by activating JAK1/vWF/TGFB1 axis which may also be a potential target for inhibiting liver cancer metastasis.Keywords: glycolysis, crosstalk, vWF, migration

Cardiovascular prosthetic devices, stents, prosthetic valves, heart-assist pumps, etc., operate in a wide regime of flows characterized by fluid dynamic flow structures, laminar and turbulent flows, unsteady flow patterns, vortices, and other flow disturbances. These flow disturbances cause shear stress, hemolysis, platelet activation, thrombosis, and other types of blood trauma, leading to neointimal hyperplasia, neoatherosclerosis, pannus overgrowth, etc. Couette-type blood-shearing devices are used to simulate and then clinically measure blood trauma, after which the results can be used to assist in the design of the cardiovascular prosthetic devices. However, previous designs for such blood-shearing devices do not cover the whole range of flow shear, Reynolds numbers, and Taylor numbers characteristic of all types of implanted cardiovascular prosthetic devices, limiting the general applicability of clinical data obtained by tests using different blood-shearing devices. This paper presents the key fluid dynamic parameters that must be met. Based on this, Couette device geometric parameters such as diameter, gap, flow rate, shear stress, and temperature are carefully selected to ensure that the device's Reynolds numbers, Taylor number, operating temperature, and shear stress in the gap fully represent the flow characteristics across the operating range of all types of cardiovascular prosthetic devices. The outcome is that the numerical data obtained from the presented device can be related to all such prosthetic devices and all flow conditions, making the results obtained with such shearing devices widely applicable across the field. Numerical simulations illustrate that the types of flow patterns generated in the blood-shearing device meet the above criteria. [ABSTRACT FROM AUTHOR]

To study the predictive value of injury severity score (ISS), shock index combined with serum multiligand proteoglycan-1 (Syndecan-1) and von Willebrand factor (VWF) at admission for traumatic coagulopathy disease (TIC) in patients with multiple trauma. 200 patients with multiple trauma who were treated in Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2019 to December 2022 were selected. Patients were divided into TIC group (61 cases) and non-TIC (NTIC) group (139 cases) according to whether TIC occurred. The ISS score, shock index, serum Syndecan-1 and VWF levels at admission were compared in two groups, the influencing factors of TIC in patients with multiple trauma were analyzed by univariate and multivariate Logistic regression, the predictive value of ISS score, shock index, serum Syndecan-1 and VWF on TIC in patients with multiple trauma were analyzed by receiver operating characteristic (ROC) curve. Among the 200 patients, a total of 61 patients with TIC occurred, with an incidence of 30.50%. The ISS score, shock index, Syndecan-1 and VWF levels in TIC group were higher than those in NTIC group (P<0.05). Multivariate Logistic regression analysis showed that, hypothermia, acidosis, Glasgow Coma Score (GCS) <6 points, complicated severe craniocerebral injury, increased ISS score at admission, increased shock index, increased serum Syndecan-1 and increased VWF were risk factors for TIC in patients with multiple trauma. ROC curve analysis showed that the combined application of ISS score, shock index, serum Syndecan-1 and VWF had the highest predictive value for TIC at admission, the area under the curve (AUC) was 0.849, the sensitivity was 0.918 and the specificity was 0.755, all of which were better than the individual prediction. The increase of ISS score, shock index, serum Syndecan-1 and VWF at admission are relate to the incidence of TIC in patients with multiple trauma. Hypothermia, acidosis, GCS<6 points, complicated severe craniocerebral injury, increase ISS score at admission, increase shock index are risk factors for TIC in patients with multiple trauma. ISS score, shock index combined with serum Syndecan-1 and VWF detection have high predictive value at admission for TIC in patients with multiple trauma. [ABSTRACT FROM AUTHOR]

This article provides guidelines for the laboratory diagnosis and monitoring of von Willebrand disease (VWD) and acquired von Willebrand syndrome (AVWS). It emphasizes the importance of accurate and standardized laboratory testing for reliable results. The article recommends specific tests, such as measuring factor VIII activity, VWF antigen, and VWF activity, for the initial investigation of VWD/AVWS. It also discusses the use of genetic testing to complement clinical and laboratory findings. The guidelines outline methodologies for genetic testing and stress the need for informed consent and accurate reporting of results. [Extracted from the article]

Objective: Non-cirrhotic intrahepatic portal hypertension (NCIPH), a portal microangiopathy affecting small portal vein radicles, is a disease of Indian sub-continent. NCIPH appears to be a complex disease with interactions between inherited and acquired factors, though the exact pathophysiological mechanism is unknown. We aimed at investigating the genetic variants that might contribute to susceptibility to NCIPH. Methods: In this case-control study, we analyzed genes associated with microangiopathy—VWF-ADAMTS13 (von Willebrand factor and its cleavase enzyme — a disintegrin and matrix metalloprotease with thrombospondin type-1 motifs member 13) and alternative complement system vitamin B12 metabolism and with familial NCIPH. Result: Eighty-four Indian patients with liver biopsy–proven NCIPH (cases) and 103 healthy controls (matched for residential region of India) were included in the study. Targeted next-generation sequencing (NGS) panel, comprising 11 genes of interest, was done on 54 cases. Genotyping of selected variants was performed in 84 cases and 103 healthy controls. We identified variants in MBL2, CD46 and VWF genes either associated or predisposing to NCIPH. We also identified a single case with a novel compound heterozygous mutation in MBL2 gene, possibly contributing to development of NCIPH. Conclusion: In this first of a kind comprehensive gene panel study, multiple variants of significance have been noted, especially in ADAMTS13-VWF and complement pathways in NCIPH patients in India. Functional significance of these variants needs to be further studied. [ABSTRACT FROM AUTHOR]

FLT1/VEGFR1 negatively regulates VEGF-A signaling and is required for proper vessel morphogenesis during vascular development and vessel homeostasis. Although a soluble isoform, sFLT1, is often mis-regulated in disease and aging, how sFLT1 is trafficked and secreted from endothelial cells is not well understood. Here we define requirements for constitutive sFLT1 trafficking and secretion in endothelial cells from the Golgi to the plasma membrane, and we show that sFLT1 secretion requires clathrin at or near the Golgi. Perturbations that affect sFLT1 trafficking blunted endothelial cell secretion and promoted intracellular mis-localization in cells and zebrafish embryos. siRNA-mediated depletion of specific trafficking components revealed requirements for RAB27A, VAMP3, and STX3 for post-Golgi vesicle trafficking and sFLT1 secretion, while STX6, ARF1, and AP1 were required at the Golgi. Live-imaging of temporally controlled sFLT1 release from the endoplasmic reticulum showed clathrin-dependent sFLT1 trafficking at the Golgi into secretory vesicles that then trafficked to the plasma membrane. Depletion of STX6 altered vessel sprouting in 3D, suggesting that endothelial cell sFLT1 secretion influences proper vessel sprouting. Thus, specific trafficking components provide a secretory path from the Golgi to the plasma membrane for sFLT1 in endothelial cells that utilizes a specialized clathrin-dependent intermediate, suggesting novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: von Willebrand disease (vWD), caused by mutations in the von Willebrand factor (vWF) coding gene, is a disease characterized by abnormal coagulation activity and a severe tendency for hemorrhage. Therefore, identifying mutations in vWF is important for diagnosing congenital vWD. Methods: We studied a 23-year-old male vWD patient and his parents. Clotting methods were used to determine activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen (FIB) levels, FVIII activity. Chromogenic substrate method was used to determine vWF antigen and activity. The platelet count was determined. Mutations were searched using whole-exome sequencing and certified by Sanger sequencing. Clinical data, including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen levels, FX activity, FX antigen levels, and the platelet count were collected. A mixing study was performed to eliminate the presence of coagulation factor inhibitors and lupus anticoagulants. Mutations were screened by using whole-exome sequencing (WES) and were verified by using Sanger sequencing. Results: The proband showed severely decreased vWF antigen, vWF activity, and FVIII activity. RIPA (RISTOCETIN-induced platelet aggregation) was 0%. Data from WES showed that the proband carried compound heterozygous variants vWF: NM_000552.5 (c.3213C>A p.Cys1071Ter) and vWF: NM_000552.5 (c.6598+2T>C). The proband's mother carried variant vWF: NM_000552.5 (c.3213C>A p.Cys1071Ter) while the proband's father carried variant vWF: NM_000552.5 (c.6598+2T>C). All laboratory test indexes of the proband's parents, including vWF antigen, vWF activity, and FVIII activity, were within the normal ranges. Conclusions: We identified a compound heterozygosis with two novel mutations in vWF (c.3213C>A, c.6598+2T >C) in a family pedigree, and our results demonstrate that the compound heterozygous mutations probably exacerbate vWD. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) was established as a treatment for severe cardiac or respiratory disease. Intra-device clot formation is a common risk. This is based on complex coagulation phenomena which are not yet sufficiently understood. The objective was the development and validation of a methodology to capture the key properties of clots deposed in membrane lungs (MLs), such as clot size, distribution, burden, and composition. One end-of-therapy PLS ML was examined. Clot detection was performed using multidetector computed tomography (MDCT), microcomputed tomography (μCT), and photography of fiber mats (fiber mat imaging, FMI). Histological staining was conducted for von Willebrand factor (vWF), platelets (CD42b, CD62P), fibrin, and nucleated cells (4′, 6-diamidino-2-phenylindole, DAPI). The three imaging methods showed similar clot distribution inside the ML. Independent of the imaging method, clot loading was detected predominantly in the inlet chamber of the ML. The μCT had the highest accuracy. However, it was more expensive and time consuming than MDCT or FMI. The MDCT detected the clots with low scanning time. Due to its lower resolution, it only showed clotted areas but not the exact shape of clot structures. FMI represented the simplest variant, requiring little effort and resources. FMI allowed clot localization and calculation of clot volume. Histological evaluation indicated omnipresent immunological deposits throughout the ML. Visually clot-free areas were covered with leukocytes and platelets forming platelet-leukocyte aggregates (PLAs). Cells were embedded in vWF cobwebs, while vWF fibers were negligible. In conclusion, the presented methodology allowed adequate clot identification and histological classification of possible thrombosis markers such as PLAs.

Abstract Background The incidence and prevalence of nonalcoholic fatty liver disease related hepatocellular carcinoma (NAFLD-HCC) are rapidly increasing worldwide. This study aimed to identify biomarker genes for prognostic prediction model of NAFLD-HCC hepatectomy by integrating text-mining, clinical follow-up information, transcriptomic data and experimental validation. Methods The tumor and adjacent normal liver samples collected from 13 NAFLD-HCC and 12 HBV-HCC patients were sequenced using RNA-Seq. A novel text-mining strategy, explainable gene ontology fingerprint approach, was utilized to screen NAFLD-HCC featured gene sets and cell types, and the results were validated through a series of lab experiments. A risk score calculated by the multivariate Cox regression model using discovered key genes was established and evaluated based on 47 patients’ follow-up information. Results Differentially expressed genes associated with NAFLD-HCC specific tumor microenvironment were screened, of which FABP4 and VWF were featured by previous reports. A risk prediction model consisting of FABP4, VWF, gender and TNM stage were then established based on 47 samples. The model showed that overall survival in the high-risk score group was lower compared with that in the low-risk score group (p = 0.0095). Conclusions This study provided the landscape of NAFLD-HCC transcriptome, and elucidated that our model could predict hepatectomy prognosis with high accuracy.

The present study was conducted to localize the immunoexpression of VEGF‐A (Vascular Endothelial Growth Factor) and von Willebrand factor (vWF) in corpora lutea of healthy buffaloes (24) collected from local slaughterhouses. CL collected were categorized into early (stage I, 1–5 days, n = 6), mid (stage II, 6–11 days, n = 6), late luteal phase (stage III, 12 to 16 days, n = 6) and regressing phase (stage IV, 17 to 20 days, n = 6). The percent positive immunostaining for VEGF‐A was significantly (p < 0.05) higher in mid‐luteal phase than the other three stages of CL. However, it was higher in early luteal phase as well indicated intense angiogenesis in both early and mid‐luteal phases. The number of capillary endothelium expressing vWF was significantly (p < 0.05) highest in mid‐luteal phase among all the phases. However, in late luteal phase, the percent area positive for VEGF‐A immunostaining was reduced but it was significantly (p < 0.05) higher than corpus albicans phase. Thus, in regressing phase or corpus albicans, it was lowest and reduced considerably. However, in late luteal phase, the number of capillaries with vWF immunoexpression reduced significantly (p < 0.05) but it was lowest in corpus albicans phase. Therefore, the immunotaining pattern for VEGF‐A and vWF concluded that there was a spositive linear correlation between the two, that is, as the VEGF‐A expression was increased, the number of vWF positive capillaries also increased and vice versa. The VEGF‐A expressed by the luteal parenchyma in different stages of development and regression of corpus luteum was thus observed to be involved in promoting the angiogenesis and luteal cell proliferation as supported by vWF expressed by endothelium of proliferating capillaries in buffalo corpus luteum throughout the estrous cycle. [ABSTRACT FROM AUTHOR]

Background: von Willebrand factor (VWF) has been widely recognized as a biomarker for endothelial cell activation in trauma and inflammation. Traumatic brain injury (TBI) is characterized by cerebral vascular injury and subsequent inflammation. The objective of this study was to investigate the correlation between VWF levels and clinical severity, as well as imaging abnormalities, in TBI patients. Additionally, the predictive value of VWF for patient outcomes was assessed. Methods: We conducted a prospective study to recruit acute TBI patients who were admitted to the emergency department within 24 h. Healthy individuals from the medical examination center were recruited as the control group. This study aimed to compare the accuracy of VWF in discriminating TBI severity and imaging abnormalities with the Glasgow Coma Scale (GCS) and Rotterdam computed tomography (CT) scores. We also analyzed the predictive value of these outcomes using the Glasgow Outcome Scale (GOS) and 6-month mortality. Results: The plasma concentration of VWF in TBI patients (84.7 ± 29.7 ng/ml) was significantly higher than in healthy individuals (40 ± 8.8 ng/ml). There was a negative correlation between VWF levels and GCS scores, as well as a positive correlation between VWF levels and Rotterdam CT scores. The area under the curve (AUC) for VWF in discriminating mild TBI was 0.76 (95% CI: 0.64, 0.88), and for predicting negative CT findings, it was 0.82 (95% CI: 0.72, 0.92). Meanwhile, the AUC of VWF in predicting mortality within 6 months was 0.70 (95% CI: 0.56, 0.84), and for a GOS score lower 4, it was 0.78 (95% CI: 0.67, 0.88). Combining VWF with either the GCS or Rotterdam CT score improved the prediction ability compared to using VWF alone. Conclusion: VWF levels were significantly elevated in patients with TBI compared with healthy individuals. Furthermore, VWF levels demonstrated a negative correlation with GCS scores and a positive correlation with Rotterdam CT scores. In terms of predicting mortality, VWF alone was not sufficient, but its predictive power was enhanced when combined with either the Rotterdam CT score or GCS. These findings suggest that VWF may serve as a potential biomarker for assessing the severity and prognosis of TBI patients. [ABSTRACT FROM AUTHOR]

ADAMTS13 is a plasma metalloprotease with the primary function of cleaving VWF to maintain hemostasis. Circulating ADAMTS13 is in the closed conformation until blood vessel injury triggers a VWF-dependant activation to the open active form of the protein. ADAMTS13 is a multi-domain protein with the domains broadly functioning to interact and cleave VWF or maintain global latency of ADAMTS13. Thrombotic Thrombocytopenic Purpura is a disease characterized by excessive thrombi formation in the microvasculature, diagnosis is made when ADAMTS13 activity is <10%. In the hereditary form, a variety of mutations are found throughout all domains of ADAMTS13, examples are given alongside details of each domain in this article. ADAMTS13 mutations can inhibit the binding and cleavage of VWF directly or indirectly through reduced secretion, leading to increased size of VWF multimers and platelet recruitment. Molecular characterization of ADAMTS13 may provide insight into the mechanisms of TTP to aid in both scientific and clinical research. [ABSTRACT FROM AUTHOR]

Background and aims: Endothelial dysfunction and portal hypertension (PH) are reflected by increased von Willebrand factor antigen (VWF-Ag) levels in advanced chronic liver disease (ACLD). This study investigated VWF release and cleavage and their association with PH and clinical outcomes. Methods: Levels of VWF-Ag, VWF-N (VWF-propeptide), and VWF-A (VWF processed by the main VWF-cleaving protease ADAMTS13) were assessed in 229 patients with clinically stable ACLD (hepatic venous pressure gradient [HVPG] ≥ 6 mmHg; absence of bacterial infections or acute decompensation) undergoing HVPG-measurement. Liver-healthy individuals served as controls (n = 24). Results: VWF-Ag and VWF-N were similarly accurate for the identification of clinically significant PH (CSPH; HVPG ≥ 10 mmHg) in compensated ACLD (AUROC: VWF-Ag 0.748; VWF-N 0.728). ADAMTS13 activity was similar between patients with ACLD and controls and did not correlate with PH and disease severity, whereas VWF cleavage decreased in patients with CSPH (i.e., VWF-Ag/-A-ratio increased). In vitro VWF activity strongly reflected VWF-Ag levels (Spearman's r = 0.874, p < 0.001), but decreased (vs. controls) in patients with CSPH when normalized to VWF-Ag levels (VWF-activity/-Ag-ratio). VWF-Act/-Ag ratio correlated negatively with ADAMTS13 activity (r =– 0.256, p < 0.001). ADAMTS13 activity was independently predictive for (i) portal vein thrombosis (PVT) and (ii) hepatic decompensation or liver-related death. Conclusions: VWF-Ag levels and its propeptide are similarly suitable surrogates of PH in patients with compensated ACLD. ADAMTS13-Act was not linked to disease and PH severity, however, when normalized to VWF-Ag, both VWF cleavage and VWF activity were decreased in patients with CSPH, as compared to liver-healthy individuals. Low ADAMTS13-Act was associated with presumably more procoagulant VWF and adverse outcomes. Clinical trial number: NCT03267615 [ABSTRACT FROM AUTHOR]

Background: The incidence and prevalence of nonalcoholic fatty liver disease related hepatocellular carcinoma (NAFLD-HCC) are rapidly increasing worldwide. This study aimed to identify biomarker genes for prognostic prediction model of NAFLD-HCC hepatectomy by integrating text-mining, clinical follow-up information, transcriptomic data and experimental validation. Methods: The tumor and adjacent normal liver samples collected from 13 NAFLD-HCC and 12 HBV-HCC patients were sequenced using RNA-Seq. A novel text-mining strategy, explainable gene ontology fingerprint approach, was utilized to screen NAFLD-HCC featured gene sets and cell types, and the results were validated through a series of lab experiments. A risk score calculated by the multivariate Cox regression model using discovered key genes was established and evaluated based on 47 patients' follow-up information. Results: Differentially expressed genes associated with NAFLD-HCC specific tumor microenvironment were screened, of which FABP4 and VWF were featured by previous reports. A risk prediction model consisting of FABP4, VWF, gender and TNM stage were then established based on 47 samples. The model showed that overall survival in the high-risk score group was lower compared with that in the low-risk score group (p = 0.0095). Conclusions: This study provided the landscape of NAFLD-HCC transcriptome, and elucidated that our model could predict hepatectomy prognosis with high accuracy. [ABSTRACT FROM AUTHOR]

A patent vascular access (VA) is a lifeline for hemodialysis (HD) patients. However, vascular access is prone to thrombosis, which, if left untreated, can lead to permanent VA loss and increased mortality. Neutrophil extracellular traps (NETs) are known to be involved in intravascular thrombosis. We evaluated the relationship between NETs and VA thrombosis and their impact on VA prognosis. A total of 189 patients with VA flow problems were enrolled. Among these, 93 patients underwent percutaneous transluminal angioplasty (PTA) for stenosis, and 96 patients underwent PTA with thrombectomy for thrombosis. Plasma nucleosome, myeloperoxidase-DNA complex, and von Willebrand factor (vWF) were measured as markers of circulating NETs and thrombosis risk, respectively. The primary outcome was permanent VA loss and the secondary outcome was recurrent thrombotic occlusion within 6 months. In addition, the presence of NETs in thrombi was evaluated by histopathological analysis. Circulating nucleosome levels were closely associated with plasma vWF levels (r = 0.172, p = 0.025), and both were higher in thrombectomy cases than in PTA alone cases (nucleosome; 0.83 ± 0.70 vs. 0.35 ± 0.26, p < 0.001, vWF: 9.0 ± 7.6 vs. 7.3 ± 6.2, p = 0.038). The highest quartile of nucleosomes (Q4) was associated with an 18-fold increased rate of access thrombotic occlusion (p < 0.001). In addition, multivariate analysis showed that the rates of permanent access loss (HR 2.77, 95 % CI 1.35–5.77) and recurrent thrombosis (HR 2.35, 95 % CI 1.22–4.54) were much higher in patients with the Q4 nucleosome group than in those with Q1–3. In addition, higher neutrophil infiltration and NET expression in thrombi were also associated with poor VA prognosis. Higher levels of circulating NETs and the amount of NET expression in thrombi may be associated with VA thrombosis and poor VA outcomes. • Circulating nucleosome and plasma vWF levels are significantly higher in patients with thrombotic VA occlusion compared to those without. • Higher levels of NETs are associated with significantly increased rates of permanent VA loss and recurrent thrombosis. • Tissue NET expression is also associated with poor VA outcomes. [ABSTRACT FROM AUTHOR]

The von Willebrand factor (vWF) is best known for its role in the hemostatic pathway, aiding platelet adhesion and aggregation, as well as circulating along with coagulation factor VIII, prolonging its half-life. However, vWF is more than a hemostatic protein and is a marker of endothelial dysfunction in patients with cirrhosis. The levels of vWF increase progressively as cirrhosis progresses. Despite its qualitative defects, it can support and carry out its hemostatic role and contribute to a pro-coagulant disbalance. Moreover, it has been shown to be a good noninvasive marker for predicting clinically significant portal hypertension (CSPH). The vWF has been shown to predict decompensation and mortality among cirrhosis patients independently of the stage of liver disease and severity of portal hypertension. Increased vWF levels in the setting of endothelial injury predict bacterial translocation and systemic inflammation. The vWF-to-thrombocyte ratio (VITRO) score adds to the diagnostic ability of vWF alone in detecting CSPH non-invasively. Not only have vWF levels been shown to help predict the risk of hepatocellular carcinoma (HCC) among cirrhosis patients, but they also predict the risk of complications post-resection for HCC and response to systemic therapies. vWF-induced portal microthrombi have been purported to contribute to the pathogenesis of acute liver failure progression as well as non-cirrhotic portal hypertension. The prospect of modulation of vWF levels using drugs such as non-selective beta-blockers, statins, anticoagulants, and non-absorbable antibiotics and its use as a predictive biomarker for the response to these drugs needs to be explored. [ABSTRACT FROM AUTHOR]

Cardiovascular prosthetic devices, stents, prosthetic valves, heart-assist pumps, etc., operate in a wide regime of flows characterized by fluid dynamic flow structures, laminar and turbulent flows, unsteady flow patterns, vortices, and other flow disturbances. These flow disturbances cause shear stress, hemolysis, platelet activation, thrombosis, and other types of blood trauma, leading to neointimal hyperplasia, neoatherosclerosis, pannus overgrowth, etc. Couette-type blood-shearing devices are used to simulate and then clinically measure blood trauma, after which the results can be used to assist in the design of the cardiovascular prosthetic devices. However, previous designs for such blood-shearing devices do not cover the whole range of flow shear, Reynolds numbers, and Taylor numbers characteristic of all types of implanted cardiovascular prosthetic devices, limiting the general applicability of clinical data obtained by tests using different blood-shearing devices. This paper presents the key fluid dynamic parameters that must be met. Based on this, Couette device geometric parameters such as diameter, gap, flow rate, shear stress, and temperature are carefully selected to ensure that the device’s Reynolds numbers, Taylor number, operating temperature, and shear stress in the gap fully represent the flow characteristics across the operating range of all types of cardiovascular prosthetic devices. The outcome is that the numerical data obtained from the presented device can be related to all such prosthetic devices and all flow conditions, making the results obtained with such shearing devices widely applicable across the field. Numerical simulations illustrate that the types of flow patterns generated in the blood-shearing device meet the above criteria.

Objective: To determine and compare plasma thrombomodulin, von Willebrand factor and von Willebrand factor-cleaving protease levels between pre-eclamptic and healthy pregnant females. Method: The cross-sectional, comparative study was conducted at the Department of Haematology, University of Health Sciences, Lahore, Pakistan, from November 2019 to December 2020, and comprised pregnant females who were divided into healthy pregnant group A and pre-eclamptic group B. Plasma thrombomodulin and von Willebrand factor-cleaving protease levels were determined by using commercially available enzyme-linked immunosorbent assay kit, and von Willebrand factor level was determined by using immuno-turbidimetric assay kit. Data was analysed using SPSS 25. Results: Of the 88 participants, there were 44(50%) females with mean age 25.5±6 years in group A and 44(50%) in group B with mean age 26±5 years. Median thrombomodulin level in group B was significantly higher than group A (p=0.003). Median von Willebrand factor-cleaving protease levels were lower in group B compared to group A (p=0.838). A significant difference in von Willebrand factor level was observed between the groups (p=0.038). Conclusion: Females with pre-eclampsia had significantly higher plasma levels of von Willebrand factor and thrombomodulin than healthy pregnant subjects. Key Words: Thrombomodulin, vWF, ADAMTS13 protein, Pre-eclampsia.

Atherosclerosis is an inflammatory disease of the vessel wall, with cholesterol crystal (CC) deposition being a hallmark of the disease. As evidence for a cross-talk between complement activation and hemostasis on CC surfaces has been limited to in vitro data, the aim of this study was to demonstrate the presence of C1q-vWF complexes in human atherosclerosis ex vivo. We used immunofluorescence staining and a proximity ligation assay (PLA, Duolink®) to examine the presence, localization, and co-localization of C1q and vWF in frozen sections of human carotid arteries with atherosclerosis or without atherosclerotic changes as well as material from thrombendarteriectomy. We observed significantly higher levels of C1q and vWF in healthy tissue compared to diseased material and greater co-localization in the PLA in healthy samples than in diseased samples. In diseased samples, fluorescence signals were highest in locations encompassing atheroma and foam cells. While there was overall reduced signal in areas with CCs, the staining was spotty, and there was evidence of co-localization on individual CCs. Thus, we demonstrate the presence of C1q-vWF complexes in human carotid arteries ex vivo, which was most abundant in healthy endothelial and subendothelial space and reduced in diseased tissue. C1q-vWF interaction can also be demonstrated on the CC surface.

Purpose: Diabetic retinopathy (DR) is a major preventable health complication of type 2 diabetes (T2DM). Hyperglycemia represents the main mechanism in the pathogenesis of DR leading eventually to endothelial dysfunction. vWF is a marker of endothelial dysfunction, but its relation to DR is not yet well-established. Methods: The present study included 60 patients with T2DM divided into three equal groups according to the presence and the stage of retinopathy. Each patient was subjected to full history taking, physical examination including fundus examination, and laboratory investigations including glycemic and lipid profile, urinary albumin to creatinine ratio (UACR), and plasma vWF level. Results: Plasma vWF was significantly higher in patients with DR than in patients without retinopathy. vWF was positively correlated to age, HbA1c, diabetes duration, and UACR in DR groups and the total sample. Univariate regression analysis revealed that HbA1c, vWF, BMI, diabetes duration, and UACR were independent risk factors for DR, while multivariate regression analysis showed none of them to be an independent risk factor for DR. A vWF cut-off value of > 180 could differentiate patients with DR from patients without DR with a sensitivity of 97.5%, specificity of 75%, and AUC 0.937*. Conclusions: vWF level is higher in patients with DR reflecting the role of endothelial dysfunction in the development of DR. Moreover, it is one of the risk factors affecting DR in univariate but not in multivariate analysis. A cut-off value of vWF level was set to differentiate between patients with and without DR. [ABSTRACT FROM AUTHOR]

The article focuses on the role of von Willebrand factor (VWF) beyond its known function in blood clotting, delving into its regulatory impact on angiogenesis. It explores how individuals with von Willebrand syndrome (VWS), lacking VWF, can exhibit angiodysplasias. Highlighting the VWF's complexity, the article examines its role in angiogenic processes, explaining how reduced VWF expression can amplify endothelial cell proliferation and migration.

Whole-exome sequencing (WES) in families with an unexplained tendency for venous thromboembolism (VTE) may favor detection of low-frequency variants in genes with known contribution to hemostasis or associated with VTE-related phenotypes. WES analysis in six family members, three of whom affected by documented VTE, filtered for MAF < 0.04 in 192 candidate genes, revealed 22 heterozygous (16 missense and six synonymous) variants in patients. Functional prediction by multi-component bioinformatics tools, implemented by a database/literature search, including ClinVar annotation and QTL analysis, prioritized 12 missense variants, three of which (CRP Leu61Pro, F2 Asn514Lys and NQO1 Arg139Trp) were present in all patients, and the frequent functional variants FGB Arg478Lys and IL1A Ala114Ser. Combinations of prioritized variants in each patient were used to infer functional protein interactions. Different interaction patterns, supported by high-quality evidence, included eight proteins intertwined in the "acute phase" (CRP, F2, SERPINA1 and IL1A) and/or in the "fibrinogen complex" (CRP, F2, PLAT, THBS1, VWF and FGB) significantly enriched terms. In a wide group of candidate genes, this approach highlighted six low-frequency variants (CRP Leu61Pro, F2 Asn514Lys, SERPINA1 Arg63Cys, THBS1 Asp901Glu, VWF Arg1399His and PLAT Arg164Trp), five of which were top ranked for predicted deleteriousness, which in different combinations may contribute to disease susceptibility in members of this family. [ABSTRACT FROM AUTHOR]

Mechanisms underlying vascular endothelial susceptibility to infection by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) are not fully understood. Emerging evidence indicates that patients lacking von Willebrand factor (vWF), an endothelial hallmark, are less severely affected by SARS‐CoV‐2 infection, yet the precise role of endothelial vWF in modulating coronavirus entry into endothelial cells is unknown. In the present study, we demonstrated that effective gene silencing by short interfering RNA (siRNA) for vWF expression in resting human umbilical vein endothelial cells (HUVECs) significantly reduced by 56% the cellular levels of SARS‐CoV‐2 genomic RNA. Similar reduction in intracellular SARS‐CoV‐2 genomic RNA levels was observed in non‐activated HUVECs treated with siRNA targeting angiotensin‐converting enzyme 2 (ACE2), the cellular gateway to coronavirus. By integrating quantitative information from real‐time PCR and high‐resolution confocal imaging, we demonstrated that ACE2 gene expression and its plasma membrane localization in HUVECs were both markedly reduced after treatment with siRNA anti‐vWF or anti‐ACE2. Conversely, siRNA anti‐ACE2 did not reduce endothelial vWF gene expression and protein levels. Finally, SARS‐CoV‐2 infection of viable HUVECs was enhanced by overexpression of vWF, which increased ACE2 levels. Of note, we found a similar increase in interferon‐β mRNA levels following transfection with untargeted, anti‐vWF or anti‐ACE2 siRNA and pcDNA3.1‐WT‐VWF. We envision that siRNA targeting endothelial vWF will protect against productive endothelial infection by SARS‐CoV‐2 through downregulation of ACE2 expression and might serve as a novel tool to induce disease resistance by modulating the regulatory role of vWF on ACE2 expression. [ABSTRACT FROM AUTHOR]

Background and Aim: Monocytes and macrophages play a crucial role in the pathogenesis of acute liver failure (ALF). We aimed to study reticuloendothelial activation and its correlation with disease severity in commonly encountered yellow phosphorus (rodenticide)‐induced hepatotoxicity patients. We also studied peripheral monocyte phenotype in a subset of patients. Methods: Reticuloendothelial activation markers were analyzed and correlated with disease severity score in a prospectively collected database of yellow phosphorus‐related hepatoxicity patients between 2018 and 2021. In a prospective cohort of these patients and age‐matched healthy controls, peripheral blood monocyte phenotyping was performed. Results: Reticuloendothelial activation markers were analyzed in 67 patients [Age: 23(12–64) years; median (range), men: 25, acute liver injury (ALI): 38, ALF: 29, model for end‐stage liver disease (MELD) score: 28 (7–40)] of yellow phosphorus‐induced hepatotoxicity. Serum ferritin (927; 10.3–34 807 ng/mL), sCD163 (4.59; 0.11–12.7 μg/mL), sCD25 (3050; 5.6–17 300 pg/mL) and plasma von Willebrand factor (423.5, 103–1106 IU/dL) were increased and showed significant correlation with liver disease severity assessed by MELD score (ρ = 0.29, ρ = 0.6, ρ = 0.56 and ρ = 0.46 respectively). Phenotyping and serum immune markers were performed in seven patients (M: 4; age: 27, 15–37 years; median, range; MELD score: 36, 21–40) and compared with eight healthy controls. Increase in classical monocytes and decrease in patrolling and intermediate monocyte subsets were observed in ALF cohort. HLA‐DRlowCD163hi (immune exhaustion), CD64hi (immune complex‐mediated response), and CCR2hi (liver homing) monocyte phenotype was noted. Conclusion: Altered peripheral monocyte phenotype with enhanced liver homing and macrophage activation, suggests important role of innate immune activation, and provides a potential therapeutic target, in yellow phosphorus‐induced hepatotoxicity. [ABSTRACT FROM AUTHOR]

الملخص: أهداف البحث: لتقييم العرض السريري والنتائج المعملية بين المرضى الذين تم تشخيص إصابتهم بمرض فون ويلبراند في وحدة الرعاية الثالثة في السعودية. طريقة البحث: تضمنت هذه الدراسة بأثر رجعي 189 مريضًا يعانون من مرض فون ويلبراند تمت متابعتهم في وحدتنا على مدار أربع سنوات ، وتم جمع البيانات السريرية والمخبرية وتحليلها باستخدام برنامج الحزمة الإحصائية للعلوم الاجتماعية. النتائج: كان متوسط عمر مجموعة الدراسة 30 عامًا (المدى 11 شهرًا - 56 عامًا). كان هناك غلبة للإناث بنسبة 32.30٪ ذكور و 66.70٪ إناث. معظم المرضى (48٪) تعرضوا لأكثر من نوع واحد من النزيف بناءً على التوطين وتم تحديدهم على أنه نزيف من مواقع مختلفة ، معظمها من المفاصل والعضلات (23.90٪) ، يليها الغشاء المخاطي (14.60٪) ، والجهاز البولي التناسلي (7.70٪) ، كدمات (2.80٪) ، ونزيف معدي معوي (2.80٪). 48٪ من الأشخاص الذين يعانون من أكثر من نوع واحد من النزيف ، 105 (58.01٪) لديهم النوع الأول ، 29 (16.02٪) لديهم النوع الثاني ، و 47 (25.96٪) لديهم النوع الثالث. كان متوسط قيمة الهيموجلوبين 116 ± 25.60 جم / لتر ؛ كان الفيريتين 75.80 ± 166.80 ميكروغرام / لتر (متوسط 28.5) ؛ كان مستضد فون ويلبراند 0.40 ± 0.27 وحدة دولية / مل ، وفون ويلبراند: كان العامل المساعد ريستوسيتين 0.32 ± 0.20 وحدة دولية / ديسيلتر 49.20٪ من الأشخاص أظهروا لفترات طويلة ، وأظهر 50.80٪ وقت الثرومبوبلاستين الجزئي الطبيعي. أظهر التحليل المقارن لفصيلة الدم من النوع أو مع النوع غير أو أن فصيلة الدم مرتبطة بشكل كبير مع العامل الثامن (قيمة ب = 0.013) ، عامل فون ويلبراند: العامل المساعد للريستوسيتين (قيمة ب = 0.004 ) ، وعامل فون ويلبراند: المستضد (قيمة ب = 0.019) الاستنتاجات: كان نزيف المفاصل والعضلات أكثر العروض السريرية شيوعا في مجموعتنا. على الرغم من أن مرض فون ويلبراند من النوع الأول كان الأكثر انتشارا في مجموعتنا ، فقد لاحظنا انتشارا أعلى نسبيا من النوع الثالث والذي قد يكون بسبب الاختلافات العرقية أو تحيز الإحالة. ومستضد عامل فون ويلبراند ، مع وجود فرق أكثر وضوحا لعامل مساعد ريستوسيتين. Abstract: Objectives: This study was aimed at assessing the clinical presentations and laboratory findings among patients diagnosed with vWD at a Saudi tertiary care unit. Methods: This retrospective study included 189 patients with vWD who were followed up in our unit over 4 years. Clinical and laboratory data were collected and analyzed in SPSS. Results: The median age of the study cohort was 30 years (range 11 months–56 years). The cohort had a female preponderance, with 32.30% males and 66.70% females. Bleeding from different sites was observed, mostly from the joints and muscles (23.90%), followed by the mucus membranes (14.60%), genitourinary areas (7.70%), ecchymoses (2.80%), and gastrointestinal areas (2.80%). A total of 48% of participants presented with more than one type of bleeding. A total of 105 (58.01%) participants had type 1; 29 (16.02%) had type 2; and 47 (25.96%) had type 3 vWD. Blood tests indicated the following mean value: hemoglobin, 116 ± 25.60 gm/L; ferritin, 75.80 ± 166.80 μg/L (median 28.5); vWAg, 0.40 ± 0.27IU/ml; and vWD:RCo, 0.32 ± 0.20IU/dL. The partial thromboplastin time was prolonged in 49.20% and normal in 50.80% of participants. Platelet function analysis values were prolonged in 92.90% and normal in 7.10% of participants. Comparative analysis of the O-type and non-O blood type showed that blood type O was significantly correlated with factor VIII (p-value = 0.013), vWF:RCo (p-value = 0.004), and vWF:Ag (p-value = 0.019). Conclusion: Joint and muscle bleeds were the most common clinical presentations in our cohort. Although type 1 vWD was most prevalent in our cohort, we observed a comparatively higher prevalence of type 3, possibly because of ethnic differences or referral bias. We found a significant difference between O and non-O blood type regarding FVIII and vWF:Ag, and observed a more pronounced difference for vWD activity measuresd by vWF:RCo with blood type O being the systematic factor.

Introduction. Neutrophil extracellular traps (NETs) and von Willebrand factor (vWF) are integral players in thrombosis and inflammation in cancer patients. It has been increasingly evident that an active interplay exists between NETs and vWF. Some studies suggest that NETs cause decrease in ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) activity, being an arm in the pathogenesis of both thrombotic microangiopathies (TMA) and other thrombotic complications during oncological process.Aim: to assess a crosstalk between NETs, vWF, and ADAMTS-13 in uterine, ovarian, breast malignant neoplasms as well as cervical canal adenocarcinoma.Materials and Methods. From September 2019 to July 2022, a prospective controlled interventional non-randomized study was carried out with 106 patients hospitalized for planned surgical treatment aged 30 to 72 years. The main group included 73 patients with malignant neoplasms of the female genital organs and mammary glands, stage I–III: uterine cancer (subgroup 1; n = 18), ovarian cancer (subgroup 2; n = 21), cervical cancer – adenocarcinoma of cervical canal (subgroup 3; n = 9) and breast cancer (subgroup 4; n = 25). The control group consisted of 33 women with female genital tract and breast benign neoplasms. In all patients, serum levels of vWF, citrullinated histone H3 (citH3), MPO (myeloperoxidase) antigen, ADAMTS-13 activity, ADAMTS-13 antigen, and D-dimer were evaluated.Results. The study revealed significant differences in the concentration of NETosis markers between the main and control groups. Patients with uterine cancer and adenocarcinoma of the cervical canal peaked at NETosis markers. At the same time, there were significant differences in citH3 concentration among patients with «early» (stage I) and «not early» (stage II–III) disease forms. While assessing level of von Willebrand factor (vWF:Ag), antigen (ADAMTS-13:Ag), and ADAMTS-13 activity (ADAMTS-13:Ac), significant differences were found between the main and control groups (p < 0.0001). The vWF in the main groups was sharply increasedwhereas ADAMTS-13 antigen concentration and activity were decreased. A сorrelation analysis among oncological patients in main group showed that while citH3 level increased, it was also paralleled with rise in vWF:Ag (ρ = 0.80; p < 0.01) and MPO:Ag (ρ = 0.87; p < 0.01); increase in MPO:Ag level was coupled to rise in vWF:Ag (ρ = 0.70; p< 0.01), but increase in vWF:Ag occurred along with decline in ADAMTS-13:Ac (ρ = –0.43; p < 0.01) and ADAMTS-13:Ag (ρ= –0.42; p < 0.01).Conclusion. The interplay between NET, vWF, and ADAMTS-13 leads to a vicious circle, reduces ADAMTS-13 activity by increasing serum vWF concentration, which positively correlates with severity and mortality in TMA, acute ischemic infarction, and COVID-19. Targeting the NETs-vWF axis may pave the way for therapeutic strategies for immunothrombosis in various diseases, including cancer.

The von Willebrand factor (vWF) is a multimeric plasma glycoprotein, which quantification has important prognostic value. The current literature review demonstrates a relationship between the disease severity and vWF level. For example, von Willebrand disease is characterized by a quantitative/qualitative genetic vWF deficiency resulting in potentially developed massive bleeding, which knowledge can prevent development of formidable complications. We should also not forget about an opportunity of developing acquired Willebrand syndrome most often occurring in response to autoimmune diseases. A marked vWF increase during pregnancy may evidence about developing preeclampsia, whereas in newborns exposed to additional risk factors, it can lead to thrombosis. In cancer patients, a substantially elevated vWF level correlates with low survival, especially in those with ovarian cancer, glioblastomas, esophageal and lung cancer. The emergence of a novel coronavirus infection COVID-19 allowed us to take a fresh look at prognostic value of vWF, because numerous studies show that increased blood plasma vWF:Ag is associated with more adverse outcome in patients with COVID-19. Here, we demonstrate an importance of determining vWF level, because early diagnostics and treatment can improve the outcomes of all such patients.

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Coronavirus disease COVID-19, which is caused by severe acute respiratory syndrome coronavirus SARS-CoV-2, has become a worldwide pandemic in recent years. In addition to being a respiratory disease, COVID-19 is a 'vascular disease' since it causes a leaky vascular barrier and increases blood clotting by elevating von Willebrand factor (vWF) levels in the blood. In this study, we analyzed in vitro how the SARS-CoV-2 spike protein S1 induces endothelial cell (EC) permeability and its vWF secretion, and the underlying molecular mechanism for it. We showed that the SARS-CoV-2 spike protein S1 receptor-binding domain (RBD) is sufficient to induce endothelial permeability and vWF-secretion through the angiotensin-converting enzyme (ACE)2 in an ADP-ribosylation factor (ARF)6 activation-dependent manner. However, the mutants, including those in South African and South Californian variants of SARS-CoV-2, in the spike protein did not affect its induced EC permeability and vWF secretion. In addition, we have identified a signaling cascade downstream of ACE2 for the SARS-CoV-2 spike protein-induced EC permeability and its vWF secretion by using pharmacological inhibitors. The knowledge gained from this study could be useful in developing novel drugs or repurposing existing drugs for treating infections of SARS-CoV-2, particularly those strains that respond poorly to the existing vaccines. [ABSTRACT FROM AUTHOR]

Introduction. Currently, endothelial dysfunction caused by inflammation and immunothrombosisis considered as one of the crucial mechanisms in developing the SARS-CoV-2 virus-mediated coronavirus disease 2019 (COVID-19). A mass endothelial damage followed by release of untypical large quantity of von Willebrand factor (vWF) multimers and subsequent consumption of metalloproteinase ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) is described during severe COVID-19. The activation of innate immune cells including neutrophils results in formation of neutrophil extracellular traps (NETs) and myeloperoxidase (MPO) release that, in turn, contributes to spread of inflammation and microvascular thrombosis.Aim: to evaluate a pathogenetic role and predictive significance for serum markers of inflammation, endothelial dysfunction and hemostatis activation such as vWF, ADAMTS-13 and MPO for in-hospital mortality in severe COVID-19 patients requiring mechanical lung ventilation.Materials and Methods. There was performed a single-center observational study with 129 severe COVID-19 patients on mechanical lung ventilation at the intensive care unit, by assessing serum in all subjects vWF, ADAMTS-13 as well as in 79 patients MPO level along with other potential predictors for in-hospital mortality.Results. A multivariate analysis revealed that increased serum level for vWF antigen (vWF:Ag) and MPO antigen (MPO:Ag) were significantly and independently related to high mortality probability: vWF:Ag (IU/ml) – adjusted odds ratio (OR) = 3.360; 95 % confidence interval (95 % Cl) = 1.562–7,228 (р = 0,0019); MPO:Ag (ng/ml) – adjusted OR = 1.062; 95 % = 1.024–1.101 (p = 0.0011). Such data allowed to obtained a simplified mortality score for categorizing patients as those having a higher or lower score compared with the median score level: a high score was associated with lower cumulative survival rate (p < 0.0001), with 50 % of the cases linked to lethal outcome on day 13 post-hospital admission.Conclusion. Severe COVID-19 patients requiring mechanical lung ventilation were found to have elevated level of serum MPO activity and vWF correlating with poor survival.

Background: The ABO blood antigens may influence the levels of vWF: Ag and put individuals at risk of coagulopathies. This study assessed the plasma vWF: Ag and its relation with ABO blood antigens among healthy adults in northern Ghana. Methods: This cross-sectional study recruited 84 blood donors, aged 18–50 years, at Tamale Teaching Hospital. Blood groups were determined using the standard tube method, and a complete blood count was measured with an automated haematology analyzer. Sandwich ELISA was used to assess plasma vWF: Ag levels. The data obtained were analyzed using SPSS version 22. Results: The frequencies of O, A, B, and AB blood groups were 34 (40.5%), 25 (29.8%), 20 (23.8%), and 5 (6.0%), respectively. vWF: Ag levels were higher among the non-O than group O individuals (p = 0.008). Plasma vWF: Ag levels were lower in group O compared to AB (p = 0.015) and A (p = 0.013) individuals. Males had higher vWF: Ag levels than females (p = 0.002). A moderately positive correlation was observed between age and vWF levels (r = 0.497, pA>B>AB. Plasma vWF: Ag levels were higher in non-group O compared with group O individuals. Males had higher vWF: Ag levels, and a positive correlation between age and vWF: Ag was observed. Again, blood group O participants had lower neutrophil counts, but higher RDW-SD. The relationship between ABO blood phenotypes and plasma vWF: Ag should be considered in clinical practice. The establishment of separate reference intervals of vWF: Ag for the various phenotypes of ABO is recommended. Also, the study recommends further multicenter studies to assess the link between ABO phenotypes and all the endothelial cell parameters. Doi: 10.28991/SciMedJ-2022-04-02-02 Full Text: PDF

Objective During pregnancy, almost all body systems undergo physiological changes, but changes in the immune system and the hemostasis system, inflammation play a special role in the adaptation of pregnancy from its early stages. From the point of view of the functioning of the immune system, pregnancy is a unique condition during which the mother's body must, on the one hand, provide protection from pathogens, and on the other, show tolerance to fetal antigens. SARS-CoV-2 infection has selective effects on both the immune system and the hemostasis system, therefore pregnant women are at high risk of complications associated with SARS-CoV-2 and its effects on the mother and fetus. Therefore, the purpose of our study was to determine the relationship between disorders of the hemostatic system and immunity after suffering from COVID-19 during pregnancy. Methods The study included 90 pregnant women and their newborn children, who were divided into two groups, the first 45 women with COVID-19 during pregnancy and a control group of 45 healthy pregnant women. In all pregnant women, the levels of fibrinogen, von Willebrand factor (vWF), ADAMTS-13, platelet aggregation, concentration of the activation marker NETs (myeloperoxidase MPO), cytokines, chemokines, cell markers, and functional activity of T-reg cells were evaluated in the peripheral blood, as well as in the umbilical cord blood of their unborn. Results In group I, hyperfibrinogenemia (p<0.001), high concentrations of vWF antigen (p<0.001), disorders in the ADAMTS-13/vWF axis (p=0.001) (fig 1) were detected in pregnant women, platelet aggregation with aggregation stimulators was increased: ADP (p<0.001), ristomycin (p<0.001), collagen (p<0.001), adrenaline (p<0.001), high MPO levels (p=0.046). High levels of cytokines and chemokines (IL 1a (p=0.018), IL 6 (p=0.032), IL-10 (p=0.003), MIP-1 (p<0.001), TNF a (p<0.001), CXCL10 (p<0.001)), MPO (p<0.001), increased expression of CD80 (p<0.001) and CD86 (p<0.001) on dendritic cells, decreased functional activity of T-reg (p<0.001) in the umbilical cord blood of group I newborns compared with the control group (Table 1). Conclusion COVID-19 causes systemic inflammatory response syndrome in both mother and fetus. In the mother, we see such changes as hyperfibrinogenemia, high concentrations of D-dimer, von Willebrand factor, a violation in the ADAMTS-13/vWF axis, platelet hyperactivation. Despite the normalization of immunological parameters and cytokine profile in mothers, by the time of delivery, the immune system is dysregulated in newborns with the development of inflammatory status and activation of the immune system and a high risk of severe systemic inflammatory response syndrome. [ABSTRACT FROM AUTHOR]

Severe coronavirus disease-19 (COVID-19) has been associated with fibrin-mediated hypercoagulability and thromboembolic complications. To evaluate potential biomarkers of coagulopathy and disease severity in COVID-19, we measured plasma levels of eight biomarkers potentially associated with coagulation, fibrinolysis, and platelet function in 43 controls and 63 COVID-19 patients, including 47 patients admitted to the intensive care unit (ICU) and 16 non-ICU patients. COVID-19 patients showed significantly elevated levels of fibrinogen, tissue plasminogen activator (t-PA), and its inhibitor plasminogen activation inhibitor 1 (PAI-1), as well as ST2 (the receptor for interleukin-33) and von Willebrand factor (vWF) compared to the control group. We found that higher levels of t-PA, ST2, and vWF at the time of admission were associated with lower survival rates, and that thrombotic events were more frequent in patients with initial higher levels of vWF. These results support a predictive role of specific biomarkers such as t-PA and vWF in the pathophysiology of COVID-19. The data provide support for the case that hypercoagulability in COVID-19 is fibrin-mediated, but also highlights the important role that vWF may play in the genesis of thromboses in the pathophysiology of COVID-19. Interventions designed to enhance fibrinolysis might prove to be useful adjuncts in the treatment of coagulopathy in a subset of COVID-19 patients. [ABSTRACT FROM AUTHOR]

Objective: Extracellular histones are known mediators of platelet activation, inflammation, and thrombosis. Von Willebrand Factor (vWF) and Toll‐like receptor 4 (TLR4) have been implicated in pro‐inflammatory and prothrombotic histone responses. The objective of this study was to assess the role of vWF and TLR4 on histone‐induced platelet adhesion in vivo. Methods: Intravital microscopy of the mouse cremaster microcirculation, in the presence of extracellular histones or saline control, was conducted in wild‐type, vWF‐deficient, and TLR4‐deficient mice to assess histone‐mediated platelet adhesion. Platelet counts following extracellular histone exposure were conducted. Platelets were isolated from vWF‐deficient mice and littermates to assess the role of vWF on histone‐induced platelet aggregation. Results: Histones promoted platelet adhesion to cremaster venules in vivo in wild‐type animals, as well as in TLR4‐deficient mice to a comparable degree. Histones did not lead to increased platelet adhesion in vWF‐deficient mice, in contrast to littermate controls. In all genotypes, histones resulted in thrombocytopenia. Histone‐induced platelet aggregation ex vivo was similar in vWF‐deficient mice and littermate controls. Conclusions: Histone‐induced platelet adhesion to microvessels in vivo is vWF‐dependent and TLR4‐independent. Platelet‐derived vWF was not necessary for histone‐induced platelet aggregation ex vivo. These data are consistent with the notion that endothelial vWF, rather than platelet vWF, mediates histone‐induced platelet adhesion in vivo. [ABSTRACT FROM AUTHOR]

Shiga toxin (Stx) can activate inflammatory signaling, leading to vascular dysfunction and promotion of a pro-thrombotic tissue microenvironment. Stx can trigger the development of the enterohemorrhagic (childhood) hemolytic uremic syndrome (eHUS), a triad of thrombocytopenia, hemolytic anemia, and acute kidney injury, often requiring dialysis. Additional features may include damage to other organs, including the gastrointestinal tract, pancreas, brain and cardiovascular system; death occurs in 2–5 %. eHUS is a thrombotic microangiopathy; thus, endothelial cell (EC) injury and platelet fibrin thrombus formation in glomerular arterioles and in the arterioles of other affected organs are likely. To elucidate mechanisms of this microangiopathy, we examined in human ECs the regulation of the platelet adhesion proteins P-selectin and von Willebrand factor (VWF), along with the downregulation of erythroblast-transformation-specific transcription factor (ERG) a key regulator of angiogenesis and megakaryocyte development. VWF, P-selectin, and ERG levels were determined using immunofluorescence and Western blot in human umbilical endothelial cells (HUVECs). HUVECs were treated with tumor necrosis factor-alpha (TNF-α), Stx-1 or both, versus normal controls. Capillary morphogenesis on Matrigel was performed using HUVECs treated, for 22 h with TNF-α, Stx-1, or both, or treated 4 h with Stx-1 alone or in combination with TNF-α for 22 h. Stx-1 significantly reduced ERG and VWF expression on HUVECs, but upregulated P-selectin expression. ERG levels decreased with Stx-1 alone or in combination with TNF-α, in the nuclear, perinuclear and cytoplasmatic regions. Stx-1 reduced capillary morphogenesis, while Stx-1-TNF-α combined treatment reduced capillary morphogenesis still further. In the presence of Stx-1 or TNF-α or both treatments, ECs were activated, expressing higher levels of P-selectin and lower levels of VWF. Our findings, further, provide evidence that Stx-1 downregulates ERG, repressing angiogenesis in vitro. [ABSTRACT FROM AUTHOR]

von Willebrand Factor (VWF) is well recognized for being dysregulated in various malignancies and has emerged as a potential biomarker for cancer detection. The present meta-analysis aimed to elucidate the association between plasma VWF and the incidence and metastasis of cancer. For this purpose, a comprehensive search was conducted across multiple databases from their inception until March 3, 2023. This culminated in the selection of 15 original studies on various types of cancer, including a collective sample of 1,403 individuals. The standardized mean difference (SMD) and 95% confidence intervals (CIs) were employed as statistical parameters to determine the association between plasma VWF and the incidence and metastasis of cancer. These were estimated using a random-effects model. The pooled data revealed that the plasma VWF levels of patients with cancer were significantly elevated compared with those of healthy controls (SMD, 0.98; 95% CI, 0.59–1.36), and a significant association was observed between plasma VWF levels and cancer metastasis (SMD, 0.69; 95% CI, 0.33–1.06). The symmetry of the Begg's funnel plots indicated that no significant bias was present in the analyses of VWF in cancer and its metastasis. In summary, the results of the present meta-analysis support the hypothesis that increased plasma VWF levels may serve as a biomarker for cancer and metastatic progression. [ABSTRACT FROM AUTHOR]

ADAMTS13 is a plasma metalloprotease with the primary function of cleaving VWF to maintain hemostasis. Circulating ADAMTS13 is in the closed conformation until blood vessel injury triggers a VWF-dependant activation to the open active form of the protein. ADAMTS13 is a multi-domain protein with the domains broadly functioning to interact and cleave VWF or maintain global latency of ADAMTS13. Thrombotic Thrombocytopenic Purpura is a disease characterized by excessive thrombi formation in the microvasculature, diagnosis is made when ADAMTS13 activity is

Von Willebrand factor antigen (VWF) is a non-invasive marker for clinically significant portal hypertension (HVPG≥10 mmHg) and confers HVPG-independent prognostic information. While quantification of increased VWF-levels is not relevant in the context of von Willebrand disease, highly elevated VWF may be of clinical significance in ACLD. Thus, we have modified our analytical approach to quantify very high VWF-levels (i.e.,>420%) and investigated their prognostic value. Patients undergoing HVPG-measurement at the Vienna Hepatic Hemodynamic Lab with evidence of ACLD and information on VWF were considered. Clinical stages (CS) were defined as follows: Probable compensated ACLD (cACLD): LSM≥10kPa&HVPG<6 mmHg; 0: cACLD&6–9 mmHg; 1: cACLD&HVPG≥10 mmHg; 2: bleeding; 3: non-bleeding decompensation; 4: ≥2 decompensations. 124 (16%) of 793 patients had VWF>420%. The proportion of VWF>420% increased with disease severity (probable cACLD-0: 5(4%) vs. 1: 22(10%) vs. 2–4: 97(23%), p ≤ 0.001) as well as across HVPG (<6mmHg: 1(2%) vs. 6–9: 6(6%) vs. 10–15: 17(9%) vs. ≥16: 100(22%), p ≤ 0.001) and MELD (<10: 17(6%) vs. 10–14: 27(10%) vs. ≥15: 79(32%), p ≤ 0.001) strata. In patients with VWF>420%, median VWF was 533 (IQR:466–611)% and VWF was unrelated to HVPG (Spearman's ρ=0.139, p = 0.123), but showed direct correlations of weak/moderate strength with MELD (ρ=0.336, p < 0.001) and CRP (ρ=0.286, p = 0.001). In the subgroup with VWF>420%, VWF was predictive of decompensation/liver-related mortality (VWF per 10%; hazard ratio (HR): 1.02(95% confidence interval (95%CI): 1.01–1.04), p = 0.008, even after adjusting for other factors (VWF per 10%; adjusted HR: 1.02(95%CI: 1.00–1.05), p = 0.031). The proportion of patients with substantially elevated VWF values steadily increases with disease progression. While VWF is not reflective of HVPG in these patients, it is correlated with hepatic dysfunction and systemic inflammation. Importantly, quantification of high values provides prognostic information. [ABSTRACT FROM AUTHOR]

Human induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) have been believed to be a promising alternative for the stem cell transplantation therapy. The exosomes (Exo) from iMSCs play an important role in several kinds of life activities. The role of exosomes from iMSCs in severe acute pancreatitis (SAP) induced myocardial injury (MI) has not been investigated. The Exo were isolated from iMSCs through differential centrifugation method. The SAP rat model was established with 5% sodium taurocholate injection into the distal end of the bilepancreatic duct. RT-PCR and western blotting were used to measure related gene expression. Masson trichrome and Sirius Red stainings were used to evaluate MI injury. Cardiac function was detected through cardiac ultrasound.Exo promoted cell viability through activating Akt/nuclear factor E2 related factors 2 (Nrf2)/heme oxygenase 1 (HO-1) signaling pathway in vitro. Exo improved MI induced by SAP through activating Akt/Nrf2/HO-1 signaling pathway. Exo improved cardiac function, and suppressed oxidative status in the SAP model. Exo increased the expression of von Willebrand Factor (vWF) and vascular endothelial growth factor (VEGF) through activating Nrf2/HO-1 signaling pathway. Our data indicated that the Exo from iMSCs could improve MI caused by SAP through activating Nrf2/HO-1 axis. These findings firstly unfold the potential application of Exo from iMSCs in treating MI induced by SAP. Abbreviations: LVEF: Left ventricular ejection fraction; LVFS: left ventricular fractional shorten; LVDd: left ventricular end-diastolic diameter; LVDs: left ventricular end-systolic diameter; MI: Myocardial infarction; MSCs: Mesenchymal stem cells; iPSCs: Human-induced pluripotent stem cells; SAP: Severe acute pancreatitis; iMSCs: iPSCs derived VEGF: MSCs; vascular endothelial growth factor; Nrf2: Nuclear factor erythroid 2-related factor; RT-PCR: Real-time polymerase chain reaction; HE: Hematoxylin-eosin; MODS: Multiple organ dysfunction syndrome; PI3K: Phosphatidylinositol 3-kinase; SOD: Superoxide dismutase; FBS: Fetal bovine serum; ECL: Enhanced chemiluminescence; IHC: Immunohistochemistry. [ABSTRACT FROM AUTHOR]

Background and Aims: Heart failure (HF) is a leading cause of mortality worldwide and characterized by significant co-morbidities and dismal prognosis. Neutrophil extracellular traps (NETs) aggravate inflammation in various cardiovascular diseases; however, their function and mechanism of action in HF pathogenesis remain underexplored. This study aimed to investigate the involvement of a novel VWF-SLC44A2-NET axis in HF progression., Methods: NET levels were examined in patients with HF and mouse models of transverse aortic constriction (TAC) HF. PAD4 knockout mice and NET inhibitors (GSK-484, DNase I, NEi) were used to evaluate the role of NETs in HF. RNA sequencing was used to investigate the downstream mechanisms. Recombinant human ADAMTS13 (rhADAMTS13), ADAMTS13, and SLC44A2 knockouts were used to identify novel upstream factors of NETs., Results: Elevated NET levels were observed in patients with HF and TAC mouse models of HF. PAD4 knockout and NET inhibitors improved the cardiac function. Mechanistically, NETs induced mitochondrial dysfunction in cardiomyocytes, inhibiting mitochondrial biogenesis via the NE-TLR4-mediated suppression of PGC-1α. Furthermore, VWF/ADAMTS13 regulated NET formation via SLC44A2. Additionally, sacubitril/valsartan amplifies the cardioprotective effects of the VWF-SLC44A2-NET axis blockade., Conclusions: This study established the role of a novel VWF-SLC44A2-NET axis in regulating mitochondrial homeostasis and function, leading to cardiac apoptosis and contributing to HF pathogenesis. Targeting this axis may offer a potential therapeutic approach for HF treatment., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

von Willebrand disease (VWD) is the most frequent inherited bleeding disorder, with an estimated symptomatic prevalence of 1 per 1000 in the general population. VWD is characterized by defects in the quantity, quality, or multimeric structure of von Willebrand factor (VWF), a glycoprotein being hemostatically essential in circulation. VWD is classified into 3 principal types: low VWF/type 1 with partial quantitative deficiency of VWF, type 3 with virtual absence of VWF, and type 2 with functional abnormalities of VWF, being classified as 2A, 2B, 2M, and 2N. A new VWD type has been officially recognized by the ISTH SSC on von Willebrand factor which has also been discussed by the joint ASH/ISTH/NHF/WFH 2021 guidelines (ie, type 1C), indicating patients with quantitative deficiency due to an enhanced VWF clearance. With the advent of next-generation sequencing technologies, the process of genetic diagnosis has substantially changed and improved accuracy. Therefore, nowadays, patients with type 3 and severe type 1 VWD can benefit from genetic testing as much as type 2 VWD. Specifically, genetic testing can be used to confirm or differentiate a VWD diagnosis, as well as to provide genetic counseling. The focus of this manuscript is to discuss the current knowledge on VWD molecular pathophysiology and the application of genetic testing for VWD diagnosis., Competing Interests: Declaration of competing interests F.P. serves on the advisory committee of CSL-Behring, BioMarin, Roche, Sanofi, and Sobi and participated in educational meetings/symposia of Takeda/Spark. D.L. reports research support from BioMarin, CSL-Behring, and Sanofi and participates in an advisory role for BioMarin, CSL-Behring, Novo Nordisk, and Pfizer. The other authors state that they have no conflict of interest., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Abstract Background/aim N-Acetylcysteine (NAC) demonstrates applications in the prevention of exacerbation of chronic obstructive pulmonary disease (COPD). COPD is often characterized by fibrosis of the small airways. This study aims at investigating the physiological mechanisms by which NAC might mediate the pulmonary fibrosis in COPD. Methods A total of 10 non-smokers without COPD and 10 smokers with COPD were recruited in this study, and COPD rat models were established. Cigarette smoke extract (CSE) cell models were constructed. The gain- or loss-of-function experiments were adopted to determine the expression of VWF and the extent of p38 MAPK phosphorylation, levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and immunoglobulins (IgG, IgM and IgA) in the serum of COPD rats and supernatant of alveolar epithelial cells and to detect cell invasion and migration and the ratio of CD3+, CD4+, CD8+ and CD4+/CD8+T lymphocytes. Results Expression of VWF and the extent of p38 MAPK phosphorylation were increased in COPD. NAC inhibited p38 MAPK phosphorylation by reducing the VWF expression. NAC could inhibit cell migration and invasion, elevate E-cadherin expression, the ratio of CD3+, CD4+, CD8+ and CD4+/CD8+T lymphocytes, and levels of IgG, IgA, and IgM, and reduce N-cadherin expression and levels of IL-6 and TNF-α in CSE cells and serum of COPD rats. NAC promoted immune response and suppressed epithelial-mesenchymal transformation (EMT) to relieve COPD-induced pulmonary fibrosis in vitro and in vivo by inhibiting the VWF/p38 MAPK axis. Conclusions Collectively, NAC could ameliorate COPD-induced pulmonary fibrosis by promoting immune response and inhibiting EMT process via the VWF/p38 MAPK axis, therefore providing us with a potential therapeutic target for treating COPD.

Numerous studies have proven a close relationship between inflammatory diseases and the state of hypercoagulability. In fact, thromboembolic complications represent one of the main causes of disability and mortality in acute and chronic inflammatory diseases, cancer and obstetric complications. Despite this, the processes of hemostasis and immune responses have long been considered separately; currently, work is underway to identify the molecular basis for a relationship between such systems. It has been identified that various pro-inflammatory stimuli are capable of triggering a coagulation cascade, which in turn modulates inflammatory responses. Neutrophil extracellular traps (NETs) are the networks of histones of extracellular DNA generated by neutrophils in response to inflammatory stimuli. The hemostasis is activated against infection in order to minimize the spread of infection and, if possible, inactivate the infectious agent. Another molecular network is based on fibrin. Over the last 10 years, there has been accumulated a whole body of evidence that NETs and fibrin are able to form a united network within a thrombus, stabilizing each other. Similarities and molecular cross-reactions are also present in the processes of fibrinolysis and lysis of NETs. Both NETs and von Willebrand factor (vWF) are involved in thrombosis as well as inflammation. During the development of these conditions, a series of events occurs in the microvascular network, including endothelial activation, NETs formation, vWF secretion, adhesion, aggregation, and activation of blood cells. The activity of vWF multimers is regulated by the specific metalloproteinase ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). Studies have shown that interactions between NETs and vWF can lead to arterial and venous thrombosis and inflammation. In addition, the contents released from activated neutrophils or NETs result in decreased ADAMTS-13 activity, which can occur in both thrombotic microangiopathies and acute ischemic stroke. Recently, NETs have been envisioned as a cause of endothelial damage and immunothrombosis in COVID-19. In addition, vWF and ADAMTS-13 levels predict COVID-19 mortality. In this review, we summarize the biological characteristics and interactions of NETs, vWF, and ADAMTS-13, the effect of NETs on hemostasis regulation and discuss their role in thrombotic conditions, sepsis, COVID-19, and obstetric complications.

Data analysis on the pathogenesis and risk factors of neonatal thrombosis was carried out. The main risk factor of any neonatal thrombosis is central catheter installment, but other maternal, fetal and neonatal factors should be taken into consideration. We discuss the epidemiology of neonatal thrombosis and the main features of the hemostasis system in newborns, the most significant risk factors, including genetic and acquired thrombophilia. We consider the von Willebrand factor activity and ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) level in the development of neonatal thrombotic microangiopathy. Finally, we discuss the basic principles of prevented neonatal thrombosis by using low molecular weight heparins.

Hadeel Al Otair,1 Khalid AlSaleh,2 Fatmah S AlQahtany,3 Khalid Al Ayed,1 Hessah Al Ammar,4 Noura Al Mefgai,4 Faisal Al Zeer5 1Department of Medicine, King Saud University Medical city (KSUMC), King Saud University, Riyadh, Saudi Arabia; 2Department of Medicine, Hematology/ oncology division, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 3Department of Pathology, Hematopathology Unit, College of Medicine, King Saud University, King Saud University Medical City, Riyadh, Saudi Arabia; 4Department of Medicine, King Saud University, Riyadh, Saudi Arabia; 5College of Medicine, King Saud University, King Saud University, Riyadh, Saudi ArabiaCorrespondence: Hadeel Al OtairDepartment of Medicine, King Saud University Medical City, King Saud University, P.O. Box 2925(38), Riyadh, 11461, Saudi ArabiaTel +966(1) 8066519Fax +966(1) 4692365Email halotair@ksu.edu.saBackground: The coagulopathy of COVID-19 still awaits more clarification, and one approach that has not been investigated is to compare the hemostatic changes between COVID-19 and non-COVID-19 infected patients.Objective: This study aims to study COVID-19 coagulopathy by measuring markers of endothelial injury and coagulation, including anticoagulants (TFPI, protein C, protein S, and AT) in COVID-19 patients and compare them with non-COVID-19 patients early in the course of the disease.Methodology: This is an observational, prospective cross-sectional study comparing the levels of protein C, protein S, antithrombin (AT) III, clotting factor (F) VIII, von Willebrand factor (vWF) and coagulation screening tests (PT and a PTT), fibrinogen, D-dimer in COVID-19 patients admitted during the same time with non-COVID-19 infections. The demographic and clinical data of the patients were collected from electronic medical records during admission. Blood tests were extracted within 24 hours of admission for both groups.Results: Fifty-four (66.7% males) consecutive COVID-19 patients and 24 (59% males) non-COVID-19 controls were enrolled in the study from October 2020 till December 2020. COVID-19 patients were significantly older than non-COVID-19 (57.7± 14.2 vs 50± 19.8 years, p= 0.005). Fibrinogen level was significantly higher in COVID-19 patients compared to controls (5.9± 1.48 vs 3.9± 1.57, p< 0.001). There was no statistically significant difference in the level of FVIII, protein C, S, ATIII, and D-dimer between the two groups. The level of vWF Ag was statistically higher in COVID-19 patients (276.7± 91.1 vs 184.7± 89.4, p=0.0001). There was significant thrombocytopenia and lymphopenia among COVID-19 patients. Inflammatory markers, CRP, ferritin, and LDH, were increased in COVID-19 patients compared to non-COVID-19, but the difference was not statistically significant. High fibrinogen and vWF AG levels were the two independent variables found in COVID-19 patients.Conclusion: The level of vWF Ag is increased early in the course of COVID-19 infection. This can be used as a biomarker for endothelial injury, which is peculiar to COVID-19 infection.Keywords: COVID-19, vWF, fibrinogen, coagulopathy, endothelium