Blood Vessels, Thrombosis & Hemostasis最新文献

{"title":"Epigenetic metabolite lipid nanoparticles alleviate venous thrombosis via bone marrow reprogramming","authors":"Lin Di ,&nbsp;Natalie E. Hong ,&nbsp;Oleksandra Pavlova ,&nbsp;Courteney Asase ,&nbsp;Stephanie Lapping ,&nbsp;Lauren E. Switala ,&nbsp;Abigail L. S. Allio ,&nbsp;Lalitha Nayak ,&nbsp;Andrei Maiseyeu","doi":"10.1016/j.bvth.2025.100086","DOIUrl":"10.1016/j.bvth.2025.100086","url":null,"abstract":"<div><h3>Abstract</h3><div>Targeting the coagulation cascade is a mainstay approach to therapy for thrombosis. One of the most prevalent complications of anticoagulation is a significant bleeding risk that can result in hospitalization. Recent studies on immunothrombosis (ie, inflammation-linked thrombosis) proposed myeloid cells, especially neutrophils, to actively participate in thrombus formation through neutrophil extracellular traps (NETosis) and activation of inflammatory pathways. Here, we developed lipid nanoparticles (LNPs) with coagulation cascade–independent action that target neutrophils to alleviate venous thrombosis. A single intravenous dose of immunomodulatory metabolite itaconate (ITA)-bearing LNPs (ITA-LNPs) targeted &gt;90% of bone marrow–resident neutrophils, but not macrophages or T lymphocytes. ITA-LNPs significantly diminished inflammation in cultured neutrophils and macrophages and improved survival in the mouse model of endotoxemia. When tested in an inferior vena cava ligation model of deep vein thrombosis, ITA-LNPs decreased the size and weight of thrombi as compared with control LNPs. In addition, the thrombi from ITA-LNP–administered mice had significantly reduced neutrophil infiltration, decreased NETosis, and interleukin-1β expression. Intriguingly, one of the mechanisms through which this occurred was histone H4K12ac deacetylation, resulting in chromatin condensation and transcriptional repression of inflammatory genes and transcription factors involved in DNA damage response. Finally, we found that ITA-LNPs were hemostatically safe and neither targeted nor activated platelets in vivo. In sum, our work explores an LNP technology with an epigenetic mode of action serving as an anti-immunothrombotic therapy that could improve clinical outcomes without additional hemorrhagic risk.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 4","pages":"Article 100086"},"PeriodicalIF":0.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitor development and clinical characteristics in children with severe hemophilia A in the ATHN 8 US cohort study","authors":"Courtney D. Thornburg ,&nbsp;H. Marijke van den Berg ,&nbsp;Martin Chandler ,&nbsp;Lynn Malec ,&nbsp;Matthew Manuel ,&nbsp;Carrie O’Neill ,&nbsp;Michael Recht ,&nbsp;Elizabeth Taggart ,&nbsp;Shannon L. Carpenter","doi":"10.1016/j.bvth.2025.100082","DOIUrl":"10.1016/j.bvth.2025.100082","url":null,"abstract":"<div><h3>Abstract</h3><div>Clotting factor concentrate (CFC), used to treat and prevent bleeding in hemophilia, is rendered ineffective if clotting factor neutralizing antibodies (inhibitors) develop. Inhibitors occur most often in children, early in treatment. The American Thrombosis and Hemostasis Network (ATHN) 8: US Cohort Study of Previously Untreated Patients (PUPs) with Congenital Hemophilia, conducted in children born in 2010 to 2020 with severe or moderate hemophilia, was designed to determine the percentage of participants who developed a confirmed, clinically significant inhibitor within the first 50 CFC exposure days (EDs). Cox proportional hazards models were used to evaluate risk factors for inhibitor development in PUPs with severe hemophilia A (HA). A total of 171 males with severe HA enrolled: 39 (22.8%) developed an inhibitor, 30 (17.5%) developed a high-titer inhibitor, and 9 (5.3%) developed a low-titer inhibitor; 82.1% within 20 EDs. Product exposure at &lt;1 month (hazard ratio [HR], 2.57; 95% confidence interval [CI], 1.22-5.44), large structural changes (HR,16.59; 95% CI, 1.94-142.20), and nonsense variants (HR, 12.53; 95% CI, 1.41-111.49) were associated with inhibitor development. Overall, inhibitor development remains a significant CFC complication especially in the first 10 to 20 EDs. Further study should evaluate the impact of new treatments on inhibitor rates and age at inhibitor development and identify strategies to reduce inhibitor development.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 3","pages":"Article 100082"},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surveying patients’ experiences and perspectives on venous thromboembolism: gaps and opportunities in health delivery","authors":"Anjlee Mahajan ,&nbsp;Anya Parekh ,&nbsp;Laura E. Dodge ,&nbsp;Antonia Chan ,&nbsp;Alexander Cermak ,&nbsp;Cilomar Martins de Oliveira Filho ,&nbsp;Ang Li ,&nbsp;Anna L. Parks ,&nbsp;Jordan K. Schaefer ,&nbsp;Alejandra Gutierrez Bernal ,&nbsp;Leben Tefera ,&nbsp;Shruti Chaturvedi ,&nbsp;Jori E. May ,&nbsp;Leslie Lake ,&nbsp;Dana E. Angelini ,&nbsp;Rushad Patell","doi":"10.1016/j.bvth.2025.100081","DOIUrl":"10.1016/j.bvth.2025.100081","url":null,"abstract":"<div><h3>Abstract</h3><div>Patient experience is an independent dimension of health care delivery. We aimed to capture patients’ experiences with venous thromboembolism (VTE) to improve health care delivery. A survey was developed by a multidisciplinary team of clinicians and patient advocates. Domains included patient demographics, health care experiences, perspectives, and potential gaps in health care received for VTE. The survey was distributed electronically between May and July 2023 through a patient advocacy group targeting individuals with a personal VTE history. The primary outcome was a binary indicator of patient satisfaction with how their VTE diagnosis was explained. Logistic regression was used to assess factors associated with satisfaction. Of 1050 participants, the majority were from the United States (81%). Most respondents were female (81%) and White (88%), and 71% were aged between 40 and 69 years. Satisfaction with clinician explanation of VTE diagnosis was reported in 55% of participants. The likelihood of satisfaction increased as the time spent with a clinician at diagnosis increased (relative to &lt;5 minutes, risk ratio (RR) of 1.65 [95% confidence interval [CI], 1.36-2.02] for 6-10 minutes to RR of 2.44 [95% CI 1.92-3.10] for 31-60 minutes). Factors associated with decreased likelihood of satisfaction included multiple visits to obtain VTE diagnosis (RR, 0.68; 95% CI, 0.59-0.79) and not being given information at the time of diagnosis (RR, 0.69; 95% CI, 0.61-0.79). From this large international survey designed to capture patient experiences and gaps in VTE care delivery, we identified several areas for improvement. Specifically, enhancing patient education and spending more time with patients at diagnosis are opportunities to improve patient satisfaction with VTE care.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 4","pages":"Article 100081"},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145049788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global coagulation assays for patients with diabetes and their utility in the prediction of atherothrombotic events","authors":"Rowena Brook ,&nbsp;Mani Suleiman ,&nbsp;Brandon Lui ,&nbsp;Ramzi A. Ajjan ,&nbsp;Harshal Nandurkar ,&nbsp;Suresh Varadarajan ,&nbsp;Prahlad Ho ,&nbsp;Hui Yin Lim","doi":"10.1016/j.bvth.2025.100079","DOIUrl":"10.1016/j.bvth.2025.100079","url":null,"abstract":"","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 3","pages":"Article 100079"},"PeriodicalIF":0.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantifying the unique mechanical properties of irreversibly sickled cells in sickle cell disease","authors":"Dillon C. Williams ,&nbsp;John M. Higgins ,&nbsp;David K. Wood","doi":"10.1016/j.bvth.2025.100077","DOIUrl":"10.1016/j.bvth.2025.100077","url":null,"abstract":"<div><h3>Abstract</h3><div>We developed a platform to measure the oxygen-dependent mechanical properties and oxygen saturation of individual irreversibly sickled cells (ISCs). We identified and measured ISCs from a cohort of 10 individuals with sickle cell disease. ISCs were found to have an average shear surface modulus 20 times that of nonsickled cells and a sixth that of red blood cells (RBCs) with detectable hemoglobin polymer. We found that the number of ISCs was significantly reduced at 53 mm Hg oxygen compared with ≥91 mm Hg oxygen, suggesting that these RBCs can still form polymer under hypoxia. We also found that the fraction of ISCs present in a blood sample had a negative correlation with donor fetal hemoglobin (HbF) fraction, suggesting that HbF could play a role in mitigating occurrence of ISCs.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 3","pages":"Article 100077"},"PeriodicalIF":0.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144679070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet recruitment kinetics are impacted by von Willebrand factor quality in hemostatic adjuncts","authors":"Kimberly A. Thomas ,&nbsp;Alice Liu ,&nbsp;David L. Bark Jr. ,&nbsp;Philip C. Spinella ,&nbsp;Susan M. Shea","doi":"10.1016/j.bvth.2025.100076","DOIUrl":"10.1016/j.bvth.2025.100076","url":null,"abstract":"<div><h3>Abstract</h3><div>Traumatic injury has the highest burden on morbidity and mortality in the United States. Early deaths from trauma are most frequently due to hemorrhage and could be prevented with more timely and efficacious treatments. A hallmark of trauma-induced coagulopathy (TIC) is hypofibrinogenemia, which is treated with fibrinogen concentrates (FibCon) or cryoprecipitate (Cryo). Pathogen reduction (PR) of Cryo (PR-CryoFC) enables extended storage after thaw at room temperature, permitting immediate availability for patients with bleeding. As Cryo contains additional concentrated plasma proteins involved in hemostasis compared with FibCon, we hypothesized that Cryo and PR-CryoFC would result in more rapid and effective clot formation. To evaluate the hemostatic capacity of these adjuncts, we simulated TIC (dilution, hyperfibrinolysis) in an ex vivo model and administered Cryo, PR-CryoFC, and FibCon, then performed hemostatic assessment to include viscoelastometry, thrombin generation, and a microfluidic model of vessel injury. Cryo and PR-CryoFC had similar resuscitation capacity in assays without flow (viscoelastometry, thrombin generation), whereas in the dynamic microfluidic model, Cryo had faster von Willebrand factor (VWF)-mediated platelet recruitment. There was no difference in intrinsic VWF function between adjuncts in static, nonflowing assays, yet in a flow-dependent vortexing assay, PR reduced VWF cleavage by ADAMTS13, despite equivalent ADAMTS13 activity, suggesting impaired biophysical elongation and extension of VWF in PR-CryoFC, resulting in reduced cleavage and platelet binding capacity. Herein, we show ex vivo simulation of coagulopathy and resuscitation differentiated hemostatic function under flow among Cryo, PR-CryoFC, and FibCon. Further exploration of effects of PR on plasma proteins is warranted as well as effects on clinical outcomes.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 3","pages":"Article 100076"},"PeriodicalIF":0.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144679069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in outcomes associated with ABO blood groups in recipients of IVIG","authors":"Laura S. Duarte ,&nbsp;Neil Blumberg ,&nbsp;Joshua Marvald ,&nbsp;Tanzy Love ,&nbsp;Jeffrey R. Andolina ,&nbsp;Suzie A. Noronha ,&nbsp;Laurie A. Steiner ,&nbsp;Kelly Henrichs ,&nbsp;Richard John Looney ,&nbsp;Majed A. Refaai ,&nbsp;Akua Asante","doi":"10.1016/j.bvth.2025.100075","DOIUrl":"10.1016/j.bvth.2025.100075","url":null,"abstract":"","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 3","pages":"Article 100075"},"PeriodicalIF":0.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144588417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of risk factors for venous thromboembolism and overall survival in lung cancer","authors":"Thomas E. Plate ∗ ,&nbsp;Asaad Trabolsi ∗ ,&nbsp;Rachel S. Kronenfeld ,&nbsp;Leticia E. Campoverde ,&nbsp;Dan Morgenstern-Kaplan ,&nbsp;Alyssa J. Mercadel ,&nbsp;Michael Caballero ,&nbsp;Wei Zhao ,&nbsp;Gerald A. Soff","doi":"10.1016/j.bvth.2025.100074","DOIUrl":"10.1016/j.bvth.2025.100074","url":null,"abstract":"<div><h3>Abstract</h3><div>Venous thromboembolism (VTE) is a frequent complication in patients with lung cancer, but the risk factors and incidence in different lung cancer subtypes have not been fully characterized. Despite multiple studies supporting the use of VTE prophylaxis in patients with cancer at increased risk of VTE based on the Khorana score (KS), routine use of VTE prophylaxis is uncommon in clinical practice. This study further characterizes the risk factors and incidence of VTE in patients with lung cancer at a university cancer center. Furthermore, we assessed the association of KS and its individual components with overall survival in this same group of patients. Using natural language processing and human review to detect thrombotic events in the electronic medical record, a 12-month incidence of 10.1% was identified in the 632 patients with lung cancer analyzed. Significant risk factors included age &lt;60 years and white blood cell (WBC) count ≥11 × 10⁹/L, but KS itself was not significantly associated with VTE. The median overall survival was 12 months with VTE. The KS, age ≥60 years, stage III to IV, WBC count ≥11 × 10⁹/L, hemoglobin &lt;10 g/dL, body mass index, surgery, and VTE were identified as significant predictors of death. These findings warrant further validation, because the KS and 2 of its individual components in this study of lung cancer were significantly associated with reduced overall survival.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 3","pages":"Article 100074"},"PeriodicalIF":0.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144654934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two live births with low factor VIII by a patient with pregnancy-associated acquired hemophilia A managed with prednisolone","authors":"Takahiro Nakashima ,&nbsp;Naohiro Matsunaga ,&nbsp;Sawako Tajiri ,&nbsp;Yuka Watanabe ,&nbsp;Aki Kondo ,&nbsp;Takaki Kikuchi ,&nbsp;Takashi Kanamori ,&nbsp;Shigeru Kusumoto ,&nbsp;Atsushi Inagaki","doi":"10.1016/j.bvth.2025.100072","DOIUrl":"10.1016/j.bvth.2025.100072","url":null,"abstract":"","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 3","pages":"Article 100072"},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144633582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From theory to platelets: unraveling the history and complexities of biased signaling","authors":"NaShea C. Kendrick ,&nbsp;Grace H. Huang ,&nbsp;Germaine J. Harvey ,&nbsp;Marvin T. Nieman","doi":"10.1016/j.bvth.2025.100073","DOIUrl":"10.1016/j.bvth.2025.100073","url":null,"abstract":"<div><h3>Abstract</h3><div>Biased signaling refers to a phenomenon where a ligand preferentially activates 1 signaling pathway over another at the same receptor. It is best described for ligands that selectively activate G protein–coupled receptors through G protein or β-arrestin pathways. The concept of biased signaling has a rich history that has been experimentally characterized in the past 40 years. As early as the 1970s, models of biased signaling suggested that ligand-bound receptors have a rigid structure, whereas free receptors are fluid proteins with multiple potential active states. Recent cell signaling studies demonstrate that ligands block select signaling pathways but amplify others. This suggests that each ligand can stabilize a unique active conformation supporting the proposed model. Additional studies expanded our understanding of biased signaling to include biased receptors and system bias, which consider the impact of genetic differences and cellular context in which the signal is being studied. This is exemplified in platelet biology. Platelets are nonnucleated cells that rely on membrane receptors such as protease-activated receptor 1 (PAR1), PAR4, and Toll-like receptor 4 (TLR4) to facilitate platelet activation. There is now evidence of biased signaling through PAR1, PAR4, and TLR4 in platelets, making them attractive therapeutic targets. Here, we describe the origins of biased signaling theory and explore the concepts of biased agonists and systems through the lens of platelet activation.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 3","pages":"Article 100073"},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144588724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}