Blood Vessels, Thrombosis & Hemostasis最新文献

{"title":"Idiopathic multicentric Castleman disease - TAFRO results in high levels of mTOR activator SVEP1, tissue factor, and endotheliopathy","authors":"Chen Lossos ,&nbsp;Jenna Brown ,&nbsp;Sara Sheikhbahaei ,&nbsp;Anne Hubben ,&nbsp;Sharon C. Liu ,&nbsp;Keith R. McCrae ,&nbsp;Shruti Chaturvedi ,&nbsp;Rakhi P. Naik ,&nbsp;Ivo M.B. Francischetti","doi":"10.1016/j.bvth.2024.100006","DOIUrl":"10.1016/j.bvth.2024.100006","url":null,"abstract":"<div><h3>Abstract</h3><p>Idiopathic multicentric Castleman disease (iMCD) is an inflammatory disease associated with a cytokine storm, activation of the PI3K/AKT/mTOR pathway, coagulopathy, and increased risk of thrombosis. The mechanisms underlying these pathologic processes remain elusive. We studied novel markers of mTOR activation and thrombosis in 1 patient with typical features of iMCD with TAFRO (thrombocytopenia, anasarca, fevers, reticulin myelofibrosis, and organomegaly) syndrome (iMCD-TAFRO). Plasma levels of SVEP1 (Sushi, von Willebrand factor type A, epidermal growth factor, and pentraxin domain–containing 1 protein), a newly identified mTOR activator associated with cardiovascular diseases and dementia, in addition to cytokines, chemokines and components of the coagulation cascade and complement system were evaluated by enzyme-linked immunosorbent assay (ELISA) and arrays. Compared with healthy controls, a 15-fold increase in SVEP1 was observed. High levels of factor VIIa/antithrombin and microparticles expressing functional tissue factor (TF) were detected. The anticoagulants thrombomodulin and soluble endothelial protein C receptor were elevated, indicating shedding from endothelial cells. Plasminogen activator inhibitor 1 was increased, consistent with hypofibrinolysis, whereas high levels of C3b and C5a are in keeping with complement activation. Furthermore, markers of endothelial cell activation (e.g. von Willebrand factor, angiopoietin-2), cell adhesion molecules, and angiogenesis mediators were upregulated. SVEP1 emerges as a potential mechanism of mTOR activation in iMCD-TAFRO, while multiple pathways influence coagulopathy. Immunothrombosis emerges as a potential therapeutic target for iMCD.</p></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"1 2","pages":"Article 100006"},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950327224000068/pdfft?md5=01d36b9f10240b963e82456d37859b0d&pid=1-s2.0-S2950327224000068-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140757920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angiopoietin-2 is associated with sickle cell complications, including stroke risk, and decreases with hydroxyurea therapy","authors":"Thomas F. Siegert ,&nbsp;Robert O. Opoka ,&nbsp;Maria Nakafeero ,&nbsp;Aubri Carman ,&nbsp;Kagan A. Mellencamp ,&nbsp;Teresa Latham ,&nbsp;Heather Hume ,&nbsp;Adam Lane ,&nbsp;Russell E. Ware ,&nbsp;John M. Ssenkusu ,&nbsp;Chandy C. John ,&nbsp;Andrea L. Conroy","doi":"10.1016/j.bvth.2024.100001","DOIUrl":"10.1016/j.bvth.2024.100001","url":null,"abstract":"<div><h3>Abstract</h3><p>Hydroxyurea reduces morbidity and mortality in children with sickle cell anemia (SCA). The endothelium is central to SCA-related complications including stroke. However, hydroxyurea’s impact on the endothelium is not well described. To address this gap, we measured plasma levels of endothelial activation markers (angiopoietin-2, P-selectin, soluble endothelial selectin [sE-selectin], soluble intercellular cellular adhesion molecule 1, and soluble vascular endothelial cellular adhesion molecule) by enzyme-linked immunosorbent assay after initiation of hydroxyurea therapy. Samples were collected from Ugandan children with SCA enrolled in a clinical trial evaluating hydroxyurea vs placebo (NOHARM trial). Samples were collected at enrollment; and then after 2, 4, and 12 months of follow-up. Longitudinal changes in biomarker levels were evaluated using linear mixed effects models. Transcranial Doppler (TCD) velocities were measured at 10 to 12 months follow-up to assess cerebral blood flow and primary stroke risk. Mediation analysis was used to explore causal pathways of hydroxyurea-mediated effects on TCD velocities. In total, 798 plasma samples were tested from 205 children (mean enrollment age, 2.2 years). At enrollment, higher levels of angiopoietin-2 were associated with a previous medical history of dactylitis, vaso-occlusive crises, acute chest syndrome, and transfusion (<em>P</em> &lt; .05 for all). Hydroxyurea therapy at a fixed dose of 20 mg/kg per day decreased plasma angiopoietin-2, P-selectin, and sE-selectin levels over the study period (<em>P</em> &lt; .05 for all). Angiopoietin-2 and sE-selectin were associated with higher TCD velocities. Mediation analysis suggests that hydroxyurea decreases TCD velocities through an increase in fetal and total hemoglobin. Increased fetal and total hemoglobin, and decreased white blood cell count may decrease TCD velocity, in part, through an angiopoiten-2–mediated pathway. This trial was registered at <span>www.ClinicalTrials.gov</span><svg><path></path></svg> as #NCT01976416.</p></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"1 1","pages":"Article 100001"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950327224000019/pdfft?md5=f1c5ca1f4a1bdaab750c18dd27ec29af&pid=1-s2.0-S2950327224000019-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139897487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating research collaboration networks among venous thromboembolism researchers before and during the COVID-19 pandemic","authors":"Divya Karsanji ,&nbsp;James A. King ,&nbsp;Jenny Godley ,&nbsp;Deborah M. Siegal ,&nbsp;Teresa M. Chan ,&nbsp;Grégoire Le Gal ,&nbsp;Marc Carrier ,&nbsp;Susan R. Kahn ,&nbsp;Tobias Tritschler ,&nbsp;Nicole J. Langlois ,&nbsp;Chad Saunders ,&nbsp;Ramy Saleh ,&nbsp;Alexandra Garven ,&nbsp;Caleb MacGillivray ,&nbsp;Marc A. Rodger ,&nbsp;Leslie Skeith","doi":"10.1016/j.bvth.2024.100004","DOIUrl":"https://doi.org/10.1016/j.bvth.2024.100004","url":null,"abstract":"","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"1 1","pages":"Article 100004"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950327224000044/pdfft?md5=aa71f0d53b40103720a335466fc1712d&pid=1-s2.0-S2950327224000044-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140113270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intraindividual bleeding outcomes in patients with hemophilia A on emicizumab prophylaxis in Australia","authors":"Radha Ramanan ,&nbsp;Sumit Parikh ,&nbsp;Lwin Lwin Aung ,&nbsp;James D. McFadyen ,&nbsp;Huyen A. Tran","doi":"10.1016/j.bvth.2024.100005","DOIUrl":"https://doi.org/10.1016/j.bvth.2024.100005","url":null,"abstract":"<div><h3>Abstract</h3><p>Emicizumab became routinely available in Australia in November 2020 as regular prophylaxis for certain patients with hemophilia A (HA). We performed an intraindividual comparison of bleeding outcomes in Australian patients with HA before and after commencement of emicizumab. Data regarding demographics, severity, treatment, inhibitors, and number and type of intraindividual treated bleeds before and after starting emicizumab in patients with HA were extracted from the Australian Bleeding Disorders Registry. As of April 2022, there were 459 eligible patients with HA on emicizumab in Australia, 397 of 459 (86%) of whom had severe disease. Overall, 59 of 459 (13%) had a current inhibitor. Adults (aged ≥18 years) composed 49% (223/459) of the population. The proportion of patients with zero bleeds increased from 54% to 63% after commencement of emicizumab (relative risk [RR], 1.24; 95% confidence interval [CI], 1.09-1.41; <em>P</em> &lt; .01). RR for zero treated bleeds after commencement was significant in subgroups including pediatric patients (RR, 1.34; 95% CI, 1.13-1.59; <em>P</em> &lt; .01) and those not on regular prophylaxis prior (RR, 1.75; 95% CI, 1.22-2.52; <em>P</em> &lt; .01). There was no significant difference in zero-bleed prevalence in the adult, standard half-life, and extended half-life subgroups. Spontaneous bleeding was reduced (RR, 1.69; 95% CI, 1.34-2.13; <em>P</em> &lt; .01), whereas provoked bleeding was not (<em>P</em> = .15). Real-world data from Australia shows a reduction in bleeding events with emicizumab prophylaxis for the overall population of patients with HA, although not in all subgroups. This reduction appears to be most pronounced in spontaneous bleeds within the pediatric population, and in those on on-demand therapy before switching.</p></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"1 1","pages":"Article 100005"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950327224000056/pdfft?md5=8cc22fa188b24204ebb134bfac882760&pid=1-s2.0-S2950327224000056-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140133985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consequences of unmet pregnancy-specific health care needs in women with immune TTP","authors":"Jenna Brown ,&nbsp;Clare Martin ,&nbsp;Marshall Mazepa ,&nbsp;Shruti Chaturvedi","doi":"10.1016/j.bvth.2024.100003","DOIUrl":"10.1016/j.bvth.2024.100003","url":null,"abstract":"","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"1 1","pages":"Article 100003"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950327224000032/pdfft?md5=cd487ef9ab6b90095df3af5a1707da99&pid=1-s2.0-S2950327224000032-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139897191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is confirmatory testing still necessary to diagnose von Willebrand disease?","authors":"John Puetz ,&nbsp;Krithika Narayana Kumanan ,&nbsp;Zidong Zhang","doi":"10.1016/j.bvth.2024.100002","DOIUrl":"10.1016/j.bvth.2024.100002","url":null,"abstract":"","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"1 1","pages":"Article 100002"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950327224000020/pdfft?md5=cf69b2a762fdaeef597cc850e4e9fe03&pid=1-s2.0-S2950327224000020-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139897712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}