Blood Vessels, Thrombosis & Hemostasis最新文献

{"title":"Refractoriness to eltrombopag in adult primary immune thrombocytopenia: utility of next-generation sequencing techniques","authors":"Tomás José González-López ,&nbsp;Ricardo Sanchez ,&nbsp;Carmen Pastoriza ,&nbsp;Pavel Olivera ,&nbsp;Silvia Bernat ,&nbsp;Fernando Fernandez-Fuertes ,&nbsp;Isabel Socorro Caparrós-Miranda ,&nbsp;Gloria Pérez-Rus ,&nbsp;Isidro Jarque ,&nbsp;Maria Esperanza Moreno-Beltrán ,&nbsp;Emma López-Abadía ,&nbsp;Erik De Cabo ,&nbsp;Shally Marcellini ,&nbsp;Gloria Pérez-Segura ,&nbsp;Carmen Fernández-Miñano ,&nbsp;María Jesús Peñarrubia ,&nbsp;Sergio Matarraz ,&nbsp;María Pérez-Caro ,&nbsp;Alberto Orfao ,&nbsp;Drew Provan ,&nbsp;Joaquín Martínez-López","doi":"10.1016/j.bvth.2025.100061","DOIUrl":"10.1016/j.bvth.2025.100061","url":null,"abstract":"<div><h3>Abstract</h3><div>Thrombopoietin receptor agonists, for example eltrombopag, are standard second-line treatment for immune thrombocytopenia (ITP). Eltrombopag has demonstrated high response rates, both in clinical trials and in routine practice studies. However, some patients with ITP are refractory to this drug. Next-generation sequencing (NGS) may help us identify underlying molecular biology variants that may be involved in eltrombopag refractoriness. Our multicenter national NGS study investigated 110 genes of the most important cell-signaling pathways involved in the mechanism of action of eltrombopag in 35 refractory cases and 35 eltrombopag-responsive controls. Our refractory population comprised 51.4% men with a median age at diagnosis of 48 (range, 38-69) years and a median platelet count of 7 × 10⁹/μL (range, 4 × 10⁹/μL to 16 × 10⁹/μL). At eltrombopag initiation, 78.3% had chronic ITP with a median platelet count of 8 × 10⁹/μL (range, 5× 10⁹/μL to 30 × 10⁹/μL). Treatment with eltrombopag was maintained for a median of 3 (range, 1-9) months before discontinuation. No major grade 3-4 side effects were observed. Several statistical differences were observed in relation to the control responders. Of the total sum of the NGS variants found, 13 variants with statistical significance (<em>P</em> ≤ .05) between case and controls were observed. Two of these have been shown to be associated with cancer. Seven variants are considered benign. Four variants are not previously described, and their significance is unknown. To our knowledge, none of the 13 variants described here has ever been correlated with ITP or eltrombopag refractoriness. Further studies are required to establish their role in this setting.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 3","pages":"Article 100061"},"PeriodicalIF":0.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221426","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":"Acquired (autoimmune) hemophilia: demographics, outcomes, and readmissions","authors":"Aditi Sharma ,&nbsp;Nikhil Vojjala ,&nbsp;Vijendra Singh","doi":"10.1016/j.bvth.2025.100062","DOIUrl":"10.1016/j.bvth.2025.100062","url":null,"abstract":"<div><h3>Abstract</h3><div>Acquired hemophilia (AHA) is a rare bleeding disorder characterized by autoantibodies against coagulation factors. It predominantly affects older adults and is associated with autoimmune disorders or malignancies. Achieving hemostasis and inhibiting autoantibody production through immunosuppression are the mainstays of treatment.We conducted a retrospective cohort study using the Nationwide Readmissions Database from 2016 to 2019 to perform a descriptive analysis of AHA, including the estimation of the 30-day readmission rate and primary diagnoses at readmission.Of 1450 admissions for AHA, 803 (55.4%) were male, and the median age at admission was 73 years. Approximately 21% had an underlying solid malignancy, 3.9% had hematologic malignancy, and 13.5% had autoimmune disease. Acute myocardial infarction occurred in 9.5%, disseminated intravascular coagulation in 1.2%, intracranial hemorrhage in 1.5%, ischemic stroke in 2.5%, and venous thromboembolism in 4.4%. Bleeding occurred in 30.2% of admissions, with 27% requiring blood transfusion. The median length of hospital stay was 7 days, and there were 101 deaths during the index admission, resulting in a 7% inpatient mortality rate. Mortality was higher in the older age group at 8% compared with 3% in those aged &lt;65 years (<em>P</em> = .03). The 30-day readmission rate was 27%, with a 10.8% mortality rate during readmission. Infections followed by bleeding were the most common causes for readmission. High rates of bleeding and thrombotic complications are seen in AHA, with bleeding and infection being the primary reasons for the elevated 30-day readmission rate, indicating significant treatment-related toxicity and disease relapse.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 2","pages":"Article 100062"},"PeriodicalIF":0.0,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143790838","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":"Prevalence of cardiovascular risk factors in persons with venous thromboembolism aged 50 years or younger","authors":"Eng Soo Yap ,&nbsp;Frits R. Rosendaal ,&nbsp;Suzanne C. Cannegieter ,&nbsp;L. J. J. Scheres","doi":"10.1016/j.bvth.2025.100059","DOIUrl":"10.1016/j.bvth.2025.100059","url":null,"abstract":"<div><h3>Abstract</h3><div>The risk of cardiovascular disease (CVD) is elevated in individuals with a history of venous thromboembolism (VTE). It is uncertain whether younger patients, aged ≤50 years, have an increased prevalence of potentially modifiable CVD risk factors, which could be targeted for prevention. We aimed to estimate the prevalence of potentially modifiable CVD risk factors (ie, overweight/obesity, smoking, alcohol use, physical inactivity, hypertension, diabetes mellitus, and dyslipidemia) in persons aged ≤50 years with a history of VTE (cases) and compare with those without VTE (controls). Using data from the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis case-control study comprising 2627 case patients with first VTE and 1908 random digit dialing control patients, all aged ≤50 years, we estimated the prevalence of risk factors. Analyses were stratified by sex and were performed separately for unprovoked and provoked events. The prevalence of hypertension, diabetes, dyslipidemia, and excessive alcohol intake was low and similar between case and control patients. The prevalence of overweight and obesity, sedentary behavior, and current smoking was higher in case than control patients. When stratified for sex, obesity was highest in women: 24.9% in case vs 9.9% in control patients. Sedentary behavior was more common in case patients than control patients: women, 57.8% vs 41.1%; and men, 48.7% vs 41.5%, respectively. In persons aged ≤50 years with recent VTE, the prevalence of hypertension, diabetes mellitus, dyslipidemia, and alcohol intake was similar to that of control patients from the general population, suggesting limited benefits from screening these factors in young patients with VTE. Weight reduction and smoking cessation strategies are key targets for CVD prevention.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 2","pages":"Article 100059"},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747947","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":"Dose-dependent effects of eltrombopag iron chelation on platelet formation","authors":"Elisabetta Bassi ,&nbsp;Vittorio Abbonante ,&nbsp;Alicia Aguilar ,&nbsp;Hana Raslova ,&nbsp;James B. Bussel ,&nbsp;Christian Andrea Di Buduo ,&nbsp;Alessandro Malara ,&nbsp;Alessandra Balduini","doi":"10.1016/j.bvth.2025.100060","DOIUrl":"10.1016/j.bvth.2025.100060","url":null,"abstract":"<div><h3>Abstract</h3><div>Iron deficiency is associated with thrombocytosis in patients, although thrombocytopenia can occur in cases of severe iron deficiency anemia. Eltrombopag (EP), a thrombopoietic agent approved for immune thrombocytopenia, also acts as an iron chelator. Our study demonstrates that megakaryocytes (MKs) exhibit an increased requirement for iron as they mature and acquire the ability to form proplatelets and release platelets. Although low EP concentrations maintain MK functions, high EP concentrations disrupt iron homeostasis, reducing proplatelet formation. Mechanistically, EP-dependent iron chelation impairs MK cytoskeletal dynamics, induces higher extracellular signal–regulated kinase 1/2 (ERK1/2) signaling, and reduces posttranslational glutathionylation of tubulin protein. Addition of exogenous iron or oxidized glutathione to high-dose EP-treated MKs counteracts the negative effect on iron status and ERK1/2 signaling, thereby rescuing proplatelet formation. Overall, these data reveal the complex role of iron status on MK cytoskeletal dynamics and platelet biogenesis and may explain the varied clinical manifestations of iron deficiency on platelet counts.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 2","pages":"Article 100060"},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839110","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":"A nonactivating ITGB3 mutation in the β3 cytoplasmic region causes macrothrombocytopenia with an impaired αIIbβ3/RhoA pathway","authors":"Keiichi Nakata ,&nbsp;Keigo Akuta ,&nbsp;Takaya Endo ,&nbsp;Midori Koike ,&nbsp;Daisuke Motooka ,&nbsp;Daisuke Okuzaki ,&nbsp;Hisashi Kato ,&nbsp;Yoshiaki Tomiyama ,&nbsp;Naoki Hosen ,&nbsp;Hirokazu Kashiwagi","doi":"10.1016/j.bvth.2024.100036","DOIUrl":"10.1016/j.bvth.2024.100036","url":null,"abstract":"<div><h3>Abstract</h3><div>Almost all mutations of <em>ITGA2B</em> or <em>ITGB3</em> identified in congenital macrothrombocytopenia induce constitutive activation of αIIbβ3. However, whether concomitant αIIbβ3 activation is essential for macrothrombocytopenia development remains unknown. Recently, we identified the β3(R760C) mutation that does not induce αIIbβ3 activation in a patient with macrothrombocytopenia. The family study showed that macrothrombocytopenia with reduced expression of αIIbβ3 and glycoprotein IV (GPVI) appeared to be associated with patients heterozygous for β3(R760C). We generated β3(R760C) knockin (KI) mice and investigated the effects of the mutation on platelet/megakaryote biology. Macrothrombocytopenia was decreased to 76% and 40% of platelet counts in heterozygous (Hetero) and homozygous (Homo) KI mice, respectively, when compared with the wild-type mice. Platelet αIIbβ3 and GPVI expression were decreased in KI mice, and αIIbβ3 activation was not detected in nonstimulated KI platelets. Thus, the hetero KI mice reproduced the phenotype of the human participant, indicating that the β3(R760C) mutation is responsible for the macrothrombocytopenia. Platelet aggregation, agonist-induced JON/A binding, and P-selectin expression were impaired in KI mice. Platelet spreading on fibrinogen was also impaired in Homo mice with adenosine 5′-diphosphate or thrombin stimulation. Filopodia and lamellipodia formation was impaired in fibrinogen-adhered megakaryocytes of Homo mice with significantly impaired RhoA activation. Proplatelet formation in Homo mice was impaired with abnormal morphology. In addition, platelet life span was shortened in Homo mice. These data indicate that the β3(R760C) mutation impairs the inside-out and outside-in signaling of αIIbβ3, and abnormal actin rearrangement and impaired RhoA activation may play major roles in macrothrombocytopenia.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 1","pages":"Article 100036"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143093714","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":"Podoplanin and microthrombi in lung injury","authors":"Jahnavi Gollamudi ,&nbsp;Ricardo Gonzalez Delgado ,&nbsp;Min Soon Cho ,&nbsp;Brianne Wharton ,&nbsp;Hani Lee ,&nbsp;Animesh Vadaparti ,&nbsp;Swapan K. Dasgupta ,&nbsp;Miguel A. Cruz ,&nbsp;Perumal Thiagarajan ,&nbsp;Vahid Afshar-Kharghan","doi":"10.1016/j.bvth.2024.100034","DOIUrl":"10.1016/j.bvth.2024.100034","url":null,"abstract":"","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 1","pages":"Article 100034"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143093756","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":"Association of high γ′ fibrinogen levels with adverse events in patients with COVID-19","authors":"Queen Revollido ,&nbsp;Lydia Buzzard ,&nbsp;David X. Lee ,&nbsp;Matthew Strnad ,&nbsp;Scott McLoud ,&nbsp;Akram Khan ,&nbsp;William B. Messer ,&nbsp;David H. Farrell","doi":"10.1016/j.bvth.2025.100048","DOIUrl":"10.1016/j.bvth.2025.100048","url":null,"abstract":"","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 1","pages":"Article 100048"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349954","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":"Altered shear stress of blood flow causes plasma membrane damage in endothelial cells","authors":"Nikita Raj ,&nbsp;Chang Pan ,&nbsp;Ann Marleen Starke ,&nbsp;Anna L. L. Matos ,&nbsp;Oliver Soehnlein ,&nbsp;Volker Gerke","doi":"10.1016/j.bvth.2024.100040","DOIUrl":"10.1016/j.bvth.2024.100040","url":null,"abstract":"<div><h3>Abstract</h3><div>The endothelial lining of blood vessels faces many mechanical challenges, including the shear stress (SS) of blood flow, which render it prone to cell membrane ruptures. Such ruptures must be repaired efficiently to maintain cellular integrity and proper vascular function. However, whether SS of blood flow can indeed affect plasma membrane integrity of endothelial cells and whether any ruptures occurring are repaired is not understood. Here, we show that alterations in the SS of fluid flow induce membrane damage in human endothelial cells, and membrane ruptures increase with increasing shear alterations. Furthermore, we show that inherent SS disturbances at aortic branches in mice are associated with endothelial membrane wounds, which are not observed in regions of laminar flow. We also show that endothelial membrane damages inflicted by shear stress alterations are repaired by a Ca²⁺-dependent process that involves early endosome exocytosis to provide membrane material for wound closure, suggesting conserved and robust membrane repair responses to endothelial damage in vitro and in vivo. Thus, shear stress alterations, which frequently occur at sites of endothelial dysfunction and before associated pathophysiology, cause membrane wounds in the endothelium, which are repaired efficiently to maintain a functional vasculature.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 1","pages":"Article 100040"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143093715","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":"Large language models for chart review: how machine learning can accelerate hematology research","authors":"Barbara D. Lam ,&nbsp;Peiqi Wang ,&nbsp;Shengling Ma ,&nbsp;Omid Jafari ,&nbsp;Iuliia Kovalenko ,&nbsp;Ang Li","doi":"10.1016/j.bvth.2025.100052","DOIUrl":"10.1016/j.bvth.2025.100052","url":null,"abstract":"","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 1","pages":"Article 100052"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349955","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":"Antithrombin regulates neutrophil activities through the stimulation of C-type lectin family 1A","authors":"Yohei Takahashi ,&nbsp;Soe Soe Htwe ,&nbsp;Dengli Wang ,&nbsp;Hidenori Wake ,&nbsp;Mariko Yata ,&nbsp;Nahoko Tomonobu ,&nbsp;Rie Kinoshita ,&nbsp;Masakiyo Sakaguchi ,&nbsp;Masahiro Nishibori","doi":"10.1016/j.bvth.2024.100032","DOIUrl":"10.1016/j.bvth.2024.100032","url":null,"abstract":"<div><h3>Abstract</h3><div>It has been suggested that a serine proteinase inhibitor, antithrombin (AT), exerts anti-inflammatory effects on different types of cells, independent of thrombin inhibition. In this study, we aimed to identify a specific receptor for AT by a screening method using a transmembrane–tethered AT ligand expressed on HEK293T cells together with the coexpression of candidate receptors, followed by the immunoprecipitation of a complex of AT ligand with a receptor. We identified C-type lectin family 1A (CLEC1A) as a receptor for AT. We confirmed the binding of AT to the extracellular domain of CLEC1A using surface plasmon resonance. Recombinant as well as native AT concentration-dependently induced the rounding of purified human neutrophils in shape, associated with the suppression of spontaneous reactive oxygen species production in vitro, but argatroban did not, indicating the independence of AT effects on thrombin inhibition. Native AT maintained the passage of neutrophils through the artificial microcapillaries. Both AT enhanced the phagocytosis of pHrodo-labeled <em>Escherichia coli</em> and prolonged the viability of the neutrophils. The cellular effects of AT were similar to those of histidine-rich glycoprotein, which has the same CLEC1A as a receptor, and were partially inhibited by the addition of anti-CLEC1A antibody to the incubation media. These results suggested that CLEC1A is a novel receptor for AT, and the stimulation of CLEC1A by AT at least in part mediates the important functional changes of human neutrophils.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 1","pages":"Article 100032"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143093757","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}