Blood Vessels, Thrombosis & Hemostasis最新文献

{"title":"Endo-chip laser-induced thrombus formation: a vessel-on-chip model for in vitro testing of antithrombotic agents","authors":"Alexander Dupuy ,&nbsp;Miao Qi ,&nbsp;Jemma C. L. Fenwick ,&nbsp;Daisie M. Yates ,&nbsp;Paul R. Coleman ,&nbsp;Jennifer R. Gamble ,&nbsp;Lining Arnold Ju ,&nbsp;Freda H. Passam","doi":"10.1016/j.bvth.2025.100096","DOIUrl":"10.1016/j.bvth.2025.100096","url":null,"abstract":"<div><h3>Abstract</h3><div>Mouse models, such as the intravital laser-induced model of thrombus formation, are commonly used for mechanistic and preclinical studies in thrombosis. However, their translational value is limited by species differences. Few in vitro models incorporate laser-induced vascular injury. Here, we developed an endothelialized microfluidic device, the Endo-chip, to model thrombus formation in response to laser injury. Citrated blood was treated with IXA4, an endoplasmic reticulum stress inducer, or with antithrombotic agents including antitissue factor antibody (5G9), antiplatelet drugs (abciximab, aspirin), and anticoagulants (argatroban, heparin). Fluorescently labeled antibodies (to platelets, fibrin, or von Willebrand factor [VWF]), annexin V or the calcium dye Cal520, were added to the blood. After recalcification at 10 mM, blood was perfused through the Endo-chip at a shear rate of 100 s^–1 or 800 s^–1. Endothelial injury was induced with a 355-nm laser pulse producing a focal 10-μm injury, and phosphatidylserine exposure on endothelial cells within ∼1 cell diameter from the injury site. Annexin V-positive endothelial cells expressed tissue factor and released VWF, supporting localized platelet and fibrin deposition. The thrombus formed a teardrop morphology aligned with flow incorporating VWF with increasing shear. IXA4 enhanced platelet cytoplasmic calcium. Platelet accumulation was inhibited by abciximab but not aspirin, whereas coagulation inhibitors (5G9, argatroban, heparin) markedly reduced thrombus formation. These findings support that the Endo-chip laser-injury model incorporates key features of thrombus formation after endothelial injury, and provides a humanized, in vitro, alternative or auxiliary to mouse models for preclinical studies and antithrombotic drug development.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 4","pages":"Article 100096"},"PeriodicalIF":0.0,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145096680","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":"F9 missense variant hot spots associated with qualitative protein defects causing hemophilia B","authors":"Tirsa T. van Duijl ,&nbsp;Samantha Gouw ,&nbsp;Ina Kronevska ,&nbsp;Alette Kooiker ,&nbsp;Wil F. Kopatz ,&nbsp;Nadia Freato ,&nbsp;Marlene Beijlevelt ,&nbsp;Henrike M. Hamer ,&nbsp;Karin Fijnvandraat ,&nbsp;Joost C. M. Meijers ,&nbsp;Maartje van den Biggelaar","doi":"10.1016/j.bvth.2025.100095","DOIUrl":"10.1016/j.bvth.2025.100095","url":null,"abstract":"<div><h3>Abstract</h3><div>Hemophilia B, a rare bleeding disorder, is caused by genetic variations in <em>F9</em>. Although quantitative factor IX (FIX) deficiencies are successfully treated by protein replacement therapy, qualitative defects may result in dysfunctional proteoforms in the circulation, potentially interfering with prophylactically or therapeutically administered recombinant FIX (rFIX) concentrates. To delineate the <em>F9</em> missense variants associated with qualitative defects, we integrated genotype and phenotype from the European Association for Haemophilia and Allied Disorders <em>F9</em> Coagulation Factor Variant Database. Of the 663 patients for whom activity (FIX:Act) and antigen (FIX:Ag) data were available, 40% of patients with severe hemophilia (n = 248), 50% of patients with moderate hemophilia (n = 244), and 47% of patients with mild hemophilia (n = 171) had cross-reactive material defined as FIX:Ag ≥40%. Variants associated with qualitative defects were predominantly localized (1) at proteolytic sites for FIX processing and activation, (2) within exosite II of the serine protease domain, and (3) at calcium ion coordinating residues within the Gla/EGF-1 domain of the FIX light chain. To study the effect of dysfunctional FIX proteoforms on thrombin generation in the presence of rFIX, we investigated 2 individuals with hemophilia B harboring a variant of unknown significance with an unexplained bleeding phenotype despite prophylaxis. Ex vivo therapeutic monitoring using patient plasma supplemented with rFIX concentrates, bypassing agent or emicizumab, enabled head-to-head comparison and revealed limited normalization of the prolonged initiation phase in coagulation. Alignment of information on genotype with functional proteotype may clarify the heterogeneity in bleeding phenotype and treatment response and provide a stepping stone for personalized care.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 4","pages":"Article 100095"},"PeriodicalIF":0.0,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145049126","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 reactivity expression score in diabetes mellitus","authors":"Carine E. Hamo ,&nbsp;Matthew A. Muller ,&nbsp;Jonathan D. Newman ,&nbsp;Joshua Beckman ,&nbsp;Kelly V. Ruggles ,&nbsp;Tessa J. Barrett ,&nbsp;Jeffrey S. Berger","doi":"10.1016/j.bvth.2025.100092","DOIUrl":"10.1016/j.bvth.2025.100092","url":null,"abstract":"","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 4","pages":"Article 100092"},"PeriodicalIF":0.0,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145020474","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 novel in vitro model of trauma-induced endotheliopathy provides a platform for studying mechanisms of coagulopathy","authors":"Jeries Abu-Hanna ,&nbsp;Gang Xu ,&nbsp;Gael B. Morrow ,&nbsp;Lewis Timms ,&nbsp;Naveed Akbar ,&nbsp;Mike Laffan ,&nbsp;Robin P. Choudhury ,&nbsp;Nicola Curry","doi":"10.1016/j.bvth.2025.100087","DOIUrl":"10.1016/j.bvth.2025.100087","url":null,"abstract":"<div><h3>Abstract</h3><div>Trauma-induced coagulopathy (TIC) significantly contributes to trauma-related mortality, driven by dysregulated coagulation and fibrinolysis. Endotheliopathy of trauma (EoT) is central to TIC, yet its underlying mechanisms remain unclear. Current in vitro models fail to replicate the complex trauma environment, including hemorrhagic shock, tissue injury, and inflammation. This study aimed to develop a novel in vitro model of EoT that mimics key TIC features, enabling the investigation of endothelial contributions to TIC. Endothelial colony-forming cells (ECFCs) were exposed to trauma-relevant factors, including epinephrine, tumor necrosis factor α, interleukin 6, high mobility group box 1, hydrogen peroxide, and hypoxia. Endothelial injury markers (syndecan-1 and thrombomodulin), hemostatic protein expression, coagulation, and fibrinolysis were analyzed using enzyme-linked immunosorbent assay, immunofluorescence, global hemostasis assays, and RNA sequencing. Plasma from healthy donors and trauma patients was used to assess clinical relevance. Traumatized ECFCs exhibited progressive dysfunction, with early surface damage and sustained fibrinolytic dysregulation. Transcriptomic analysis showed activation of inflammatory pathways, metabolic shifts, and epigenetic changes. Surface expression of anticoagulant proteins decreased, whereas procoagulant tissue factor increased, heightening thrombogenic potential. Initially, traumatized ECFCs promoted fibrinolysis via thrombomodulin shedding but later secreted antifibrinolytic plasminogen activator inhibitor 1, mimicking the biphasic TIC phenotype. Plasma assays revealed thrombin generation and clot lysis changes similar to trauma patients. This in vitro model successfully replicates EoT and TIC-associated hemostatic imbalances, capturing the time-dependent evolution of endothelial dysfunction. It provides mechanistic insights into TIC and serves as a platform for testing targeted interventions to mitigate endothelial-driven coagulopathy in trauma.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 4","pages":"Article 100087"},"PeriodicalIF":0.0,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144934228","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":"M protein and the evolving spectrum of platelet-activating anti-PF4 disorders and MGTS and their linkage","authors":"Tajamul H. Mir ,&nbsp;Rushad Patell ,&nbsp;Jason A. Freed","doi":"10.1016/j.bvth.2025.100093","DOIUrl":"10.1016/j.bvth.2025.100093","url":null,"abstract":"","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 4","pages":"Article 100093"},"PeriodicalIF":0.0,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932255","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":"How genetic advances are being translated into improved diagnostic outcomes for patients with inherited bleeding disorders","authors":"Megan Chaigneau ,&nbsp;Mackenzie Bowman ,&nbsp;Andrea Guerin ,&nbsp;Paula James","doi":"10.1016/j.bvth.2025.100090","DOIUrl":"10.1016/j.bvth.2025.100090","url":null,"abstract":"<div><h3>Abstract</h3><div>Inherited bleeding disorders are a heterogenous group of conditions characterized by the presence of abnormal bleeding. Currently, the diagnostic odyssey for patients with a suspected bleeding disorder is lengthy, costly, resource intensive, emotionally draining, and often futile, because up to half of patients will remain without a clear diagnosis. Genetic testing has been suggested as a possible remedy for these diagnostic challenges and is increasingly incorporated into clinical care. In this review, we outline 3 factors that contributed to the translation of genetic advances into improved diagnostic outcomes. These include the early success experienced with hemophilia, advances in genetic sequencing technology, and significant investment by the hemostasis scientific community. We also identify 3 areas for improvement to facilitate ongoing translation, highlighting the need to optimize integration of genetic and genomic testing into diagnostic pathways and improve variant classification through ongoing research and curation efforts, and reconsider whether incidental and secondary findings represent a disadvantage or an opportunity.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 4","pages":"Article 100090"},"PeriodicalIF":0.0,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144934227","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":"Bacterial infection and activation of the contact pathway of coagulation","authors":"André L. Lira ,&nbsp;Cristina Puy ,&nbsp;Joseph J. Shatzel ,&nbsp;Florea Lupu ,&nbsp;Owen J. T. McCarty","doi":"10.1016/j.bvth.2025.100091","DOIUrl":"10.1016/j.bvth.2025.100091","url":null,"abstract":"<div><h3>Abstract</h3><div>The excessive inflammatory and prothrombotic response to a bacterial infection creates a life-threatening medical condition in sepsis. The transition from localized to systemic thrombin generation is a hallmark of disseminated intravascular coagulation (DIC), a severe prothrombotic disorder resulting in microvascular thrombosis and subsequent multiorgan failure. The contact pathway of coagulation has been shown to play roles both in the initiation and amplification of thrombin generation in models of sepsis. The contact pathway consists of the coagulation factors XII (FXII) and XI (FXI), prekallikrein, and high- molecular-weight kininogen. Activation of the contact pathway can be triggered by binding to anionic surfaces, such as the ionized phosphoryl and carboxylate groups present on bacterial surface macromolecules. In particular, FXII has been shown to bind to the components of the bacterial envelope, including adhesins, peptidoglycan, lipopolysaccharides from gram-negative bacteria, and lipoteichoic acids from gram-positive bacteria. This review discusses the molecular pathways linking activation of the contact pathway by the envelope structures of bacterial and downstream thrombin generation and inflammation associated with sepsis-induced coagulopathies. We highlight the potential for FXII and FXI as potential therapeutic options for safely preventing DIC in sepsis.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 4","pages":"Article 100091"},"PeriodicalIF":0.0,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145020443","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":"Ticagrelor promotes arterial healing and shows superiority to clopidogrel in preventing neoatherosclerosis","authors":"Romain Solinhac ∗ ,&nbsp;Amandine Wahart ∗ ,&nbsp;Adrien Lupieri ,&nbsp;Clément Servoz ,&nbsp;Natalia F. Smirnova ,&nbsp;Marie-Pierre Gratacap ,&nbsp;Bernard Payrastre ,&nbsp;Nicole Malet ,&nbsp;Kevin Cormier ,&nbsp;Stéphanie Gayral ,&nbsp;Nathalie Augé ,&nbsp;Hugo Cavalerie ,&nbsp;Didier Carrié ,&nbsp;Thibault Lhermusier ,&nbsp;Damien Ramel ,&nbsp;Muriel Laffargue","doi":"10.1016/j.bvth.2025.100089","DOIUrl":"10.1016/j.bvth.2025.100089","url":null,"abstract":"","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 4","pages":"Article 100089"},"PeriodicalIF":0.0,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145049789","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":"The kinetics and interplay of thrombin inhibition by 4 plasma proteinase inhibitors","authors":"Allen Ma ,&nbsp;Dougald M. Monroe ,&nbsp;Maureane Hoffman","doi":"10.1016/j.bvth.2025.100088","DOIUrl":"10.1016/j.bvth.2025.100088","url":null,"abstract":"<div><h3>Abstract</h3><div>A novel therapeutic approach for restoring hemostasis in hemophilia is to reduce antithrombin (AT) to rebalance reduced thrombin generation. In plasma, multiple inhibitors including AT, heparin cofactor II (HCII), α₂-macroglobulin (A2M), and α₁-proteinase inhibitor (A1PI) play a role in thrombin inhibition. The goal was to study the kinetics of thrombin inhibition and the roles of various inhibitors across a broad range of AT levels. Thrombin inhibition was measured at varied concentrations of AT with and without A2M, HCII, and A1PI. Reducing AT to 0 from plasma levels in the presence HCII, A2M, and A1PI, results in slower thrombin inhibition with the time required to inhibit half the thrombin increasing approximately fourfold. Computational models of thrombin inhibition and thrombin generation in hemophilia were constructed and used to analyze thrombin inhibition and the relative contribution of each inhibitor. In a model of thrombin generation, decreased thrombin inhibition resulted in increased peak thrombin and increased area under the thrombin curve. Even at high concentrations of thrombin, all of the thrombin was inhibited with the relative contribution of other inhibitors increasing as AT was decreased. These studies show that in a system without heparin-like glycosaminoglycans, AT is the dominant inhibitor of thrombin, followed by A2M, HCII, and, finally, A1PI. As AT levels decrease, thrombin inhibition is slower, resulting in higher levels of thrombin in a computational model of thrombin generation. Ultimately, the other inhibitors compensate for AT to maintain a level of thrombin regulation.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 4","pages":"Article 100088"},"PeriodicalIF":0.0,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026295","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":"Evaluation of an IgG anti-PF4/H chemiluminescent immunoassay in the diagnosis of heparin-induced thrombocytopenia","authors":"Carla Rial ∗ ,&nbsp;Nicolas Gendron ∗ ,&nbsp;Christine Le Beller ,&nbsp;Shaya Sable ,&nbsp;Aurélie Sarthou ,&nbsp;Laetitia Mauge ,&nbsp;Justine Piazza ,&nbsp;Roya Nili ,&nbsp;Maude Laney ,&nbsp;Isabelle Presot ,&nbsp;Jean-Luc Diehl ,&nbsp;Anne Godier ,&nbsp;Agnès Lillo-Le Louet ,&nbsp;David M. Smadja ,&nbsp;Dominique Helley","doi":"10.1016/j.bvth.2025.100084","DOIUrl":"10.1016/j.bvth.2025.100084","url":null,"abstract":"<div><h3>Abstract</h3><div>Heparin-induced thrombocytopenia (HIT) is a life-threatening complication of heparin therapy, mediated by immunoglobulin G (IgG) antibodies targeting platelet factor 4/heparin (PF4/H) complexes. Prompt and accurate diagnosis is critical to ensure appropriate treatment and improve outcomes. We aimed to evaluate the performance of the rapid chemiluminescent immunoassay (CLIA) HemosIL AcuStar HIT-IgG (Werfen) for detecting IgG anti-PF4/H antibodies for HIT diagnosis compared with the Zymutest HIA IgG (Hyphen BioMed) enzyme-linked immunosorbent assay (ELISA). This single-center retrospective cohort included all patients with suspected HIT (4Ts score &gt;3). CLIA and ELISA were performed and compared, and results were evaluated against the serotonin-release assay. We included 113 patients with suspected HIT, and HIT was confirmed in 43 (38.1%). Discordant results occurred in 5 patients (4.4%) with confirmed HIT: 3 patients had positive ELISA and negative CLIA, one had both negative ELISA and CLIA, and one had negative ELISA and positive CLIA. CLIA demonstrated a high diagnostic accuracy, with a sensitivity of 90.7% (95% confidence interval [CI], 82.0-99.4) and specificity of 80.0% (95% CI, 70.6-89.3). ELISA showed a sensitivity of 95.3% (95% CI, 89.1-100.0) and negative predictive value of 96.3% (95% CI, 91.3-100.0) compared with 93.3% (95% CI, 87.0-99.6) for CLIA. No significant difference was observed between the 2 tests for sensitivity or specificity. Positive and negative percent agreements were 86.4% (95% CI, 77.7-95.2) and 96.3% (95% CI, 91.3-101.3), respectively. Overall percent agreement was 91.2% (95% CI, 85.9-96.4). This study supports the utility of CLIA as a rapid diagnostic tool for HIT optimizing clinical decision-making and patient management.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 4","pages":"Article 100084"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145158456","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}