Seminars in thrombosis and hemostasis最新文献

{"title":"Platelet-Red Blood Cell Interactions in Thrombosis: Integrating Hemodynamic, Molecular, and Clinical Evidence-A Systematic Review.","authors":"Amin A Alamin, Amar I O Yahia, Eiman Ibrahim, Ghaliah Obaid Alnefaie","doi":"10.1055/a-2878-9698","DOIUrl":"10.1055/a-2878-9698","url":null,"abstract":"<p><strong>Abstract: </strong>There is growing recognition that red blood cells (RBCs) play a role in thrombosis beyond their traditional role as passive cellular components. This systematic review synthesizes contemporary evidence on RBC-platelet interactions in the mechanistic, structural, and clinical domains. A comprehensive search of PubMed, Scopus, Web of Science, and ScienceDirect from January 2014 to March 2026 identified 45 eligible studies, predominantly experimental and in vitro studies, with fewer animal, computational, and clinical/translational studies. Available evidence suggests that RBCs may contribute to thrombosis through several partially overlapping pathways, including shear-dependent platelet margination, phosphatidylserine-associated thrombin generation, direct RBC-platelet adhesion, and EV-associated procoagulant activity. In addition, the biophysical properties of RBCs influence thrombus architecture, density, and stability. Clinical studies have suggested an association between altered RBC function and thrombotic risk in conditions such as polycythemia, diabetes mellitus, and sickle cell disease. However, despite consistent mechanistic evidence, clinical validation remains limited, particularly in large-scale human studies. Overall, these findings support a more integrated cellular framework of thrombosis, in which RBCs may modulate platelet behavior, coagulation dynamics, and thrombus architecture. However, because most of the included studies were experimental or mechanistic, clinical translation remains limited. Future research should prioritize standardized experimental platforms, harmonized outcome measures, and prospective multicenter clinical studies before RBC-related parameters can be considered for biomarker development and therapeutic targeting.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"572-592"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148034697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Red Blood Cells in Thrombosis: Active Participants in Clot Formation and Stability- A Systematic Review.","authors":"Amin A Alamin, Amar I O Yahia, Hatim M Hussien","doi":"10.1055/a-2552-9525","DOIUrl":"10.1055/a-2552-9525","url":null,"abstract":"<p><strong>Abstract: </strong>Thrombosis, the formation of blood clots within blood vessels, has traditionally been attributed to platelets and clotting factors. Red blood cells (RBCs) play a significant role in thrombosis by impacting clot formation, stability, and fibrinolysis through mechanisms such as platelet margination, thrombin generation, and microvesicle release. However, their prothrombotic functions remain insufficiently studied. In this systematic review, which follows PRISMA guidelines, the aim is to explore how RBCs contribute to thrombus formation, stabilization, and resolution. This review analyzed peer-reviewed English-language studies and reviews on RBC involvement in thrombosis, focusing on clot formation, stability, and fibrinolysis. Studies in humans and relevant animal models were included, while case reports, non-English studies, and articles lacking methodological details were excluded. The research commenced in September 2024, utilizing PubMed, Scopus, SpringerLink, and Web of Science databases, with searches conducted up to that date. The risk of bias was assessed using the Newcastle-Ottawa Scale, and data were synthesized qualitatively. A total of 37 studies were included. RBCs contribute to thrombosis by influencing blood viscosity, interacting with platelets, and integrating into clots. Procoagulant activity induced by phosphatidylserine exposure and RBC-derived microvesicle products that promote thrombin generation and clot stability were also identified as key mechanisms. In conclusion, RBCs play an active role in thrombosis formation, contributing to clot formation and stability. Targeting RBC-mediated processes, such as aggregation, deformability, and microvesicle release, may offer novel strategies for thrombosis management. Further research and meta-analyses are needed to refine these therapeutic approaches.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"515-522"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erythrocyte Heterogeneity as a Driver of Thrombus Architecture and Treatment Response.","authors":"Regan Bucciol, Armita Zandi, Alyssa Qian, Isabell Kearn, Maha Othman","doi":"10.1055/a-2883-1203","DOIUrl":"10.1055/a-2883-1203","url":null,"abstract":"<p><strong>Abstract: </strong>Thrombi are not uniform structures, and neither are the red blood cells (RBCs) that populate them. Most models of thrombosis, however, implicitly treat erythrocytes as mechanically and biologically uniform, obscuring a key determinant of clot architecture: RBC heterogeneity. Circulating RBCs vary widely in size, shape, deformability, membrane composition, and biochemical state, generating subpopulations that behave differently under flow and within forming thrombi. These differences actively govern how RBCs marginate, where they localize during thrombus growth, how they interact with fibrin and platelets, and how they resist or accommodate platelet-driven contraction. The outcome is not merely variable RBC content but spatially organized thrombi with region-specific mechanics, permeability, and fibrinolytic susceptibility. Experimental models and analyses of patient-derived thrombi demonstrate that RBCs are unevenly distributed within clots. This spatial variability shapes local fibrin architecture, platelet activity, and clot mechanics in ways that cannot be inferred from total RBC content or average erythrocyte properties, highlighting RBC heterogeneity as a critical, yet underrecognized, determinant of thrombus formation. In this review, we present a conceptual framework of thrombus heterogeneity along three coupled axes, namely, mechanical, structural, and biochemical, illustrating how erythrocyte subpopulations influence clot formation and function. We synthesize emerging evidence, discuss approaches for identifying RBC subpopulations, and explore implications for thrombosis modeling, thrombolysis, thrombectomy, and clinical outcomes.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"550-560"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148034686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Red Blood Cells in Hemostasis and Thrombosis: Mechanisms, Interactions, and Clinical Implications.","authors":"Regan Bucciol, Maha Othman","doi":"10.1055/a-2876-0956","DOIUrl":"https://doi.org/10.1055/a-2876-0956","url":null,"abstract":"","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":"52 5","pages":"495-496"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148309353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Red Blood Cell Piezo1 Activation Drives Faster Coagulation and Structural Alterations in Blood Clots through Red Blood Cell Deformability Impairment.","authors":"Bita Asghariastanehei, Marie Martin, Elie Nader, Hamdi Rezigue, Anaëlle de Wreede, Yesim Dargaud, Christophe Nougier, Philippe Joly, Angélica Niñoé, Stéphane Egée, Lars Kaestner, Philippe Connes","doi":"10.1055/a-2846-3643","DOIUrl":"10.1055/a-2846-3643","url":null,"abstract":"<p><strong>Objective: </strong>Red blood cells (RBCs) must be highly deformable to pass through capillaries narrower than their own diameter for delivering oxygen to the tissues. Ion channels are central regulators of RBC deformability and volume. Gain-of-function mutations in <i>Piezo1</i>, as seen in hereditary xerocytosis, cause RBC dehydration and have been associated with an increased risk of thromboembolism. Here we investigated how pharmacological RBC-Piezo1 activation affects RBC membrane potential, RBC ion content, RBC deformability, coagulation dynamics, and clot structure.</p><p><strong>Study design: </strong>Blood samples were collected from healthy donors. RBCs were isolated and incubated with Yoda1, a drug known to activate Piezo1. Membrane potential was measured using the Macey-Bennekou-Egée method. Intracellular Na⁺/K⁺ content was determined by flame photometry. RBC deformability was measured by ektacytometry. Coagulation dynamics were investigated by rotational thromboelastometry, and clot structure was observed by electron microscopy.</p><p><strong>Results: </strong>Yoda1 treatment led to RBC membrane hyperpolarization, reduced cell volume, a decrease in intracellular K⁺, an increase in Na⁺, and a reduction in RBC deformability. ROTEM analysis showed shorter clotting and lysis times in Yoda1-treated samples compared with samples treated with the vehicle (control condition), independently of RBC phosphatidylserine exposure. Electron microscopy revealed structural alterations in Yoda1-treated samples, with less compacted RBCs.</p><p><strong>Conclusion: </strong>Altogether, these findings indicate that Piezo1 activation disrupted RBC ion balance and membrane potential, leading to dehydration and decreased deformability. These alterations contributed to accelerated coagulation and compromised clot structure, suggesting a potential role of Piezo1 in modulating thrombotic risk in RBC-related disorders.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"601-612"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147594199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Red Blood Cells are Critical for Hemostasis and Thrombosis.","authors":"Hyunjung Kim, Katie Houck, Sam Neuffer, Jing-Fei Dong","doi":"10.1055/a-2640-3081","DOIUrl":"10.1055/a-2640-3081","url":null,"abstract":"<p><strong>Abstract: </strong>Hemostasis in humans has traditionally been considered to be a function of platelets, coagulation, and the subendothelial matrix, but the role of red blood cells (RBCs) has been increasingly recognized. RBCs regulate hemostasis through biophysical and biochemical means. For the former, faster-moving RBCs in the center of vessels marginalize platelets and plasma to the vessel walls, where the platelets constantly probe the endothelial surface for injury. RBC counts also determine blood viscosity, which regulates the shear stress of laminar blood flow. For the latter, RBCs are the largest pool of adenosine triphosphate (ATP), which, upon release, is rapidly hydrolyzed to adenosine diphosphate (ADP). Both ATP and ADP activate platelets. Quantitative and qualitative abnormalities in RBCs have also been consistently identified as significant risk factors for arterial and venous thrombosis. Thrombosis is a major complication associated with diseases such as polycythemia vera, secondary erythrocytosis, and sickle cell anemia, all of which present with changes in numbers and physical properties of RBCs. Thrombosis is also common in conditions with significant hemolysis, such as paroxysmal nocturnal hemoglobinuria, severe infections, and when patients are on mechanical support. In this review, we discuss findings from clinical observations and mechanistic studies of how RBCs regulate hemostasis and contribute to thrombosis.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"507-514"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Erythrocyte-ROS Axis in Thrombosis and Hemostasis.","authors":"Serena Borghi, Francesca Nencini, Elvira Giurranna, Claudia Fiorillo, Matteo Becatti","doi":"10.1055/a-2615-0136","DOIUrl":"10.1055/a-2615-0136","url":null,"abstract":"<p><strong>Abstract: </strong>Thrombosis and hemostasis are critical processes that maintain vascular integrity, yet imbalances can lead to life-threatening cardiovascular events. Traditionally, erythrocytes were considered passive bystanders in coagulation, but emerging evidence highlights their active role in thrombogenesis, particularly through redox biology. Erythrocytes generate reactive oxygen and nitrogen species (RONS) via Hb autoxidation, NADPH oxidase activation, and external uptake from other blood components. This oxidative environment induces structural and functional modifications, including increased rigidity, phosphatidylserine exposure, microvesicle release, and enhanced adhesion to endothelial cells and platelets, all contributing to a prothrombotic phenotype. Hemorheological alterations such as increased aggregation and decreased deformability further exacerbate blood stasis and thrombus formation. Oxidative stress also accelerates hemolysis, releasing free Hb and heme, which trigger inflammatory responses and endothelial dysfunction, further amplifying thrombogenic potential. Additionally, erythrocyte-derived microvesicles act as carriers of procoagulant factors, enhancing thrombin generation and fibrin network formation. These mechanisms underscore the erythrocyte-ROS axis as a crucial determinant of thrombosis. Despite these insights, the full scope of erythrocyte-mediated redox signaling in thrombotic processes remains incompletely understood. This review discusses the multifaceted impact of erythrocyte oxidative stress on thrombosis and hemostasis, exploring its implications in cardiovascular diseases, metabolic disorders, and hematological conditions. Understanding these pathways may lead to novel therapeutic approaches targeting erythrocyte redox homeostasis to mitigate thrombotic risk and improve patient outcomes.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"523-536"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Red Blood Cell Extracellular Vesicles as Key Players in Thromboinflammation.","authors":"Denis F Noubouossie, Nigel S Key","doi":"10.1055/a-2664-0871","DOIUrl":"10.1055/a-2664-0871","url":null,"abstract":"<p><strong>Abstract: </strong>Thromboinflammation is an emerging concept which highlights the interactions between coagulation and inflammation in various disease states. Activation of coagulation and inflammation are both hallmarks of hemolytic states. However, the mechanisms by which they cause adverse outcomes in hemolytic disorders is incompletely understood. A body of literature suggests that red blood cells (RBCs) play a role in thrombosis and in immune regulation. RBCs release extracellular vesicles (RBC-EVs), with increased numbers found in the circulation of patients with hemolytic disorders. In this review, we summarize the existing literature addressing the interaction of RBC-EVs with coagulation and inflammatory pathways <i>in vitro</i> and <i>in vivo</i>. Additionally, we discuss the potential contribution of RBC-EV-induced thromboinflammation in the pathogenesis of certain complications of sickle cell disease as a model of a severe hemolytic disorder.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"537-549"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Red Blood Cells and Tranexamic Acid in the Inhibition of Fibrinolysis.","authors":"Nikolett Wohner, Kata Balog Virag, Alexandra Raska, Krasimir Kolev","doi":"10.1055/a-2609-3677","DOIUrl":"10.1055/a-2609-3677","url":null,"abstract":"<p><strong>Abstract: </strong>Tranexamic acid (TXA) is a widely used and cost-effective antifibrinolytic agent that has been utilized for decades in various clinical situations involving bleeding complications. Over time, a growing amount of clinical evidence has emerged, offering a robust basis for its applications.</p><p><strong>Abstract: </strong>However, in certain clinical scenarios, TXA appears to be less effective, highlighting the need for further research into its mechanisms of action beyond its well-known antifibrinolytic effects. One area of particular interest is the interaction between TXA and blood cells, especially red blood cells (RBCs). This interaction has garnered significant attention due to intriguing findings from large clinical trials, such as the WOMAN-1 and -2 studies, which evaluated the efficacy of TXA in preventing bleeding in postpartum hemorrhage, a major childbirth complication. These trials revealed that TXA was less effective in anemic patients, raising important questions about its broader mechanisms of action.</p><p><strong>Abstract: </strong>Emerging evidence suggests that the relationship between TXA and blood cells plays a crucial role at various stages of hemostasis, expanding its established role in fibrinolysis inhibition. Recent investigations into the interactions between TXA and RBCs have been particularly compelling and may provide valuable insights for improving clinical outcomes.</p><p><strong>Abstract: </strong>This review provides a fresh look at the interplay between RBCs, TXA, and the hemostatic system, focusing on basic molecular mechanisms and their potential implications for clinical practice.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"593-600"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13290354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Too Old for PESI?: Risk Stratification of Octogenarians with Pulmonary Embolism in the Emergency Department.","authors":"Alexandra J Lipa, Karin Janata-Schwatczek, Max Sterz, Roman Brock, Andrea Kornfehl, Harald Herkner, Christian Schoergenhofer, Michael Schwameis, Juergen Grafeneder","doi":"10.1055/a-2896-8297","DOIUrl":"10.1055/a-2896-8297","url":null,"abstract":"<p><strong>Abstract: </strong>Pulmonary embolism (PE) in octogenarians (i.e., patients > 80 years) is associated with substantial morbidity and mortality, yet this population remains underrepresented in major studies. We compared the predictive performance of the Pulmonary Embolism Severity Index (PESI), simplified PESI (sPESI), European Society of Cardiology (ESC) risk classes, and National Early Warning Score (NEWS) for mortality prediction in octogenarians versus younger emergency department (ED) patients. In this single-center retrospective cohort study, adults with confirmed PE presenting to an ED in Vienna, Austria, between January 2017 and December 2024 were included. Patients were categorized as octogenarians or ≤80 years. Clinical characteristics, treatment, and outcomes were compared. Predictive performance for 30-day mortality was assessed using receiver operating characteristic analyses and diagnostic accuracy measures. Sensitivity analyses and evaluation of 7-day mortality were also performed. Among 773 patients, 114 were octogenarians. Compared with younger patients, octogenarians had more cardiovascular comorbidities, higher cardiac biomarker levels, more right ventricular strain, and significantly higher 30-day mortality. PESI showed the most consistent overall prognostic performance but was less accurate in octogenarians. sPESI demonstrated limited specificity because most octogenarians were classified as high risk. ESC risk classes provided moderate discrimination. NEWS ≥ 7 showed prognostic value for short-term mortality among octogenarians, although the differences from PESI were not statistically significant. Established PE prognostic tools perform less well in octogenarians. PESI showed the most consistent overall performance, while NEWS demonstrated promising short-term prognostic value that warrants further investigation.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148339929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}