Journal of Thrombosis and Haemostasis最新文献

{"title":"Interleukin-1α alters megakaryocyte maturation, promotes emperipolesis, and induces a distinct proteomic profile.","authors":"Robert Kolman, Hannah Voß, Ivana Bertović, Josip Peradinović, Ivana Munitić, Daniel Robert Engel, Olga Shevchuk, Antonija Jurak Begonja","doi":"10.1016/j.jtha.2025.08.037","DOIUrl":"10.1016/j.jtha.2025.08.037","url":null,"abstract":"<p><strong>Background: </strong>Megakaryocytes (MKs) are large, polyploid cells and precursors of blood platelets. Interleukin (IL)-1α is a proinflammatory cytokine and a known mediator of emergency thrombopoiesis. However, its effect on MK maturation in vitro has not been studied in detail.</p><p><strong>Objectives: </strong>We aimed to investigate the phenotypical and molecular consequences of IL-1α-based MK maturation.</p><p><strong>Methods: </strong>Murine bone marrows were cultured in the presence of IL-1α, in addition to thrombopoietin (TPO), in vitro and analyzed for MK maturation at days 3 and 5 of culture. Furthermore, proteome analysis of MKs cultured with IL-1α and/or TPO was performed.</p><p><strong>Results: </strong>IL-1α induced differentiation of a greater number of larger MKs with higher ploidy and increased the release of platelet-like particles, but had decreased expression of maturation markers. Interestingly, we found a significantly higher rate of emperipolesis, characterized by transiently present Ly6G+ neutrophils within the MK cytoplasm in early cultures, which was dependent on IL-1α. At later stages, IL-1α-cultured MKs were morphologically indistinguishable from TPO-cultured MKs, although they kept the ability to produce more platelet-like particles. Proteome analysis further revealed a significantly higher abundance of neutrophil-related proteins, antimicrobial peptides, and inflammation-related proteins in early-stage IL-1α-cultured MKs, a pattern that persisted throughout late maturation.</p><p><strong>Conclusion: </strong>Taken together, these results shed light on the modulatory role of IL-1α on MK maturation, influencing not only platelet biogenesis but also promoting emperipolesis and an immune-driven proteomic MK phenotype.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091873","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":"Upper extremity post-thrombotic syndrome score: consensus results from an international Delphi study.","authors":"Tjep Hoedemakers, Eline S van Hattum, Bart-Jeroen Petri, Gert J de Borst","doi":"10.1016/j.jtha.2025.08.026","DOIUrl":"10.1016/j.jtha.2025.08.026","url":null,"abstract":"<p><strong>Background: </strong>There is no gold standard to diagnose or classify upper extremity post-thrombotic syndrome (UE-PTS). Recently, 2 Delphi consensus studies were conducted to develop a score for diagnosing and classifying UE-PTS.</p><p><strong>Objectives: </strong>The aim of the present study was to gain expert consensus on the definitions of the individual components of the UE-PTS score to enable the consistent application of this score.</p><p><strong>Methods: </strong>The Delphi approach was chosen as the appropriate method to gain expert consensus, and 53 experts were invited to participate. Definitions were collaboratively developed by a Delphi Steering Committee together with UE-PTS patients. Experts were asked to provide feedback and rated the proposed definitions across 3 Delphi rounds using a 9-point Likert scale, with consensus defined as ≥75% of scores ≥7.</p><p><strong>Results: </strong>Thirty-five of the 53 (66%) experts agreed to participate in this Delphi study. The expert panel included vascular surgeons, internists, hematologists, and physical therapists. In round 1, 45 alternative definitions or comments were collected. In round 2, no consensus was reached for any statement. In round 3, consensus was reached for all statements, with the highest level of consensus being 96% for the symptoms: heavy feeling of the arm, fatigue when using arm, and pain (chronic or during specific exercises).</p><p><strong>Conclusion: </strong>Consensus was reached on the optimal definitions of 5 symptoms and 2 clinical signs of the UE-PTS score. The next step is to validate and finalize the UE-PTS score in a patient cohort before it can be implemented in future research and clinical practice.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091913","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":"Walking capacity and venous claudication after deep vein thrombosis: prospective follow-up, risk factors, and quality of life.","authors":"Daniel Steiner, Stephan Nopp, Timothy Hoberstorfer, Ingrid Pabinger, Eva Dassler, Moritz Staudacher, Markus Müller, Sabine Steiner, Benedikt Weber, Philip Kienzl, Cihan Ay, Oliver Schlager","doi":"10.1016/j.jtha.2025.08.038","DOIUrl":"10.1016/j.jtha.2025.08.038","url":null,"abstract":"<p><strong>Background: </strong>Data on the course of walking capacity after acute deep vein thrombosis (DVT) are scarce.</p><p><strong>Objectives: </strong>The aim of this prospective observational study was to assess the course of walking impairment and venous claudication after DVT and the association with clinical characteristics and quality of life (QoL).</p><p><strong>Methods: </strong>Walking capacity was assessed by standardized treadmill exercise tests (TETs) at DVT diagnosis and after 3 months. Pain-free walking distance (PWD) and maximum walking distance (MWD) were recorded. Venous claudication during TET was evaluated and documented by trained biomedical scientists according to a standardized protocol. QoL was evaluated with the EuroQoL Group 5-Dimension 5-Level and the VEnous INsufficiency Epidemiologic and Economic Study (VEINES-QoL/Sym) questionnaires.</p><p><strong>Results: </strong>Seventy-three patients (30.1% women; median age, 53.8 years; IQR, 42.9-60.0 years) were included. PWD and MWD generally improved over time, with a median change of 305 m (IQR, 33-710 m) and 30 m (IQR, 0-258 m), respectively. However, 16 (28.1%) patients reported persistent venous claudication after 3 months. Patients with venous claudication after 3 months tended to have higher rates of suprainguinal DVT, higher body mass index, and higher rates of arterial hypertension and were admitted to the hospital at DVT diagnosis more often. Generic and disease-specific QoL improved overall, but patients with venous claudication had significantly lower QoL scores than those without.</p><p><strong>Conclusion: </strong>Walking capacity generally improved after DVT, but about one-third of patients had persisting venous claudication after 3 months, which was associated with poorer QoL. Suprainguinal DVT, higher body mass index, arterial hypertension, and hospital admission at diagnosis were more common in patients with venous claudication 3 months after DVT.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091994","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":"Platelets as evolution's answer to both hemorrhage and infection.","authors":"Gerard Gurumurthy, Jecko Thachil","doi":"10.1016/j.jtha.2025.09.002","DOIUrl":"10.1016/j.jtha.2025.09.002","url":null,"abstract":"<p><p>Hemorrhage and infections have remained substantial causes of mortality and morbidity throughout history. Platelets are classically known for their role in thrombosis. However, our recent understanding has revealed their role in innate immunity. This historical sketch explores the evolutionary origins of platelets through the concept of immunothrombosis. We trace the emergence of hemocytes in invertebrates, the development of thrombocytes in early vertebrates, and the eventual rise of anucleate platelets in mammals. Mammalian platelet fragments retain immune capabilities alongside their clotting abilities. These include pathogen sensing, antimicrobial peptide release, and coordination with leukocytes. Evolutionary pressures may have shaped blood-based systems that rapidly respond to both vascular injury and microbial invasion. We argue that platelets represent an elegant solution to the evolution's threats of hemorrhage and infection.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091812","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":"Obituary: Gualtiero Palareti (1943-2025).","authors":"Giancarlo Castaman, Valerio De Stefano","doi":"10.1016/j.jtha.2025.08.035","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.08.035","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145301607","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":"Platelet-immune cell communication in pregnancy: exploring a new frontier in maternal immunology.","authors":"Shrey Kohli, Sandra M Blois","doi":"10.1016/j.jtha.2025.08.031","DOIUrl":"10.1016/j.jtha.2025.08.031","url":null,"abstract":"<p><p>Pregnancy requires immune tolerance to the semiallogeneic fetus, mediated by regulatory T-cells and antiinflammatory cytokines (eg, interleukin 10 and transforming growth factor β), alongside a hypercoagulable state with elevated procoagulant factors and suppressed anticoagulants. In preeclampsia, a major cause of maternal and perinatal morbidity affecting 5% to 8% of pregnancies, excessive T-helper 1/ T-helper 17 responses, reduced Treg activity, and heightened platelet activation drive systemic inflammation, endothelial dysfunction, and microvascular thrombosis are established. Platelets, beyond hemostasis, modulate immune responses by interacting with neutrophils, monocytes, and T-cells via mediators such as P-selectin and CD40 ligand, promoting platelet-leukocyte aggregates, neutrophil extracellular traps, and proinflammatory cytokines (eg, interleukin 6 and tumor necrosis factor α). These interactions amplify coagulation via tissue factor expression, creating a pathogenic immune-hemostatic feedback loop. Deficiencies in coagulation regulators such as thrombomodulin and endothelial protein C receptor, exacerbate platelet activation and embryonic lethality, while galectins (eg, galectin 1 and 3) may mediate platelet-immune crosstalk. This article highlights the need for interdisciplinary research to elucidate these mechanisms, offering potential for novel biomarkers and therapeutic targets to improve management of vascular complications in pregnancy and maternal-fetal outcomes.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065027","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":"Toward targeting of inflammasome signaling in venous thrombosis.","authors":"Rana Dhar, Rinaldo R Dos Passos, R Michael Gower, Abhishek Jain, Colin E Evans","doi":"10.1016/j.jtha.2025.08.032","DOIUrl":"10.1016/j.jtha.2025.08.032","url":null,"abstract":"<p><p>Deep vein thrombosis (DVT) is a serious and debilitating vascular condition with sequelae that include postthrombotic syndrome and pulmonary embolism. Current treatments for DVT are limited by their contraindications and suboptimal safety profiles. Pharmacological approaches that safely and effectively reduce thrombus formation are being investigated in laboratory and clinical settings, including agents that aim to inhibit the interplay between thrombosis and inflammation. Recent studies have shown that inflammasome complexes-multiprotein inflammatory complexes activated by pathogen-associated molecular patterns and damage-associated molecular patterns-play a role in the development and propagation of DVT. Thus, inflammasome complexes have attracted considerable interest as possible therapeutic targets for the treatment of DVT. This review summarizes the current knowledge on inflammasome complexes and discusses studies on their role and therapeutic potential in DVT. An improved understanding of inflammasome-dependent regulation of DVT could lead to the development of safe and effective treatments for patients affected by this condition.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064996","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 hepatic Odyssey of Adeno-associated virus: from gene delivery to long-term outcomes.","authors":"Giulia Simini, Paul Batty","doi":"10.1016/j.jtha.2025.08.028","DOIUrl":"10.1016/j.jtha.2025.08.028","url":null,"abstract":"<p><p>Adeno-associated virus (AAV) vectors are the most developed approach for in vivo gene therapy. This treatment has resulted in therapeutically meaningful treatment responses for a range of monogenic inherited disorders, including hemophilia. Understanding the core stages in the lifecycle of AAV supports the shared decision-making process for clinicians and individuals considering gene therapy. These key steps start after vector infusion, including receptor engagement, cellular uptake, endosomal escape, nuclear entry, and transgene expression. All these stages could influence transduction efficiency, which could result in differences in treatment outcomes between individuals. The natural history of how AAV persists in cells could provide insights into long-term efficacy and safety. The immune system may also pose an obstacle to successful outcomes. Studies have shown that preexisting immunity to natural AAV is common and may exclude some individuals from receiving gene therapy. Additionally, asymptomatic liver enzyme elevation, which can result in loss of expression, is an important area in which more research is required. Ongoing advances in vector engineering and a better understanding of host-pathogen interactions are helping to address these challenges. This review provides a primer on the hepatic lifecycle of AAV and an introduction to the cellular and immune processes involved in AAV transduction and persistence in the liver.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058417","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":"Perioperative use of factor concentrates and blood products-a survey of clinical practices in the United States: communication from the ISTH Subcommittee on Perioperative and Critical Care.","authors":"Jerrold H Levy, Joseph R Shaw, Kamrouz Ghadimi, Cheryl L Maier, James Douketis, Keyvan Karkouti, Michael Mazzeffi, Alex C Spyropoulos, Kenichi A Tanaka, Jean M Connors, Roman M Sniecinski","doi":"10.1016/j.jtha.2025.08.029","DOIUrl":"10.1016/j.jtha.2025.08.029","url":null,"abstract":"<p><strong>Background: </strong>Educational efforts to improve perioperative physician knowledge on managing bleeding and oral anticoagulants may have influenced clinical practice. This study evaluated management strategies for major bleeding and use of fibrinogen and prothrombin complex concentrates (PCCs) across different clinical scenarios.</p><p><strong>Objectives: </strong>To assess contemporary perioperative practices in bleeding management and anticoagulant reversal among anesthesiologists in the United States.</p><p><strong>Methods: </strong>A 20-question electronic survey addressing perioperative bleeding and anticoagulant reversal management was distributed to American Society of Anesthesiologists members between June and August 2023. Responses were analyzed descriptively.</p><p><strong>Results: </strong>Among 1030 respondents (98.5% in the United States), PCCs were most frequently selected for warfarin reversal before emergency surgery (62.5%) and for perioperative major bleeding (71.5%), with 4-factor PCCs being predominant. For direct oral anticoagulant reversal, PCCs were preferred for emergency surgery (76.9%) and major bleeding (81.7%). Over half (53.1%) reported discretionary access to PCCs. Fresh frozen plasma was less commonly chosen for warfarin reversal (38.3%) and major bleeding (45.9%). Cryoprecipitate was the leading treatment for fibrinogen replacement in bleeding patients (65.9%). Most respondents (92.9%) reported a massive transfusion protocol, with 44.3% indicating inclusion of cryoprecipitate rather than fibrinogen concentrate. For severe factor deficiencies, fresh frozen plasma remained the first-line choice in cardiac surgery (60.0%), liver surgery (66.9%), and postpartum hemorrhage (71.3%).</p><p><strong>Conclusion: </strong>These findings provide an updated overview of perioperative anticoagulant reversal and bleeding management practices. The results highlight increasing reliance on PCCs and cryoprecipitate in emergency and perioperative settings, underscoring evolving trends in therapeutic decision making among anesthesiologists in the United States.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054199","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":"Simvastatin competitively inhibits cellular signaling of lipid-binding antiphospholipid antibodies.","authors":"Dominika Marova, Paul Frankenbach, Anne Hollerbach, Susanne Strand, Wolfram Ruf, Karl J Lackner, Nadine Müller-Calleja","doi":"10.1016/j.jtha.2025.08.027","DOIUrl":"10.1016/j.jtha.2025.08.027","url":null,"abstract":"<p><strong>Background: </strong>Antiphospholipid antibodies (aPLs) cause antiphospholipid syndrome (APS), a disease characterized by thrombotic events and/or pregnancy morbidity. Some clinical studies suggest that statins may beneficially affect the course of APS.</p><p><strong>Objectives: </strong>In this study, we studied the effect of statins on aPL-induced monocyte activation, aPL-triggered tissue factor (TF) activation, and the underlying cellular mechanisms.</p><p><strong>Methods: </strong>Cultured monocytes were treated with human monoclonal lipid-binding aPLs or total immunoglobulin G fractions positive for cardiolipin antibodies with or without statins. Expression of TF and tumor necrosis factor α (TNFα) messenger RNA was measured by real-time quantitative polymerase chain reaction. TF activity was determined using clotting assay. The effects of statins on the binding and internalization of aPL were determined by confocal microscopy and flow cytometry.</p><p><strong>Results: </strong>Simvastatin completely inhibited the induction of TNFα and TF messenger RNA by human lipid-binding aPLs. Simvastatin also prevented TF activation by aPL on the cell surface. These effects were not mediated by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition, but simvastatin and other statins prevented lipid-binding aPLs from binding to their cell-surface target, ie, lysobisphosphatidic acid (LBPA) presented by the endothelial protein C-receptor (EPCR) by displacement of LBPA. Competition experiments indicate that statins displace LBPA from the hydrophobic groove of EPCR. Consequently, aPLs could not induce any downstream cellular effects.</p><p><strong>Conclusion: </strong>Our data show that statins prevent monocyte activation and TF-triggered coagulation by interfering with binding of lipid-binding aPLs to the EPCR/LBPA complex on the cell surface of monocytes. These findings may help to understand the observed beneficial effects of statins in APS.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054258","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}