{"title":"The influence of metastasis on clinical outcomes in patients with cancer-associated isolated distal deep vein thrombosis: A pre-specified subgroup analysis from the ONCO DVT study","authors":"Michihisa Umetsu , Yugo Yamashita , Takeshi Morimoto , Nao Muraoka , Yuji Nishimoto , Takuma Takada , Yoshito Ogihara , Tatsuya Nishikawa , Nobutaka Ikeda , Kazunori Otsui , Daisuke Sueta , Yukari Tsubata , Masaaki Shoji , Ayumi Shikama , Yutaka Hosoi , Yasuhiro Tanabe , Ryuki Chatani , Kengo Tsukahara , Naohiko Nakanishi , Kitae Kim , Takeshi Kimura","doi":"10.1016/j.thromres.2025.109453","DOIUrl":"10.1016/j.thromres.2025.109453","url":null,"abstract":"<div><h3>Background</h3><div>The risk–benefit balance of extended anticoagulation in patients with metastatic cancer remains unclear.</div></div><div><h3>Objectives</h3><div>This prespecified subgroup analysis aimed to evaluate the efficacy and safety of 12-and 3-month edoxaban treatment in patients with cancer-associated isolated distal deep vein thrombosis (DVT) based on cancer metastasis.</div></div><div><h3>Methods</h3><div>The ONCO DVT study, a randomized clinical trial, included 601 patients with cancer-associated isolated distal DVT, divided into metastasis (<em>N</em> = 147) and no metastasis subgroups (<em>N</em> = 454). The primary endpoint was symptomatic recurrent venous thromboembolism (VTE) or VTE-related death at 12 months, and the major secondary endpoint was major bleeding at 12 months.</div></div><div><h3>Results</h3><div>The cumulative incidence of the primary endpoint was lower in the 12-month edoxaban group than in the 3-month edoxaban group in both metastasis (3.2 % vs. 21.6 %, Log-rank <em>P</em> = 0.01) and no metastasis subgroups (0.5 % vs. 5.0 %, Log-rank <em>P</em> = 0.006). The cumulative incidence of the major secondary endpoint did not differ between the 2 groups in the metastasis subgroup (13.7 % vs. 16.2 %, Log-rank <em>P</em> = 0.42), but it was numerically higher in the 12-month group than in the 3-month group in the no metastasis subgroup (9.6 % vs. 4.7 %, Log-rank <em>P</em> = 0.051).</div></div><div><h3>Conclusions</h3><div>Compared with 3-month edoxaban treatment, the 12-month treatment significantly reduced thrombotic risk in cancer-associated isolated distal DVT without increasing bleeding risk in patients with metastasis, suggesting that prolonged anticoagulation therapy had potential benefits for these patients. However, the bleeding risk was higher in the 12-month compared with 3-month edoxaban treatment in patients without metastasis.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"254 ","pages":"Article 109453"},"PeriodicalIF":3.4,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yucao Ma , Wenjing Yao , Haiyan Lang , Yuxin Cheng , Ruhua Ren , Yuecan Chen , Sitong Cheng , Sun Shuo
{"title":"Geographic and diagnostic variations in thrombosis risk among patients with immune thrombocytopenia: A systematic review and meta-analysis","authors":"Yucao Ma , Wenjing Yao , Haiyan Lang , Yuxin Cheng , Ruhua Ren , Yuecan Chen , Sitong Cheng , Sun Shuo","doi":"10.1016/j.thromres.2025.109450","DOIUrl":"10.1016/j.thromres.2025.109450","url":null,"abstract":"<div><h3>Background</h3><div>While immune thrombocytopenia (ITP) is primarily characterized by bleeding manifestations, emerging evidence suggests a paradoxical predisposition to thrombotic events. This study aims to systematically evaluate the incidence of thrombosis in patients with ITP and identify associated risk factors, thereby providing evidence-based guidance for clinical practice.</div></div><div><h3>Methods</h3><div>PubMed, EMBASE, Cochrane Library, Web of Science, and CNKI were searched for literature on thrombosis in ITP patients from the inception of each database to April 1, 2025. Two independent researchers conducted study selection, data extraction, and quality assessment using the Newcastle-Ottawa Scale (NOS). Statistical analyses were performed using R software.</div></div><div><h3>Results</h3><div>From 20 included studies involving 100,446 ITP patients, we identified 9010 thrombotic events. The pooled incidence of thrombosis was 6.03 % (95 % CI: 4.39–8.24), increasing to 10.43 % (95 % CI: 7.17–14.93) after trim-and-fill adjustment for publication bias. Significant regional variation was observed (North America: 7.13 %; Asia: 4.50 %; Europe: 6.92 %). Incidence also varied by diagnostic criteria, ranging from 2.08 % (2020 CMACSH) to 8.18 % (2011 ASH). No significant differences were found based on gender or type of thrombosis. Key independent risk factors included advanced age (HR = 7.53), lupus anticoagulant positivity (HR = 9.9), elevated IgG-aCL (HR = 7.5), hypertension (HR = 4.12), multiple prior therapies (HR = 3.19), secondary ITP (HR = 1.29), and the use of thrombopoietin receptor agonists (HR = 3.15).</div></div><div><h3>Conclusion</h3><div>Patients with ITP have a significantly increased risk of thrombosis, highlighting the need for targeted screening and preventive strategies in high-risk populations. Future research should focus on high-quality, multicenter prospective cohort studies and the development of more accurate thrombotic risk prediction models to guide clinical decision-making.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"254 ","pages":"Article 109450"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aernoud Pieter Bavinck , Waander van Heerde , Saskia Schols
{"title":"Viscoelastic testing in patients with very rare bleeding disorders of secondary hemostasis, a scoping review","authors":"Aernoud Pieter Bavinck , Waander van Heerde , Saskia Schols","doi":"10.1016/j.thromres.2025.109449","DOIUrl":"10.1016/j.thromres.2025.109449","url":null,"abstract":"<div><h3>Introduction</h3><div>Very rare bleeding disorders (VRBDs) are hereditary disorders which cause increased risk of bleeding. In general, VRBDs consists of rare platelet function disorders, very rare coagulation factor deficiencies (other than Factor (F) VIII or FIX) and disorders of the fibrinolytic pathway. The rarity of these disorders along with the scarcity of specialized hemostasis laboratories capable to perform the necessary diagnostic tests, results in significant challenges in diagnosing and monitoring patients with VRBD. Viscoelastic testing could potentially address these challenges.</div><div>Aim</div><div>This scoping review aims to assess the validity of viscoelastic assays for diagnosing, monitoring, and risk prediction in patients with VRBDs in the secondary hemostasis.</div></div><div><h3>Methods</h3><div>Relevant studies were identified on PubMed and categorized based on the clinical scenario addressed in the study.</div></div><div><h3>Results</h3><div>Viscoelastic assays can consistently detect severe factor deficiencies, but the sensitivity is lower in patients with mild factor deficiencies. In addition to the residual factor activity, sensitivity depends on the specific viscoelastic assay used and the potential underlying genetic abnormality. Only in FXI deficiency, multiple reports reveal correlations between assay outcomes and clinical phenotype, though clinical benefit of these findings is limited by the mild strength of these correlations. In many studies, viscoelastic assays were able to monitor the effects of treatment, but just a few found associations between the assay results and risk prediction.</div></div><div><h3>Conclusion</h3><div>Severe coagulation factor deficiencies can reliably be ruled out based on viscoelastic assays. Low-quality evidence showed benefit of these assays in monitoring treatment and risk prediction in VRBDs.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"254 ","pages":"Article 109449"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145003823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thrombosis researchPub Date : 2025-09-01Epub Date: 2025-08-06DOI: 10.1016/j.thromres.2025.109426
Haoyue Jin, Binru Wang, Huina Zhu
{"title":"Comment on: \"Who am I to say that I'm not going to take it\": Patient perspectives on decisions about antithrombotic therapy in the context of advanced cancer.","authors":"Haoyue Jin, Binru Wang, Huina Zhu","doi":"10.1016/j.thromres.2025.109426","DOIUrl":"10.1016/j.thromres.2025.109426","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"253 ","pages":"109426"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Increased contact system activity three months after starting combined oral contraceptives.","authors":"Jesper Strandberg, Jette Nybo, Inger Lise Gade, Yaseelan Palarasah, Else-Marie Bladbjerg, Søren Risom Kristensen","doi":"10.1016/j.thromres.2025.109428","DOIUrl":"10.1016/j.thromres.2025.109428","url":null,"abstract":"<p><strong>Introduction: </strong>Combined oral contraceptives (COC) are associated with an increased risk of venous thromboembolism (VTE). The contact system (CAS) can, when activated, stimulate coagulation, and may play a role in thrombus formation. Our recent case-control study showed increased CAS capacity and in vivo activity in COC users, indicating a systemic activation that could contribute to VTE risk during COC treatment. Aim This study investigates intraindividual changes in CAS in women before and after start of COC treatment.</p><p><strong>Materials and methods: </strong>Twenty-four women aged between 15 and 34 years, who were starting treatment with COC, were included in the study. A baseline blood sample was drawn before start of COC, and a follow-up blood sample 3-4 months later. The capacity and activity of CAS, i.e. factor XII (FXII), prekallikrein (PK), H-kininogen (HK), C1-esterase inhibitor (C1inh), cleaved HK (cHK) and endogenous kallikrein potential (EKP), were analyzed.</p><p><strong>Results: </strong>Our study showed significantly increased levels of FXII (median 29.4 vs 42.9 mg/L; p < 0.0001) and decreased levels of C1inh (0.21 vs 0.20 g/L; p = 0.005). Increased EKP (1859 vs 2203 nmol/L*min; p = 0.0004) demonstrated an increased capacity of CAS, and increased levels of cHK (0.70 vs 0.96 μg/L; p < 0.0001) indicated an increased activity of CAS in vivo. The levels of PK and HK showed no significant changes.</p><p><strong>Conclusion: </strong>This study demonstrates an increased intraindividual CAS capacity as well as an increased CAS activity during treatment with COC supporting the previous research. These effects on CAS may contribute to the increased thrombotic risk caused by COC.</p>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"253 ","pages":"109428"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jose Pardos-Gea , Jordi Barquinero , Iñaki Alvarez , Vicente Cortina , Iris Garcia Martínez , Laura Martín Fernández , Francisco Vidal
{"title":"A comprehensive review of the autoimmune pathogenesis of acquired hemophilia A","authors":"Jose Pardos-Gea , Jordi Barquinero , Iñaki Alvarez , Vicente Cortina , Iris Garcia Martínez , Laura Martín Fernández , Francisco Vidal","doi":"10.1016/j.thromres.2025.109444","DOIUrl":"10.1016/j.thromres.2025.109444","url":null,"abstract":"<div><div>Acquired haemophilia A (AHA) constitutes the most frequent form of autoimmunity againts coagulation factors. The pathogenic basis of anti-FVIII autoantibodies production remains unknown and our narrative review explores the possible causes and provides an overview of evidence data.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"254 ","pages":"Article 109444"},"PeriodicalIF":3.4,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144917652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vanessa L. Gauvin , Marie-France N. Soucy , Jaël D. Richard , Kate A. Graham , Alexis J. Matthew , Mathieu P.A. Hébert , Jérémie A. Doiron , Mathieu Johnson , Eric P. Allain , David A. Barnett , Sandra Turcotte , Luc H. Boudreau
{"title":"The role of 12-lipoxygenase in regulating megakaryocyte maturation and platelet-like particles production","authors":"Vanessa L. Gauvin , Marie-France N. Soucy , Jaël D. Richard , Kate A. Graham , Alexis J. Matthew , Mathieu P.A. Hébert , Jérémie A. Doiron , Mathieu Johnson , Eric P. Allain , David A. Barnett , Sandra Turcotte , Luc H. Boudreau","doi":"10.1016/j.thromres.2025.109445","DOIUrl":"10.1016/j.thromres.2025.109445","url":null,"abstract":"<div><div>Megakaryocytes, a type of myeloid cell primarily produced in the bone marrow, are essential for releasing platelets into the bloodstream. Through platelet production, megakaryocytes transfer their own biological content to these cells, including inflammatory enzymes. Amongst these enzymes, 12-lipoxygenase (12-LO) has been shown to modulate platelet activation and is involved in several chronic inflammatory conditions. However, the role of 12-LO in megakaryocyte maturation and the subsequent release of platelets remains uninvestigated. This study demonstrates the importance of 12-LO expression in megakaryocyte maturation and functions. Flow cytometry and fluorescence microscopy were utilized to analyze DAMI cell differentiation. Inflammatory enzyme profiles were assessed through Western blot analysis and LC-MS/MS. To evaluate megakaryocyte functionality, platelet-type 12-LO knockout mice were employed. Differentiation of DAMI cells into mature megakaryocytes resulted in increased surface marker expression, enhanced platelet-like particle production, reduced cell proliferation, and elevated cell death. The arachidonic acid release from cell membranes was increased in differentiated cells as well as the expression of several inflammatory enzymes such as 12-LO, cyclooxygenase-1 and thromboxane synthase. The production of 12(<em>S</em>)-hydroxyeicosatetraenoic acid and thromboxane was also increased in these cells. In DAMI cells deficient in 12-LO expression (ALOX12<sup>−/−</sup>), we found no difference in CD41 expression following differentiation compared to ALOX12<sup>+/+</sup> cells. However, 12-LO-deficient cells produced fewer proplatelets and, consequently, fewer platelet-like particles. <em>In vivo</em>, platelet counts in 12-LO-deficient mice were comparable to those in wild-type mice, and the number of bone marrow megakaryocytes remained consistent between the groups. <em>Ex vivo</em> analysis revealed that megakaryocytes lacking 12-LO produced fewer platelets. These findings indicate that 12-LO may play a regulatory role in megakaryocyte function, particularly in proplatelet formation and platelet release.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"254 ","pages":"Article 109445"},"PeriodicalIF":3.4,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144911789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nancy Charó , Roberto G. Pozner , Mara C.A.M. Aguiar , Silvio Tatti , Mirta Schattner , Ricardo M. Gómez
{"title":"Yellow fever virus infection triggers proinflammatory and prothrombotic responses in endothelial cells through NF-κB and MAPK signaling pathways","authors":"Nancy Charó , Roberto G. Pozner , Mara C.A.M. Aguiar , Silvio Tatti , Mirta Schattner , Ricardo M. Gómez","doi":"10.1016/j.thromres.2025.109439","DOIUrl":"10.1016/j.thromres.2025.109439","url":null,"abstract":"<div><div>Yellow fever (YF), caused by the Yellow Fever Virus (YFV), is a disease endemic in South America and Africa with clinical manifestations ranging from fever to fatal organ failure and hemorrhagic complications. The role of the endothelium in the pathogenesis of YFV is not completely understood. To investigate the effects of YFV infection on human endothelial cells (EC), human umbilical vein endothelial cells (HUVEC) and human microvascular endothelial cells (HMEC-1) were infected with the YFV 17DD strain. Viral infection, cell death, cell adhesion, adhesion molecules, cytokines, von Willebrand factor (VWF), nitric oxide (NO), tissue factor (TF), interferon-I, clotting time and signaling pathways were analyzed by plaque assays, immunofluorescence, cytometry, ELISA, RT-qPCR, DAF-FM DA probe, Griess reaction and Western blot.</div><div>The results showed that HUVEC and HMEC-1 were susceptible to YFV infection according to virus titer and presence of intracellular dsRNA, which induced an increase in apoptosis at 3- and 7-days post-infection (pi), respectively. At earlier time points (4–48 h pi), infected EC exhibited upregulation of E-selectin and ICAM-1, secretion of IL-1β, IL-6 and VWF, decreased eNOS mRNA, NO production, clotting time, and increased TF and interferon-I mRNA levels, as well as increased adhesion of platelets and leukocytes to EC. Mechanistically, YFV infection led to activation of the NF-κB and MAPK signaling pathways.</div><div>We conclude that YFV infection triggers a proinflammatory and prothrombotic response in EC that likely contributes to the vascular dysfunction and hemorrhagic manifestations observed in YF. These findings point to potential targets for therapeutic intervention.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"254 ","pages":"Article 109439"},"PeriodicalIF":3.4,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144892818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"When clots go to court: Clinical insights from litigation for venous thromboembolism in orthopedic surgery","authors":"Kushal T. Kadakia , Behnood Bikdeli","doi":"10.1016/j.thromres.2025.109442","DOIUrl":"10.1016/j.thromres.2025.109442","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"254 ","pages":"Article 109442"},"PeriodicalIF":3.4,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}