{"title":"Loss of von Willebrand factor large multimers in patients undergoing hemodialysis: A single-center, retrospective study","authors":"Yoshinari Fujii , Satomi Nagaya , Taro Kanno , Shinya Yamada , Misako Suzuki , Kota Goto , Hisanori Horiuchi , Masanori Matsumoto , Eriko Morishita","doi":"10.1016/j.thromres.2025.109316","DOIUrl":"10.1016/j.thromres.2025.109316","url":null,"abstract":"<div><h3>Introduction</h3><div>Von Willebrand factor (VWF) is produced by vascular endothelial cells as large multimers and is cleaved by ADAMTS13 into an appropriate size in a shear stress-dependent manner. Excessive shear stress enhances VWF cleavage, leading to a hemorrhagic disease known as acquired von Willebrand syndrome. No clear reports on the prevalence of the loss of VWF large multimers in patients receiving hemodialysis are currently available. Therefore, this study investigated the prevalence of the loss of VWF large multimers in patients undergoing hemodialysis.</div></div><div><h3>Methods</h3><div>This single-center, retrospective study involved 90 patients undergoing hemodialysis and 32 healthy participants as controls. VWF antigen levels (VWF:Ag), VWF activity (VWF:RCo), and ADAMTS13 activity were measured. VWF multimer analysis was performed by modified western blotting with an agarose gel electrophoresis, followed by densitometric evaluation of band intensities to calculate the VWF large multimer index (VWF-LMI). A VWF-LMI <80 % was defined as the loss of VWF large multimers, and the prevalence of the loss of VWF large multimers was calculated.</div></div><div><h3>Results</h3><div>VWF:Ag and VWF:RCo levels in patients undergoing hemodialysis were significantly higher than those in healthy individuals (<em>p</em> < 0.01 both) and were negatively correlated with ADAMTS13 activity (<em>p</em> < 0.01, R = −0.353 and <em>p</em> < 0.01, R = −0.392, respectively). A VWF-LMI <80 % was present in 24 of 90 patients.</div></div><div><h3>Conclusions</h3><div>The loss of VWF large multimers was identified in 26.7 % of patients receiving hemodialysis. However, the prevalence of the loss of VWF multimers in these patients may be underestimated, as their relatively high VWF activity makes significant bleeding manifestations less likely.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"249 ","pages":"Article 109316"},"PeriodicalIF":3.7,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748278","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}
Alessandro Squizzato, Federica De Pascali, Vittorio Pengo, Marco P Donadini
{"title":"Efficacy and safety of low-dose acetylsalicylic acid for the prevention of thromboembolic events in individuals positive for antiphospholipid antibodies: A systematic review and meta-analysis.","authors":"Alessandro Squizzato, Federica De Pascali, Vittorio Pengo, Marco P Donadini","doi":"10.1016/j.thromres.2025.109313","DOIUrl":"https://doi.org/10.1016/j.thromres.2025.109313","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":" ","pages":"109313"},"PeriodicalIF":3.7,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773370","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}
Katarzyna Mayger , Johanna Young , Rui Leite , Kiran Parmar , Beverley J. Hunt
{"title":"Investigation of the impact of antithrombin deficiency on the inflammatory response: Results from a single centre cohort study","authors":"Katarzyna Mayger , Johanna Young , Rui Leite , Kiran Parmar , Beverley J. Hunt","doi":"10.1016/j.thromres.2025.109315","DOIUrl":"10.1016/j.thromres.2025.109315","url":null,"abstract":"<div><h3>Background</h3><div>Antithrombin signalling may exert an anti-inflammatory effect; therefore we hypothesised that individuals with inherited antithrombin deficiency (ATD) may have an altered inflammatory state.</div></div><div><h3>Aims</h3><div>To assess the inflammatory state in those with ATD compared with healthy controls (HCs), by measuring inflammatory markers.</div></div><div><h3>Methods</h3><div>A case-control study of age- and sex-matched HCs (<em>n</em> = 51) with ATD patients (n = 51). Seven inflammatory makers were selected. ELISA assays quantified: high-sensitivity C-reactive protein (hsCRP), intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1) and complement C3a-des-Arg. Circulating nucleosomes were measured using a chemiluminescence immunoassay (Nu.Q®NETs). Clauss fibrinogen and HemosIL VWF activity were also measured. Results are expressed as median (range).</div></div><div><h3>Results</h3><div>Overall analysis of ATD vs HCs showed elevated circulating nucleosomes 29.3 ng/mL [0.5–309.3] vs 21.3 ng/mL [3.7–86.3], <em>p</em> = 0.012 but no differences were observed for C3a, VCAM-1, ICAM-1, VWF and fibrinogen. ATD patients were separated into two groups based on the history of VTE. PF1 + 2 levels were decreased in ATD with previous VTE due to anticoagulation. Increased circulating nucleosomes 38.4 ng/mL [11.6–309.3] vs 24.2 ng/mL [9.3–46.5], <em>p</em> = 0.003 and VCAM-1858.3 ng/mL [564.4–2483.2] vs 746.2 ng/mL [460.6–1034.8], <em>p</em> = 0.016 was observed in ATD with previous VTE vs HCs, respectively. Decreased ICAM-1 and VWF levels were noted in the ATD with no history of VTE when compared to HCs. No significant relationships between AT activity and inflammatory markers were found.</div></div><div><h3>Conclusion</h3><div>Those with ATD did not have an altered inflammatory state as measured by a group of biomarkers except for increased circulating nucleosomes and VCAM-1 compared to paired healthy controls which can be attributed to previous VTE; while those with no personal history of VTE had reduced ICAM-1 and VWF. No correlation was observed between AT activity and levels of inflammatory markers.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"249 ","pages":"Article 109315"},"PeriodicalIF":3.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143783694","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":"Comment on: “Efficacy and safety of low-dose acetylsalicylic acid for the prevention of thromboembolic events in individuals positive for antiphospholipid antibodies: A systematic review and meta-analysis”","authors":"Shubham Kumar , Nosaibah Razaqi , Rachana Mehta , Ranjana Sah","doi":"10.1016/j.thromres.2025.109312","DOIUrl":"10.1016/j.thromres.2025.109312","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"249 ","pages":"Article 109312"},"PeriodicalIF":3.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748279","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}
Jiamei Li , Ruohan Li , Xuting Jin , Jiajia Ren , Jingjing Zhang , Ya Gao , Yanli Hou , Xiaoling Zhang , Gang Wang
{"title":"Platelet count trajectory patterns and prognosis in critically ill patients with thrombocytopenia: Based on latent growth mixture model analysis","authors":"Jiamei Li , Ruohan Li , Xuting Jin , Jiajia Ren , Jingjing Zhang , Ya Gao , Yanli Hou , Xiaoling Zhang , Gang Wang","doi":"10.1016/j.thromres.2025.109314","DOIUrl":"10.1016/j.thromres.2025.109314","url":null,"abstract":"<div><h3>Background</h3><div>The role of longitudinal platelet count trajectories in critically ill patients with thrombocytopenia is unclear. This study aimed to identify the association between trajectory patterns and prognosis and assess whether these patterns could enhance the predictive capability of Acute Physiology and Chronic Health Evaluation (APACHE) IV or Sequential Organ Failure Assessment (SOFA) scores for mortality.</div></div><div><h3>Methods</h3><div>This retrospective cohort study employed latent growth mixture modeling (LGMM) to identify platelet count trajectory patterns. Cox proportional hazards model was used to evaluate the association between the patterns and mortality. Receiver Operating Characteristic (ROC) curves were plotted, and the areas under the curves (AUCs) were compared between models using the APACHE IV or SOFA score alone and those incorporating trajectory patterns.</div></div><div><h3>Results</h3><div>A total of 1683 patients from the eICU Collaborative Research Database (eICU-CRD) and 931 patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were included. Two trajectory patterns were identified: Class 1, characterized by “Gradual increase,” and Class 2, with “Persistent low.” Patients in Class 2 had higher ICU mortality (eICU-CRD: 2.273[1.457–3.546]; MIMIC-IV database: 1.991[1.162–3.412]). Incorporating trajectory patterns into the APACHE IV or SOFA scores substantially enhanced the AUC of these scoring systems alone in predicting ICU mortality (eICU-CRD: <em>P</em> < 0.001; MIMIC-IV database: <em>P</em> = 0.0018).</div></div><div><h3>Conclusion</h3><div>The longitudinal platelet count trajectory patterns are complementary predictors of survival in critically ill patients with thrombocytopenia. Persistently low platelet counts are significantly associated with unfavorable clinical outcomes.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"249 ","pages":"Article 109314"},"PeriodicalIF":3.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haobing Zhang , Xiaoxuan Lu , Zhuangjie Guo , Xuehan Jiang , Wensi Zhang , Shuang Wang , Qiwei Liu , Xiaotong Dong , Yishan Li , Lina Guo , Yu Zhang , Jixiang Liu , Zhu Zhang , Wanmu Xie , Wanlu Song , Hong Zhang , Zhenguo Zhai , Peiran Yang
{"title":"Development of a clinically relevant rat model of chronic thromboembolic pulmonary hypertension by combining splenectomy with pulmonary thromboembolism","authors":"Haobing Zhang , Xiaoxuan Lu , Zhuangjie Guo , Xuehan Jiang , Wensi Zhang , Shuang Wang , Qiwei Liu , Xiaotong Dong , Yishan Li , Lina Guo , Yu Zhang , Jixiang Liu , Zhu Zhang , Wanmu Xie , Wanlu Song , Hong Zhang , Zhenguo Zhai , Peiran Yang","doi":"10.1016/j.thromres.2025.109310","DOIUrl":"10.1016/j.thromres.2025.109310","url":null,"abstract":"<div><h3>Background</h3><div>Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe condition resulting from unresolved thrombi in the pulmonary arteries, leading to increased pulmonary vascular resistance and right heart failure. Currently, the scarcity of clinically relevant animal models of CTEPH significantly hampers mechanistic studies and drug development.</div></div><div><h3>Methods</h3><div>This study aimed to establish a rat model of CTEPH by combining splenectomy with thrombus injection, simulating key clinical risk factors associated with the disease. Rats underwent splenectomy and subsequent intravenous administration of thrombi, followed by hemodynamic and histological measurements as well as lung tissue RNA sequencing.</div></div><div><h3>Results</h3><div>Splenectomized rats exhibited significant increases in platelets and delayed thrombolysis. Five weeks after splenectomy and thrombus injection, the rats exhibited thrombus retention in large pulmonary arteries, increased right ventricular systolic pressure, and pulmonary vascular remodeling, which were characteristic of CTEPH. Transcriptomic analysis revealed increased expression of inflammatory cytokines <em>Ccl2</em> and <em>Ccl3</em>, as well as the B cell marker <em>Cd79a</em>, which was confirmed as an increase in CD79A<sup>+</sup> B cells in the lung tissue.</div></div><div><h3>Conclusions</h3><div>Overall, this novel approach of combining splenectomy with thrombus injection provides a clinically relevant model for studying CTEPH pathophysiology and evaluating potential therapeutic interventions.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"249 ","pages":"Article 109310"},"PeriodicalIF":3.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682773","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":"Metabolomics profiling in venous thromboembolism and its chronic sequelae - A systematic review","authors":"Zahra Amirsardari , Asal Khalili , Mohammadhasan Sharafi , Reza Mehrizi , Shana Ahadi , Amirhossein Roshanshad , Mahshid Malakootian","doi":"10.1016/j.thromres.2025.109309","DOIUrl":"10.1016/j.thromres.2025.109309","url":null,"abstract":"<div><h3>Background</h3><div>High-throughput metabolomics studies have advanced the identification of novel biomarkers and enhanced the understanding of the pathogenesis of venous thrombosis. This systematic review aims to summarize metabolomics research conducted on venous thromboembolism (VTE), as well as its chronic sequelae, including chronic thromboembolic pulmonary hypertension (CTEPH) and post-thrombotic syndrome (PTS), encompassing both pre-clinical and clinical investigations.</div></div><div><h3>Methods</h3><div>A systematic search using relevant keywords related to metabolomics profiling and venous thromboembolism was conducted across four databases (PubMed, Embase, Scopus, and Web of Science). Quality assessment for animal studies was performed using SYRCLE, and for human studies, QUADOMICS was used. The study protocol is registered in PROSPERO under registry code CRD42024529490.</div></div><div><h3>Results</h3><div>Multiple metabolic disturbances were identified in various venous thrombotic conditions, including dysregulations in cellular respiration and the metabolism of carbohydrates, amino acids, lipids, and nucleic acids. Notably, altered levels of serum amino acids and their derivatives were frequently reported in patients with venous thrombosis, though findings regarding specific amino acids such as alanine, arginine, and tryptophan were inconsistent. Additionally, disruptions in tricarboxylic acid (TCA) cycle metabolites were commonly observed. Pathway enrichment analysis revealed significant involvement of several metabolic pathways, including valine, leucine, and isoleucine biosynthesis; alanine and aspartate metabolism; <span>d</span>-glutamine and D-glutamate metabolism; and arginine metabolism.</div></div><div><h3>Conclusions</h3><div>This systematic review offers a comprehensive overview of metabolomics research in venous thromboembolism and its chronic sequelae, identifying the most affected metabolic pathways associated with disease progression.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"249 ","pages":"Article 109309"},"PeriodicalIF":3.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682772","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}
Susanna Ranta , Ester Zapotocka , Nadine G. Andersson , Kathelijn Fischer , Gili Kenet , Marloes de Kovel , Christoph Königs , Veerle Labarque , Christoph Male , Martin Olivieri , Jayashree Motwani
{"title":"A survey on clinical practice in monitoring and management of bleeding in children with haemophilia A on emicizumab prophylaxis in the PedNet centres","authors":"Susanna Ranta , Ester Zapotocka , Nadine G. Andersson , Kathelijn Fischer , Gili Kenet , Marloes de Kovel , Christoph Königs , Veerle Labarque , Christoph Male , Martin Olivieri , Jayashree Motwani","doi":"10.1016/j.thromres.2025.109307","DOIUrl":"10.1016/j.thromres.2025.109307","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"249 ","pages":"Article 109307"},"PeriodicalIF":3.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682774","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}