Thrombosis research最新文献

{"title":"Thrombomodulin Arg403Lys mutation impairs protein C activation and increases thrombosis risk","authors":"Zhe Lai ,&nbsp;Junwei Yuan ,&nbsp;Fang Li ,&nbsp;Shijie Zhou ,&nbsp;Xi Wu ,&nbsp;Nifei Chen ,&nbsp;Wenman Wu ,&nbsp;Qiulan Ding ,&nbsp;Jing Dai ,&nbsp;Xiaobo Hu ,&nbsp;Xuefeng Wang ,&nbsp;Yeling Lu","doi":"10.1016/j.thromres.2025.109375","DOIUrl":"10.1016/j.thromres.2025.109375","url":null,"abstract":"<div><div>Thrombomodulin (TM) is an important regulator in various physiological processes, including coagulation, fibrinolysis and inflammation. TM exerts its cofactor activities for protein C (PC) activation and thrombin-activatable fibrinolysis inhibitor (TAFI) activation through its binding with thrombin. Numerous studies have reported that mutations of TM are associated with thromboembolic diseases. Here we report a heterozygous substitution of arginine to lysine at amino acid residue 403 (Arg403Lys, R403K) within the fourth epidermal growth factor (EGF)-like domain of TM, which was identified in five unrelated patients with thrombophilia. To elucidate the role of the R403K mutation in TM, we constructed expression plasmids for both the full-length (residues Met1 to Leu575) and extracellular fragment (residues Met1 to Ser515) of TM to study its functions on surface of endothelial cells and in vitro system as well. We observed a reduced cofactor activity of PC activation by the TM-R403K variant across several assays and demonstrated a weakened interaction between the mutant and PC as well. These results indicate that the R403K mutation in TM induces detrimental alterations in the anticoagulant function of TM, which might elucidate the thrombotic predisposition observed in patients. This study provides further compelling evidence suggesting that mutation at the terminus of the EGF4 domain in TM may be associated with thrombophilia, thereby enhancing our comprehension of the physiological role of TM.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"252 ","pages":"Article 109375"},"PeriodicalIF":3.7,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144241638","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":"Neutrophil extracellular traps-related markers in chronic limb threatening ischemia - a relation with progression and prognosis","authors":"Tomasz Nowakowski ,&nbsp;Krzysztof Malinowski ,&nbsp;Joanna Natorska ,&nbsp;Anetta Undas","doi":"10.1016/j.thromres.2025.109378","DOIUrl":"10.1016/j.thromres.2025.109378","url":null,"abstract":"<div><h3>Background</h3><div>Neutrophil extracellular traps (NETs) formation is involved in atherothrombosis, though little is known about this phenomenon in peripheral artery disease (PAD). We investigated whether NETs-associated markers are related with the PAD severity and long-term outcomes after endovascular treatment and if they affect fibrin properties and thrombin generation.</div></div><div><h3>Patients and methods</h3><div>We studied 85 patients with chronic limb threatening ischemia (CLTI) and restenosis within one year after endovascular treatment and 47 age-sex-matched PAD controls without restenosis. NETs-associated markers, i.e. circulating citrullinated histone H3 (H3cit), myeloperoxidase (MPO), protein arginine deaminase 4 (PAD4), cell-free DNA (cfDNA) along with DNAse-I, together with fibrin clot permeability (Ks), clot lysis time (CLT), thrombin generation and fibrinolysis markers were determined. During follow-up a composite endpoint including re-intervention, amputation and death was assessed.</div></div><div><h3>Results</h3><div>Compared with the control group, patients with CLTI and restenosis had higher H3cit (59.8 %), MPO (58.4 %) and cfDNA (35.3 %; all <em>p</em> &lt; 0.01). Rutherford class positively correlated with H3cit, MPO, PAD4 and cfDNA in the restenosis group and with H3cit in controls (all <em>p</em> &lt; 0.05). In the restenosis group Ks negatively correlated with H3cit and cfDNA while CLT positively correlated solely with H3cit (all <em>p</em> &lt; 0.05). At a median follow-up of 66 months, 56 patients who died (65.9 %) had higher H3cit, MPO and cfDNA concentrations than survivors (all <em>p</em> &lt; 0.05). On multivariable analysis H3cit, ETP, α2-antiplasmin and Ks were independent predictors of combined re-intervention, amputation and death.</div></div><div><h3>Conclusion</h3><div>Higher levels of NETs-associated markers in relation to prothrombotic fibrin clot properties characterize endovascularly treated PAD patients at risk of 1-year restenosis and worse long-term outcomes.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"252 ","pages":"Article 109378"},"PeriodicalIF":3.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144253688","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":"Sex-based differences in access to reperfusion therapies for pulmonary embolism in Spain during the 2016–2022 period","authors":"José Antonio Rueda-Camino ,&nbsp;María Angelina-García ,&nbsp;Davinia Trujillo-Luque ,&nbsp;María Dolores Joya-Seijo ,&nbsp;Laura Teigell-Prieto ,&nbsp;José Ángel Novalbos-Partida ,&nbsp;Francisco Javier Gimena-Rodríguez ,&nbsp;Raquel Barba-Martín","doi":"10.1016/j.thromres.2025.109371","DOIUrl":"10.1016/j.thromres.2025.109371","url":null,"abstract":"<div><h3>Background/objectives</h3><div>Evidence on sex-based differences in access to reperfusion therapies for PE remains conflicting. This study evaluated such differences in Spain during the 2016–2022 period.</div></div><div><h3>Methods</h3><div>We identified all patients with PE in the Registro de Actividad Especializada-Conjunto Mínimo Básico de Datos from 2016 to 2022. The proportions of men and women undergoing systemic fibrinolysis, catheter-directed thrombolysis, embolectomy, or extracorporeal membrane oxygenation were compared. Multivariable adjustment was performed using logistic regression.</div></div><div><h3>Results</h3><div>We identified 113,787 women and 115,941 men. Women were significantly older (73 vs 68 years) and were more likely to have heart failure (15.1 % vs 11.8 %) and dementia (13.3 % vs 7.4 %), whereas men were more likely to have coronary artery disease (4.5 % vs 2.0 %), chronic obstructive pulmonary disease (20.8 % vs 12.0 %), and cancer (23.7 % vs 18.6 %). However, the overall comorbidity burden was similar between groups, with a median Charlson's Index of 1 for both. Crude analysis showed similar proportions of reperfusion therapy for men and women: 5.36 % (95 % CI: 5.22 %–5.48 %) vs 5.23 % (95 % CI: 5.10 %–5.36 %) respectively. Comorbidity emerged as the variable with the greatest impact on adjustment in the multivariable regression. After adjustment, women appeared to have a lower probability of receiving these treatments (POR 0.98; 95 % CI: 0.94–1.01).</div></div><div><h3>Conclusions</h3><div>After adjusting for confounders, women diagnosed with PE may have been less likely to undergo reperfusion therapies in Spain during the period from 2016 to 2022.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"252 ","pages":"Article 109371"},"PeriodicalIF":3.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212753","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":"Comparing fibrinolytic strategies in intermediate-high-risk pulmonary embolism: Insights from a multicenter registry","authors":"Dzudovic Boris ,&nbsp;Simpson Tamara ,&nbsp;Matijasevic Jovan ,&nbsp;Pekovic Sandra ,&nbsp;Salinger Sonja ,&nbsp;Miloradovic Vladimir ,&nbsp;Kovacevic-Preradovic Tamara ,&nbsp;Kos Ljiljana ,&nbsp;Mitevska Irena ,&nbsp;Mitrovic Bojan ,&nbsp;Neskovic Aleksandar ,&nbsp;Obradovic Slobodan","doi":"10.1016/j.thromres.2025.109372","DOIUrl":"10.1016/j.thromres.2025.109372","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"252 ","pages":"Article 109372"},"PeriodicalIF":3.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230094","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":"Genetic insights into cytokine-thrombosis cross-talk: an integrated multi-omics network analysis","authors":"Wei Zhou ,&nbsp;Xiaoyi Qin ,&nbsp;Honglei Xu ,&nbsp;Jingye Pan","doi":"10.1016/j.thromres.2025.109376","DOIUrl":"10.1016/j.thromres.2025.109376","url":null,"abstract":"<div><h3>Background</h3><div>The mechanisms shared and unique to thrombotic diseases (TDs) remain unclear. This study explores the causal relationships between inflammatory cytokines and TDs via multi-omics integration to identify targeted therapeutic alternatives.</div></div><div><h3>Methods</h3><div>We conducted two-sample Mendelian randomization (MR) using three genetic instruments to evaluate the causal effects of 47 cytokines on 13 TD traits. Findings were validated through colocalization, replication, and transcriptomic analyses. Two-step MR assessed mediation effects of 1400 metabolites and 731 immune cells. Druggability and infection-related pleiotropy of TD-associated cytokines were systematically evaluated.</div></div><div><h3>Results</h3><div>Primary MR identified 86 cytokine-TD correlated pairs, with 21 pairs providing acceptable evidence support, meriting their designation as hub pairs for further analysis. Colocalization evidence emerged for two pairs, whereas replication consistency was robust. Five of the 15 cytokine gene-TD pairs revealed differential expression, aligning with the MR effects. Mediation analyses showed five metabolites and immune cell subtypes modulating cytokine-TD pathways. Four cytokines exhibited therapeutic promise for thrombosis, whereas six showed dual effects on TDs and infections.</div></div><div><h3>Conclusions</h3><div>Our integrated analysis reveals shared and autonomous mechanisms governing inflammatory-thrombotic interactions and identifies a cytokine-mediated therapeutic target that may avoid bleeding complications linked to standard antithrombotic therapy.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"252 ","pages":"Article 109376"},"PeriodicalIF":3.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144223001","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":"Activation of the pentose phosphate pathway mitigates platelet storage lesions and improves platelet preservation quality","authors":"Liujun Guo ,&nbsp;Chengrui Qian ,&nbsp;Chengyan Gao ,&nbsp;Hasiyati Heililahong ,&nbsp;Min Xin ,&nbsp;Lei Hang ,&nbsp;Can Lou ,&nbsp;Jiaming Li ,&nbsp;Xuefeng Wang ,&nbsp;Jing Dai ,&nbsp;Xuemei Fan ,&nbsp;Xiaohong Cai","doi":"10.1016/j.thromres.2025.109377","DOIUrl":"10.1016/j.thromres.2025.109377","url":null,"abstract":"<div><h3>Background</h3><div>Platelet storage lesions (PSLs) impact platelet lifespan and transfusion quality. This study explores platelet storage metabolism for potential interventions.</div></div><div><h3>Methods</h3><div>Samples were collected on days 1, 3, and 5 for untargeted metabolomics analysis to identify metabolites that differ with storage time and potential metabolic pathways. The activities of glucose-6-phosphate dehydrogenase (G6PD) and cyclooxygenase-1 (COX-1) in platelets during storage were measured. Meanwhile, flow cytometry was used to assess changes in apoptosis and mitochondrial function of stored platelets treated with either a G6PD inhibitor, a G6PD activator, or a COX-1 inhibitor. Platelet aggregation was used to evaluate platelet function. Megakaryocyte/platelet-specific <em>G6pd</em> knockout mice were used to assess the role of G6PD in PSLs.</div></div><div><h3>Results</h3><div>The pentose phosphate pathway (PPP), arachidonic acid metabolism, and linoleic acid metabolism were enriched during storage. A total of 4832 platelet metabolites and 6468 plasma metabolites were identified, with 44 and 108 showing nominally significant changes respectively. An increase in G6PD activity was observed at the early stages. Inhibiting G6PD with G6PDi-1 damages mitochondria, increases phosphatidylserine externalization, and impairs platelet aggregation. Mouse <em>G6pd</em>^−/− platelets exhibited increased PSLs. Activation of G6PD with AG1 reduces mitochondrial reactive oxygen species (mtROS) and phosphatidylserine externalization while enhancing platelet aggregation. Additionally, although COX-1 activity in the arachidonic acid metabolism pathway increases at the early stage, its inhibition by the COX-1 inhibitor aspirin does not significantly alter PSL-related indicators.</div></div><div><h3>Conclusion</h3><div>The pentose phosphate pathway maintains platelet mitochondrial function via G6PD regulation, making G6PD a critical target for reducing PSLs.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"252 ","pages":"Article 109377"},"PeriodicalIF":3.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144272603","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":"Response to letter to the editor","authors":"Ting Wei Teo ,&nbsp;Sarah Ming Li Tan ,&nbsp;Pipin Kojodjojo ,&nbsp;Yinghao Lim","doi":"10.1016/j.thromres.2025.109373","DOIUrl":"10.1016/j.thromres.2025.109373","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"252 ","pages":"Article 109373"},"PeriodicalIF":3.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144241636","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":"Critique and advice of a multicenter mechanical thrombectomy registry in intermediate-risk PE","authors":"Shifei He","doi":"10.1016/j.thromres.2025.109374","DOIUrl":"10.1016/j.thromres.2025.109374","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"253 ","pages":"Article 109374"},"PeriodicalIF":3.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556947","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":"Treating the mind and body: implementation of a psychosocial wellbeing assessment in the deep vein thrombosis clinic","authors":"Emma Gee,&nbsp;Victoria Speed,&nbsp;Philip Alexander,&nbsp;Simon Guppy,&nbsp;Jig Patel,&nbsp;Sinead Duffy,&nbsp;Rachel Clapham,&nbsp;Roopen Arya","doi":"10.1016/j.thromres.2025.109360","DOIUrl":"10.1016/j.thromres.2025.109360","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"252 ","pages":"Article 109360"},"PeriodicalIF":3.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144263275","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":"The effect of exercise-based rehabilitation on objective physical activity levels in patients with persistent dyspnoea following pulmonary embolism","authors":"Stacey Haukeland-Parker ,&nbsp;Øyvind Jervan ,&nbsp;Waleed Ghanima ,&nbsp;Martijn A. Spruit ,&nbsp;Aliaksandr Hubin ,&nbsp;Mazdak Tavoly ,&nbsp;Jostein Gleditsch ,&nbsp;Trude Støver ,&nbsp;Knut Stavem ,&nbsp;Hege Hølmo Johannessen","doi":"10.1016/j.thromres.2025.109362","DOIUrl":"10.1016/j.thromres.2025.109362","url":null,"abstract":"<div><h3>Background</h3><div>Rehabilitation improves exercise capacity following pulmonary embolism (PE), but it is unclear whether this improvement is transferred into increased physical activity.</div><div><strong>Objectives.</strong></div><div>To explore the effect of exercise-based rehabilitation on objective measures of physical activity in patients with persistent dyspnoea following PE compared to standard care.</div></div><div><h3>Methods</h3><div>This pre-planned substudy compared an eight-week exercise-based rehabilitation program to usual care. Number of steps per day and time spent in sedentary, low, moderate and vigorous physical activity (in number of metabolic equivalent of tasks) were measured for seven consecutive days at baseline prior to intervention start and at post-intervention using accelerometery. Data were analysed with a mixed-effect generalised linear model.</div></div><div><h3>Results</h3><div>Complete data was provided by 48 patients at both timepoints (mean age 58 years, 54 % men) with 54 % randomised to rehabilitation. There were no significant differences between groups at baseline. The majority of time (717 min per day) was spent in sedentary activity and mean number of steps per day was 6701. At post-intervention, there were no significant differences between groups in any of the objectively measured physical activity parameters (<em>p</em> &gt; 0.05).</div></div><div><h3>Conclusion</h3><div>In this cohort, exercise-based rehabilitation following PE did not change daily physical activity levels compared to usual care control group.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"252 ","pages":"Article 109362"},"PeriodicalIF":3.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144222941","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}