Thrombosis research最新文献

{"title":"Thrombin generation assay in venous thromboembolism: A scoping review","authors":"Maria Eduarda Machado Souza ,&nbsp;Letícia Gonçalves Resende Ferreira ,&nbsp;Nádia Regina Oliveira Silva ,&nbsp;Livian Rabelo Lopes ,&nbsp;Maria das Graças Carvalho ,&nbsp;Danyelle Romana Alves Rios","doi":"10.1016/j.thromres.2025.109384","DOIUrl":"10.1016/j.thromres.2025.109384","url":null,"abstract":"<div><h3>Objective</h3><div>To describe the relationship, through a scoping review, between thrombin generation assay (TGA) parameters and venous thromboembolism (VTE).</div></div><div><h3>Material and methods</h3><div>A systematic search was carried out in the PubMed/MEDLINE, Embase, Cochrane, Virtual Health Library, Web of Science, and Scopus databases using descriptors for VTE and thrombin generation. Human studies assessing the association between TGA parameters and the occurrence of VTE were included. Screening of the title/abstract and full text was carried out independently by two researchers and divergent classifications were resolved by a third examiner.</div></div><div><h3>Results</h3><div>5204 studies were found, of which 90 were included after screening and full reading. The articles were grouped according to the study population and the factors associated with VTE: unprovoked VTE [33], cancer [20], hereditary/acquired thrombophilias [12], trauma/hospitalization [11], use of hormone replacement therapy/combined oral contraceptives [6], pregnancy [4] and use of anticoagulants [4]. The studies included were predominantly conducted in European countries between 2001 and 2024. Most of the studies were prospective cohort studies and used the Calibrated Automated Thrombogram (CAT) method to perform the TGA. The TGA parameters evaluated were mainly ETP and peak, which were elevated in patients with VTE in all the subgroups assessed. The TGA was able to predict the risk of primary and recurrent VTE and proved to be a useful tool for managing therapeutic regimens with anticoagulants in patients who suffered VTE.</div></div><div><h3>Conclusion</h3><div>The included studies demonstrated that TGA is a promising test in the context of VTE.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"252 ","pages":"Article 109384"},"PeriodicalIF":3.7,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329649","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":"Disseminated intravascular coagulation with hyperfibrinolysis induced by a degenerating uterine leiomyoma: A rare case report","authors":"Furong Tang ,&nbsp;Ping Nie ,&nbsp;Hongjing Wang ,&nbsp;Jianguo Hu","doi":"10.1016/j.thromres.2025.109383","DOIUrl":"10.1016/j.thromres.2025.109383","url":null,"abstract":"<div><div>Disseminated intravascular coagulation (DIC) is typically associated with malignancy, sepsis, or obstetric complications. Its occurrence in benign tumors, particularly uterine leiomyomas, is extremely rare. We report a case of a 49-year-old woman with two months of menorrhagia. Laboratory tests revealed anemia, prolonged clotting times, hypofibrinogenemia, and markedly elevated D-dimer and fibrin degradation products (FDP) levels. Coagulation factor activities (V, VIII, XII) were reduced. Thrombin-antithrombin complex (TAT) and plasmin-α2-plasmin inhibitor complex (PIC) were elevated, and thromboelastography (TEG) indicated hypocoagulability with hyperfibrinolysis. Image revealed a large degenerating uterine fibroid. Comprehensive workup excluded autoimmune, neoplastic, and inherited causes. After perioperative antifibrinolytic and coagulation management, hysterectomy was performed. Pathology confirmed extensive intratumoral thrombosis. Coagulation parameters normalized postoperatively without requiring transfusion, and no thrombotic events were observed. This case highlights a rare but important cause of DIC with hyperfibrinolysis secondary to a benign uterine tumor. It underscores the value of TEG and molecular markers in diagnosis and management, and the need to consider benign tumors in the differential diagnosis of unexplained coagulopathy.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"252 ","pages":"Article 109383"},"PeriodicalIF":3.7,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144297702","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":"Identification of phenotypes and predictors for dyspnea, echocardiographic probability of pulmonary hypertension, and confirmed CTEPH in patients with acute pulmonary embolism: Analysis of two large patient cohorts","authors":"Elva Mendoza-Zambrano ,&nbsp;Aitor Ballaz-Quincoces ,&nbsp;Jose Luis Lobo ,&nbsp;Covadonga Gomez-Cuervo ,&nbsp;Raquel Lopez ,&nbsp;Pablo Javier Marchena-Yglesias ,&nbsp;Carmen Fernández ,&nbsp;Patricia Lopez-Miguel ,&nbsp;David Jimenez ,&nbsp;Iria Francisco-Albesa ,&nbsp;María Alfonso ,&nbsp;Jose Maria Pedrajas-Navas ,&nbsp;Marina Lumbierres-Burgues ,&nbsp;Ana Núñez-Ares ,&nbsp;Miguel Angel Aibar-Arregui ,&nbsp;Consolación Rodriguez-Matute ,&nbsp;Juan Bosco Lopez-Saez ,&nbsp;Javier de Miguel-Díez ,&nbsp;Montserrat Perez-Pinar ,&nbsp;Maria Barca-Hernando ,&nbsp;Luis Jara-Palomares","doi":"10.1016/j.thromres.2025.109379","DOIUrl":"10.1016/j.thromres.2025.109379","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"252 ","pages":"Article 109379"},"PeriodicalIF":3.7,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144491357","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":"Evaluating strategies for preventing splanchnic vein thrombosis after splenectomy in cirrhosis: Evidence from published trials and retrospective cohort data","authors":"Yuan-Ming Xing ,&nbsp;Wei-Jia Huang ,&nbsp;Si-Nan Ma ,&nbsp;Yang-Xi Liu ,&nbsp;Ke-Yu Chen ,&nbsp;Di Wei ,&nbsp;Shuang Yang ,&nbsp;Wen-Bing Ma ,&nbsp;Lei Liu ,&nbsp;Yan Wang ,&nbsp;Li Zhang","doi":"10.1016/j.thromres.2025.109381","DOIUrl":"10.1016/j.thromres.2025.109381","url":null,"abstract":"<div><h3>Background</h3><div>Splanchnic vein thrombosis (SVT) is a common complication following splenectomy in cirrhotic patients, yet the optimal prophylactic antithrombotic regimen remains unclear. This study combines data from published trials with our institutions to assess the efficacy of various strategies.</div></div><div><h3>Methods</h3><div>We systematically searched five English and Chinese databases from inception to October 2024 for randomized controlled trials (RCTs) and cohort studies focused on SVT prevention after splenectomy, then conducting a network comparison to evaluate SVT incidence across different prophylactic regimens. Additionally, a retrospective dual-center cohort study was conducted to explore the diversity and effectiveness of prevention strategies in clinical practice.</div></div><div><h3>Results</h3><div>The network comparison included four RCTs and two cohort studies (<em>n</em> = 429), showed that rivaroxaban ± aspirin significantly reduced SVT incidence from postoperative month (POM) 1 to 6 compared to warfarin + low-molecular-weight heparin (LMWH) + aspirin/dipyridamole (POM 3: relative risk [RR] 0.36, 95 % confidence interval [CI] 0.14–0.88, <em>P</em> = 0.03) and aspirin + LMWH + dipyridamole (POM 3: RR 0.12, 95 % CI 0.05–0.32, <em>P</em> &lt; 0.001), respectively. However, the efficacy of rivaroxaban was reported in only one of the four RCTs, limits its robustness<strong>.</strong> Conversely, our retrospective cohort study (six interventions: no antithrombotic, LMWH, aspirin, rivaroxaban, warfarin + LMWH + aspirin, and rivaroxaban + aspirin, <em>n</em> = 281) revealed no superiority of one strategy over others.</div></div><div><h3>Conclusions</h3><div>Strategies to prevent SVT post-splenectomy in cirrhosis vary widely, with no consensus on the best approach. Larger, well-designed RCTs are needed to determine the effectiveness of prophylaxis.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"252 ","pages":"Article 109381"},"PeriodicalIF":3.7,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144280639","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":"Clinical phenotypes and risk of early hemodynamic deterioration in intermediate-high-risk patients with acute pulmonary embolism","authors":"Marco Zuin ,&nbsp;Gregory Piazza ,&nbsp;Gianluca Rigatelli ,&nbsp;Amedeo Bongarzoni ,&nbsp;Iolanda Enea ,&nbsp;Franco Casazza ,&nbsp;Claudio Picariello ,&nbsp;Claudio Bilato ,&nbsp;Loris Roncon","doi":"10.1016/j.thromres.2025.109380","DOIUrl":"10.1016/j.thromres.2025.109380","url":null,"abstract":"<div><h3>Introduction</h3><div>Intermediate-high-risk pulmonary embolism (PE) patients face elevated risks of sudden clinical deterioration in early hours after symptoms onset. We performed a hierarchical cluster analysis among intermediate-high risk PE patients to identify phenotypic subgroups and assess their association with hemodynamic deterioration risk within 48 h of admission.</div></div><div><h3>Methods</h3><div>A post hoc analysis of patients with intermediate-high risk PE enrolled in the Italian Pulmonary Embolism Registry (<span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>: <span><span>NCT01604538</span><svg><path></path></svg></span>) was performed. Hierarchical clustering (Ward's linkage) and principal component analysis identified phenotypic clusters among a population of intermediate-high-risk PE.</div></div><div><h3>Results</h3><div>The study involved 420 patients with intermediate-high risk PE (mean age 72.4 ± 13.8 years, 63.8 % males). Three distinct phenotypic clusters were identified: Cluster 1, characterized by patients with systolic blood pressure between 90 and 110 mmHg, acute onset dyspnea, and right ventricular strain at ECG; Cluster 2, featuring males &lt;65 years with pleuritic chest pain; and Cluster 3, females ≥65 years with chest pain. The rates of 48-h hemodynamic deterioration were 14.6 % in Cluster 1, 7.5 % in Cluster 2, and 4.5 % in Cluster 3. Multivariate analysis showed Cluster 1 had a significantly higher risk of deterioration compared to Clusters 2 (HR: 1.42, 95 % CI: 1.38–1.46, <em>p</em> &lt; 0.001) and 3 (HR: 1.51, 95 % CI: 1.15–1.62, <em>p</em> = 0.01), adjusting for age, sex, and treatment.</div></div><div><h3>Conclusions</h3><div>Cluster analysis identified 3-statistically-identified phenotypic clusters among patients with intermediate high-risk PE with different risk of hemodynamic deterioration within 48 h from admission. Further phenotyping is warranted to inform patient care and optimize clinical trial designs.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"252 ","pages":"Article 109380"},"PeriodicalIF":3.7,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144253689","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":"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}