Thrombosis research最新文献

{"title":"Gene variants in a family with inherited coagulation factor XI deficiency and identification of novel mutations","authors":"Yalin Yu , Bingxian Li , Dongyan Fu, Xiaomei Lu, Lei Wang, Jiaoyu Zhao, Juan Ren, Jiawei Zheng, Duanyang Wang, Gang Wang, Linhua Yang","doi":"10.1016/j.thromres.2026.109690","DOIUrl":"10.1016/j.thromres.2026.109690","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"261 ","pages":"Article 109690"},"PeriodicalIF":3.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781969","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 outcomes following catheter-related venous thrombo-embolism among children with acute lymphoblastic leukemia","authors":"Marie-Claude Pelland-Marcotte ,&nbsp;Thai Hoa Tran ,&nbsp;Chantal Éthier ,&nbsp;Camille Beaulieu ,&nbsp;Thien Vu Truong ,&nbsp;Olivia Perrone ,&nbsp;Nadia Tarhini ,&nbsp;Juliann Duzan ,&nbsp;Lynda M. Vrooman ,&nbsp;Melissa Burns ,&nbsp;Lewis B. Silverman ,&nbsp;Riten Kumar","doi":"10.1016/j.thromres.2026.109691","DOIUrl":"10.1016/j.thromres.2026.109691","url":null,"abstract":"<div><div>Venous thrombo-embolism (VTE) occurs in 10–15% of pediatric patients with acute lymphoblastic leukemia (ALL), yet the optimal duration of anticoagulation remains unclear. In this retrospective multi-center cohort study, we reported the clinical outcomes of pediatric patients treated for ALL with a history of central venous catheter (CVC)-related VTE and compared outcomes based on duration of anticoagulation.</div><div>Patients aged 1–21 years old with newly-diagnosed ALL (2010−2023), receiving asparaginase-containing chemotherapy, experiencing a radiologically-proven CVC-related VTE requiring medical intervention, were included. Cumulative incidence and 95% confidence interval (CI) were estimated for VTE progression/recurrence and clinically relevant bleeding. Cox proportional hazard models were performed to compare clinical outcomes based on anticoagulation duration, categorized as a) asparaginase-based (following a 6-week course of anticoagulation, until the end of asparaginase’ expected effects or earlier) or extended (later than asparaginase's expected effects), and b) before vs. after CVC removal.</div><div>We included 106 patients (median age: 10 years, 59% male). Overall, 22 patients sustained a VTE progression/recurrence (cumulative incidence: 22%, 95% CI: 14–30%). Most progression/recurrences occurred while patients were still on anticoagulation, at a median of 54 days after index VTE. Duration of anticoagulation was not associated with VTE progression/recurrence (extended vs. asparaginase-based: HR = 1.49, 95%CI: 0.60–3.69, <em>p</em> = 0.392; after vs. before CVC removal: HR = 1.36, 95% CI: 0.49–3.74, <em>p</em> = 0.552). Clinically relevant bleeding occurred in 11/106 patients (cumulative incidence: 12%, 95% CI: 6–19%) and was not associated with anticoagulation duration.</div><div>In summary, VTE progression/recurrence was common in pediatric patients with ALL. Further investigation into alternative approaches to reduce VTE progression/recurrence is warranted.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"261 ","pages":"Article 109691"},"PeriodicalIF":3.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782018","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":"Toward an endothelium-centered framework for obstetric disseminated intravascular coagulation: Harmonizing pathophysiology, diagnosis, and treatment","authors":"Ryo Kamidani ,&nbsp;Hideshi Okada","doi":"10.1016/j.thromres.2026.109694","DOIUrl":"10.1016/j.thromres.2026.109694","url":null,"abstract":"<div><h3>Background</h3><div>Obstetric disseminated intravascular coagulation (DIC) is a life-threatening coagulopathy triggered by placental abruption, amniotic fluid embolism, HELLP syndrome, and postpartum hemorrhage. Although rapid hemostasis and transfusion are central to management, growing evidence implicates endothelial injury, particularly endothelial glycocalyx (eGCX) degradation, in amplifying coagulopathy and organ dysfunction. This review integrates endothelial pathophysiology into modern diagnostic and therapeutic frameworks for obstetric DIC.</div></div><div><h3>Methods</h3><div>We conducted a narrative synthesis of studies and guidelines published through 2025, examining (1) the pathophysiologic interplay among coagulation, fibrinolysis, and endothelial injury; (2) clinical utility of endothelial biomarkers; and (3) diagnostic criteria updates, including the 2024 revised Japanese obstetric DIC score.</div></div><div><h3>Results</h3><div>eGCX degradation, indicated by elevated syndecan-1, heparan sulfate, and hyaluronic acid levels, has been associated with disease severity and may reflect early endothelial dysfunction in obstetric DIC. Crystalloid overload, ischemia–reperfusion injury, and inflammatory cytokines promote glycocalyx shedding, exacerbating vascular permeability and consumption coagulopathy. The 2024 revised Japanese obstetric DIC criteria showed high sensitivity for pregnancy-specific coagulopathy and highlighted fibrinogen decline and fibrin-related markers as key diagnostic variables. Integrating endothelial biomarkers with these laboratory parameters may enhance early risk stratification and inform personalized resuscitation strategies addressing hemostasis and endothelial protection.</div></div><div><h3>Conclusions</h3><div>Preservation of endothelial integrity represents a new therapeutic paradigm in obstetric DIC. Alongside optimized transfusion practices, timely fibrinogen replacement, and interventional hemostasis, targeting eGCX protection and endothelial recovery may redefine management goals. The 2024 Japanese obstetric DIC score provides a foundation for this integrative, endothelium-centered approach to improving maternal outcomes.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"261 ","pages":"Article 109694"},"PeriodicalIF":3.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147803914","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":"Corrigendum to “The effects of an aggressive breast tumor on thrombosis after antithrombin downregulation in a hypercoagulable mouse model” [Thromb. Res. 244 (2024) 109200]","authors":"B. Ünlü,&nbsp;M. Heestermans,&nbsp;E.H. Laghmani,&nbsp;J.T. Buijs,&nbsp;R.F.P. van den Akker,&nbsp;B.J.M. van Vlijmen,&nbsp;H.H. Versteeg","doi":"10.1016/j.thromres.2026.109692","DOIUrl":"10.1016/j.thromres.2026.109692","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"261 ","pages":"Article 109692"},"PeriodicalIF":3.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821029","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":"Blood product supplementation modulates clotting kinetics, mechanics, and fibrin architecture in an in vitro model of trauma-induced coagulopathy","authors":"Andrew R. Gosselin ,&nbsp;Sameer Ahmad ,&nbsp;Joseph S. Hanna ,&nbsp;Julie Goswami ,&nbsp;Valerie Tutwiler","doi":"10.1016/j.thromres.2026.109666","DOIUrl":"10.1016/j.thromres.2026.109666","url":null,"abstract":"<div><h3>Background</h3><div>Trauma-induced coagulopathy (TIC) worsens patient outcomes and increases transfusion requirements. Resuscitation strategies following injury have evolved to improve clinical outcomes. However, the mechanisms by which these strategies impact coagulation and whether they restore native coagulation in the presence of TIC are poorly understood.</div></div><div><h3>Methods</h3><div>We compared coagulation parameters and vital signs of patients who did (<em>n</em> = 26) and did not (<em>n</em> = 37) receive transfusion following injury. Transfusion products administered to patients were recreated <em>in vitro</em>, and their influence on a simulated model of TIC was measured. Optical turbidity, rheology, thromboelastography, and confocal microscopy were used to evaluate the clotting properties of platelet-poor plasma and whole blood models of hypocoagulable and hypercoagulable TIC. Transfusion models were supplemented with Saline, Plasma, Fibrinogen Concentrate, or Red Blood Cells (RBC).</div></div><div><h3>Results</h3><div>Transfused patients exhibited faster time to mortality, clot stiffness, and fibrinogen concentration compared to non-transfused patients. In the simulated transfusion model, saline reduced clot stiffness, increased fibrinolytic rate, and affected network structure. Plasma increased clot stiffness and density, and reduced fibrinolysis. Fibrinogen concentrate enhanced clot stiffness in plasma-based models but also increased fibrinolytic rate. RBC supplementation had variable impacts, causing weaker blood clots and accelerated fibrinolysis in hypocoagulable models, but delayed fibrinolysis in hypercoagulable models.</div></div><div><h3>Discussion</h3><div>Resuscitation products exert context-dependent effects on clot formation and breakdown that may not restore hemostasis during TIC. Saline induced dilutional hypocoagulability and increased clot failure risk, plasma enhanced clot stability, fibrinogen improved clot formation, and RBCs exerted endogenous coagulation-specific effects. These results support coagulation phenotyping to guide targeted transfusion strategies.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"260 ","pages":"Article 109666"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147601513","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":"Stroke etiology, thrombus composition, and patient outcomes: A histopathological and clinical perspective","authors":"Andreas M. Baranowski ,&nbsp;Jonas Koette ,&nbsp;Florian C. Roessler","doi":"10.1016/j.thromres.2026.109661","DOIUrl":"10.1016/j.thromres.2026.109661","url":null,"abstract":"<div><h3>Background</h3><div>Growing evidence suggests that thrombus composition may influences embolic stroke severity, treatment response, and patient outcomes. While previous studies have characterized histopathological differences between cardioembolic stroke (CES) and atheroembolic stroke (AES), less is known about embolic strokes of undetermined source (ESUS). This study examines the relationship between embolic stroke etiology, thrombus composition, and clinical outcomes to improve classification and guide therapeutic strategies.</div></div><div><h3>Methods</h3><div>This retrospective study included 323 patients with acute embolic ischemic stroke treated with mechanical thrombectomy. Stroke etiology was classified as CES (<em>n</em> = 151), AES (<em>n</em> = 71), or ESUS (<em>n</em> = 81). Histopathological examination was performed on 127 retrieved thrombi, assessing fibrin architecture, platelet distribution, neutrophil content, and red blood cell integrity. Clinical parameters, including National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), length of hospital stay, and in-hospital mortality, were analyzed. Statistical models examined associations between thrombus characteristics, stroke etiology, and functional recovery.</div></div><div><h3>Results</h3><div>CES thrombi exhibited higher platelet and neutrophil content, with a dense, centrally concentrated platelet distribution consistent with fibrin-rich, compact thrombi. In contrast, AES thrombi showed a more diffuse, net-like distribution of platelets, aligning with high-shear conditions in stenotic arteries. ESUS thrombi closely resembled AES but contained a heterogeneous fibrin profile, including the highest proportion of compact fibrin, suggesting alternative thrombus maturation mechanisms. Patients with AES exhibited the poorest functional recovery (lowest NIHSS and mRS improvement), despite successful recanalization. ESUS had the highest in-hospital mortality. Stroke mechanism was significantly associated with both thrombus composition and patient outcomes in this study.</div></div><div><h3>Conclusions</h3><div>Thrombus histopathology varies significantly by stroke etiology, with platelet distribution emerging as a strong classifier. ESUS thrombi exhibit hybrid features, emphasizing the need for improved classification. Clinical outcomes differed across etiologies, with AES patients experiencing the slowest recovery and ESUS patients exhibiting the highest in-hospital mortality. Integrating thrombus characteristics into risk stratification models, secondary prevention strategies, and artificial intelligence-driven classification may enhance acute stroke management.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"260 ","pages":"Article 109661"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147601512","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":"Preferences of pregnant individuals and family members for maternal-fetal health states related to anticoagulant use in pregnancy","authors":"Rohan D'Souza ,&nbsp;George Tomlinson ,&nbsp;Kyra Bonasia ,&nbsp;Danielle Wuebbolt ,&nbsp;Vanessa Nguyen ,&nbsp;Wynn Peterson ,&nbsp;Bakhtawar M.Hanif Khowaja ,&nbsp;Prakesh S. Shah ,&nbsp;Murray Krahn ,&nbsp;Kellie E. Murphy ,&nbsp;Beate Sander","doi":"10.1016/j.thromres.2026.109649","DOIUrl":"10.1016/j.thromres.2026.109649","url":null,"abstract":"<div><h3>Background</h3><div>A considerable number of pregnant individuals are prescribed anticoagulants in pregnancy.</div></div><div><h3>Objective(s)</h3><div>To obtain and compare preference values for combined maternal-fetal health states arising from anticoagulant use in pregnancy from pregnant individuals and their family members.</div></div><div><h3>Study design</h3><div>We conducted a cross-sectional study at a tertiary referral centre in Toronto, Canada from July to October 2015. A diverse group of pregnant individuals receiving anticoagulants and family members involved in medical decision-making were interviewed individually and together. Participants assigned values to seven maternal-fetal health states using the visual analogue scale (VAS), time trade-off (TTO), and standard gamble (SG) instruments on a 0–100 scale, where 0 represented maternal-fetal death and 100 perfect maternal-fetal health.</div></div><div><h3>Results</h3><div>We recruited 57 pregnant individuals and 43 family members, of which 40 pairs completed all interviews. There were significant differences between preferences based on instruments, scenarios, and respondents. Across interviews and instruments, participants assigned lowest preference values to health states involving major fetal malformations and fetal death. Preferences obtained through shared interviews showed a significant shift away from those obtained from pregnant individuals and towards those of family members. Participants better understood and preferred the VAS and SG over the TTO.</div></div><div><h3>Conclusion(s)</h3><div>This study in addition to generating patient-preference values to inform decision analysis and economic evaluation studies, also highlights the importance families attribute to fetal complications while making clinical decisions during pregnancy. The role of shared interviews and the use of SG in eliciting preferences for pregnancy health states needs further exploration.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"260 ","pages":"Article 109649"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147594907","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":"Central line–associated thrombosis and infections in patients with acute leukemias: The chicken or the egg dilemma","authors":"Tamim Alsuliman ,&nbsp;Pedro Henrique De Lima Prata ,&nbsp;Paolo Musiu ,&nbsp;Nicolas Stocker ,&nbsp;Reda Garidi ,&nbsp;Ali Alrstom ,&nbsp;Hassina Aftisse ,&nbsp;Djedjiga SiTayeb ,&nbsp;Chahrazad Benchouk ,&nbsp;Lugien Alasadi ,&nbsp;Zora Marjanovic ,&nbsp;Corinne Frere","doi":"10.1016/j.thromres.2026.109665","DOIUrl":"10.1016/j.thromres.2026.109665","url":null,"abstract":"<div><div>Central venous catheters (CVCs) are frequently used in the management of acute leukemia, providing safe and convenient access for the safe delivery of chemotherapy, transfusions, and supportive care. However, these devices are associated with a high risk of complications, including CVC-related thrombosis (CRT) and CVC–related infection (CRI). These complications can occur concomitantly, highlighting the challenging dilemma of which comes first and which leads to the other. This review explores the complex, intricately intertwined pathophysiological mechanisms underlying this relationship in patients with acute leukemia. Catheter bacterial colonization, frequently reinforced by biofilm formation, and bloodstream infections provoke immunothrombosis, playing a part in local infection management. Platelets and the coagulation process may amplify the inflammatory responses <em>via</em> their interactions with the endothelium, immune cells, and the complement system. Conversely, thrombosis creates a nidus for bacterial adhesion, thereby perpetuating infection. In patients with acute leukemia, Virchow's triad— vessel wall injury, stasis, and hypercoagulability —is exacerbated by chemotherapy-induced toxicity, malignancy-related hypercoagulability, and immunosuppression. Management requires balancing infection control and thrombosis prevention. Future studies should focus on exploring the mechanistic bidirectional links between CRT and CRI as well as developing targeted preventive strategies to improve outcomes.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"260 ","pages":"Article 109665"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147594949","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":"Functional and structural consequences of fibrinogen γ-chain variants associated with thrombotic phenotype in congenital fibrinogen disorders","authors":"Tomas Simurda ,&nbsp;Eliska Ceznerova ,&nbsp;Zuzana Kolkova ,&nbsp;Dusan Loderer ,&nbsp;Miroslava Drotarova ,&nbsp;Monika Brunclikova ,&nbsp;Ingrid Skornova ,&nbsp;Sohaib Mukhtar Agouba ,&nbsp;Veronika Voskova Gemelova ,&nbsp;Kristina Maria Belakova ,&nbsp;Jan Stasko ,&nbsp;Roman Kotlin","doi":"10.1016/j.thromres.2026.109664","DOIUrl":"10.1016/j.thromres.2026.109664","url":null,"abstract":"<div><div>Fibrinogen is a key determinant of clot formation and stability in the final phase of coagulation. Genetic variants in the fibrinogen γ-chain gene (<em>FGG</em>) are a frequent cause of congenital fibrinogen disorders (CFDs) and are associated with marked heterogeneity of clinical presentation, including thrombosis. Increasing evidence indicates that genetic findings alone are insufficient to predict thrombotic risk. We performed a comprehensive molecular, functional, and ultrastructural characterization of 20 patients from Czechia and Slovakia carrying <em>FGG</em> variants. Genetic analysis was combined with fibrin polymerization and fibrinolysis assays, fibrinopeptide release measurements, and scanning electron microscopy of fibrin clots. Five previously unreported pathogenic fibrinogen variants γp.T60A, γp.Y237H, γp.Y306C, γp.G310E, and γp.H333Y were identified. Although 60% of patients were clinically asymptomatic, 30% developed thrombotic manifestations in the absence of established thrombotic risk factors. Functional studies demonstrated delayed fibrin polymerization, reduced clot optical density, and prolonged fibrinolysis despite residual fibrin formation. Ultrastructural analysis revealed markedly altered fibrin clot architecture, characterized by abnormal fiber diameters and increased fiber density compared with controls, consistent with a dense, poorly lysable fibrin network. These findings indicate that <em>FGG</em> variants may promote thrombosis through qualitative alterations of fibrin structure and impaired fibrinolysis rather than fibrinogen deficiency alone. Integration of genetic, functional, and structural analyses is therefore essential for accurate assessment of thrombotic risk in patients with CFDs.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"260 ","pages":"Article 109664"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147601514","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":"Cold exposure promotes thrombotic risk in ischemic stroke by activating the platelet cGAS-STING pathway","authors":"Yuchen Li ,&nbsp;Miaomiao Wei ,&nbsp;Yumeng Gu ,&nbsp;Jin Deng ,&nbsp;Xiaokun Guo ,&nbsp;Lin Wang ,&nbsp;Xin Li","doi":"10.1016/j.thromres.2026.109663","DOIUrl":"10.1016/j.thromres.2026.109663","url":null,"abstract":"<div><h3>Background</h3><div>Ischemic stroke (IS) incidence increases in cold periods, implicating cold exposure as a key environmental risk factor. However, the underlying biological mechanisms remain unclear.</div></div><div><h3>Methods</h3><div>We performed a cross-sectional study in acute IS patients (<em>n</em> = 623) to compare platelet and coagulation profiles between cold- and non-cold-season admissions, analyzing temperature associations using Generalized Additive Models and age-cold interactions via additive measures. Parallel rat experiments examined cold effects on platelet function, hemostasis, cerebral ischemia, and the cGAS-STING pathway.</div></div><div><h3>Results</h3><div>Patients in cold periods exhibited significantly elevated platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), ADP-induced aggregation, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, and D-dimer. Lower daily temperature correlated with increased ADP-aggregation and PDW. A significant positive additive interaction existed between cold exposure and older age (≥65 years) for PLT, MPV, PDW, ADP-aggregation, APTT and FIB. In rats, cold shortened bleeding time, enhanced platelet aggregation, spreading, clot retraction, and microvesicle release, increasing cerebral infarct volume. Mechanistically, cold upregulated platelet cyclic GMP-AMP synthase (cGAS)- stimulator of interferon genes (STING), effects blunted by the cGAS inhibitor RU.521.</div></div><div><h3>Conclusion</h3><div>Cold exposure acts as an independent risk factor and exerts a synergistic effect with aging to promote a prothrombotic state in elderly stroke patients. Our findings suggest that activation of the platelet cGAS-STING pathway may serve as a potential mechanistic link. Importantly, pharmacological inhibition of this pathway was associated with attenuated pro-thrombotic phenotype and brain injury in cold-exposed animals. These findings support the platelet cGAS-STING axis as a candidate therapeutic target for mitigating seasonal stroke risk.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"260 ","pages":"Article 109663"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147601515","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}