Thrombosis and haemostasis最新文献

{"title":"Small interfering RNA targeting protein Z-dependent protease inhibitor improves hemostasis in Von Willebrand factor- and Factor X-deficient mice.","authors":"Rim Hamze, Mariem Khamari, Kaitlyn R Calabro, Antoine Jehl, Christine Becker, Alexandre J Debacker, Natalie W Prusell, Damian Elle, Lijuan Pang, Ya Sun, Qian Wang, Qiugang Lei, Song Chen, Alice Guérin, Geneviève McCluskey, Caterina Casari, Elsa P Bianchini, Olivier D Christophe, Alan V Whitmore, Peter J Lenting, Cecile Denis","doi":"10.1055/a-2979-5643","DOIUrl":"https://doi.org/10.1055/a-2979-5643","url":null,"abstract":"<p><p>Non-factor therapeutics have transformed the treatment paradigm in hemophilia A. Owing to their mode of action, these agents may also provide benefit for other rare bleeding disorders (RBDs) such as von Willebrand disease (VWD)-type 3 and Factor X (FX) deficiency. Targeting protein Z-dependent protease inhibitor (ZPI), a natural anticoagulant, is a novel strategy to enhance hemostasis. We evaluated the effects of ZPI post-transcriptional silencing using a GalNAc-conjugated siRNA (mTGM-148) in von Willebrand factor-deficient (VwfKO) mice and in mice with strongly reduced factor X levels (< 1%; f10low-mice). mTGM-148 reduced plasma ZPI antigen below 15% in both models. In VwfKO-mice, mTGM-148 significantly enhanced contact activation-initiated thrombin generation and normalized INTEM clotting parameters. In f10low-mice, thrombin generation was minimally affected, but EXTEM clotting parameters were significantly ameliorated. Importantly, mTGM-148 treatment significantly reduced blood loss in the tail clip model for both VwfKO-mice and f10low-mice. These data suggest that ZPI post-transcriptional silencing is a viable strategy to improve the hemostatic potential in both VWD-type 3 and FX deficiency. As such, ZPI inhibition represents a promising non-factor therapeutic approach for selected RBDs.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antithrombotic Therapy in Coronary Embolism: A Multicenter Study.","authors":"Alberto Vera, Eva Jover, Jeanne Varlot, Eduardo Pozo-Osinalde, Lidia Vilches, Raquel Ajo-Ferrer, Arturo Lanaspa, Adela Navarro, Pilar Jiménez, César Jiménez-Méndez, Rut Álvarez, Laura Cuesta Margolles, Nieves Gonzalo, María Ajo-Ferrer, Anai Moreno, Carlod García-Filloy, Ancor Sanz-García, Virgina Álvarez, Fernando Alfonso, Valeriano Ruiz-Quevedo, Batric Popovic","doi":"10.1055/a-2980-6716","DOIUrl":"https://doi.org/10.1055/a-2980-6716","url":null,"abstract":"<p><p>Background Coronary embolism (CE) is an uncommon cause of acute myocardial infarction, and the optimal post-discharge antithrombotic strategy remains uncertain. Methods Retrospective multicenter study including patients with definite or probable CE. Three groups of patients were identified: i) requiring with specific management, ii) with atrial fibrillation (AF), and iii) with no indication for oral anticoagulation (OAC). The latter two groups were further classified according to the antithrombotic treatment received, and long-term outcomes (composite of recurrent CE, stroke, systemic embolism, cardiovascular or all cause death and major bleeding at 5 years) were subsequently evaluated Results A total of 489 patients were considered. Among 189 patients with AF, 85 received direct oral anticoagulants (DOAC) and 104 vitamin K antagonists (VKAs). VKA users showed a higher rate of the composite endpoint compared with DOACs (40% vs. 18%, p < 0.001) with the difference primarily driven by all-cause mortality. In multivariable analysis, VKA therapy remained independently associated with worse outcomes (HR 1.9, 95% CI 1.02-3.5; p=0.04). In the 182 patients without an indication for anticoagulation, 115 received antiplatelet therapy and 67 OAC. Those treated with OAC had a higher incidence of the composite outcome (16% vs. 7%, p=0.049) with the difference primarily driven by all-cause mortality. Multivariable analysis confirmed OAC as an independent predictor of adverse prognosis (HR 3.4 (95%CI 1.2-9.7;p=0.02). Conclusions In patients with CE, stratification based on underlying etiology and embolic risk before hospital discharge might serve as a decision-making approach for determining optimal antithrombotic strategies and improved clinical outcomes.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning Models for Suspected Pulmonary Embolism in Emergency Department Patients: A Multicentre Diagnostic Study.","authors":"Christophe A Fehlmann, Ben Meuleman, Helia Robert-Ebadi, Marc Righini, Arnaud Perrier, Marlieke E A de Kraker, Mohamed Abbas","doi":"10.1055/a-2939-4076","DOIUrl":"10.1055/a-2939-4076","url":null,"abstract":"<p><p>Pulmonary embolism (PE) is frequently suspected in emergency departments (EDs). Safely ruling out PE without additional testing could reduce imaging use and ED crowding. Machine learning (ML) may improve accuracy and efficiency.To evaluate ML models for ruling out PE without additional testing in ED patients with suspected PE, while maintaining a failure rate <2%.We retrospectively analyzed pooled data from four prospective European studies of ED patients with suspected PE (2000-2013). A total of 5,038 patients were randomly split into training (<i>n</i> = 2,400) and validation (<i>n</i> = 2,638) datasets. ML models classified patients into low, intermediate, and high pre-test probability groups. In intermediate-risk patients, post-test probability was refined using either a fixed D-dimer threshold or a second ML model. The primary outcome was the failure rate assessed in the validation cohort and defined as the proportion of missed PE diagnoses.The best-performing algorithm combined weighted ridge regression (pre-test) with weighted random forest (post-test), achieving a failure rate of 1.44% (95% CI: 1.04-1.99) and a Matthews correlation coefficient of 0.470 (95% CI: 0.440-0.500). This model ruled out PE without any testing in 9.7% of patients, with an estimated imaging proportion of 54.1%, comparable to 4-level Pulmonary Embolism Clinical Probability Score (4PEPS; 52.9%) and lower than Pulmonary Embolism Rule-out Criteria (PERC; 66.8%).A two-step ML algorithm performed comparably to the best existing clinical decision rules, with a failure rate whose confidence interval remained below the prespecified 2% criterion and an estimated imaging proportion similar to 4PEPS. Prospective external validation is warranted.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimates, temporal evolution, and contributors of the stroke burden due to air pollution and non-optimal temperature across G20 nations, 1990-2023.","authors":"Renfang Zhang, Fei Lin, Yongbin Wang","doi":"10.1055/a-2977-5555","DOIUrl":"https://doi.org/10.1055/a-2977-5555","url":null,"abstract":"<p><strong>Background: </strong>Air pollution and non-optimal temperature are major modifiable environmental risk factors for stroke. This study assessed their attributable stroke burden across G20 countries from 1990 to 2023 and projected trends to 2040.</p><p><strong>Methods: </strong>Using data from the GBD 2023, we analyzed age-standardized mortality (ASMR) and disability-adjusted life year rates (ASDR) for stroke attributable to air pollution (ambient particulate matter and household air pollution from solid fuels) and non-optimal temperature (high and low), and stratified according to the Socio-demographic Index (SDI). Joinpoint regression, decomposition analysis, and ARIMA modeling were employed.</p><p><strong>Results: </strong>The ASMR for stroke attributable to these environmental risks in G20 countries declined from 52.81 (95% UI: 32.05-71.82) to 17.46 (95% UI: 10.58-24.53) per 100,000 from 1990 to 2023, with an estimated annual percentage change (EAPC) of -3.44% (95% CI: -3.57 to -3.30). The ASDR declined from 1,148.95 (95% UI: 693.62-1,576.02) to 394.91 (95% UI: 229.91-550.54) per 100,000 (EAPC: -3.29%, 95% CI: -3.41 to -3.17). This was driven by a sharp decrease in household air pollution burden. However, burdens attributable to ambient particulate matter and high temperature increased or remained stable, exhibiting marked geographical disparities, with low- and middle-SDI G20 nations bearing a disproportionately high burden. Projections to 2040 indicate a continued overall decline, but burdens attributable to ambient particulate matter and high temperature are expected to persist.</p><p><strong>Conclusions: </strong>While progress has been made, ambient particulate matter pollution and high temperature remained important contributors to the estimated GBD-attributable stroke burden in the G20, underscoring the need for targeted intervention.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of Triglyceride Glucose Index-related Obesity Indices, Genetic Susceptibility, and the Risk of Venous Thromboembolism: Insights from a Prospective Cohort Study.","authors":"Yuyang Sun, Jun Deng, Xi Cao, Liang V Tang, Xingjie Hao, Yu Hu","doi":"10.1055/a-2969-4582","DOIUrl":"https://doi.org/10.1055/a-2969-4582","url":null,"abstract":"<p><strong>Background: </strong>The triglyceride glucose (TyG) index and related obesity metrics are commonly recognized as important indicators of insulin resistance. However, the associations of several novel TyG-related obesity indices developed with venous thromboembolism (VTE) risk and their interactions with genetic susceptibility remain unclear.</p><p><strong>Methods: </strong>Cox proportional hazards models were applied to evaluate the associations between TyG-related obesity indices and VTE risk. Restricted cubic spline analyses were conducted to examine the linear and nonlinear relationships. Kaplan-Meier curves were performed to assess the cumulative risk of VTE. The additive interactions were assessed using the relative excess risk due to interaction, attributable proportion due to interaction. Discriminative performance was assessed using receiver operating characteristic curves.</p><p><strong>Results: </strong>Participants in the highest quartiles of TyG, TyG-BMI, TyG-WC, TyG-WHtR, TyG-BRI, TyG-ABSI, TyG-WWI, and TyG-VAI exhibited elevated risk of VTE, with HRs (95% CIs) of 1.11 (1.04-1.17), 1.86 (1.76-1.98), 2.08 (1.94-2.22), 1.78 (1.67-1.89), 1.80 (1.70-1.92), 1.24 (1.17-1.33), 1.37 (1.29-1.46), and 1.19 (1.12-1.25), respectively. Individuals in the highest quartiles of TyG-related obesity indices had a higher cumulative incidence of VTE. ROC analysis indicated that TyG-WC and TyG-BRI showed comparatively better discriminative performance for VTE risk compared with other TyG-related obesity indices. Participants with both high genetic risk and high TyG-related obesity indices showed an increased risk of VTE.</p><p><strong>Conclusion: </strong>Higher TyG-related obesity indices were associated with an increased risk of VTE. Individuals with both higher quartiles of TyG-related obesity indices and high genetic susceptibility exhibited the highest VTE risk. Additive interactions were observed between TyG-related obesity indices and high genetic risk.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design Update for Refining Validated Tools for Pulmonary Embolism Identification in Electronic Databases: The PE-EHR+ Extension Study.","authors":"Julia Malejczyk, Sina Rashedi, Christopher Amalan, Darsiya Krishnathasan, Esme Flood, Mariana B Pfeferman, Ammar Dharani, Baoren Liu, Ziqin Sha, Taiyang Chen, Antoine Bejjani, Candrika D Khairani, David Jiménez, Syed Moin Hassan, Farbod Nicholas Rahaghi, George R Washko, Ang Li, Cesar Caraballo, Samuel Z Goldhaber, Li Zhou, Eric A Secemsky, Zhenqui Lin, Pedro Ruiz Artacho, Harlan M Krumholz, Liqin Wang, Gregory Piazza, Behnood Bikdeli","doi":"10.1055/a-2958-5047","DOIUrl":"10.1055/a-2958-5047","url":null,"abstract":"","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ML Models for early and accurate prediction of disseminated intravascular coagulation: The diagnosis of DIC depends on the diagnostic tool.","authors":"Hideo Wada","doi":"10.1055/a-2972-1645","DOIUrl":"https://doi.org/10.1055/a-2972-1645","url":null,"abstract":"<p><p>No Abstract.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond the Average Effect: Identifying the Trauma Patients Who Benefit Most from Tranexamic Acid.","authors":"Eva Soler-Espejo, Vanessa Roldán","doi":"10.1055/a-2848-3364","DOIUrl":"10.1055/a-2848-3364","url":null,"abstract":"","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"1014-1016"},"PeriodicalIF":5.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147780914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing the Accuracy of Natural Language Processing Tools for Pulmonary Embolism Detection Through Integration with Claims Data: The PE-EHR+ Study.","authors":"Sina Rashedi, Syed Bukhari, Darsiya Krishnathasan, Candrika D Khairani, Antoine Bejjani, Mariana B Pfeferman, Julia Malejczyk, Mehrdad Zarghami, Eric A Secemsky, Farbod N Rahaghi, Mohamad A Hussain, Hamid Mojibian, Samuel Z Goldhaber, David Jiménez, Manuel Monreal, Richard Yang, Li Zhou, Gregory Piazza, Harlan M Krumholz, Liqin Wang, Behnood Bikdeli","doi":"10.1055/a-2796-1975","DOIUrl":"10.1055/a-2796-1975","url":null,"abstract":"<p><strong>Background: </strong>Rule-based natural language processing (NLP) tools can identify pulmonary embolism (PE) via radiology reports. However, their external validity remains uncertain.</p><p><strong>Methods: </strong>In this cross-sectional study, 1,712 hospitalized patients (with and without PE) at Mass General Brigham (MGB) hospitals (2016-2021) were analyzed. Two previously published NLP algorithms were applied to radiology reports to identify PE. Chart review by two physicians was the reference standard. We tested three approaches: (A) NLP applied to all patients; (B) NLP limited to radiology reports of patients with principal or secondary International Classification of Diseases 10th revision (ICD-10) PE discharge codes; and (C) NLP applied to patients with PE discharge codes or a Present-on-Admission (POA) indicator (\"Y\") for PE. All others were assumed PE-negative in Approaches B and C to minimize NLP false positives. Weighted estimates were derived from the MGB hospitalized cohort (<i>n</i> = 381,642) to calculate F1 scores (as the harmonic mean of sensitivity and positive predictive value [PPV]).</p><p><strong>Results: </strong>In Approach A, both NLP tools showed high sensitivity (82.5%, 93.0%) and specificity (98.9%, 98.7%) but low PPV (60.3%, 59.6%). Approach B improved PPV (95.2%, 94.9%) but reduced sensitivity (74.1%, 76.2%), while Approach C preserved both high sensitivity (82.5%, 93.0%) and PPV (95.6%, 95.8%). Approach C demonstrated the best performance, yielding significantly higher F1 scores for both NLP tools (88.6%, 94.4%) compared with Approach A (69.7%, 72.6%) and Approach B (83.3%, 84.5%) (<i>P</i> < 0.001).</p><p><strong>Conclusion: </strong>The accuracy of PE detection improves when rule-based NLP algorithms are operationalized using administrative claims data in addition to radiology reports.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"1049-1056"},"PeriodicalIF":5.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146150598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Evidence and Future Directions for Colchicine in the Prevention of Atherosclerotic Cardiovascular Disease.","authors":"Aimée M H van Zelm, Aernoud T L Fiolet, Robert J Hinchliffe, Shirley Jansen, Martin Teraa, Noel C Chan","doi":"10.1055/a-2724-4543","DOIUrl":"10.1055/a-2724-4543","url":null,"abstract":"<p><p>Chronic inflammation plays a key role in the development and progression of atherosclerotic cardiovascular disease (ASCVD) and its complications. Despite the use of blood pressure-, lipid-, and glucose-lowering therapies as well as antithrombotic agents, the lifetime residual cardiovascular (CV) risk in patients with ASCVD remains high. Because chronic inflammation remains an unaddressed risk factor, anti-inflammatory therapy has the potential to further lower residual CV risk in these patients. Low-dose colchicine (0.5 mg daily) has emerged as a promising low-cost oral anti-inflammatory therapy for this indication. In patients with chronic coronary syndrome (CCS), low-dose colchicine was well-tolerated and reduced the risk of myocardial infarction, stroke, coronary revascularization, and CV death. However, trials in patients with acute coronary syndrome (ACS) yielded conflicting results, and two trials in patients with ischemic stroke did not show a benefit. In patients with peripheral artery disease (PAD), preliminary observational data suggested a potential benefit, and a randomized trial is currently underway to examine its efficacy in reducing CV and limb events. The long-term safety data for low-dose colchicine in ASCVD are reassuring. Although pooled data from trials in ASCVD show a small (0.55%) absolute increase in the risk of hospitalization for gastrointestinal events, adverse signals were not observed for serious infection, cancer, or severe myotoxicity. In this article, we review the clinical studies of colchicine that examined its risk-benefit for the prevention of CV events in patients with ASCVD, discuss clinical and research implications, and highlight knowledge gaps.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"991-1005"},"PeriodicalIF":5.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145356135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}