Maria Mulet, Rubén Osuna-Gómez, Laura Martínez-España, Iris Artesero, Pol Duch-Llorach, Paula Vera-Artázcoz, Maria Torrens-Sonet, Núria Rodríguez-Farré, Noelia Vilalta, Andrés Abril-Gamboa, Montserrat Seres, Elisabet Cantó, Ma Àngels Ortiz, Joaquín López-Contreras, Silvia Vidal
{"title":"A distinctive immunophenotypic signature in thrombocytopenic septic patients: platelet and neutrophil dysregulations as key contributors to disease severity.","authors":"Maria Mulet, Rubén Osuna-Gómez, Laura Martínez-España, Iris Artesero, Pol Duch-Llorach, Paula Vera-Artázcoz, Maria Torrens-Sonet, Núria Rodríguez-Farré, Noelia Vilalta, Andrés Abril-Gamboa, Montserrat Seres, Elisabet Cantó, Ma Àngels Ortiz, Joaquín López-Contreras, Silvia Vidal","doi":"10.1016/j.jtha.2025.09.006","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.09.006","url":null,"abstract":"<p><strong>Background: </strong>Thrombocytopenia is frequently associated with increased mortality in sepsis; however, the underlying immunological mechanisms remain poorly understood. This study characterizes molecular and phenotypic changes associated with thrombocytopenia in sepsis, focusing on platelets (PLTs), neutrophils, and their interactions, and evaluates their contributions to poor outcomes.</p><p><strong>Methods: </strong>Blood samples were collected from 19 healthy donors (HD), 27 non-thrombocytopenic (N-TP) and 22 thrombocytopenic (TP) patients with community-acquired sepsis at baseline (diagnosis), and at 24, 48, and 72 hours after admission. Plasma levels of PLT-derived mediators and neutrophil surrogate markers were quantified by ELISA. PLT and neutrophil phenotypes and neutrophil degranulation were assessed by flow cytometry, while extracellular DNA release, as a surrogate approximation of NETosis, was measured by SYTOX<sup>TM</sup> Green fluorescence and validated by MPO-DNA ELISA.</p><p><strong>Results: </strong>TP patients showed higher percentages of PD-L1+ PLTs and increased CXCR4 expression on PLTs compared to N-TP patients. Their plasma also contained elevated sP-selectin and VEGF levels. Compared to HD, TP patients exhibited fewer neutrophil-PLT complexes; however, a greater proportion of these complexes were PD-L1+ and expressed higher CXCR4 levels than those in N-TP patients. Despite reduced extracellular DNA release upon stimulation, TP patients had higher plasma MPO-DNA complexes and MPO, NE, and S100A8/A9 levels. Clinically, TP patients had worse outcomes, with lower sCD40L levels and impaired in vitro extracellular DNA release correlating with disease severity (SOFA ≥8).</p><p><strong>Conclusions: </strong>Our findings suggest a distinct immune signature in TP septic patients, defined by enhanced PLT activation and neutrophil dysfunction, potentially contributing to poor prognosis.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213045","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}
Katie Harris, Mark Woodward, Aaron R Folsom, Pamela L Lutsey, Ethan Cannon, Neil A Zakai, Mary Cushman, Nels C Olson, Nithya Kannan, Ryan Packer, Katherine Wilkinson, S Goya Wannamethee, Christopher C Patterson, Yoav Ben-Shlomo, Gordon D O Lowe
{"title":"ASSOCIATIONS BETWEEN PLASMA LEVELS OF COAGULATION FACTORS VIII AND IX AND INCIDENT CARDIOVASCULAR DISEASE AND MORTALITY: SYSTEMATIC REVIEW AND META-ANALYSIS.","authors":"Katie Harris, Mark Woodward, Aaron R Folsom, Pamela L Lutsey, Ethan Cannon, Neil A Zakai, Mary Cushman, Nels C Olson, Nithya Kannan, Ryan Packer, Katherine Wilkinson, S Goya Wannamethee, Christopher C Patterson, Yoav Ben-Shlomo, Gordon D O Lowe","doi":"10.1016/j.jtha.2025.09.008","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.09.008","url":null,"abstract":"<p><strong>Background: </strong>Associations of plasma levels of coagulation factors VIII (FVIII) and IX (FIX) with incident cardiovascular disease (CVD) and mortality remain uncertain.</p><p><strong>Objective: </strong>To clarify associations of FVIII and FIX with CVD and mortality in a meta-analysis in general population prospective studies.</p><p><strong>Methods: </strong>We conducted a systematic literature review up to 19 July 2024, of PubMed and Cochrane databases, reporting estimates (and measures of variability) of associations of plasma levels of FVIII or FIX with risks of incident CVD. Pooled risk ratios (RRs), adjusted for age, sex, systolic blood pressure, total cholesterol, smoking and diabetes, were estimated in a random effects meta-analysis for effects of FVIII and FIX levels on incident CVD, and CVD and total mortality.</p><p><strong>Results: </strong>In 7 studies (8888 cases in 32,123 participants) for FVIII and 4 studies (2273 cases in 6951 participants) for FIX the pooled RRs (95% confidence interval) for incident CVD per 1 SD higher were 1.12 (1.09, 1.14) and 1.05 (1.00, 1.12), respectively. Corresponding CVD mortality and total mortality RRs for FVIII were 1.17 (1.07, 1.28) and 1.16 (1.12, 1.19), and for FIX;1.14 (1.06, 1.22) and 1.13 (1.07, 1.18), respectively. Comparing factor levels above versus below the 90th percentile, pooled RRs were 1.34 (1.25, 1.44) for FVIII; and 1.02 (0.85, 1.22) for FIX.</p><p><strong>Conclusions: </strong>Risks of CVD, CVD mortality and total mortality increase across higher population distributions of FVIII levels. Risks of CVD mortality and total mortality also increase across FIX levels, but no evidence of an independent effect for incident CVD risk.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213050","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}
Michael Hack, Donald M Arnold, Rumi Clare, Yi Zhang, Nikola Ivetic, Hina Bhakta, Jan Zlamal, John G Kelton, Ishac Nazy
{"title":"Persistence of anti-platelet factor 4 antibodies in vaccine-induced immune thrombocytopenia and thrombosis for 3 years.","authors":"Michael Hack, Donald M Arnold, Rumi Clare, Yi Zhang, Nikola Ivetic, Hina Bhakta, Jan Zlamal, John G Kelton, Ishac Nazy","doi":"10.1016/j.jtha.2025.08.039","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.08.039","url":null,"abstract":"<p><strong>Background: </strong>Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare and potentially life-threatening complication of adenoviral vector-based vaccines against SARS-CoV-2. In VITT, antibodies against platelet factor 4 (PF4, CXCL4) cause platelet activation, which then lead to thrombocytopenia and thrombosis. VITT resembles the immune-mediated drug reaction heparin-induced thrombocytopenia (HIT); however, unlike HIT antibodies which have been shown to be transient, VITT antibodies appear to persist for much longer.</p><p><strong>Methods: </strong>In this study, we followed a Canadian cohort of VITT patients (n=30) for nearly 3 years from their initial presentation and report serial testing for anti-PF4 antibody levels by enzyme immunoassay (EIA), as well as their ability to activate platelets in the PF4-serotonin release assay (PF4-SRA). The median latest follow-up was 715 days (range 126-1065 days) post-vaccination.</p><p><strong>Results: </strong>Using Kaplan-Meier analysis, we found 65.2% of VITT patients continued to test positive for anti-PF4 antibodies and 34.1% of patients continued to test positive for platelet activating anti-PF4 antibodies. There were no cases of recurrent thrombosis; however, 7/8 (87.5%) VITT patients with persistent platelet-activating anti-PF4 antibodies remained on anticoagulant or antiplatelet therapy.</p><p><strong>Conclusion: </strong>Our findings demonstrate VITT antibodies can persist for nearly 3 years in some patients and a proportion of those maintain their ability to activate platelets in vitro. The complete duration of VITT antibody persistence remains unknown and whether this has clinical implications requires ongoing surveillance with further evaluation.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186124","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":"Annoucements","authors":"","doi":"10.1016/S1538-7836(25)00585-9","DOIUrl":"10.1016/S1538-7836(25)00585-9","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 10","pages":"Pages 3406-3407"},"PeriodicalIF":5.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134899","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}
Marisa Ninivaggi , Bas de Laat , Romy de Laat–Kremers
{"title":"Effects of hormonal therapy on thrombin generation testing in transgender individuals","authors":"Marisa Ninivaggi , Bas de Laat , Romy de Laat–Kremers","doi":"10.1016/j.jtha.2025.05.037","DOIUrl":"10.1016/j.jtha.2025.05.037","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 10","pages":"Pages 3073-3074"},"PeriodicalIF":5.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134817","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":"Assessing loss of platelet sialic acid using lectin flow cytometry","authors":"Marie A. Hollenhorst","doi":"10.1016/j.jtha.2025.07.003","DOIUrl":"10.1016/j.jtha.2025.07.003","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 10","pages":"Pages 3079-3081"},"PeriodicalIF":5.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134819","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}
Nikola Vladic, Stephan Nopp, Ingrid Pabinger, Walter Ageno, Jean M Connors, Sabine Eichinger, Cihan Ay
{"title":"Large language models versus thrombosis experts: A comparative study on patient education and clinical decision-making in venous thromboembolism.","authors":"Nikola Vladic, Stephan Nopp, Ingrid Pabinger, Walter Ageno, Jean M Connors, Sabine Eichinger, Cihan Ay","doi":"10.1016/j.jtha.2025.09.004","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.09.004","url":null,"abstract":"<p><strong>Background: </strong>Large language models (LLMs) have demonstrated remarkable capabilities in various medical fields, yet their performance in thrombosis and haemostasis, particularly in patient education and complex clinical decision-making, is unexplored.</p><p><strong>Objectives: </strong>We aimed to compare the quality of responses from LLMs versus thrombosis experts and assess clinician's ability to distinguish between them.</p><p><strong>Methods: </strong>Three experts on thrombosis and haemostasis and three LLMs (Le Chat Pixtral Large, DeepSeek-R1, ChatGPT-4.5) answered three patient education and three clinical decision-making queries. Thirty-seven physicians rated responses for adequacy (1 = \"very poor\", 10 = \"excellent\") and estimated their origin (1 = \"certainly LLM,\" 10 = \"certainly human\"). Mean differences were assessed via t-tests, medians via Wilcoxon tests, and correlations via Spearman's test. All p values were Bonferroni-adjusted.</p><p><strong>Results: </strong>LLMs provided significantly better patient education responses than experts. Mean adequacy score differences were: Le Chat Pixtral Large +1.6 (95% CI: 1.3-2.0, p<0.01), DeepSeek-R1 +1.7 (95% CI: 1.3-2.1, p<0.001), and ChatGPT-4.5 +1.9 (95% CI: 1.6-2.3, p<0.001). In clinical decision-making, DeepSeek-R1 outperformed experts, (+1.4; 95% CI: 1.1-1.8, p<0.001), whereas Le Chat Pixtral Large (-0.3; 95% CI, -0.8-0.1, p=0.96) and ChatGPT-4.5 (+0.5; 95% CI: 0.0-0.9, p=0.18), performed comparably to experts. Evaluators couldn't distinguish between expert (median: 6.0, interquartile range [IQR]: 3.0-8.0) and LLM-generated responses (median 6.0, IQR: 4.0-8.0).</p><p><strong>Conclusion: </strong>LLMs outperform experts in VTE-related patient education and match or exceed them in clinical decision-making, providing responses indistinguishable from experts. Though major barriers need to be addressed, LLMs have strong potential to support clinical management and patient education in VTE.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182018","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}
Arielle L Langer, Brandon Togioka, Nicole A Smith, Bethany T Samuelson Bannow
{"title":"Managing Anticoagulation Peripartum.","authors":"Arielle L Langer, Brandon Togioka, Nicole A Smith, Bethany T Samuelson Bannow","doi":"10.1016/j.jtha.2025.09.003","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.09.003","url":null,"abstract":"<p><p>Due to the elevated thrombosis risk during pregnancy, anticoagulants are amongst the most common medications prescribed during gestation. For patients on anticoagulation antepartum, planning for delivery in advance is central to a safe and patient-centered delivery. Peripartum anticoagulation management must balance the benefits of continued therapy against the risks of postpartum hemorrhage and potential limitations in offering neuraxial anesthesia. Key considerations for delivery planning for patients on anticoagulation include 1) prophylactic versus therapeutic dosing; 2) mode of delivery (vaginal vs cesarean); 3) scheduled vs spontaneous delivery; 4) specific indications for neuraxial anesthesia (e.g. twin gestation, difficult airway); 5) the patient's valuation of neuraxial anesthesia; 6) time since diagnosis of venous thromboembolism (VTE) where applicable. Optimal patient management requires prenatal collaboration between thrombosis experts, obstetrics, and anesthesia to develop a personalized plan for delivery that balances risk of thrombosis, the potential for hemorrhagic complications, and patient preferences. This includes evaluating whether a patient on low molecular weight heparin should switch prior to delivery to subcutaneous unfractionated heparin (UFH) for prophylaxis or UFH continuous infusion, for those at high risk from a break in therapeutic anticoagulation. We also review postpartum anticoagulation options, emphasizing the importance of adherence during this high-risk period. Our discussion is limited to anticoagulation indicated for VTE.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182079","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":"Commentary on “Novel p.C252G and p.C280X mutations in EGF-1 domain of thrombomodulin lead to a thrombosis–bleeding syndrome”","authors":"Takayuki Iwaki","doi":"10.1016/j.jtha.2025.07.009","DOIUrl":"10.1016/j.jtha.2025.07.009","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 10","pages":"Pages 3082-3083"},"PeriodicalIF":5.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134820","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}