Thrombosis research最新文献

{"title":"Efficacy and safety of reduced-dose versus full-dose direct oral anticoagulants for extended treatment of venous thromboembolism: A meta-analysis with trial sequential analysis and reconstructed time-to-event data","authors":"Ahmed Ibrahim ,&nbsp;Laila Shalabi ,&nbsp;Sofian Zreigh ,&nbsp;Abdelrahman M. Tawfik ,&nbsp;Belal Mohamed Hamed ,&nbsp;Mohamed Elsawy ,&nbsp;Atul Pathak ,&nbsp;Mamas A. Mamas ,&nbsp;Giuseppe Andò ,&nbsp;Islam Y. Elgendy ,&nbsp;Pierre Sabouret","doi":"10.1016/j.thromres.2025.109476","DOIUrl":"10.1016/j.thromres.2025.109476","url":null,"abstract":"<div><h3>Background</h3><div>While current guidelines recommend extended therapeutic anticoagulation for venous thromboembolism (VTE), the optimal dosing strategy for direct oral anticoagulants (DOACs) remains uncertain, particularly in cancer-associated VTE. This meta-analysis evaluates the efficacy and safety of reduced-dose versus full-dose DOACs for extended VTE treatment.</div></div><div><h3>Methods</h3><div>We conducted a comprehensive search of major electronic databases through April 2025 for randomized controlled trials (RCTs) comparing reduced-dose versus full-dose DOACs for VTE treatment. Pooled risk ratios (RR) with 95 % confidence intervals (CI) were calculated using random-effects models. Time-to-event data were reconstructed from Kaplan-Meier curves. Trial sequential analysis (TSA) was employed to assess the conclusiveness of the evidence.</div></div><div><h3>Results</h3><div>Our analysis included five RCTs involving 8781 patients. Reduced-dose DOACs were associated with comparable efficacy to full-dose therapy in preventing recurrent VTE (RR, 0.94; 95 % CI, 0.68–1.29; <em>P</em> = 0.70), supported by time-to-event analysis (HR, 0.89; 95 % CI 0.78–1.02; <em>p</em> = 0.10). However, reduced-dose regimens significantly reduced major or clinically relevant non-major bleeding (RR, 0.71; 95 % CI 0.61–0.82; <em>P</em> &lt; 0.0001), with consistent findings on Kaplan-Meier analysis (HR, 0.61; 95 % CI 0.57–0.66; <em>P</em> &lt; 0.001). Subgroup analyses showed consistent results in patients with and without active cancer, and also across different DOAC types (apixaban and rivaroxaban). No differences were observed in all-cause mortality. TSA confirmed sufficient evidence for both efficacy and safety outcomes.</div></div><div><h3>Conclusion</h3><div>Reduced-dose DOACs were as effective as full-dose regimens in preventing recurrent VTE, with a better safety profile, suggesting they may be preferred for patients requiring extended anticoagulation, especially those at high risk of recurrence.</div></div><div><h3>Prospero ID</h3><div>CRD420251048675.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"254 ","pages":"Article 109476"},"PeriodicalIF":3.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076083","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 utility of thrombin generation using ST-Genesia® in patients with hereditary and acquired thrombophilia: A cross-sectional study","authors":"Lina Caspary ,&nbsp;Joseph R. Shaw ,&nbsp;Odile Stalder ,&nbsp;Justine Brodard ,&nbsp;Anne Angelillo-Scherrer ,&nbsp;Kristina Vrotniakaite-Bajerciene","doi":"10.1016/j.thromres.2025.109454","DOIUrl":"10.1016/j.thromres.2025.109454","url":null,"abstract":"<div><h3>Background</h3><div>The role of thrombin generation (TG) in the setting of thrombophilia testing remains unclear. Hence, we aimed to investigate the diagnostic utility of TG with ST-Genesia® instrument to discriminate between patients with and without different thrombophilias.</div></div><div><h3>Methods</h3><div>We conducted a single-center cross-sectional study of all non-anticoagulated patients who underwent conventional thrombophilia testing for factor V Leiden, prothrombin gene G20210A mutation (PTM), protein C, S and antithrombin deficiency (PCD, PSD, ATD), and antiphospholipid antibody syndrome (APS) because of previous venous thromboembolism (VTE), unexplained arterial thrombosis or a positive family history for VTE. To assess the diagnostic utility of TG, we calculated the area under the receiver operating curve (AUC), thresholds for 85 %, 95 % and 99 % sensitivity and specificity, positive and negative predictive values and likelihood ratios, cohort-related diagnostic failure and efficacy rates and the diagnostic yield of each TG parameter for different thrombophilias.</div></div><div><h3>Results</h3><div>A total of 467 patients were enrolled in the study, mostly investigated because of previous VTE (<em>n</em> = 283, 61 %). Thrombophilia testing was positive in 161/467 (35 %) patients. Normalized endogenous thrombin potential (ETP) effectively discriminated for ATD (AUC =79 [95 %CI 72–87]) and PTM (AUC 86 [95 %CI 79–93]) and ETP inhibition with thrombomodulin for PCD/PSD (AUC 90 [95 %CI 85–95]). With the established best performing TG parameter cut-offs, PCD/PSD, PTM, ATD, and low-risk APS could be safely (&lt;3 % failure rate) excluded in 62 %, 58 %, 27 %, and 29 % of cohort patients, respectively.</div></div><div><h3>Conclusions</h3><div>TG assessment using ST-Genesia® system shows promise as a supportive screening tool in thrombophilia work-up and warrants further validation.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"254 ","pages":"Article 109454"},"PeriodicalIF":3.4,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081731","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":"Inhibiting mTORC1 pathway by rapamycin restores the balance of CD8+ T cell subsets and reduces CD8+ T cell-mediated platelet destruction in immune thrombocytopenia","authors":"Xiaofei Ni ,&nbsp;Jinghan Guo ,&nbsp;Xiaojing Zhu ,&nbsp;Haoyi Wang ,&nbsp;Lingjun Wang ,&nbsp;Yajing Zhao ,&nbsp;Tianshu Yu ,&nbsp;Shouqing Han ,&nbsp;Yubin Li ,&nbsp;Hai Zhou ,&nbsp;Ming Hou ,&nbsp;Jihua Qiu","doi":"10.1016/j.thromres.2025.109475","DOIUrl":"10.1016/j.thromres.2025.109475","url":null,"abstract":"<div><h3>Background</h3><div>CD8⁺ T cells contribute to platelet destruction in immune thrombocytopenia (ITP). Rapamycin, a mechanistic target of rapamycin complex 1 (mTORC1) inhibitor, has demonstrated efficacy in relapsed/refractory ITP. However, its impact on CD8⁺ T cells in ITP remains unexplored.</div></div><div><h3>Methods</h3><div>Gene expression profiles from GSE43177 dataset were analyzed using gene set enrichment analysis (GSEA). Activation of the mTORC1 pathway and CD8⁺ T cell subsets was evaluated using flow cytometry. CD8⁺ T cell cytotoxicity was assessed by measuring perforin, granzyme B expression and platelet apoptosis. Additionally, an active ITP murine model was established for validation.</div></div><div><h3>Results</h3><div>GSEA of the GSE43177 dataset revealed significant enrichment of mTOR pathway in ITP patients with high CD8⁺ T cell abundance. CD8⁺ T cells from peripheral blood of ITP patients exhibited enhanced mTORC1 pathway activation, as evidenced by elevated phosphorylation levels of mTOR, p70S6K, and 4EBP1. Additionally, CD8⁺ T cell subsets were imbalanced in ITP patients, with reduced naïve T cells, increased effector memory T cells, and decreased CD28⁻ T cells, alongside elevated cytotoxicity. <em>In vitro</em> treatment with rapamycin restored the homeostasis of CD8⁺ T cell subsets and reduced CD8⁺ T cell-mediated platelet apoptosis. Furthermore, rapamycin effectively ameliorated thrombocytopenia and modulated CD8⁺ T cell subsets in the active ITP murine model.</div></div><div><h3>Conclusion</h3><div>Our findings demonstrate that inhibition of mTORC1 by rapamycin restores the homeostasis of CD8⁺ T cell subsets and reduces CD8⁺ T cell-mediated platelet destruction in ITP. These results provide a mechanistic rationale for the clinical application of rapamycin in ITP management.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"254 ","pages":"Article 109475"},"PeriodicalIF":3.4,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045163","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":"Risk factors for thrombocytopenia in adult patients with sepsis: A systematic review and meta-analysis","authors":"Pufan Han ,&nbsp;Jiaqian Qi ,&nbsp;Ziyan Zhang ,&nbsp;Peng Wang ,&nbsp;Xiaofei Song ,&nbsp;Yue Han","doi":"10.1016/j.thromres.2025.109456","DOIUrl":"10.1016/j.thromres.2025.109456","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis-induced thrombocytopenia (SIT) is a frequent hematological complication in critically ill patients. However, the independent risk factors for SIT remain controversial. This meta-analysis aims to identify independent predictors of SIT in adult septic patients.</div></div><div><h3>Objective</h3><div>To identify risk factors for SIT and explore their potential implications for early risk stratification and platelet-targeted intervention in sepsis.</div></div><div><h3>Methods</h3><div>PubMed, Embase, Cochrane Library, Web of Science, CNKI, and Wanfang databases were searched from inception to April 2025. Studies reporting multivariable-adjusted associations between candidate risk factors and SIT were included. Data extraction and quality assessment were performed independently by two reviewers. Newcastle-Ottawa Scale was used for quality assessment. Pooled odds ratios (ORs) and mean differences (MDs) were calculated using RevMan 5.3 and Stata 15.0.</div></div><div><h3>Results</h3><div>A total of 14 studies involving 14,316 septic patients were included. The pooled incidence of SIT was 37.9 %. In the primary analysis using the conventional threshold of PLT &lt;100 × 10⁹ L⁻¹, elevated lactate, higher SOFA scores, and lower WBC count were associated with SIT. Subgroup analyses at PLT &lt;150 × 10⁹ L⁻¹ yielded consistent results for lactate and WBC, while SOFA retained significance only at the stricter definition. No significant publication bias was detected.</div></div><div><h3>Conclusions</h3><div>This meta-analysis demonstrated that elevated serum lactate, higher SOFA scores, and lower white blood cell count are significantly associated with SIT. Given the structural overlap between SOFA score and thrombocytopenia, further studies are needed to validate its independent role. Early identification of these predictors may help improve risk stratification and clinical management in septic patients.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"254 ","pages":"Article 109456"},"PeriodicalIF":3.4,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045238","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":"Assessment of thrombophilia in patients with lupus anticoagulant","authors":"Elena Pontara ,&nbsp;Maria Grazia Cattini ,&nbsp;Elisa Bison ,&nbsp;Marta Tonello ,&nbsp;Margherita Zen ,&nbsp;Cristina Vicenzetto ,&nbsp;Andrea Giordani ,&nbsp;Anna Baritussio ,&nbsp;Alida L.P. Caforio ,&nbsp;Vittorio Pengo","doi":"10.1016/j.thromres.2025.109474","DOIUrl":"10.1016/j.thromres.2025.109474","url":null,"abstract":"<div><h3>Background</h3><div>A close link between anti phosphatidyl-serine/prothrombin antibodies (aPS/PT), Lupus Anticoagulant (LA) potency and thrombophilia detected by activated protein C Resistance (aPC-R) in triple-positive antiphospholipid syndrome (APS) patients (LA+/anticardiolipin-aCL+/aβ2-Glycoprotein I-aβ2GPI+) has been observed. Whether this interdependence is present in patients with isolated LA is not known.</div></div><div><h3>Objectives</h3><div>This cross-sectional study evaluates aPS/PT and aPC-R in isolated LA patients in relation on how the diagnosis of the coagulation inhibitor was made.</div></div><div><h3>Methods</h3><div>LA was determined using the diluted Russell Viper Venom Time (dRVVT) and the Silica Clotting Time (SCT). IgG and IgM aCL, aβ2GPI and aPS/PT were measured by ELISA. APC-R was determined by thrombin generation assay.</div></div><div><h3>Results</h3><div>We studied 32 patients with isolated LA (LA+/aCL-/aβ2GPI-), 53 triple positive patients (LA+/aCL+/aβ2GPI+) and 24 controls. Total (IgG + IgM) aPS/PT antibody titer was lower and aPC-R weaker in isolated LA compared to triple-positive patients. When isolated LA was diagnosed by both coagulation positive tests (dRVVT and SCT), total aPS/PT titers were higher and aPC-R stronger than when isolated LA was diagnosed by a single positive test (either dRVVT or SCT). Total aPS/PT and aPC-R in patients positive for SCT only (dRVVT-, SCT+), were like those of control subjects.</div></div><div><h3>Conclusions</h3><div>The relation between LA, aPS/PT and aPC-R is linked to the way the coagulation inhibitor is diagnosed. These data may be useful to clinicians when interpreting the clinical value of isolated LA.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"254 ","pages":"Article 109474"},"PeriodicalIF":3.4,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026737","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 determinants of activated factor VII-antithrombin plasma levels and mortality in patients with coronary artery disease","authors":"Nicola Osti ,&nbsp;Gerardo Musuraca ,&nbsp;Barbara Lunghi ,&nbsp;Martino Donini ,&nbsp;Francesco Presa ,&nbsp;Hafiz Jarriullah ,&nbsp;Marianna Spizzo ,&nbsp;Gabriele Mango ,&nbsp;Patrizia Pattini ,&nbsp;Giuseppe Argentino ,&nbsp;Annalisa Castagna ,&nbsp;Marcello Baroni ,&nbsp;Matthieu Grusse ,&nbsp;Francesca Pizzolo ,&nbsp;Antonio Ferro ,&nbsp;Patrick Van Dreden ,&nbsp;Domenico Girelli ,&nbsp;Simonetta Friso ,&nbsp;Francesco Bernardi ,&nbsp;Nicola Martinelli","doi":"10.1016/j.thromres.2025.109459","DOIUrl":"10.1016/j.thromres.2025.109459","url":null,"abstract":"<div><h3>Background</h3><div>Activated factor VII-antithrombin complex (FVIIa-AT) is an indirect plasma biomarker of the interaction between tissue factor (TF) and FVIIa. High FVIIa-AT levels have been associated with an increased risk of mortality.</div></div><div><h3>Methods</h3><div>We investigated the genetic determinants of FVIIa-AT plasma levels by a candidate gene approach in a cohort of 610 subjects with (<em>n</em> = 478) or without (<em>n</em> = 132) angiographically-demonstrated coronary artery disease (CAD).</div></div><div><h3>Results</h3><div>Plasma concentration of FVIIa-AT did not differ between CAD and CAD-free subjects, but predicted the mortality risk in CAD during a median follow-up of 64-months. Among 7 polymorphisms in 4 candidate genes, codifying for FVII, TF, Endothelial Protein C Receptor (EPCR), and Low-density lipoprotein receptor-Related Protein 1 (LRP1), none was associated with CAD. Three of them were independently associated with FVIIa-AT plasma concentration. F3 -603 A &gt; G polymorphism predicted mortality in CAD consistent with the influence on FVIIa-AT levels, with the G allele-carriers having both higher FVIIa-AT concentration (86.4 with 95 %CI 82.4–90.5 <em>versus</em> 76.7 with 95 %CI 71.0–82.8 pM) and higher mortality risk (HR 1.92 with 95 %CI 1.08–3.41) as compared with AA homozygotes. Conversely, the F7 -323 A1/A2, the strongest genetic predictor of FVIIa-AT variability, and EPCR Ser219Gly polymorphisms were associated with FVIIa-AT levels but were not predictive of mortality.</div></div><div><h3>Conclusions</h3><div>Our results indicate that FVIIa-AT plasma levels are influenced by distinct genetic determinants linked to either TF or FVII expression. The heterogeneous association of FVIIa-AT-related polymorphisms with mortality risk in CAD suggests a predominant role of TF expression rather than FVII levels in the setting of secondary cardiovascular prevention.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"254 ","pages":"Article 109459"},"PeriodicalIF":3.4,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045164","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":"Incidence and risk factors for ischemic stroke in patients with cancer: A retrospective observational study","authors":"Hiroaki Terada ,&nbsp;Kenji Nakamura ,&nbsp;Shoto Fujita ,&nbsp;Yasufumi Gon ,&nbsp;Tomohiro Kawano ,&nbsp;Takaya Kitano ,&nbsp;Junji Takasugi ,&nbsp;Hideaki Kanki ,&nbsp;Ling Zha ,&nbsp;Masayo Komatsu ,&nbsp;Tetsuhisa Kitamura ,&nbsp;Tsutomu Sasaki","doi":"10.1016/j.thromres.2025.109455","DOIUrl":"10.1016/j.thromres.2025.109455","url":null,"abstract":"<div><h3>Background</h3><div>Patients with cancer have an elevated risk of ischemic stroke, which can interrupt cancer treatment and worsen survival outcomes. However, epidemiological data on stroke incidence and risk factors in this population remain limited.</div></div><div><h3>Methods</h3><div>We conducted a retrospective observational study of 35,862 patients with cancer registered at the University of Osaka Hospital between 2007 and 2020. Patients were followed for one year after cancer diagnosis to evaluate the cumulative incidence of ischemic stroke, accounting for death as a competing risk. Risk factors were assessed using the Fine and Gray competing risk model, with subdistribution hazard ratios (SHRs) and their 95 % confidence intervals (CIs) calculated.</div></div><div><h3>Results</h3><div>During the study period, 188 patients experienced a stroke. Of these, ischemic stroke was the most common type, occurring in 143 patients (76.1 %), followed by intracerebral hemorrhage in 38 patients (20.2 %) and subarachnoid hemorrhage in 7 patients (3.7 %). The 1-year cumulative incidence of ischemic stroke was 0.42 %. In multivariable analysis, independent risk factors for ischemic stroke included older age (adjusted SHR, 1.01; 95 % CI, 1.00–1.03), hypertension (1.59; 95 % CI, 1.10–2.30), dyslipidemia (1.60; 95 % CI, 1.09–2.36), atrial fibrillation (2.42; 95 % CI, 1.54–3.81), and advanced stages (1.74; 95 % CI, 1.12–2.70). Elevated leukocyte count (≥11,000/μL) and platelet count (≥350,000/μL) at cancer diagnosis were also independent predictors of ischemic stroke.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that older age, hypertension, dyslipidemia, atrial fibrillation, advanced stages, and elevated leukocyte and platelet count could represent potential risk factors for ischemic stroke in patients with cancer.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"254 ","pages":"Article 109455"},"PeriodicalIF":3.4,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026837","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":"CIB1 and platelet integrin αIIbβ3: Molecular mechanisms, disruption strategies and antithrombotic opportunities","authors":"Emadeldin M. Kamel ,&nbsp;Sulaiman A. Alsalamah ,&nbsp;Ahmed A. Allam ,&nbsp;Noha A. Ahmed ,&nbsp;Faris F. Aba Alkhayl ,&nbsp;Al Mokhtar Lamsabhi","doi":"10.1016/j.thromres.2025.109457","DOIUrl":"10.1016/j.thromres.2025.109457","url":null,"abstract":"<div><div>Platelet integrin αIIbβ3 is the final common effector of arterial thrombosis: it switches from a low-affinity to a high-affinity state, binds fibrinogen, and initiates the outside-in signals that stabilize a growing clot. Calcium- and integrin-binding protein 1 (CIB1) emerged as the first endogenous partner of the αIIb cytoplasmic tail and is now recognized as a dual-role adaptor. At rest, Ca²⁺-free CIB1 tethers the inner membrane clasp and restrains premature integrin activation; after ligand engagement, Ca²⁺-bound CIB1 docks onto αIIb, recruits focal-adhesion kinase and amplifies Src-dependent cytoskeletal remodeling. Genetic deletion uncouples these phases—Cib1−/− platelets aggregate normally but fail to spread, yielding unstable arterial thrombi with only modest prolongation of bleeding time—thereby validating the CIB1–αIIbβ3 interface as a selective antithrombotic checkpoint. Structural work reveals a latch-and-groove mechanism in which Ca²⁺ exposure frees a hydrophobic pocket on CIB1 that recognizes the αIIb GFFKR motif. This pocket now anchors low-nanomolar macrocyclic peptides and first-generation small molecules that displace CIB1, block outside-in signaling, and inhibit human platelet aggregation without occupying the integrin's ligand-binding site. Beyond platelets, CIB1 modulates other α-integrins, drives pathological angiogenesis, and scaffolds oncogenic AKT and ERK pathways, indicating both therapeutic opportunities and safety considerations. Future priorities include high-resolution structures of the full cytoplasmic complex, real-time competition kinetics with talin/kindlin, potency optimization of drug leads, and in-vivo validation in thrombosis and cancer models. Collectively, these advances could inaugurate a new class of antiplatelet agents that temper pathologic clot growth while preserving physiological hemostasis.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"254 ","pages":"Article 109457"},"PeriodicalIF":3.4,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019653","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":"Warfarin reduces circulating white blood cell count: Post-hoc analysis of two randomized trials","authors":"Stefano Barco ,&nbsp;Christina Abele ,&nbsp;Walter Ageno ,&nbsp;Frederikus A. Klok ,&nbsp;Philip Wenzel ,&nbsp;Alice Trinchero ,&nbsp;Luca Malcovati ,&nbsp;Stavros V. Konstantinides ,&nbsp;Luca Valerio","doi":"10.1016/j.thromres.2025.109452","DOIUrl":"10.1016/j.thromres.2025.109452","url":null,"abstract":"<div><div>Warfarin is a widely used vitamin K antagonist (VKA) with known pleiotropic effects beyond anticoagulation. Preclinical and case-control evidence suggests that warfarin may affect hematopoiesis, but longitudinal human evidence is lacking. To explore this potential effect, we conducted a post-hoc analysis of participants in the Hokusai-VTE and ENGAGE AF-TIMI 48 trials, which randomized patients to warfarin or the direct oral anticoagulant edoxaban with routine laboratory testing at predefined follow-up visits. We analyzed changes in total circulating white blood cells (WBC) and subpopulations (lymphocytes, monocytes, granulocytes) using linear regression and mixed-effects models, adjusting for baseline counts, age, sex, and time. Among 23,618 patients enrolled in the two phase 3 trials, warfarin use was associated with a modest but statistically significant reduction in WBC count (−2.3 %, 95 % CI −2.9 % to −1.7 %) and granulocyte count (−3.6 %, 95 % CI −4.5 % to −2.7 %) compared with edoxaban, while lymphocyte and monocyte counts did not differ. The associations remained consistent across multiple sensitivity analyses. No increase in clinically relevant granulocytopenia was observed. In the context of two large randomized trials, these findings support a subtle hematologic effect of warfarin, particularly in granulocytes, that aligns with preclinical findings and warrants further investigation into the long-term impact of VKAs on hematopoiesis.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"254 ","pages":"Article 109452"},"PeriodicalIF":3.4,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019555","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":"Effectiveness of health-related quality of life assessment scales in patients with haemophilia after treatment: Systematic review","authors":"John Sieh Dumbuya ,&nbsp;Bashir Ahmad ,&nbsp;Yuanlong Li ,&nbsp;Cizheng Zeng ,&nbsp;Xiuling Chen ,&nbsp;Chuan Tian ,&nbsp;Jun Lu","doi":"10.1016/j.thromres.2025.109451","DOIUrl":"10.1016/j.thromres.2025.109451","url":null,"abstract":"<div><h3>Background</h3><div>Haemophilia is a hereditary bleeding disorder that impacts patients' physical, psychological, and social well-being. While advancements in treatments have improved clinical outcomes, the tools used to assess their effect on health-related quality of life (HRQoL) vary widely. This study evaluates the effectiveness and variability of HRQoL assessment scales in haemophilia patients after treatment and identifies factors influencing QoL outcomes.</div></div><div><h3>Methods</h3><div>A systematic review, adhering to PRISMA guidelines, was conducted on studies published up to December 2024. Included studies involved haemophilia patients and reported QoL outcomes post-treatment. Data were extracted on study characteristics, patient demographics, interventions, and quality assessment using the Cochrane Risk of Bias Tool. Findings were synthesised to identify key themes affecting QoL.</div></div><div><h3>Results</h3><div>The review included 52 studies, covering treatments such as prophylactic therapies, factor replacement, and gene therapy. Most studies showed significant QoL improvements, particularly in severe cases, with reductions in annual bleed rates (ABR) up to 99 % and improved joint health. Outcome variability was heavily influenced by the choice of HRQoL instruments, with 55.8 % of studies using a combination of generic and disease-specific scales. Disease-specific scales (e.g., Haemo-QOL) effectively captured haemophilia-related symptoms, while generic scales (e.g., EQ-5D) measured broader health dimensions. However, inconsistencies in instrument application contributed to disparities in reported QoL improvements. Dual-scale approaches provided more comprehensive insights, though moderate haemophilia was underrepresented.</div></div><div><h3>Conclusions</h3><div>The study emphasises the need for standardised and comprehensive QoL assessment tools to evaluate haemophilia treatments accurately. Prophylactic therapies and extended half-life factor concentrates showed significant QoL improvements. Future research should focus on standardising assessment scales and integrating psychosocial dimensions to fully capture treatment impacts.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"254 ","pages":"Article 109451"},"PeriodicalIF":3.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026836","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}