Journal of Thrombosis and Haemostasis最新文献

{"title":"Thrombotic rates in individuals with inherited bleeding disorders treated with concentrate or bispecific antibody. Fifteen-year EUHASS data.","authors":"M Makris, K Fischer, A Gatt, S Gouw, R Hollingsworth, N Kabera, R Kaczmarek, T Lambert, R Lassila, F Peyvandi","doi":"10.1016/j.jtha.2026.09.035","DOIUrl":"https://doi.org/10.1016/j.jtha.2026.09.035","url":null,"abstract":"<p><strong>Background: </strong>Although inherited bleeding disorders are associated with a reduced risk of thrombosis, the rate of thrombosis following treatment of the bleeding disorders is unknown.</p><p><strong>Objective: </strong>To determine the rates of thrombosis in persons with inherited bleeding disorders treated with clotting factor concentrates or a bispecific antibody.</p><p><strong>Methods: </strong>Analysis of the thrombotic events reported to the EUHASS system. EUHASS is the European surveillance system for adverse events in persons with all inherited bleeding disorders treated with clotting factor concentrates and/or emicizumab. 95 sentinel centres from 27 countries participated. From 10/2008 to 12/2023, thrombotic events occurring within 30 days of product administration, and the number of persons treated with each product were reported. Annual thrombosis rates (95% confidence intervals-CI) according to the product were compared using rate ratios.</p><p><strong>Results: </strong>During the 15-year period, 204 episodes of thrombosis occurred in 209,842 treatment years 113 events were in hemophilia A, 22 in hemophilia B, 22 in von Willebrand disease, and 47 in other bleeding disorders. The rates of thrombosis following plasma-derived FVIII was 1.10, recombinant standard half-life FVIII 0.70 and extended half-life FVIII 0.52 per 1000 patient years. The rate for emicizumab (Hemlibra) was 0.92 per 1000 patient years. The highest rate was in persons treated with fibrinogen concentrate at 11.56 per 1000 patient years.</p><p><strong>Conclusion: </strong>The rate of thrombosis in persons with hemophilia A and B treated with FVIII and IX concentrates, respectively, is less than 1.0 per 1000 patient years. This information can be used in comparisons with rates for newly introduced products.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111409","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":"Fragility Analysis Should Complement Statistical Reporting in Thrombosis Trials: Lessons from Reduced-Dose Direct Oral Anticoagulants for Cancer-Associated Venous Thromboembolism.","authors":"Ronald Chow, Sumeet Talwar, Manu Beniwal, Jameel Abdulrehman, Peter L Gross","doi":"10.1016/j.jtha.2026.09.039","DOIUrl":"https://doi.org/10.1016/j.jtha.2026.09.039","url":null,"abstract":"<p><p>Randomized trials and meta-analyses in thrombosis are traditionally interpreted using effect estimates, confidence intervals, and p-values. While indispensable, these metrics often provide limited insight into the robustness of trials reporting statistically significant findings. Fragility analysis offers a complementary approach by quantifying the minimum number of event-status changes that would reverse statistical significance. Despite increasing adoption across oncology, ophthalmology, orthopedics, and cardiovascular medicine, fragility analysis remains underutilized in thrombosis studies. Using a recent meta-analysis comparing reduced- versus full-dose direct oral anticoagulants (DOACs) for extended treatment of cancer-associated venous thromboembolism as an illustrative example, we demonstrate how fragility analysis provides additional context regarding the stability of trial findings. More importantly, we argue that fragility analysis should become a routine adjunct to conventional statistical reporting in thrombosis trials and systematic reviews to facilitate interpretation of evidence, improve transparency, and enhance shared decision making.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111349","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":"KRAS Mutation and Venous Thromboembolism Risk in Colorectal Cancer: A Danish Population-Based Cohort Study.","authors":"Jannik Wheler, Frederikke Schønfeldt Troelsen, Emese Katalin Vágó, Erzsébet Horváth-Puhó, Nick van Es, Florian Moik, Cihan Ay, Henrik Toft Sørensen","doi":"10.1016/j.jtha.2026.09.040","DOIUrl":"https://doi.org/10.1016/j.jtha.2026.09.040","url":null,"abstract":"<p><strong>Introduction: </strong>Kirsten rat sarcoma viral proto-oncogene (KRAS) mutations may promote a prothrombotic state through tumor-related activation of coagulation pathways. However, evidence for an association with venous thromboembolism (VTE) in colorectal cancer (CRC) patients remains inconclusive. We examined the association between KRAS mutation status and VTE risk.</p><p><strong>Methods: </strong>We conducted a population-based cohort study using Danish nationwide registries. We included patients diagnosed with stage I-IV CRC who underwent somatic KRAS mutation testing between 2015 and 2023. We computed 1-year risks of VTE, deep vein thrombosis (DVT), and pulmonary embolism (PE) using the Aalen-Johansen method and calculated adjusted hazard ratios (HRs) using cause-specific Cox proportional hazards regression.</p><p><strong>Results: </strong>The study included 10,544 patients with CRC who underwent KRAS testing (4,602 [44%] with KRAS mutations; median age 71 years; 56% male). During one year of follow-up, 399 VTE events occurred. The 1-year risk of VTE was 4.6% (95% confidence interval [CI], 4.0-5.2) in the KRAS-mutated group and 3.1% (95% CI, 2.7-3.6) in the KRAS-wildtype group. The adjusted HR for VTE comparing KRAS mutations vs. wildtype was 1.37 (95% CI, 1.12-1.67), with estimates of 1.44 (95% CI, 1.13-1.84) for PE and 1.22 (95% CI, 0.85-1.75) for DVT. Substantial heterogeneity was observed across KRAS subtypes, with the highest hazards for unspecified codon 13 mutations (adjusted HR, 2.19; 95% CI, 1.38-3.46) compared with those with KRAS wildtype.</p><p><strong>Conclusion: </strong>KRAS mutations were associated with an increased risk of VTE in patients with CRC who underwent KRAS testing.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111319","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":"Thrombin Generation in Critically Ill Adults: A Systematic Review of Venous Thromboembolism and Pharmacological Thromboprophylaxis.","authors":"Caseng Zhang, Kevin Durr, Marc Carrier, Deborah M Siegal, Bram Rochwerg, Patricia C Liaw, Jerrold H Levy, Hugo Ten Cate, Shannon M Fernando, David Williamson, Salmaan Kanji, Risa Shorr, Joseph R Shaw, Alexandre Tran","doi":"10.1016/j.jtha.2026.09.037","DOIUrl":"https://doi.org/10.1016/j.jtha.2026.09.037","url":null,"abstract":"<p><strong>Background: </strong>Venous thromboembolism (VTE) remains an important complication in critically ill adults despite standard pharmacological thromboprophylaxis. Thrombin generation assays (TGAs) offer a global functional assessment of coagulation by capturing the kinetics and magnitude of thrombin formation and may complement conventional measures of coagulation such as anti-Xa activity.</p><p><strong>Methods: </strong>The review was conducted according to JBI methodology and reported per PRISMA guidelines. We searched MEDLINE, Embase, and CENTRAL from inception to December 18, 2025. We included studies of adults (≥18 years) managed in high-acuity or intensive care settings with TGA measurements reported in relation to VTE incidence or thromboprophylaxis effect.</p><p><strong>Results: </strong>We included 15 eligible prospective studies comprising 2,250 patients (9 surgical trauma cohorts, 4 medical ICU cohorts, 2 mixed ICU cohorts). Calibrated automated thrombography (CAT) was the most used TGA platform (80.0%). Eleven studies (73.3%) evaluated associations between TGA and VTE incidence, with inconsistent findings. Some trauma cohorts identified shorter time-to-peak thrombin or lag time as predictors of VTE, while other studies found no significant associations. Of eight studies (53.3%) assessing TGA pharmacodynamics, seven measured anti-Xa activity, which correlated with lower endogenous thrombin potential and peak thrombin.</p><p><strong>Conclusion: </strong>TGA most consistently served as a pharmacodynamic measure of low-molecular-weight heparin effect: anti-Xa activity correlated with suppressed endogenous thrombin potential and peak thrombin. TGA did not reliably predict VTE, though shorter time-to-peak and lag time preceded thrombosis in trauma cohorts. TGA should be advanced as a coagulation-phenotyping tool in prospective ICU studies with standardized assays, consistent sampling in relation to dose timing, and concurrent anti-Xa and thrombin generation measurement.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111368","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":"Disseminated intravascular coagulation in cirrhosis: moving to disease-specific diagnosis","authors":"Fuat H. Saner","doi":"10.1016/j.jtha.2026.07.003","DOIUrl":"10.1016/j.jtha.2026.07.003","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 10","pages":"Pages 3438-3439"},"PeriodicalIF":5.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149078538","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":"Ambient temperature, air pollutants, and pulmonary embolism onset: a 17-year nationwide study in China","authors":"Lu Zhou,&nbsp;Mengjie Duo,&nbsp;Bingzhang Zou,&nbsp;Zhu Zhang,&nbsp;Hong Chen,&nbsp;Yuanhua Yang,&nbsp;Jun Wan,&nbsp;Xiaomao Xu,&nbsp;Yingqun Ji,&nbsp;Guoru Yang,&nbsp;Ping Zhang,&nbsp;Jing Han,&nbsp;Kejing Ying,&nbsp;Qixia Xu,&nbsp;Ling Zhu,&nbsp;Yingyun Fu,&nbsp;Qin Luo,&nbsp;Haobo Li,&nbsp;Dingyi Wang,&nbsp;Yunxia Zhang,&nbsp;Zhenguo Zhai","doi":"10.1016/j.jtha.2026.04.020","DOIUrl":"10.1016/j.jtha.2026.04.020","url":null,"abstract":"<div><h3>Background</h3><div>The short-term effects of the interaction between ambient temperature and air pollution on the onset of pulmonary embolism (PE) remain a critical public health concern. Evidence from large-scale, multicenter studies is limited.</div></div><div><h3>Objectives</h3><div>To quantify the associations of ambient temperature, fine particulate matter (PM_2.5), nitrogen dioxide (NO₂), and ozone (O₃) with PE onset in China.</div></div><div><h3>Methods</h3><div>We conducted a nationwide time-stratified case-crossover analysis of 48 589 PE cases from hospital-based registries across China (2005-2021). Meteorological data were obtained from fixed-site monitoring stations. PM_2.5, NO₂, and O₃ concentrations were obtained using high-resolution satellite-based models. Conditional logistic regression models were used to evaluate the associations of PM_2.5, NO₂, and O₃ concentrations with the onset of PE.</div></div><div><h3>Results</h3><div>Ambient low temperature significantly increased the risk of PE onset, with an odds ratio (OR) of 1.47 (95% CI, 1.19-1.80) at an extremely low temperature (−11.6 °C) compared with the reference (23.4 °C). At lag day 0, each 10 μg/m³ increase in NO₂ was significantly associated with PE onset (OR, 1.011; 95% CI, 1.003-1.018). PM_2.5 showed a weaker effect (OR, 1.004), while O₃ showed no significant association. Significant pollutant effects were observed exclusively during the warm season. NO₂ remained significantly associated with PE onset despite overall improvements in air quality after 2014.</div></div><div><h3>Conclusion</h3><div>Ambient low temperature, NO₂, and PM_2.5 significantly increase the risk of PE onset. China's air quality improvements reduced the health risks of PM_2.5 but not those of NO₂. PE prevention should prioritize targeted NO₂ emission control alongside climate-adapted measures.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 10","pages":"Pages 3544-3552"},"PeriodicalIF":5.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864218","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":"Predicting deep venous thrombosis and pulmonary embolism in community patients with superficial venous thrombosis: a model development study","authors":"Florien S. van Royen,&nbsp;Maarten van Smeden,&nbsp;Sander van Doorn,&nbsp;Patrick Souverein,&nbsp;Wouter A.C. van Amsterdam,&nbsp;Frans H. Rutten,&nbsp;James P. Sheppard,&nbsp;Geert-Jan Geersing","doi":"10.1016/j.jtha.2026.06.036","DOIUrl":"10.1016/j.jtha.2026.06.036","url":null,"abstract":"<div><h3>Background</h3><div>In general practice, superficial venous thrombosis (SVT) is considered a benign condition that does not require anticoagulant treatment. However, a small but not insignificant subgroup of patients will develop serious thrombotic complications, such as deep venous thrombosis (DVT) and/or pulmonary embolism (PE). Tailored anticoagulant treatment in high-risk patients might prevent these complications, yet tools for clinical decision-making are currently lacking.</div></div><div><h3>Objectives</h3><div>To develop a multivariable prediction model to identify specific SVT subgroups at higher or lower risk of developing DVT/PE to aid clinical decision-making.</div></div><div><h3>Methods</h3><div>Data from general practices in the longitudinal routine care UK Clinical Practice Research Datalink Aurum database were used in this study, covering the period from 2000 to 2021. A multivariable prediction model was developed for adult SVT patients to predict the outcome of DVT and/or PE within 90 days after the first consultation for SVT. Prespecified predictors were biological sex, age, (history of) cancer, history of DVT/PE, and absence of varicose veins. The model’s performance was evaluated using bootstrapping and internal-external cross-validation.</div></div><div><h3>Results</h3><div>Of all identified patients with SVT (<em>N</em> = 293 166; median age, 61 years [IQR, 46-73]; 33% male), 10 301 (3.5%) developed DVT or PE within 90 days. The risk was highest in the first days after the SVT consultation: 51% of DVTs/PEs were diagnosed within 1 week, and 77% within 30 days. The C-statistic of the model was 0.66 (95% CI, 0.66-0.67), and the model showed good calibration (intercept = 0.04, slope = 1.01). High-risk patients with a predicted risk of ≥5% (9.7% of the total population) had a history of DVT/PE or were male with (a history of) cancer.</div></div><div><h3>Conclusion</h3><div>In community SVT patients, the average risk of DVT/PE development within 90 days of follow-up is 3.5%. This simple prediction model showed good performance in predicting the short-term risk of DVT/PE and could be used to rule out thrombotic complications in this setting, but also to identify a subgroup of patients at higher risk in whom further diagnostic testing for concomitant DVT/PE and/or short-term preventive anticoagulant treatment should be considered to prevent clot progression.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 10","pages":"Pages 3637-3646"},"PeriodicalIF":5.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405199","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}

{"title":"Explaining recurrent thrombotic events and predicting bleeding in critically ill neonates diagnosed with umbilical central venous catheter-related portal vein thrombosis","authors":"Katherine Goren,&nbsp;Leonardo R. Brandão,&nbsp;Kyong-Soon Lee,&nbsp;Leen Hilwah,&nbsp;Athena Mancini,&nbsp;Jennifer Vincelli,&nbsp;Laura Avila","doi":"10.1016/j.jtha.2026.06.039","DOIUrl":"10.1016/j.jtha.2026.06.039","url":null,"abstract":"<div><h3>Background</h3><div>The short-term risk of recurrent venous thrombotic events (VTEs) and bleeding in hospitalized neonates after umbilical venous catheter (UVC)-related portal vein thrombosis (PVT) is unknown.</div></div><div><h3>Objectives</h3><div>The primary objective was to determine the incidence of recurrent VTEs in neonates with UVC-related PVT who required subsequent central vascular access. Secondary objectives included investigating the incidence of bleeding events, variables that explained VTE recurrence, and bleeding predictors.</div></div><div><h3>Methods</h3><div>This longitudinal retrospective cohort study included neonates diagnosed with UVC-related PVT at the Hospital for Sick Children between 2016 and 2024. An explanatory model for VTE recurrence (using mixed models for repeated observations) and an exploratory predictive model for bleeding events (using logistic regression) were developed.</div></div><div><h3>Results</h3><div>Three hundred neonates requiring 684 subsequent central venous accesses were included. In total, 78 recurrent events were identified in 62 patients at median age 32 days (Q1-Q3, 14-67 days) for the first recurrence. Incidence proportion of recurrent VTEs was 21%; incidence rate was 0.45 per 100-catheter days. Throughout follow-up, 216 neonates (72%) sustained 328 bleeding events; 50% of patients experienced major bleeding at median age 5 days (Q1-Q3, 3-15 days), including microbleeds and small central nervous system bleeds. Younger age at vascular access placement and larger catheter diameter explained VTE recurrence risk. The exploratory model suggested that gestational age, sex, and underlying conditions predicted bleeding risk.</div></div><div><h3>Conclusion</h3><div>There was a high frequency of bleeding and thrombosis in this cohort of acutely ill neonates. Strategies to decrease recurrent thrombosis risk are relevant to avoid thrombotic complications during the highest bleeding-risk period.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 10","pages":"Pages 3659-3668"},"PeriodicalIF":5.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405233","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":"The role of mutant p53R175H in de novo activation of von Willebrand factor expression in tumor cells","authors":"Noorossadat Seyyedi,&nbsp;Chu Shiun Lo,&nbsp;Parnian Alavi,&nbsp;Manijeh Pasdar,&nbsp;Nadia Jahroudi","doi":"10.1016/j.jtha.2026.07.005","DOIUrl":"10.1016/j.jtha.2026.07.005","url":null,"abstract":"<div><h3>Background</h3><div>The glycoprotein von Willebrand Factor (VWF) is essential for primary hemostasis and is normally expressed strictly in endothelial cells and megakaryocytes. However, VWF is aberrantly expressed in some nonendothelial/megakaryocytic cancer cells. We previously showed <em>de novo</em> VWF expression in osteosarcoma cells linked to increased GATA6 (activator) and reduced NF-IB (repressor) binding to the VWF promoter. NF-IB is a downstream target of transcription factor and tumor suppressor p53, which is frequently mutated in cancer. We have also shown that the cell-cell adhesion protein plakoglobin restores the tumor suppressive function of some p53 mutants, including p53^R175H.</div></div><div><h3>Objectives</h3><div>We explored the role of p53 in <em>de novo</em> activation of VWF expression in cancer cells of non-endothelial/megakaryocytic origin.</div></div><div><h3>Methods</h3><div>The analyses of 100 VWF-positive cancer cell lines revealed NF-IB downregulation and/or p53 mutation. Using p53-null and plakoglobin-deficient H1299 lung carcinoma cell line, we examined the effect of exogenously expressed p53 (wild type and mutants) on VWF expression. The findings were validated in ovarian cancer lines with endogenous p53 variants. We assessed the functional consequences and molecular mechanisms of <em>de novo</em> VWF expression.</div></div><div><h3>Results</h3><div>Specifically, p53^R175H activated <em>de novo</em> expression of VWF by interacting with NF-IB and GATA6, preventing NF-IB’s repressive and promoting GATA6’s activating functions on the VWF promoter. VWF expression mediates cancer cell-platelet heteroaggregate formation. Plakoglobin coexpression or VWF knockdown reversed these effects.</div></div><div><h3>Conclusion</h3><div>These findings identify a novel mechanism of VWF expression involving p53^R175H in cancer cells and reveal plakoglobin as a potent antagonist of this pathway.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 10","pages":"Pages 3505-3519"},"PeriodicalIF":5.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447743","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}

{"title":"Rab31 promotes platelet activation and arterial thrombosis via ERK–PLCβ3 signaling and regulation of CD151","authors":"Yixian Wang,&nbsp;Jiajia Luo,&nbsp;Jingjing Liu,&nbsp;Qingyuan Yang,&nbsp;Xiaowen Wu,&nbsp;Yifan Guo,&nbsp;Qian Liu,&nbsp;Changran Liu,&nbsp;Yan Yan,&nbsp;Dongxing Chen,&nbsp;Satya P. Kunapuli,&nbsp;Zhigang Cai,&nbsp;Zhongren Ding","doi":"10.1016/j.jtha.2026.07.015","DOIUrl":"10.1016/j.jtha.2026.07.015","url":null,"abstract":"<div><h3>Background</h3><div>Ras-related protein in brain (Rab) guanosine triphosphatases regulate vesicular trafficking and membrane dynamics, processes essential for platelet activation. Although several Rab family members are expressed in platelets, the role of Rab31 remains undefined.</div></div><div><h3>Objectives</h3><div>To determine the role of Rab31 in platelet activation, thrombosis, and hemostasis and to explore the underlying mechanisms.</div></div><div><h3>Methods</h3><div>Rab31 expression was examined in human and murine platelets. Platelet function was evaluated in Rab31^−/− and wild-type mice using aggregation, adenosine triphosphate release, spreading, and clot retraction assays. <em>In vivo</em> thrombosis and hemostasis were assessed by ferric chloride–induced mesenteric arterial injury, collagen/epinephrine-induced pulmonary embolism, tail-snip bleeding, and platelet depletion and repletion experiments. Quantitative proteomic and phosphoproteomic analyses were performed to identify Rab31-dependent signaling pathways in platelets.</div></div><div><h3>Results</h3><div>Rab31 was expressed in human and murine platelets at both messenger ribonucleic acid and protein levels. Rab31 deficiency significantly reduced platelet aggregation, adenosine triphosphate secretion, spreading, and clot retraction. <em>In vivo</em>, Rab31^−/− mice showed delayed arterial thrombus formation and reduced pulmonary embolism, whereas tail bleeding time and blood loss remained unchanged. Platelet depletion and repletion experiments confirmed the platelet intrinsic role of Rab31 in thrombosis. Phosphoproteomic analysis revealed decreased extracellular signal-regulated kinase 2 and phospholipase C beta 3 phosphorylation in Rab31-deficient platelets, and quantitative proteomics identified reduced CD151 antigen expression. These findings were validated by immunoblotting.</div></div><div><h3>Conclusion</h3><div>Rab31 promotes platelet activation and arterial thrombosis without affecting physiological hemostasis, likely through regulation of ERK–phospholipase C beta 3 signaling and CD151 antigen expression.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 10","pages":"Pages 3746-3760"},"PeriodicalIF":5.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584663","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}