Journal of Thrombosis and Haemostasis最新文献

{"title":"Hereditary antithrombin deficiency and venous thrombosis in pregnancy-results of a retrospective multicenter study.","authors":"Ingunn Dybedal, Nina Iversen, Anne Flem Jacobsen, Line Bjørge, Roza Chaireti, Carola Elisabeth Henriksson, Nina Hagenrud Schultz, Anne Mette Hvas, Per Morten Sandset, Harald Weedon-Fekjær, Katarina Bremme, Ulrich Abildgaard","doi":"10.1016/j.jtha.2025.03.001","DOIUrl":"10.1016/j.jtha.2025.03.001","url":null,"abstract":"<p><strong>Background: </strong>The optimal anticoagulant regimen to prevent pregnancy-related venous thrombosis (VT) in women with antithrombin (AT) deficiency is unknown.</p><p><strong>Objectives: </strong>This study aims to identify optimal doses of low-molecular-weight heparin (LMWH) to prevent pregnancy-related VT and to investigate if AT concentrate peripartum could reduce postpartum VT in women with AT deficiency.</p><p><strong>Methods: </strong>This retrospective study includes 115 pregnancies in 57 women with subclassified AT deficiency treated with LMWH in Denmark, Norway, and Sweden (1991-2017).</p><p><strong>Results: </strong>In pregnancies with high-risk AT deficiency, LMWH doses of <5000 IU/24 h, 5000 to 12 500 IU/24 h, and >12 500 IU/24 h revealed different VT risks (P = .02). The hazard ratios for VT were 1.0 (reference), 0.5 (95% CI [0.1, 2.3]), and 0 (95% CI [0, ∞]), correspondingly. Of the additional risk factors, only previous VT reached statistical significance. In 100 pregnancies with high-risk AT deficiency, 15 VTs occurred in contrast to none in the 15 pregnancies with low-/intermediate-risk AT deficiency. Six of the 12 antepartum VTs occurred before week 9. All had a prior VT, and 5 were hormone-associated. Of these 5, 1 had received a LMWH dose of 7500 IU/24 h and 3 had received a LMWH dose of 10 000 IU/24 h, respectively. AT concentrate, given peripartum in 66 of the 74 term pregnancies, resulted in 1 VT (1.5%). Without AT concentrate (8 pregnancies), 2 VTs occurred (25%; 95% CI [2, 61]). Peripartum hemorrhage (>1000 mL) occurred in 8 (11%) term pregnancies. Six had received therapeutic LMWH doses.</p><p><strong>Conclusion: </strong>In high-risk AT deficiency pregnancies with previous VT, our results support prophylaxis with high prophylactic doses of LMWH from confirmed pregnancy. Hence, AT concentrate should be given peri-/postpartum.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630557","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":"Factor VIII, a coagulation cofactor, is a relevant survival factor in bladder cancer cell lines.","authors":"Gillian E Walker, Ester Borroni, Rida Haider, Cristina Olgasi, Chiara Borsotti, Antonia Follenzi","doi":"10.1016/j.jtha.2025.03.002","DOIUrl":"10.1016/j.jtha.2025.03.002","url":null,"abstract":"<p><strong>Background: </strong>Factor (F)VIII, an essential coagulation cofactor and independent cancer-associated thrombotic risk factor, has recently been shown to be synthesized directly by a broad profile of cancers. With evident extracoagulative functions, it remains to be understood if FVIII can play a functional role in cancer.</p><p><strong>Objectives: </strong>Establish if FVIII plays a direct role in bladder cancer cell models.</p><p><strong>Methods: </strong>Bladder cancer cell lines 5637 and ECV-304 were treated with recombinant human FVIII (rFVIII) B-domain-deleted or full-length rFVIII (rFVIII-FL) in low serum conditions, where cell cycle, migration, and cell survival were assessed. Cell cycle was measured by 7-aminoactinomycin D incorporation and migration by Transwell or wound healing assays. Cell survival was assessed by crystal violet (optical density 592) and 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (optical density 570) assays. Cell adhesion was determined with integrin β₁ and α_V protein levels, annexin-V-FITC/7-aminoactinomycin D staining, and Bcl2 with procaspase3 levels for apoptosis. Cancer cell-derived effects were assessed by silencing FVIII using short hairpin RNA.</p><p><strong>Results: </strong>In both bladder cancer cell lines, cell cycle progression was pushed, and migration was advanced by rFVIII. More dramatic were the survival effects for rFVIII-FL, confirmed in a cell line of diverse origin, the osteosarcoma U2OS, through the maintenance of cell adhesion and inhibition of apoptosis. Further, silencing cell-derived FVIII retarded both cell cycle progression and migration. More importantly, cell survival was dramatically reduced and could be blocked by the administration of rFVIII-FL.</p><p><strong>Conclusion: </strong>Overall, this investigation highlights FVIII as a relevant survival factor in bladder cancer cells and provides evidence of its role in cancer.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630542","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":"Patient and healthcare providers' perspectives on participation in a postpartum pilot trial of venous thromboembolism prophylaxis: a qualitative study.","authors":"Lauren Andrew, Alexandra Garven, Taryn S Taylor, Shannon M Bates, Lisa Duffett, Suzanne Dubois, A Kinga Malinowski, Darine El-Chaâr, Wee-Shian Chan, Jennifer Donnelly, Céline Chauleur, Wessel Ganzevoort, Claire McCarthy, Hanke Wiegers, Fionnuala Ní Áinle, Andrea Buchmuller, Paul S Gibson, Saskia Middeldorp, Marc A Rodger, Leslie Skeith","doi":"10.1016/j.jtha.2025.02.039","DOIUrl":"10.1016/j.jtha.2025.02.039","url":null,"abstract":"<p><strong>Background: </strong>There is a need to better understand barriers to recruitment and participation in randomized controlled trials evaluating postpartum thromboprophylaxis, as previous trials had low recruitment and were not feasible.</p><p><strong>Objectives: </strong>In a qualitative interview study of a feasibility trial of low-dose aspirin vs placebo for 6 weeks postpartum (pilot PARTUM (Postpartum Aspirin to Reduce Thromboembolism Undue Morbidity) trial), we explored the facilitators and barriers to trial involvement.</p><p><strong>Methods: </strong>Patients eligible for the pilot PARTUM trial, including those who declined to join the trial, were invited to participate in a qualitative study. Physicians whose clinical practice included caring for eligible patients were also invited to participate. Thirty-minute semistructured interviews were conducted by 2 researchers. Data were analyzed iteratively using reflexive thematic analysis.</p><p><strong>Results: </strong>There were 19 patients and 13 physician interviews conducted at a single Canadian center. Nine pilot PARTUM participants and 10 nonparticipants were included. Patients identified the simple study design and familiar oral medication (\"Participating as an Easy Ask\") and helping other parents (\"Helping Other Parents by Providing Knowledge\") as facilitators to participate in the trial. Most patients invoked altruism; however, their decision to participate in the trial was influenced by their perception of venous thromboembolism risk (\"Venous Thromboembolism Risk Perception and Communication\"), their birth experience (\"Birth Experience Informs Perspective\"), and their opinion of their obstetrical care provider (\"Engaging Trusted Care Providers\").</p><p><strong>Conclusion: </strong>Trial participation is uniquely affected by experiences during pregnancy, delivery, and new parenthood. Improved understanding of the factors most important to patients will inform the design and conduct of future patient-focused clinical trials.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630482","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":"Perioperative Management of Direct Oral Anticoagulants in Patients having a High-Bleed-Risk Surgery or Neuraxial Procedure: The PAUSE-2 Pilot Randomized Trial.","authors":"James D Douketis, Na Li, Melanie St John, Joanne Nixon, Karen Moffat, Joseph Shaw, Summer Syed, Sam Schulman, Peter L Gross, Alex C Spyropoulos","doi":"10.1016/j.jtha.2025.03.003","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.03.003","url":null,"abstract":"<p><strong>Background: </strong>There is uncertainty about the perioperative management of patients who are receiving a direct oral anticoagulant (DOAC) and require an elective high-bleed-risk surgery, including those who are undergoing a neuraxial or deep peripheral nerve block procedure.</p><p><strong>Methods: </strong>The Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE)-2 pilot trial was a proof-of-concept, open-label, randomized controlled trial that assessed the feasibility of comparing perioperative DOAC management using an American Society of Regional Anesthesia (ASRA)-based or PAUSE-based approach in patients with atrial fibrillation who needed an elective high-bleed-risk surgery/procedure and/or any neuraxial anesthesia/procedure.</p><p><strong>Results: </strong>There were 159 patients enrolled (86 on apixaban, 12 on dabigatran, and 61 on rivaroxaban), of whom 141 had pre-operative DOAC level testing done. The median (IQR) residual DOAC level was 19 (19-24) ng/mL in the ASRA group, and 20 (19-24) ng/mL in the PAUSE group (standardized difference=-0.02). The percentage of patients in the ASRA and PAUSE groups with pre-operative residual DOAC levels <30 ng/mL was 95.6% and 94.4%; the percentage with residual DOAC levels 30-50 ng/mL was 1.4% and 2.8%, and the percentage with levels >50 ng/mL was 2.9% and 2.8%.</p><p><strong>Conclusion: </strong>In this pilot trial, we found that recruitment of DOAC-treated patients who needed an elective high-bleed-risk surgery or neuraxial procedure was feasible and that pre-operative residual DOAC levels appeared similar according to ASRA-based and PAUSE-based management approaches, providing the foundation for a larger trial comparing ASRA- and PAUSE-based perioperative DOAC management.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630508","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":"Corrigendum to ‘Anticoagulation in adult patients supported with extracorporeal membrane oxygenation: guidance from the Scientific and Standardization Committees on Perioperative and Critical Care Haemostasis and Thrombosis of the International Society on Thrombosis and Haemostasis.’","authors":"Julie Helms ,&nbsp;Corinne Frere ,&nbsp;Thomas Thiele ,&nbsp;Kenichi A. Tanaka ,&nbsp;Matthew D. Neal ,&nbsp;Marie E. Steiner ,&nbsp;Jean M. Connors ,&nbsp;Jerrold H. Levy","doi":"10.1016/j.jtha.2025.02.021","DOIUrl":"10.1016/j.jtha.2025.02.021","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 5","pages":"Page 1739"},"PeriodicalIF":5.5,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586193","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":"2-Methoxybenzoic acid ameliorates arterial thrombosis via inhibiting carbon anhydrase activity in platelet.","authors":"Yunchong Liu, Zhengde Zhao, Xiuyi Huang, Ying Xiao, Na Li, Wenchao Yang, Ruijia Feng, Weiqi Feng, Ting Long, Haoliang Wu, Guiyan Peng, Sifan Chen, Guangqi Chang, Kan Huang, Zilun Li","doi":"10.1016/j.jtha.2025.02.027","DOIUrl":"10.1016/j.jtha.2025.02.027","url":null,"abstract":"<p><strong>Background: </strong>2-Methoxybenzoic acid (2MOA) is a natural compound with potential salicylate-like effects; however, its impact on arterial thrombosis remains unclear.</p><p><strong>Objectives: </strong>This study aimed to investigate the effects of 2MOA on thrombogenesis and its underlying mechanisms.</p><p><strong>Methods: </strong>FeCl₃-induced carotid artery injury and laser-induced cremaster artery injury thrombosis assays were used to explore the effect of 2MOA on thrombogenesis in vivo. Various ex vivo platelet function assays were conducted to evaluate the impacts of 2MOA on platelet activity. In addition, untargeted metabolomics analysis was performed to identify the alterations in intraplatelet metabolites following 2MOA treatment.</p><p><strong>Results: </strong>We found that 2MOA significantly ameliorated thrombosis in a dose-dependent manner, without affecting the normal hemostasis in C57BL/6J mice. 2MOA suppressed platelet reactivity as indicated by decreased spreading, retraction, and aggregation in both mouse and human platelets. Metabolomics analysis revealed significantly alterations in purine metabolism following 2MOA treatment, which increased cyclic guanosine monophosphate production in platelets. Mechanistically, 2MOA inhibited the activity of carbonic anhydrase, leading to elevated intraplatelet cGMP level, and subsequent suppression of cytosolic phospholipase A2 phosphorylation.</p><p><strong>Conclusion: </strong>Our study illustrates that 2MOA efficaciously inhibits platelet reactivity and alleviates thrombogenesis via suppressing carbonic anhydrase activity, which should be a promising reagent in the prevention and treatment of arterial thrombotic events.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586163","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":"Thrombotic response to mechanical circulatory support devices.","authors":"Tiffany Goh, Lining Arnold Ju, Anna Waterhouse","doi":"10.1016/j.jtha.2025.02.037","DOIUrl":"10.1016/j.jtha.2025.02.037","url":null,"abstract":"<p><p>Cardiovascular mechanical circulatory support (MCS) device use triggers thrombosis and hemostatic disorders, which may become fatal if thrombi occlude circulation or cause embolic complications. Consequently, antithrombotic medications are administered, which often cannot eliminate thrombosis and further compromise patient survival by introducing an additional risk of severe bleeding events. MCS thrombosis is induced and affected by the combined interplay of patient pathology, the foreign artificial biomaterial's surface properties, and pathological flow conditions. From a device design perspective, the latter 2 may be controlled for and redesigned to minimize the thrombotic response. This review examines how MCS thrombosis is affected by the biomaterial properties of surface roughness and topography, chemistry and charge, wettability, and bioactive coatings and the hemodynamic flow properties of margination, low flow and coagulation, high flow and platelet activation, von Willebrand factor activation, and hemolysis. For each property, we explain its well-established underlying biological, chemical, or physical effects on thrombosis and highlight current and proposed design strategies that could reduce MCS thrombosis. We review the potential reasons thrombosis still complicates MCS devices and postulate that an improved understanding of the dominant thrombotic process occurring at specific regions of devices and mechanistic insights into the combined effects of material properties with flow are still required. Together, we provide a guide for potential biomaterial and flow design changes to reduce thrombosis in MCS, emphasizing that novel biomaterials and device geometries should be tested under operationally and clinically relevant flow conditions to develop safer future-generation devices with reduced thrombotic responses.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586210","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":"Real-world evaluation of a novel automated method for measuring ADAMTS-13 activity using the Ceveron s100 analyzer.","authors":"Bérangère S Joly, Hélène Deniau, Chloé Doinel, Adeline Brouillard, Virginie Siguret, Paul Coppo, Agnès Veyradier","doi":"10.1016/j.jtha.2025.02.038","DOIUrl":"10.1016/j.jtha.2025.02.038","url":null,"abstract":"<p><strong>Background: </strong>Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy characterized by a severe functional deficiency of ADAMTS-13. Measuring ADAMTS-13 activity is crucial for diagnosing TTP (<10 IU/dL), monitoring treatments, and detecting relapses (<20 IU/dL). The Technofluor assay (Technoclone) allows a rapid ADAMTS-13 activity measurement using the Ceveron s100 analyzer (Technoclone).</p><p><strong>Objectives: </strong>This study aimed to evaluate the analytical and clinical performance of this new test under real-world conditions.</p><p><strong>Methods: </strong>ADAMTS-13 activity was measured using 2 fluorometric methods: the Technofluor ADAMTS-13 activity on the Ceveron s100 (Technoclone) and our reference fluorescence resonance energy transfer-VWF73 method, in plasma samples collected under real-life conditions (January 12, 2024, to April 4, 2024) and retrospectively selected samples from our biobank. The analytical and clinical performance of the new test was assessed, focusing on the critical low levels (<30 IU/dL).</p><p><strong>Results: </strong>Four hundred samples were tested under real-world conditions and 100 others tested retrospectively. The Technofluor assay showed excellent analytical performance, with a detection limit of 0.1 IU/dL, repeatability coefficient of variation of <11%, and reproducibility coefficient of variation of 6.1% (high level, 90 IU/dL) and 7.5% (low level, 40 IU/dL). Clinical performances were strong at diagnosis (threshold, 10 IU/dL; sensitivity and positive predictive value, 1.0) and during the follow-up (threshold, 20 IU/dL; specificity, 1.0; 95% CI, 0.99-1.00; positive predictive value, 0.96; 95% CI, 0.90-1.01; negative predictive value, 0.98; 95% CI, 0.97-1.00). No analytical interference was observed.</p><p><strong>Conclusion: </strong>The Technofluor assay on the Ceveron s100 is a fast, reliable method for measuring ADAMTS-13 activity, proving effectiveness for diagnosis and monitoring of TTP patients. However, it remains crucial to interpret ADAMTS-13 activity measurement with clinical context to ensure accurate diagnosis and management.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586207","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":"How to deal with interference on heparin anti-Xa activity caused by oral factor FXa inhibitors: communication from the ISTH SSC Subcommittee on Control of Anticoagulation.","authors":"Nicolas Gendron, Adam Cuker, Robert C Gosselin, Lana A Castellucci, Jecko Thachil","doi":"10.1016/j.jtha.2025.02.026","DOIUrl":"10.1016/j.jtha.2025.02.026","url":null,"abstract":"<p><p>Monitoring unfractionated heparin (UFH) to ensure effective anticoagulation may be performed using anti-factor Xa activity (anti-Xa) instead of the activated partial thromboplastin time. However, in patients who have been treated with oral factor (F)Xa inhibitors (apixaban, rivaroxaban, and edoxaban) while switching to UFH therapy, there is a risk that these oral anti-FXa drugs could interfere with UFH-calibrated anti-Xa monitoring. This may lead to inappropriate anticoagulation management. This report of the International Society on Thrombosis and Haemostasis (ISTH) Subcommittee on Control of Anticoagulation summarizes the evidence on the risk of interference from previous treatment with oral FXa inhibitors and UFH anti-Xa after heparin initiation. This communication provides pragmatic recommendations for UFH initiation and management with anti-Xa monitoring after switching from oral FXa inhibitors.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586200","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":"Red blood cell Rpl13a small noncoding nucleolar RNAs guides 2'-O-methylation on peroxidasin messenger RNA promoting venous thrombosis in aging.","authors":"Waseem Chauhan, Sudharshan Sj, Shirin Ferdowsi, Akib Sohel, Rahima Zennadi","doi":"10.1016/j.jtha.2025.02.036","DOIUrl":"10.1016/j.jtha.2025.02.036","url":null,"abstract":"<p><strong>Background: </strong>Oxidative stress is one of the aging hallmarks. Small noncoding nucleolar RNAs (snoRNAs) of the ribosomal protein L13a (Rpl13a) locus are master regulators of reactive oxygen species (ROS) and oxidative stress, and their loss protects mice from diabetes. Yet, whether excess ROS in red blood cells (RBCs) is regulated by Rpl13a snoRNAs in aging and mediate venous thrombosis (VT)/thromboembolism (VT/E) is unknown.</p><p><strong>Objectives: </strong>We investigated if RBCs retain Rpl13a snoRNAs and contribute to RBC ROS-mediated VT in a mid-life stage population.</p><p><strong>Methods: </strong>Blood samples were collected from healthy mid-life stage (55-68 years old) and young (21-30 years old) adults, VT/E patients, and young wild-type mice at 12 to 24 weeks of age, and aged wild-type and aged Rpl3a snoRNA knockout mice at 72 to 96 weeks of age (equivalent to humans 21-30 and 55-68 years old, respectively).</p><p><strong>Results: </strong>RBCs from mid-life stage adults and VT/E patients showed higher ROS production and prothrombotic potential than that in those from the younger cohort. RBC ROS levels and prothrombotic potential were associated with abnormal Rpl13a snoRNAs levels. In aging, Rpl13a snoRNAs regulated human and murine RBC ROS levels and prothrombotic activation by modulating peroxidase activity. This was due largely to Rpl13a snoRNAs-guided 2'-O-methylation on RBC peroxidasin (Pxdn) messenger RNA, a modification that inhibited the messenger RNA translation and Pxdn activity. In vivo Rpl13a snoRNA knockout in aged mice blunted RBC ROS generation and decreased thrombi size, thrombi RBC content, and RBCs-triggering prothrombin activation.</p><p><strong>Conclusion: </strong>These findings point out to a novel role of RBC Rpl13a snoRNAs in VT by dysregulating Pxdn expression in aging.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586205","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}