Journal of Thrombosis and Haemostasis最新文献

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Hereditary antithrombin deficiency and venous thrombosis in pregnancy - results of a retrospective multicenter study.
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2025-03-12 DOI: 10.1016/j.jtha.2025.03.001
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
{"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":"https://doi.org/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>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<5000 IU/24h, 5000-12500 IU/24h and>12500 IU/24h revealed different VT risks (p=0.02). The hazard ratio for VT was 1.0 (reference), 0.5 (95% confidence interval; CI [0.1, 2.3] and 0 (95% CI [0,∞]), correspondingly. Of additional risk factors, only previous VT reached statistical significance. In the 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, five were hormone-associated. Of these five, one had received LMWH 7500- and three 10000 IU/24h, respectively. AT concentrate, given peripartum in 66 of the 74 term pregnancies, resulted in one VT (1.5%). Without AT concentrate (8 pregnancies) two VTs occurred (25%, CI [2, 61]). Peripartum haemorrhage (>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.</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}
引用次数: 0
Factor VIII a coagulation co-factor is a relevant survival factor in bladder cancer cell lines.
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2025-03-12 DOI: 10.1016/j.jtha.2025.03.002
Gillian E Walker, Ester Borroni, Rida Haider, Cristina Olgasi, Chiara Borsotti, Antonia Follenzi
{"title":"Factor VIII a coagulation co-factor 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":"https://doi.org/10.1016/j.jtha.2025.03.002","url":null,"abstract":"<p><strong>Background: </strong>Factor VIII (FVIII), an essential coagulation co-factor and independent cancer associated thrombotic risk factor, has recently been shown to be synthesized directly by a broad profile of cancers. With evident extra-coagulative functions, it remains to understand 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 B-domain deleted (rFVIII-BDD) or full-length (rFVIII-FL) in low serum conditions, where cell cycle, migration, and cell survival were assessed. Cell cycle by 7-Aminoactinomycin D (7-AAD) incorporation, and migration by Transwell or wound healing assays. Cell survival by crystal violet (CV;OD592) and 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT;OD570) assays. Cell adhesion with integrin β1 (Intβ1) and αV (IntαV) protein levels, Annexin-V-FITC/7-AAD staining and Bcl2 with procaspase3 levels, for apoptosis. Cancer cell-derived effects were assessed by silencing FVIII using short hairpin RNA (shFVIII).</p><p><strong>Results and conclusions: </strong>In both bladder cancer cell lines cell cycle progression was pushed, and migration 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. Overall, this investigation highlights FVIII as a relevant survival factor in bladder cancer cells and provides evidence of a 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}
引用次数: 0
Patient and healthcare providers' perspectives on participation in a postpartum pilot trial of venous thromboembolism prophylaxis: A qualitative study.
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2025-03-12 DOI: 10.1016/j.jtha.2025.02.039
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
{"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":"https://doi.org/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 (RCTs) evaluating postpartum thromboprophylaxis, as previous trials had low recruitment and were not feasible. In a qualitative interview study of the pilot PARTUM trial (a feasibility trial of low-dose aspirin versus placebo for six weeks postpartum), 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 joining 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 semi-structured interviews were conducted by two researchers. Data were analyzed iteratively using reflexive thematic analysis.</p><p><strong>Results: </strong>There were 19 patient and 13 physician interviews conducted at a single Canadian centre. Nine pilot PARTUM participants and 10 non-participants 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 VTE risk ('VTE Risk Perception and Communication'), their birth experience ('Birth Experience Informs Perspective'), and 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}
引用次数: 0
Perioperative Management of Direct Oral Anticoagulants in Patients having a High-Bleed-Risk Surgery or Neuraxial Procedure: The PAUSE-2 Pilot Randomized Trial.
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2025-03-12 DOI: 10.1016/j.jtha.2025.03.003
James D Douketis, Na Li, Melanie St John, Joanne Nixon, Karen Moffat, Joseph Shaw, Summer Syed, Sam Schulman, Peter L Gross, Alex C Spyropoulos
{"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}
引用次数: 0
2-Methoxybenzoic acid ameliorates arterial thrombosis via inhibiting carbon anhydrase activity in platelet.
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2025-03-07 DOI: 10.1016/j.jtha.2025.02.027
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
{"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>FeCl<sub>3</sub>-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}
引用次数: 0
Thrombotic response to mechanical circulatory support devices.
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2025-03-07 DOI: 10.1016/j.jtha.2025.02.037
Tiffany Goh, Lining Arnold Ju, Anna Waterhouse
{"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":"https://doi.org/10.1016/j.jtha.2025.02.037","url":null,"abstract":"<p><p>Cardiovascular mechanical circulatory support (MCS) device use triggers thrombosis and haemostatic disorders, which may become fatal if thrombi occlude circulation or cause embolic complications. Consequently, anti-thrombotic 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 relationships of patient pathology, the foreign artificial biomaterial's surface properties, and pathological flow conditions. From a device design perspective, the latter two may be controlled for and redesigned to minimise 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 haemodynamic flow properties of margination, low flow and coagulation, high flow and platelet activation, von Willebrand's factor activation, and haemolysis. 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, emphasising 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}
引用次数: 0
Real-world evaluation of a novel automated method for measuring ADAMTS13 activity using the Ceveron® s100 analyzer.
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2025-03-07 DOI: 10.1016/j.jtha.2025.02.038
Bérangère S Joly, Hélène Deniau, Chloé Doinel, Adeline Brouillard, Virginie Siguret, Paul Coppo, Agnès Veyradier
{"title":"Real-world evaluation of a novel automated method for measuring ADAMTS13 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":"https://doi.org/10.1016/j.jtha.2025.02.038","url":null,"abstract":"<p><strong>Introduction: </strong>Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy characterized by a severe functional deficiency of ADAMTS13. Measuring ADAMTS13 activity is crucial for diagnosing TTP (<10 IU/dL), monitoring treatments, and detecting relapses (<20 IU/dL). The Technofluor® assay allows a rapid ADAMTS13 activity measurement using the CEVERON® s100 analyzer. This study aims to evaluate the analytical and clinical performance of this new test under real-world conditions.</p><p><strong>Materials and methods: </strong>ADAMTS13 activity was measured using two fluorometric methods: the Technofluor® ADAMTS13 activity on the CEVERON® s100 (Technoclone, Austria) and our reference FRETS-VWF73 method, in plasma samples collected under real-life conditions (01/12/2024-04/04/2024) 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 CV <11%, and reproducibility CV 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 [0.90;1.01]; negative predictive value: 0.98 [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 ADAMTS13 activity, proving effectiveness for diagnosis and monitoring of TTP patients. However, it remains crucial to interpret ADAMTS13 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}
引用次数: 0
RBC Rpl13a snoRNAs guides 2'-O-methylation on peroxidasin mRNA promoting venous thrombosis in aging.
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2025-03-07 DOI: 10.1016/j.jtha.2025.02.036
Waseem Chauhan, Sudharshan Sj, Shirin Ferdowsi, Akib Sohel, Rahima Zennadi
{"title":"RBC Rpl13a snoRNAs guides 2'-O-methylation on peroxidasin mRNA 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 non-coding 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 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>Patients/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 (WT) mice at 12-24 weeks of age, and aged WT and aged Rpl3a snoRNA knockout mice at 72-96 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 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 prothrombic activation by modulating peroxidase activity. This was due largely to Rpl13a snoRNAs-guided 2'-O-methylation on RBC peroxidasin (Pxdn) mRNA; a modification that inhibited the mRNA translation and Pxdn activity. In vivo Rpl13a snoRNA knockout in aged mice blunted RBC ROS generation, 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}
引用次数: 0
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.': [Journal of Thrombosis and Haemostasis (2023) Volume 21, Issue 2, February 2023, Pages 373-396].
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2025-03-07 DOI: 10.1016/j.jtha.2025.02.021
Julie Helms, Corinne Frere, Thomas Thiele, Kenichi A Tanaka, Matthew D Neal, Marie E Steiner, Jean M Connors, Jerrold H Levy
{"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.': [Journal of Thrombosis and Haemostasis (2023) Volume 21, Issue 2, February 2023, Pages 373-396].","authors":"Julie Helms, Corinne Frere, Thomas Thiele, Kenichi A Tanaka, Matthew D Neal, Marie E Steiner, Jean M Connors, Jerrold H Levy","doi":"10.1016/j.jtha.2025.02.021","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.02.021","url":null,"abstract":"","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":"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}
引用次数: 0
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.
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2025-03-07 DOI: 10.1016/j.jtha.2025.02.026
Nicolas Gendron, Adam Cuker, Robert C Gosselin, Lana A Castellucci, Jecko Thachil
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