Journal of Thrombosis and Haemostasis最新文献

{"title":"Impact of ischemic stroke on the risk of venous thromboembolism in the general population: the Tromsø Study and the Trøndelag Health Study","authors":"Birgitte G. Tøndel ,&nbsp;Vânia M. Morelli ,&nbsp;Ellisiv B. Mathiesen ,&nbsp;Maja-Lisa Løchen ,&nbsp;Tom Wilsgaard ,&nbsp;Kristian Hveem ,&nbsp;John-Bjarne Hansen ,&nbsp;Sigrid K. Brækkan","doi":"10.1016/j.jtha.2025.07.008","DOIUrl":"10.1016/j.jtha.2025.07.008","url":null,"abstract":"<div><h3>Background</h3><div>Data on venous thromboembolism (VTE) after ischemic stroke in the general population is limited.</div></div><div><h3>Objectives</h3><div>We aimed to explore the impact of ischemic stroke on overall VTE and VTE subtypes and by biological sex at the population level and to evaluate whether the risk of stroke-related VTE changed between 1994-2007 and 2008-2019.</div></div><div><h3>Methods</h3><div>Participants (<em>N</em> = 107 321) were recruited from 3 surveys of the Tromsø Study (enrollment:1994-2008) and 2 surveys of the Trøndelag Health Study (enrollment:1995-2008) and followed through 2014 and 2019, respectively. Hazard ratios (HRs) of VTE were calculated using Cox models with stroke as time-varying exposure. Cumulative incidences of VTE were estimated with death as a competing event.</div></div><div><h3>Results</h3><div>Ischemic stroke was diagnosed in 5974 individuals, of whom 199 developed VTE during follow-up. Within 3 months poststroke, the cumulative incidence and HR of VTE was 1.13% and 13.47 (95% CI, 9.41-19.27) in women and 0.76% and 9.50 (95% CI, 6.38-14.14) in men, respectively. Stroke conferred a 19-fold increased risk of provoked VTE (HR, 18.67; 95% CI, 14.01-24.88) and a 3-fold increased risk of unprovoked VTE (HR, 3.05; 95% CI, 1.45-6.45) within 3 months. The risk estimates of VTE after stroke did not change between the 2 time periods.</div></div><div><h3>Conclusion</h3><div>Sex-specific risk estimates for VTE were only marginally higher in women than in men. Ischemic stroke was associated with particularly high risk of provoked VTE, emphasizing the potentiating effect of additional risk factors. The risk of VTE after ischemic stroke has not declined over the past decades.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 10","pages":"Pages 3307-3318"},"PeriodicalIF":5.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667843","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":"Plasma levels measurement of the 4 direct oral anticoagulants in patients with atrial fibrillation at the time of acute thromboembolic and bleeding events.","authors":"Cosmo Godino, Riccardo Mazza, Carlo Gaspardone, Alessia Minerva, Rachele Sena, Gianmarco Cozzani, Anna Salerno, Michela Cera, Massimo Slavich, Leila Anna De Lorenzo, Giulio Leo, Giulia Nemola, Annalisa Fattorini, Luciano Crippa, Patrizia Della Valle, Alberto Margonato, Armando D'Angelo","doi":"10.1016/j.jtha.2025.06.031","DOIUrl":"10.1016/j.jtha.2025.06.031","url":null,"abstract":"<p><strong>Background: </strong>Direct oral anticoagulants (DOACs) are standard therapy to prevent thromboembolic events in nonvalvular atrial fibrillation (NVAF) and are generally used without routine monitoring of plasma anti-Xa or anti-IIa levels.</p><p><strong>Objectives: </strong>This study aimed to assess whether plasma levels of anti-Xa or anti-IIa at the time of presentation are associated with acute thromboembolic or bleeding events in DOAC-treated patients with NVAF.</p><p><strong>Methods: </strong>This prospective case-control study included consecutive long-term DOAC-treated patients with NVAF presenting to a European emergency department with acute thromboembolic or bleeding events (cases), or for other medical reasons (controls). DOAC plasma levels were measured using drug-specific chromogenic anti-Xa assays (rivaroxaban, apixaban, and edoxaban) or diluted thrombin time (dabigatran), categorized into quartiles, and analyzed according to event type.</p><p><strong>Results: </strong>Among 1794 patients (mean age 82 years, 49% female), 8% had thromboembolic events, 15% bleeding events, and 77% other presentations. DOAC treatment included apixaban (45%), dabigatran (17%), rivaroxaban (17%), and edoxaban (21%). Thromboembolic events were more common in patients with DOAC plasma levels in the first quartile (Q1: 50% vs 26%; P < .001), while bleeding events were more common in the fourth quartile (Q4: 46% vs 23%; P < .001). Q1 levels were associated with increased odds of thromboembolic events (OR, 2.04; 95% CI, 1.36-3.08), and Q4 levels with bleeding events (OR, 2.05; 95% CI, 1.49-2.82).</p><p><strong>Conclusion: </strong>DOAC plasma levels show substantial interindividual variability and are associated with acute thromboembolic and bleeding events. These observations may help generate hypotheses for future studies aimed at better defining the role of DOAC plasma monitoring in clinical practice.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667842","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":"Impact of streptozotocin-induced hyperglycemia on the host response to sepsis","authors":"Sean Carlin ,&nbsp;Dhruva J. Dwivedi ,&nbsp;Erblin Cani ,&nbsp;Neha Sharma ,&nbsp;Daniel E. Venegas-Pino ,&nbsp;Manoj Lalu ,&nbsp;Asher A. Mendelson ,&nbsp;Braedon McDonald ,&nbsp;Geoff H. Werstuck ,&nbsp;Patricia C. Liaw ,&nbsp;Canadian Critical Care Translational Biology Group (CCCTBG)","doi":"10.1016/j.jtha.2025.07.004","DOIUrl":"10.1016/j.jtha.2025.07.004","url":null,"abstract":"<div><h3>Background</h3><div>Diabetes is a common comorbidity in patients with sepsis, yet the influence of baseline glycemic status on sepsis outcomes remains unclear. Clinical studies report conflicting associations between diabetes and sepsis mortality.</div></div><div><h3>Objectives</h3><div>To evaluate how short-term (ie, 4-5 weeks) preinfection hyperglycemia influences the host response to sepsis using a model of fecal-induced peritonitis.</div></div><div><h3>Methods</h3><div>Hyperglycemia was induced in C57BL/6 mice (both sexes) via streptozotocin injections. Hyperglycemic and normoglycemic mice were subjected to fecal-induced peritonitis, with endpoints at 8 hours and 48 hours postinfection. Blood glucose, insulin, advanced glycation end-products, cytokines (interleukins 6 and 10), coagulation markers (thrombin-antithrombin and protein C), cell-free DNA (cfDNA), lung myeloperoxidase, bacterial loads, organ injury, and survival were assessed.</div></div><div><h3>Results</h3><div>Streptozotocin-treated mice exhibited low insulin and elevated blood glucose, advanced glycation end-products, thrombin-antithrombin, and cfDNA compared with normoglycemic mice. Despite these baseline differences, the trajectory of sepsis was similar in both groups. Blood glucose rapidly dropped postinfection, converging at approximately 2 mM within 12 hours in nonsurvivors and partially recovering in survivors. Plasma insulin increased in both groups in response to sepsis, returning to baseline levels by 48 hours in survivors. No significant differences were found between the groups in sepsis-related outcomes, including sepsis scores, body temperature, inflammatory and coagulation responses, cfDNA, lung myeloperoxidase, bacterial burden, organ injury, or survival.</div></div><div><h3>Conclusion</h3><div>Short-term hyperglycemia did not alter the course of sepsis compared with normoglycemic mice. Blood glucose levels partially recovered in surviving mice, suggesting that restoring glucose homeostasis may improve outcomes.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 10","pages":"Pages 3386-3398"},"PeriodicalIF":5.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667840","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":"Mathematical analysis of emicizumab: affinity-driven complex formation and lipid-surface reactions","authors":"Jamie Madrigal ,&nbsp;Dougald M. Monroe ,&nbsp;Suzanne S. Sindi ,&nbsp;Karin Leiderman","doi":"10.1016/j.jtha.2025.07.002","DOIUrl":"10.1016/j.jtha.2025.07.002","url":null,"abstract":"<div><h3>Background</h3><div>Emicizumab is a bispecific antibody that binds activated factor (F)IXa with 1-arm and FX with the other. Binding bridges FIXa and FX, replacing the function of FVIII in hemophilia A. Unlike FVIII, emicizumab does not bind directly to lipid surfaces.</div></div><div><h3>Objectives</h3><div>This study aimed to investigate emicizumab’s lipid-surface dependent mechanisms through mathematical modeling and biochemical assays.</div></div><div><h3>Methods</h3><div>We expanded our mathematical model of tissue factor (TF):VIIa activation of FX to incorporate emicizumab and FIXa interactions. We calibrated our model using experimental data.</div></div><div><h3>Results</h3><div>High concentrations of emicizumab inhibit FX activation by TF:VIIa. Our mathematical model explains these observations only when FX bound to emicizumab is partially restricted from binding to lipid surfaces and to TF:VIIa. Lipid enhances FX activation of FIXa in the presence of emicizumab. In our 2-arm interaction model, we estimated kinetic rates for emicizumab-dependent activation of FX on the lipid surface. The model successfully predicted FIXa activation of FX with and without emicizumab across many experimental conditions. Ternary complexes (FIXa, FX, and emicizumab) in solution decreased when lipid increased while ternary complexes on lipid increased. Sensitivity analysis, which varied lipid, dissociation constants, and catalytic rates, highlighted the impact of binding-arm affinity on reaction velocities.</div></div><div><h3>Conclusion</h3><div>High concentrations of emicizumab decrease TF:VIIa activation of FX by reducing FX binding to both the lipid surface and TF:VIIa. Emicizumab enhances FIXa activation of FX on the lipid surface by preferentially binding to lipid-bound FX and subsequently to lipid-bound FIXa with an enhanced association rate due to colocalization on the lipid surface.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 10","pages":"Pages 3111-3123"},"PeriodicalIF":5.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667841","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":"Venous thromboembolism in patients with cancer and factor XI deficiency","authors":"Pavlina Chrysafi ,&nbsp;Andriy Derkach ,&nbsp;Vasiliki Xirou ,&nbsp;Maly Fenelus ,&nbsp;Rushad Patell ,&nbsp;Jeffrey I. Zwicker ,&nbsp;Avi Leader","doi":"10.1016/j.jtha.2025.06.030","DOIUrl":"10.1016/j.jtha.2025.06.030","url":null,"abstract":"<div><h3>Background</h3><div>Factor (F)XI deficiency is associated with reduced venous thromboembolism (VTE) risk without increased spontaneous bleeding in the general population. Factor XI inhibitors show promise in preventing VTE in orthopedic surgery and are currently being investigated in cancer-associated VTE. However, there currently are no data regarding the potential efficacy of FXI inhibition for the management of hypercoagulability in cancer.</div></div><div><h3>Objectives</h3><div>This study aimed to evaluate the incidence of VTE among patients with cancer and FXI deficiency compared with that of a matched control population.</div></div><div><h3>Methods</h3><div>This is a retrospective study performed at Memorial Sloan Kettering Cancer Center evaluating VTE incidence in patients with cancer and FXI deficiency (<em>n</em> = 73) and matched controls with cancer and normal partial thromboplastin time (<em>n</em> = 185). Index date was the date of first visit at Memorial Sloan Kettering Cancer Center for cancer evaluation. Patients were followed up until VTE, death or last follow-up, whichever occurred first. Patients from the 2 cohorts were matched for age, sex, surgery within 30 days from index date, primary cancer site and stage, and platelet and hemoglobin levels at index.</div></div><div><h3>Results</h3><div>At 12 months, the cumulative incidence of VTE in the cohort with FXI deficiency was 4.1% (95% CI, 1.1%-11%) compared with 10.6% (95% CI: 6.6%-16%; Gray test, <em>P</em> = .052) in the matched controls. Major surgery-related bleeding occurred in 12.9% of patients with FXI deficiency undergoing surgery from the index date through the end of follow-up, compared with 2.1% in the control cohort.</div></div><div><h3>Conclusion</h3><div>Factor XI deficiency appears to be associated with reduced VTE risk in individuals with cancer.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 10","pages":"Pages 3286-3294"},"PeriodicalIF":5.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667857","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":"Evaluating the combined effect of antifibrinolytics and estrogen on the risk of thromboembolism: a scoping review.","authors":"Danielle Meschino, Daniel Lindsay, Grace H Tang, Paula James, Michael Fralick, Michelle Sholzberg","doi":"10.1016/j.jtha.2025.06.033","DOIUrl":"10.1016/j.jtha.2025.06.033","url":null,"abstract":"<p><strong>Background: </strong>Up to 30% of reproductive-aged women seek medical attention for heavy menstrual bleeding (HMB). Estrogen-containing contraceptives and antifibrinolytics are first-line treatments. Despite evidence for these agents for HMB and for antifibrinolytics in other high-estrogen states (eg, postpartum), many antifibrinolytic monographs warn against use with concurrent estrogen-containing contraception given theoretical thromboembolic risk.</p><p><strong>Objectives: </strong>This study aimed to systematically evaluate the literature that explores the combined effect of pharmacologic or high physiologic estrogen and antifibrinolytic agents on thromboembolic risk in women of reproductive age when used for heavy menstrual or postpartum bleeding.</p><p><strong>Methods: </strong>A systematic literature search was performed of records until April 2023. Publications written in English describing risk or reported cases of thromboembolism in reproductive-age women prescribed antifibrinolytics with estrogen-containing contraceptives or with a physiologic estrogenic state were included.</p><p><strong>Results: </strong>We identified 4302 publications; 55 publications with 199 228 participants were included. Two case reports and one case series described thromboembolism with concomitant estrogen-containing contraceptives and antifibrinolytic use. Four of 5 patients in the case series had other thrombotic risk factors. Fifty-two publications investigated antifibrinolytic use postpartum. Four RCTs of postpartum antifibrinolytic use assessed thromboembolism as a secondary outcome, none of which reported increased risk with antifibrinolytics. One case report suggested possible thrombotic risk wherein the patient had other provoking risk factors.</p><p><strong>Conclusion: </strong>We found no strong evidence that intermittent antifibrinolytic use in physiologic estrogenic states is associated with increased reported cases or risk of thromboembolic events. Prospective studies are warranted to assess the thrombotic risk of combined estrogen-containing contraceptives and antifibrinolytics.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667839","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":"Validation of the ToDay, a simplified diagnostic algorithm for deep vein thrombosis.","authors":"Sasha Sharma, Linnea Soon, Kerstin de Wit, Sangita Sharma, Marc Afilalo, Grégoire Le Gal, Sudeep Shivakumar, Shannon M Bates, Cynthia Wu, Alejandro Lazo-Langner, Frederick D' Aragon, Jean-Francois Deshaies, Sameer Parpia","doi":"10.1016/j.jtha.2025.06.029","DOIUrl":"10.1016/j.jtha.2025.06.029","url":null,"abstract":"<p><strong>Background: </strong>The current deep vein thrombosis (DVT) diagnostic algorithms are rarely followed in clinical practice due to complexity and time constraints. Simplified alternatives are needed to enhance adherence while maintaining diagnostic accuracy. The ToDay algorithm was developed to address these concerns by combining physician implicit assessment of DVT likelihood with D-dimer testing.</p><p><strong>Objectives: </strong>The objective of the study is to validate the ToDay algorithm using previously collected data.</p><p><strong>Methods: </strong>This analysis used data from the 4D study (NCT02038530), a multicenter study evaluating DVT diagnostic strategies. The ToDay algorithm considers DVT excluded without further testing if DVT is considered most likely and D-dimer <500 ng/mL or if DVT is not considered most likely and D-dimer less than age-adjusted threshold. The primary outcome was 90-day symptomatic venous thromboembolism (VTE). Secondary outcome was not requiring ultrasound imaging.</p><p><strong>Results: </strong>Among 1497 patients, 163 (10.9%) were diagnosed with DVT. Of the 1334 patients who had DVT excluded by the ToDay algorithm, 10 patients were found to have VTE during follow-up, a failure rate of 0.75% (95% CI, 0.41-1.37). Of all patients, 38.6% (95% CI, 36.2-41.1) did not require ultrasound imaging.</p><p><strong>Conclusion: </strong>The ToDay algorithm was found to be a safe and efficient alternative for DVT testing, reducing reliance on ultrasound imaging. It simplifies the diagnostic process, making it more feasible for emergency settings. Prospective validation is required before clinical adoption.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667856","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 autophagy-related markers Beclin-1, LC3, and P62 in the pathogenesis of immune thrombocytopenia in children","authors":"Nada El-Sayed Taha El-Sayed ,&nbsp;Nagwa Mansour Badr Eldin ,&nbsp;Mohammad Abd Elrahman Sweilam ,&nbsp;Amira Yousef Ahmed ,&nbsp;Eslam Elsayed Elhawary","doi":"10.1016/j.jtha.2025.06.034","DOIUrl":"10.1016/j.jtha.2025.06.034","url":null,"abstract":"<div><h3>Background</h3><div>Immune thrombocytopenic purpura (ITP) is an autoimmune disorder in which thrombocytopenia results from antiplatelet autoantibody-mediated destruction and/or suppression of platelet production. Autophagy also plays an important role in the regulation of the innate and adaptive immune systems, and when autophagy becomes inefficient, it may lead to diverse autoimmune diseases.</div></div><div><h3>Objectives</h3><div>We aimed to assess autophagy-related markers Beclin-1, LC3, and P62 expression in ITP and to investigate the relation between autophagy markers and antiplatelet autoantibodies in pediatric ITP.</div></div><div><h3>Methods</h3><div>Gene expressions of Beclin-1, LC3, and P62 messenger RNA were assessed by quantitative real-time polymerase chain reaction in 30 children diagnosed with ITP and 20 healthy controls.</div></div><div><h3>Results</h3><div>The results showed that the relative gene expression of both Beclin-1 and LC3 genes was significantly increased in ITP patients compared with the control group, while P62 relative gene expression was significantly decreased in ITP patients compared with the control group. The relative gene expression of Beclin-1 and LC3 was significantly increased in ITP patients with positive antiplatelet antibodies compared with those with negative antiplatelet antibodies, while the relative gene expression of P62 was significantly decreased in ITP patients with positive antiplatelet antibodies compared with those with negative antiplatelet antibodies.</div></div><div><h3>Conclusion</h3><div>The results demonstrated a possible role of dysregulation of autophagy genes in the pathogenesis of ITP. Furthermore, the correlation between impaired autophagy and autoantibodies, a known mechanism of the pathogenesis of ITP, supports a possible role of impaired autophagy in the pathogenesis of ITP.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 10","pages":"Pages 3362-3369"},"PeriodicalIF":5.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659528","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":"Anti-citrullinated histone H3 immunoglobulin G: new antibodies highly correlate with anti-neutrophil extracellular traps antibodies and thrombosis in antiphospholipid syndrome","authors":"Shengqiang Pei,&nbsp;Zixin Chen,&nbsp;Dabuxilite Bayartaikishigtai,&nbsp;Danyu Song,&nbsp;Ximing Wang,&nbsp;Dongze Yu,&nbsp;Zhou Zhou,&nbsp;Yang Zhang","doi":"10.1016/j.jtha.2025.07.001","DOIUrl":"10.1016/j.jtha.2025.07.001","url":null,"abstract":"<div><h3>Background</h3><div>Neutrophil extracellular traps (NETs) are involved in the development of thrombosis. Discovering anti-NETs antibodies has provided new understanding of how NETs and thrombotic processes are connected. However, these antibodies are currently only recognized as a diverse group, with their exact makeup still unknown.</div></div><div><h3>Objectives</h3><div>To identify anti-citrullinated histone H3 (CitH3) immunoglobulin (Ig) G and analyze its relationship with anti-NETs antibodies and thrombosis.</div></div><div><h3>Methods</h3><div>We studied 38 antiphospholipid antibody-positive patients to measure anti-CitH3 IgG and anti-NETs IgG in their plasma. We examined the relationship between these antibodies and the link between anti-CitH3 IgG and thrombotic events. Additionally, we explored how anti-CitH3 IgG affects NETs clearance and platelet activation through various experiments to understand their prothrombotic mechanisms.</div></div><div><h3>Results</h3><div>This study demonstrated an increased incidence of thrombosis in individuals with elevated anti-CitH3 IgG levels and confirmed a robust correlation between anti-CitH3 IgG and anti-NETs IgG. Both <em>in vitro</em> and <em>in vivo</em> experiments revealed that the anti-CitH3 IgG impeded the clearance of NETs. The introduction of this antibody into a coculture of platelets and NETs resulted in elevated levels of P-selectin and CD40L, suggesting enhanced platelet activation. Furthermore, in a murine model, the presence of anti-CitH3 IgG led to increased rates of thrombosis, corroborating its role in thrombosis.</div></div><div><h3>Conclusion</h3><div>Anti-CitH3 IgG and anti-NETs IgG are similar and important. Anti-CitH3 IgG indirectly enhances platelet activation and exacerbates thrombosis by inhibiting NETs degradation, making it valuable for predicting thrombosis and potentially serving as a new biomarker for assessing thrombosis risk.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 10","pages":"Pages 3295-3306"},"PeriodicalIF":5.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659527","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":"Effects of milvexian alone or with heparin on catheter-induced clotting and thrombin generation","authors":"Ruiqi Yin ,&nbsp;James C. Fredenburgh ,&nbsp;Jeffrey I. Weitz","doi":"10.1016/j.jtha.2025.06.028","DOIUrl":"10.1016/j.jtha.2025.06.028","url":null,"abstract":"<div><h3>Background</h3><div>Milvexian, an oral factor (F)XIa inhibitor, is undergoing phase 3 evaluation for acute coronary syndrome. Such patients often require percutaneous coronary intervention (PCI). The PCI catheters trigger clotting by inducing activation of FXII and FXI. It is unknown whether milvexian blocks this or if adjunctive heparin is needed.</div></div><div><h3>Objectives</h3><div>To (a) compare the effect of FXII depletion or FXI depletion on catheter clotting, (b) investigate catheter-induced FXI activation, and (c) determine the effect of milvexian alone or with heparin on catheter-induced clotting and thrombin generation.</div></div><div><h3>Methods</h3><div>In a 96-well plate assay, catheter-induced clotting and thrombin generation were assessed in recalcified control or depleted plasmas supplemented with control plasma by monitoring absorbance and thrombin substrate hydrolysis, respectively. FXI activation by catheters, FXIIa, or thrombin was evaluated by chromogenic assay. Milvexian, dabigatran, heparin, or milvexian plus heparin were added to control plasma to assess effects.</div></div><div><h3>Results</h3><div>Catheters promoted autoactivation of FXI and augmented FXIIa- and thrombin-mediated FXI activation. Clotting was attenuated in FXII-depleted plasma and abolished in FXI-depleted plasma. Even small amounts of FXI triggered clotting. Milvexian and dabigatran at clinically relevant concentrations did not prevent catheter-induced clotting or thrombin generation. Heparin potentiated milvexian’s inhibitory effect on catheter-induced clotting.</div></div><div><h3>Conclusion</h3><div>Catheters promote FXI autoactivation, bypassing FXII, and highlighting the critical role of FXI. The limited capacity of milvexian supports the need for adjunctive heparin in patients treated with milvexian undergoing PCI.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 10","pages":"Pages 3198-3207"},"PeriodicalIF":5.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626651","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}