Research and Practice in Thrombosis and Haemostasis最新文献

{"title":"Safety and efficacy of direct oral anticoagulants in patients with liver cirrhosis: a meta-analysis","authors":"Daniel Tham ,&nbsp;Wenhui Yu ,&nbsp;Lucy Zhao ,&nbsp;Roger Kou ,&nbsp;Jayhan Kherani ,&nbsp;Pei Yi Li ,&nbsp;Shreyas Sreeraman ,&nbsp;Ali Eshaghpour ,&nbsp;Allen Li ,&nbsp;Mark A. Crowther","doi":"10.1016/j.rpth.2025.103296","DOIUrl":"10.1016/j.rpth.2025.103296","url":null,"abstract":"<div><h3>Background</h3><div>Direct oral anticoagulants (DOACs) are the standard of care for treatment of venous thromboembolism and stroke prophylaxis in atrial fibrillation. Since patients with Child-Pugh (CP) B or C liver cirrhosis are underrepresented in trials, the safety of DOACs in this population is unclear.</div></div><div><h3>Objectives</h3><div>This study synthesized primary evidence on the safety profile of DOACs in patients with advanced liver cirrhosis.</div></div><div><h3>Methods</h3><div>A literature search of MEDLINE and Embase from inception to October 2025 identified randomized and nonrandomized cohort studies comparing DOAC with vitamin K antagonists or low-molecular-weight heparin in patients with liver cirrhosis. Screening and data collection were conducted in duplicate. The primary outcome was major bleeding defined by International Society on Thrombosis and Haemostasis criteria, stratified by CP class. Data were meta-analyzed using a random-effects model, presented as odds ratios (OR) with corresponding 95% CIs.</div></div><div><h3>Results</h3><div>Of 797 articles captured in the literature search, 15 nonrandomized (<em>n</em> = 17,387) and 1 randomized (<em>n</em> = 70) study were included. DOACs reduced major bleeding in both CP class B and C exclusive subgroup and a subgroup with unspecified CP stages of liver cirrhosis (CP B and C: OR, 0.53; 95% CI, 0.36-0.80; CP unspecified: OR, 0.66; 95% CI, 0.46-0.98).</div></div><div><h3>Conclusion</h3><div>Based on the findings of this meta-analysis, DOACs may be associated with a reduced risk of major bleeding compared with vitamin K antagonists or low-molecular-weight heparin in patients with liver cirrhosis, including those with CP class B and C cirrhosis. The results of this meta-analysis should be interpreted in the context of methodological limitations. Future analysis should evaluate the impact of specific DOACs and dosage on safety outcomes in this patient population.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103296"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A cecal slurry mouse model of polymicrobial abdominal sepsis to evaluate the effects of antiplatelet agents","authors":"Alexandre Mansour ,&nbsp;Isabelle Gouin-Thibault ,&nbsp;Elisa Rossi ,&nbsp;Aurore Marchelli ,&nbsp;Tiphaine Belleville-Rolland ,&nbsp;Nicolas Nesseler ,&nbsp;Pascale Gaussem ,&nbsp;Christilla Bachelot-Loza","doi":"10.1016/j.rpth.2025.103292","DOIUrl":"10.1016/j.rpth.2025.103292","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103292"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discrepancy between international normalized ratio measurements in a heterozygous carrier of F10:p.Gly244Arg with recurrent venous thromboembolism: a case report","authors":"Nikolaj Julian Skrøder Nytofte,&nbsp;Emil List Larsen","doi":"10.1016/j.rpth.2025.103298","DOIUrl":"10.1016/j.rpth.2025.103298","url":null,"abstract":"<div><h3>Background</h3><div>The international normalized ratio (INR) is designed to monitor vitamin K antagonist (VKA) treatment. Before patients start a self-managing VKA program, parallel measurements are conducted to compare point-of-care testing (POCT) INR with venous INR samples. Previously, genetic variants in <em>F7</em> have shown discrepancies in INR measurements when thromboplastins from different species were used. It is unknown whether genetic variants in <em>F10</em> affect INR measured with thromboplastins from different species.</div></div><div><h3>Key Clinical Question</h3><div>Does <em>F10</em>:p.Gly244Arg heterozygosity affects the INR when measured using rabbit compared with human thromboplastin?</div></div><div><h3>Clinical Approach</h3><div>A patient self-managing warfarin treatment had a recurrent venous thromboembolism during VKA treatment. The POCT therapeutic range was low (ie, 1.6-2.4) based on parallel measurements of POCT INR (human thromboplastin) and venous INR (rabbit thromboplastin). Subsequently, it was noted that the patient had a spontaneous increase in INR (1.3), and the patient was found to be a heterozygous carrier of <em>F10</em>:p.Gly244Arg.</div></div><div><h3>Conclusion</h3><div>Genetic variants in <em>F10</em> may also interfere with INR or prothrombin time measurements when different thromboplastins are used. This case illustrates that discrepancies in INR measurements with different thromboplastins should prompt consideration of genetic variants in <em>F10</em> and <em>F7</em> to ensure sufficient anticoagulant VKA treatment.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103298"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety, tolerability, pharmacokinetics, and pharmacodynamics of KN060, a humanized anti-FXI/FXIa dual-domain antibody, following single ascending doses in healthy Chinese subjects","authors":"Jie Huang ,&nbsp;Jinlong Liu ,&nbsp;Yaxin Liu ,&nbsp;Yichen Cao ,&nbsp;Wei Sun ,&nbsp;Yanrong Dong ,&nbsp;Yuwei Li ,&nbsp;Jing Li ,&nbsp;Qian Wu ,&nbsp;Xiaoyan Yang ,&nbsp;Shuang Yang ,&nbsp;Chuanpin Chen ,&nbsp;Guoping Yang","doi":"10.1016/j.rpth.2025.103322","DOIUrl":"10.1016/j.rpth.2025.103322","url":null,"abstract":"<div><h3>Background</h3><div>KN060 is a humanized dual-domain antibody targeting coagulation factor XI (FXI) and factor XIa (FXIa) and is currently being developed for the prevention of thromboembolic diseases.</div></div><div><h3>Objectives</h3><div>This study aims to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of a single intravenous administration of KN060 in healthy Chinese subjects.</div></div><div><h3>Methods</h3><div>This single-center, randomized, double-blind, placebo-controlled clinical study was conducted in 38 healthy Chinese subjects. The study included 6 dose groups (0.1, 0.3, 1.0, 2.5, 5.0, and 10.0 mg/kg), with KN060 administered via a single ascending-dose regimen.</div></div><div><h3>Results</h3><div>KN060 demonstrates good tolerability and safety, with no significant treatment-emergent adverse events. A single intravenous infusion of KN060, ranging from 0.1 to 10.0 mg/kg, resulted in an average <em>T</em>_max ranging from 1.02 to 3.34 hours. For a dose range of 0.3 to 10.0 mg/kg, the average half-life ranged from 122.96 to 146.47 hours. Pharmacokinetic and pharmacodynamic analyses revealed that within the dose range of 0.1 to 10.0 mg/kg, drug concentration was positively correlated with activated partial thromboplastin time and negatively correlated with factor (F)XI activity and free FXI content. Immunogenicity analysis showed that all subjects were negative for antidrug antibodies.</div></div><div><h3>Conclusion</h3><div>The study results demonstrated that KN060 was well tolerated and safe. Based on pharmacokinetic and pharmacodynamic data, KN060 is a promising humanized dual-domain antibody simultaneously targeting FXI/FXIa for the prevention of thromboembolic diseases.</div></div><div><h3>Trial Registration</h3><div><span><span>https://www.chictr.org.cn</span><svg><path></path></svg></span>, identifier: ChiCTR2200056926; <span><span>http://www.chinadrugtrials.org.cn</span><svg><path></path></svg></span>, identifier: CTR20222339.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103322"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Venous thromboembolism in patients with breast, ovarian, and uterine cancer. A comparative analysis from the Registro Informatizado Enfermedad TromboEmbólica registry","authors":"Olga Gavín Sebastián ,&nbsp;Javier Trujillo-Santos ,&nbsp;María del Carmen Díaz-Pedroche ,&nbsp;Pablo Demelo-Rodríguez ,&nbsp;Sonia Otálora ,&nbsp;Benjamin Brenner ,&nbsp;José María Pedrajas ,&nbsp;Alessandra Bura-Riviere ,&nbsp;Luis Hernández-Blasco ,&nbsp;Manuel Monreal","doi":"10.1016/j.rpth.2025.103301","DOIUrl":"10.1016/j.rpth.2025.103301","url":null,"abstract":"<div><h3>Background</h3><div>The risk of recurrent venous thromboembolism (VTE) and bleeding during anticoagulation may vary by the cancer type.</div></div><div><h3>Objectives</h3><div>We assessed outcomes during anticoagulation in women with breast, ovarian, or uterine cancer and VTE.</div></div><div><h3>Methods</h3><div>We analyzed data from the Registro Informatizado Enfermedad TromboEmbólica registry on 4721 women with active breast (<em>n</em> = 2929), ovarian (<em>n</em> = 886), or uterine (<em>n</em> = 906) cancer and acute VTE. We assessed VTE recurrences, bleeding, and mortality according to cancer type and anticoagulant type. Multivariate Cox models were adjusted for age, metastases, anemia, renal function, and treatment at VTE onset.</div></div><div><h3>Results</h3><div>Uterine cancer patients had the highest rates of major bleeding (11.1 per 100 patient-years) and fatal bleeding (1.07 per 100 patient-years), while ovarian cancer patients had the highest rate of VTE recurrences (7.29 per 100 patient-years). In contrast, breast cancer patients had the lowest event rates overall. Among low-molecular-weight heparin–treated patients, major bleeding was higher in uterine (6.37 per 100 patient-years) and ovarian (4.62 per 100 patient-years) cancer than breast cancer patients (1.89 per 100 patient-years). Direct oral anticoagulant use was associated with low recurrence rates in breast cancer (0.58 per 100 patient-years), but outcomes in uterine cancer remained less favorable. Multivariable models confirmed cancer-specific risks.</div></div><div><h3>Conclusions</h3><div>VTE outcomes vary significantly by cancer type. Patients with uterine cancer face an elevated bleeding risk, potentially impacting anticoagulant continuity and contributing to VTE recurrence. These findings support the need for cancer-specific risk assessment and individualized anticoagulation strategies adapted to the specific cancer type.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103301"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics of thrombocytopenia in tropical diseases and management in resource-limited settings","authors":"Gerard Gurumurthy ,&nbsp;Juditha Gurumurthy ,&nbsp;Samantha Gurumurthy ,&nbsp;Lianna Reynolds ,&nbsp;Dawn Swan ,&nbsp;Jecko Thachil","doi":"10.1016/j.rpth.2025.103323","DOIUrl":"10.1016/j.rpth.2025.103323","url":null,"abstract":"<div><div>Platelets play a central role in the pathogenesis of tropical infectious diseases. Infections such as malaria, dengue, and leptospirosis are often accompanied by thrombocytopenia. While the platelet count is typically monitored as a measure of thrombocytopenia, other platelet indices may better determine bleeding severity. Platelet dysfunction in these conditions requires a nuanced approach to management. Prophylactic platelet transfusions have shown limited efficacy in preventing hemorrhagic complications and carry additional risks. These include transfusion-transmitted infections, logistical challenges, and the high cost of platelet concentrates. Herein, we review current insights into platelet biology in major tropical infections, examine the varied mechanisms underlying thrombocytopenia in these conditions, and discuss the latest evidence on transfusion guidelines. We also propose evidence-based approaches to thrombocytopenia management and platelet transfusion. We aim to summarize approaches that may improve care for populations disproportionately affected by tropical infectious diseases in resource-limited settings.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103323"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selection and optimization strategy for Rap1-targeting single-domain antibodies as platelet activation markers","authors":"Marie-Christine Alessi ,&nbsp;Maxime Moulard ,&nbsp;Daniele Boulay-Moine ,&nbsp;Cyril Pons ,&nbsp;Marielle Margier ,&nbsp;Cléa Vessière ,&nbsp;Marjorie Poggi ,&nbsp;Theo Pigaglio ,&nbsp;Francoise Dignat-George ,&nbsp;Alain Roussel ,&nbsp;Stéphane Burtey ,&nbsp;Laurent Bonello ,&nbsp;Patrick Chames ,&nbsp;Remi Bonjean ,&nbsp;Franck Peiretti","doi":"10.1016/j.rpth.2025.103294","DOIUrl":"10.1016/j.rpth.2025.103294","url":null,"abstract":"<div><h3>Background</h3><div>Rap1 is critical for platelet activation, functioning as a key node of the platelet activation pathways.</div></div><div><h3>Objectives</h3><div>This study aimed to develop VHH-Fc (minibodies) against Rap1 for the purpose to quantify active Rap1 levels in platelets.</div></div><div><h3>Methods</h3><div>We have produced the first generation of VHHs against active Rap1 through a series of negative and positive screenings of a synthetic phage display library, utilizing both inactive and active Rap1B. We performed random mutagenesis, followed by yeast 2-hybrid screening to optimize variants.</div></div><div><h3>Results</h3><div>Among 122 VHH clones, 2 with the highest redundancy were subcloned as VHH-Fc. Both selectively detected active Rap1B G12V in HeLa cells but failed to recognize the inactive Rap1B S17N isoform. They successfully captured Rap1 from platelet lysates incubated with GTPγS and from thrombin receptor activator peptide 6–stimulated platelets. Further optimization yielded 2 superbinder VHH clones: VHH-Fc B89 and VHH-Fc B14. VHH-Fc B89 exhibited a <em>K</em>_D of 4.4 nM and showed enhanced capacity to capture active GTP-bound Rap1 compared with the original VHH-Fc. Additionally, it was able to detect overexpressed active Rap1B G12V in HeLa cells. An ELISA setup combining VHH-Fc B14 and a commercial monoclonal antibody targeting total Rap1 was highly effective in detecting both GTPγS-bound Rap1 and endogenous active Rap1 in platelets.</div></div><div><h3>Conclusion</h3><div>This study identifies, that accurately capture active Rap1 in platelets, thereby establishing them as promising tools for future research. We also developed a reliable ELISA test that can facilitate clinical studies to monitor platelet Rap1 activation in various medical contexts.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103294"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct oral anticoagulant interference and removal in the factor VIII inhibitor assay","authors":"Rick Timmerije ,&nbsp;Saskia E.M. Schols ,&nbsp;Daniëlle Meijer ,&nbsp;Wideke Barteling ,&nbsp;An K. Stroobants ,&nbsp;Sanna R. Rijpma","doi":"10.1016/j.rpth.2025.103334","DOIUrl":"10.1016/j.rpth.2025.103334","url":null,"abstract":"<div><h3>Background</h3><div>Direct oral anticoagulants (DOACs) interfere with clot-based assays, including factor (F)VIII testing and the Nijmegen–Bethesda assay, potentially leading to false-positive results for FVIII inhibitors. Misinterpretation of these results carries serious clinical consequences. Activated charcoal-based products, such as DOAC Remove, may restore assay accuracy, but data supporting their use in FVIII inhibitor assays are limited.</div></div><div><h3>Objectives</h3><div>In this study, we aim to determine DOAC interference in FVIII inhibitor testing and evaluate effectivity of DOAC removal to restore assay reliability.</div></div><div><h3>Methods</h3><div>Normal pooled plasma was spiked with therapeutic and supratherapeutic concentrations of apixaban, edoxaban, rivaroxaban, and dabigatran. Plasma pools from persons with acquired hemophilia A were spiked with DOACs and retested with and without DOAC removal treatment to evaluate workflow performance. FVIII inhibitor activity was measured with and without activated charcoal-based DOAC removal to establish DOAC interference and removal efficacy.</div></div><div><h3>Results</h3><div>Spiking experiments with DOACs caused concentration-dependent false-positive FVIII inhibitor results (&gt;0.6 Nijmegen Bethesda Units/mL), with dabigatran showing the strongest interference and apixaban the weakest. DOAC removal substantially reduced or eliminated interference across all drugs. Post-removal FVIII inhibitor values closely matched baseline concentrations in both spiked normal pooled plasma and pooled patient plasma, with most results within ±20% of the assay variability.</div></div><div><h3>Conclusion</h3><div>DOACs significantly interfere with FVIII inhibitor assays, potentially causing clinically significant false-positive results. Activated charcoal-based DOAC removal treatment provides a practical solution to restore assay reliability. These findings support the integration of DOAC removal into anti-FVIII testing protocols for patients on anticoagulant therapy.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103334"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of biomarkers with hypoattenuated leaflet thickening after transcatheter aortic valve replacement","authors":"David Hesselbarth ,&nbsp;Michelle D’Orazio ,&nbsp;Giovanni Ciccarone ,&nbsp;Diona Gjermeni ,&nbsp;Carina Jülch ,&nbsp;Philipp Breitbart ,&nbsp;Philipp Ruile ,&nbsp;Manuel Hein ,&nbsp;Marius Wessinger ,&nbsp;Mariya Maslarska ,&nbsp;Jonathan Rilinger ,&nbsp;Christopher Schlett ,&nbsp;Fabian Bamberg ,&nbsp;Klaus Kaier ,&nbsp;Daniel Duerschmied ,&nbsp;Torben Pottgiesser ,&nbsp;Constantin von zur Mühlen ,&nbsp;Dirk Westermann ,&nbsp;Christoph B. Olivier","doi":"10.1016/j.rpth.2025.103341","DOIUrl":"10.1016/j.rpth.2025.103341","url":null,"abstract":"<div><h3>Background</h3><div>Patients after transcatheter aortic valve replacement (TAVR) have a high incidence of hypoattenuating leaflet thickening (HALT). However, data on biomarkers related to HALT remain limited.</div></div><div><h3>Objectives</h3><div>To identify hemostatic markers associated with HALT following TAVR.</div></div><div><h3>Methods</h3><div>This prospective single-center cohort study assessed hemostatic profiles of patients undergoing TAVR between November 2020 and June 2022 using thrombelastography, light transmission aggregometry, and conventional laboratory markers. The primary outcome was moderate-to-severe HALT (grade 3/4) or reduced leaflet motion (grade 2/3) detected by computed tomography angiography at 6 months post-TAVR.</div></div><div><h3>Results</h3><div>Of the 107 patients included, 68 had interpretable computed tomography angiography at 6 months. The primary outcome occurred in 14 (20%) patients. Biomarkers were measured at a median of 4 days (IQR, 3-6) after TAVR. Shortened clot formation time (R-time with heparin neutralization) indicated an association with HALT at 6 months (odds ratio [OR], 1.12 [95% CI, 1.00; 1.25]; <em>P</em> = .05) and demonstrated moderate discriminatory ability, with an optimal cutoff of 4.9 minutes (sensitivity 79%; specificity 74%; area under the curve, 0.74 [95% CI, 0.60; 0.89]; <em>P</em> = .005). Increased platelet count (OR, 1.08 [95% CI, 1.01; 1.15]; <em>P</em> = .03), elevated protein S (OR, 1.21 [95% CI, 1.01; 1.44]; <em>P</em> = .04), and higher C-reactive protein levels (OR, 1.19 [95% CI, 1.00; 1.41]; <em>P</em> = .05) also demonstrated associations with HALT. However, after adjustment for multiple testing using the Benjamini–Hochberg procedure, none of these associations was statistically significant.</div></div><div><h3>Conclusion</h3><div>This exploratory study identified associations between HALT and biomarkers of hypercoagulability and inflammation, which did not persist after correction for multiple testing. These findings should be regarded as hypothesis-generating and warrant confirmation in future studies.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103341"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antithrombotic therapy in lower extremity peripheral artery disease patients with venous thromboembolism: a nationwide cohort study","authors":"Jamilla Goedegebuur ,&nbsp;Elena Butera ,&nbsp;Qingui Chen ,&nbsp;Behnood Bikdeli ,&nbsp;Walter Ageno ,&nbsp;Roberto Pola ,&nbsp;Angelo Porfidia ,&nbsp;Stefano Barco ,&nbsp;Thijs E. van Mens ,&nbsp;Joost R. van der Vorst ,&nbsp;Suzanne C. Cannegieter ,&nbsp;Frederikus A. Klok","doi":"10.1016/j.rpth.2025.103291","DOIUrl":"10.1016/j.rpth.2025.103291","url":null,"abstract":"<div><h3>Background</h3><div>Antithrombotic therapy (ATT) is recommended for patients with symptomatic lower extremity peripheral arterial disease (PAD). Optimal management of “breakthrough” venous thromboembolic events (VTEs) in these patients remains unclear. This study aims to describe current ATT prescription patterns in PAD patients before, during, and after VTE (treatment) and subsequent clinical outcomes.</div></div><div><h3>Methods</h3><div>Using Dutch nationwide data, this cohort study identified patients with a reimbursement code for PAD between 2013 and 2021. Within this source population, patients with an International Classification of Diseases-10 code for VTE were identified and followed from VTE date until end-of-study date or death, whichever occurred first. ATT prescriptions, determined from pharmacy records, were mapped in 3 timeframes: 3 months before VTE, during VTE treatment, and 4 to 12 months after VTE.</div></div><div><h3>Results</h3><div>Patients with PAD (<em>N</em> = 1866) and a concurrent VTE were included, with a mean age of 71.7 years and a median survival of 3.8 years. Before the VTE, 64% used antiplatelet therapy only, in contrast to 12% after VTE treatment. During the VTE treatment period, direct oral anticoagulants were the most frequently dispensed ATT type (40%), whereas 27% received anticoagulation plus antiplatelet therapy during this time. The one-year cumulative incidences of arterial thromboembolic events and clinically relevant bleedings were 6.1% (95% CI: 4.9-7.3) and 1.8% (95% CI, 1.2-2.4), respectively.</div></div><div><h3>Conclusion</h3><div>Immediate treatment of VTE and long-term ATT use in PAD patients were heterogeneous in our cohort. A substantial proportion of patients had prescriptions for both antiplatelet therapy and anticoagulation during the VTE treatment period. Our findings highlight the need for consensus on this complex clinical dilemma.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103291"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}