Thrombosis research最新文献

{"title":"A human-cell recombinant prethrombin-2 platform producing thrombin with enhanced fibrinogen processing for in vitro applications","authors":"Hadeel Swaid,&nbsp;Soraia R. Mendes,&nbsp;Pablo Fuentes-Prior,&nbsp;Arturo Rodríguez-Banqueri,&nbsp;F. Xavier Gomis-Rüth","doi":"10.1016/j.thromres.2026.109863","DOIUrl":"10.1016/j.thromres.2026.109863","url":null,"abstract":"<div><div>Thrombin is a central mediator of haemostasis, immune responses, and inflammation. It arises from prothrombin upon prothrombinase cleavage at R³²⁰–I³²¹, which triggers the allosteric maturation typical of chymotrypsin-like serine peptidases. Further processing yields the physiologically dominant α-thrombin (αT), whose competent active site centres on catalytic S⁵²⁵. Despite widespread biomedical and biotechnological use, plasma-derived αT is heterogeneous and risks pathogen or prion transmission, motivating recombinant alternatives. These have largely relied on suboptimal bacterial or non-human eukaryotic systems, with human-cell efforts focused mainly on prothrombin or engineered variants. Here, we report the recombinant production in Expi293F cells of prethrombin-2 (PE2), a zymogen retaining 13 residues upstream of αT, alongside its catalytically-impaired S⁵²⁵A counterpart (PE2–S⁵²⁵A). Controlled <em>in vitro</em> maturation was achieved with a matched recombinant system for ecarin, a snake-venom metallopeptidase cleaving R³²⁰–I³²¹, which yielded active PE2a and inactive PE2a–S⁵²⁵A. PE2a exhibited thermal stability, cleavage activity against the chromogenic substrate S-2238, and performance in thrombin-time assays comparable to those of commercial human αT. By contrast, it cleaved the physiological substrate fibrinogen, including its fluorescein-labelled form, more efficiently. Fresh PE2a slowly underwent autolysis at R²⁸⁴–T²⁸⁵, yielding αT after one week. The direct thrombin inhibitors argatroban and dabigatran further enhanced thermal stability while efficiently blocking substrate cleavage. This fully recombinant workflow provides a practical platform for basic haematological research, structural biology, and inhibitor screening <em>in vitro</em>.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"266 ","pages":"Article 109863"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Factor VII mutation F7 c.760T>C (FVIIp.Cys254Arg) is causative for Factor VII deficiency by impairing secretion","authors":"Malte M. Bartylla,&nbsp;Sarah Cunningham,&nbsp;Susanne Achenbach,&nbsp;Jakob Zierk,&nbsp;Holger Hackstein,&nbsp;Martin Chada,&nbsp;Sabine Schneider","doi":"10.1016/j.thromres.2026.109846","DOIUrl":"10.1016/j.thromres.2026.109846","url":null,"abstract":"<div><h3>Background</h3><div>Hereditary Factor VII (FVII) deficiency is a bleeding disorder caused by mutations in the <em>F7</em> gene, a diagnosis that is complicated by a weak genotype-phenotype correlation. However, accurate pathogenicity assessment of FVII variants is essential for effective clinical management.</div></div><div><h3>Objectives</h3><div>Here, we report about the FVII_p.Cys254Arg variant, caused by the <em>F7</em> c.760T&gt;C mutation. This mutation was found in two patients, father and son, both presenting with FVII deficiency. We aimed to identify the molecular mechanism responsible for the underlying pathogenicity.</div></div><div><h3>Methods</h3><div>Characterization of the FVII_p.Cys254Arg variant was performed using <em>in silico</em> analysis as well as an <em>in vitro</em> expression system. Subcellular localization and secretion of recombinant FVII protein were investigated using Western blotting, a bioluminescent protein quantification assay and confocal laser scanning microscopy.</div></div><div><h3>Results</h3><div>The FVII_p.Cys254Arg variant results in the loss of a disulfide bond in the protease domain near the catalytic triad, which potentially destabilizes the tertiary protein structure. This leads to impaired secretion, as demonstrated in HEK293T cells and further supported by the FVII deficiency in the patients co-segregating with the mutation.</div></div><div><h3>Conclusion</h3><div>The molecular analysis confirms the <em>in silico</em> prediction of the FVII_p.Cys254Arg variant as highly pathogenic and establishes this mutation as causative for hereditary FVII deficiency.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"266 ","pages":"Article 109846"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apixaban for thromboprophylaxis in paediatric cardiology patients: Real-world data from a single institution","authors":"Alessandra Bosch,&nbsp;Florian Berger,&nbsp;Hitendu Dave,&nbsp;Manuela Albisetti","doi":"10.1016/j.thromres.2026.109893","DOIUrl":"10.1016/j.thromres.2026.109893","url":null,"abstract":"<div><h3>Background</h3><div>Thrombosis is a major complication in children with congenital or acquired heart disease, contributing to significant morbidity and mortality. Direct oral anticoagulants (DOACs), including apixaban, are increasingly used for thromboprophylaxis in this population yet real-world paediatric data remain limited.</div></div><div><h3>Objectives</h3><div>To evaluate the safety and effectiveness of apixaban as thromboprophylaxis in paediatric cardiac patients receiving commercially available adult tablet formulations outside a clinical trial setting.</div></div><div><h3>Patients/methods</h3><div>This retrospective cohort study included patients aged ≤18 years with congenital or acquired heart disease who received apixaban at the University Children's Hospital Zurich from October 2022 to June 2025. Dosing was approximated to the SAXOPHONE trial using commercially available tablets that were split or crushed, without therapeutic laboratory monitoring. Outcomes included incident thrombosis (primary), major bleeding, clinically relevant non-major bleeding (CRNMB), and all-cause mortality.</div></div><div><h3>Results</h3><div>Sixty-seven patients were included with a median age of 4.6 years (IQR 3.3–9.8) and median apixaban exposure of 210 days (IQR 83–461), totalling 18,799 patient-days (51.5 patient-years). Single ventricle physiology was the most common underlying diagnosis (40/67, 60%) and Fontan circulation the most frequent indication (34/67, 51%). Two thrombotic events occurred (incidence rate 3.9 per 100 patient-years), both in the context of additional thrombotic risk factors. No major bleeding or CRNMB events were recorded.</div></div><div><h3>Conclusions</h3><div>Apixaban appeared safe and effective as thromboprophylaxis in this paediatric cardiology cohort, with no major or CRNMB and a low rate of thrombotic events. These findings add to the growing body of real-world evidence supporting DOAC use in children with cardiac disease.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"266 ","pages":"Article 109893"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to the Letter to the Editor regarding “Comparing perioperative heparin bridging strategies in mechanical heart valve patients undergoing surgery: A systematic review and Bayesian meta-analysis”","authors":"Pedro Gomes Batista,&nbsp;Marcela Vasconcelos Montenegro,&nbsp;Giulia Caldeira Gaelzer,&nbsp;Maria Eduarda Molinari,&nbsp;Mushrin Malik,&nbsp;Railla Raquel Albino dos Santos Silva,&nbsp;Larissa Araujo de Lucena,&nbsp;Caroline O. Fischer Bacca,&nbsp;Juliana Giorgi","doi":"10.1016/j.thromres.2026.109843","DOIUrl":"10.1016/j.thromres.2026.109843","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"266 ","pages":"Article 109843"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082227","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":"Complement activation characterizes a high mortality subgroup in pulmonary embolism: An observational proteomic study","authors":"Annelie Barrueta Tenhunen,&nbsp;Oskar Eriksson,&nbsp;Bo Nilsson,&nbsp;Asanda Mazubane,&nbsp;Kazal Hawez,&nbsp;Miklos Lipcsey,&nbsp;Anders Larsson,&nbsp;Mikael Åberg,&nbsp;Gerhard Wikström,&nbsp;Michael Marks-Hultström","doi":"10.1016/j.thromres.2026.109870","DOIUrl":"10.1016/j.thromres.2026.109870","url":null,"abstract":"<div><h3>Background</h3><div>Complement and coagulation pathways are mechanistically linked in thromboinflammation, yet the contribution of complement activation to pulmonary embolism (PE) pathophysiology and risk stratification remains largely unexplored. We used plasma proteomics and functional assays to identify thromboinflammatory endotypes in patients with suspected PE.</div></div><div><h3>Methods</h3><div>We enrolled 196 patients referred for CT pulmonary angiography at Uppsala University Hospital (2019–2022). Plasma was analyzed using the Olink Explore 384 Inflammation II panel. Differentially expressed proteins (PE vs no-PE) were used for supervised feature selection, followed by unsupervised clustering to define diagnostic clusters in all patients and prognostic endotypes in confirmed PE cases. Complement and coagulation activation were validated using functional assays.</div></div><div><h3>Results</h3><div>Eighty-nine patients (45%) had confirmed PE. Twenty-one proteins differed between PE and non-PE (FDR &lt; 0.05), including complement C9 (log2FC 0.53, FDR 2.7 × 10⁻⁵), associated with increased soluble C5b-9 (sC5b-9) supporting terminal complement activation. Three diagnostic clusters were identified; the PE-enriched cluster showed higher mortality and evidence of complement and coagulation activation (increased sC5b-9 and thrombin-antithrombin complexes), with intermediate native complement protein levels consistent with consumption. Among confirmed PE cases, three prognostic endotypes emerged, including a high-mortality cluster (50% one-year mortality) with reduced complement protein levels, without parallel increase in functional activation markers.</div></div><div><h3>Conclusions</h3><div>Targeted proteomic profiling identified elevated terminal complement C9 in PE, and evidence of complement and coagulation activation, alongside reduced native complement levels. Complement protein levels were also reduced in the high-mortality prognostic endotype. These findings support proteomic endotyping as a biologically informative approach to PE risk stratification.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"266 ","pages":"Article 109870"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A survey on the current clinical practices among obstetricians for the management of venous thromboembolism prevention in various hospitals in China","authors":"Hongwei Ma,&nbsp;Yuanyuan Hu,&nbsp;Jie Ruan,&nbsp;Xinghui Liu","doi":"10.1016/j.thromres.2026.109807","DOIUrl":"10.1016/j.thromres.2026.109807","url":null,"abstract":"<div><h3>Background</h3><div>Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is one of the major causes of mortality in pregnant women. Clinical practices followed by obstetricians in different hospitals might influence the incidence and prevalence rates of VTE. This obstetrician-based survey was conducted to understand the establishment of VTE prevention and treatment system and its current scenario in various hospitals for preventing VTE during pregnancy.</div></div><div><h3>Objectives</h3><div>An obstetrician-based survey was conducted to understand the establishment of VTE prevention and treatment system during pregnancy and its current scenario in various hospitals across China.</div></div><div><h3>Methods</h3><div>A questionnaire-based survey was conducted among 1128 obstetricians from July 1 to 312,024 in 22 provinces, 5 autonomous regions and 4 municipalities across China. Responses on hospital infrastructure (grade, type, resource allocation) with respect to VTE management, VTE prevention and treatment system establishment, and health education was collected. The data was analyzed by using R software and <em>P</em> value of &lt;0.05 was considered significant.</div></div><div><h3>Results</h3><div>Ultrasonography of the lower extremity veins was not performed in 11.89% of the hospitals, while the unavailability of computed tomographic pulmonary angiography (CTPA) and pulmonary ventilation/perfusion (V/Q) scintigraphy was reported in over 50% and 80% of the hospitals, respectively. Tertiary hospitals outperformed primary and secondary hospitals in all VTE prevention system indicators (<em>P</em> &lt; 0.001), and general hospitals surpassed specialized hospitals in multiple aspects (<em>P</em> &lt; 0.05). Only 67.1% of physicians performed VTE risk assessment on all pregnant women, with significant disparities by hospital level (<em>P</em> &lt; 0.001). VTE patient education was not universal and varied significantly by hospital level (<em>P</em> &lt; 0.001), being most comprehensive in tertiary hospitals.</div></div><div><h3>Conclusion</h3><div>VTE prevention and treatment infrastructure in some Chinese hospitals are insufficient. The survey identified gaps between the clinical practice of obstetricians and national/international guidelines or consensus requirements. Following uniform clinical practices across the different hospital settings would help to improve VTE prevention in pregnant women in China.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"265 ","pages":"Article 109807"},"PeriodicalIF":3.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adherence and satisfaction with prophylactic low molecular weight heparin (LMWH) after orthopaedic trauma: A commentary on Horzum et al","authors":"Nicole Namath,&nbsp;Kenichi A. Tanaka,&nbsp;Kenneth E. Stewart","doi":"10.1016/j.thromres.2026.109806","DOIUrl":"10.1016/j.thromres.2026.109806","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"265 ","pages":"Article 109806"},"PeriodicalIF":3.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851656","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":"Letter to the editors: “Impact of aetiology and liver stiffness on thrombin generation in compensated cirrhosis”: Reply to the comments from Alhamami et al.","authors":"Maxime G. Zermatten,&nbsp;Cindy Pereira Portela,&nbsp;Debora Bertaggi Calderara,&nbsp;Alessandro Aliotta,&nbsp;Élise Mdawar-Bailly,&nbsp;Darius Moradpour,&nbsp;Lorenzo Alberio,&nbsp;Montserrat Fraga","doi":"10.1016/j.thromres.2026.109800","DOIUrl":"10.1016/j.thromres.2026.109800","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"265 ","pages":"Article 109800"},"PeriodicalIF":3.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851606","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":"ReSTORE-PE (Rehabilitation to Support Total Recovery after Pulmonary Embolism): Development of a co-designed rehabilitation programme for post–pulmonary embolism syndrome","authors":"Caoimhe Kenny,&nbsp;Fiona Curran,&nbsp;Frederikus A. Klok,&nbsp;Olive Lennon,&nbsp;James Matthews,&nbsp;Fionnuala Ni Ainle,&nbsp;Rachel P. Rosovsky,&nbsp;Grainne O'Donoghue","doi":"10.1016/j.thromres.2026.109829","DOIUrl":"10.1016/j.thromres.2026.109829","url":null,"abstract":"<div><h3>Introduction</h3><div>Approximately 50% of pulmonary embolism (PE) survivors experience persistent physical and psychological symptoms consistent with post-pulmonary embolism syndrome (PPES), negatively affecting quality of life, functional recovery, and engagement in healthy lifestyle behaviours. Although rehabilitation is recommended following PE, limited evidence exists to guide intervention design for this population.</div></div><div><h3>Aim</h3><div>To develop a rehabilitation programme prototype to support physical and psychological recovery in individuals living with PPES using a theory-informed co-design process.</div></div><div><h3>Methods</h3><div>Intervention development followed the United Kingdom Medical Research Council framework and incorporated the Behaviour Change Wheel, Theoretical Domains Framework (TDF), Behaviour Change Techniques Ontology, Behaviour Change Intervention Ontology, and Theory and Techniques Tool. A three-stage co-design process was undertaken: (1) behavioural analysis, (2) selection of intervention components, and (3) refinement of the intervention prototype. Development was informed by two reviews, semi-structured interviews with people living with PPES (<em>n</em> = 31), and three co-design workshops involving people living with PPES (<em>n</em> = 5), clinicians, and academics (<em>n</em> = 8).</div></div><div><h3>Results</h3><div>Behavioural analysis identified all 14 TDF domains, with key determinants including knowledge, beliefs about capabilities, emotion, environmental context, and social influences. These were mapped to eight intervention functions and more than 50 behaviour change techniques. Strongest evidence supported goal setting, self-monitoring, feedback, action planning, and graded tasks. A clinician-led, community-based rehabilitation programme was developed, integrating supervised exercise, education, psychological support, and self-management training.</div></div><div><h3>Conclusion</h3><div><em>ReSTORE-PE</em> is a theory-informed, co-designed rehabilitation programme for people living with PPES that is ready for feasibility and acceptability testing. The transparent development process supports future implementation, evaluation, and replication.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"265 ","pages":"Article 109829"},"PeriodicalIF":3.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931171","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":"Letter: In response to a recent letter by Kane et al.","authors":"Kamiyu Ii,&nbsp;Ryo Hisamune,&nbsp;Masafumi Nii,&nbsp;Tomoaki Oda,&nbsp;Kazuma Yamakawa","doi":"10.1016/j.thromres.2026.109825","DOIUrl":"10.1016/j.thromres.2026.109825","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"265 ","pages":"Article 109825"},"PeriodicalIF":3.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148937231","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}