Journal of Thrombosis and Haemostasis最新文献

{"title":"Association of fibrinogen γ’ with recurrent thrombosis: a nested case-control study","authors":"Nora Arvesen,&nbsp;Else-Marie Bladbjerg,&nbsp;Nadja Bødker Pedersen,&nbsp;Gabriele Berg-Beckhoff,&nbsp;Moniek P.M. de Maat,&nbsp;Søren Paaske Johnsen,&nbsp;Anna-Marie Bloch Münster","doi":"10.1016/j.jtha.2026.07.012","DOIUrl":"10.1016/j.jtha.2026.07.012","url":null,"abstract":"<div><h3>Background</h3><div>Fibrinogen γ’ is a natural variant of the fibrinogen γ chain, accounting for 10% to 15% of fibrinogen in human blood. Studies have found an association between fibrinogen γ’ plasma levels and the risk of first-time arterial and venous thrombosis, but how fibrinogen γ’ associates with recurrent thrombosis is unknown.</div></div><div><h3>Objectives</h3><div>To investigate the association between fibrinogen γ’ levels and recurrent thrombosis in patients previously diagnosed with arterial or venous events.</div></div><div><h3>Methods</h3><div>We conducted a nested case-control study of 265 patients who experienced arterial or venous thrombosis between 1995 and 2013. Patients were followed prospectively until recurrent thrombosis; we identified 113 cases (with recurrence) and 152 controls (without recurrence) matched for sex, age, and date of blood sampling. Baseline plasma fibrinogen γ’ levels were compared between cases and controls. We used logistic regression to determine the association between fibrinogen γ’ levels and the risk of recurrent thrombosis.</div></div><div><h3>Results</h3><div>In the arterial group, cases had higher absolute and relative fibrinogen γ’ levels (<em>P</em> &lt; .01). Absolute increases of 50 μg/mL or relative increases of 5% were associated with odds ratios of recurrent thrombosis of 1.11 (95% CI, 1.00, 1.16; <em>P</em> &lt; .01) and 1.31 (95% CI, 1.06, 1.63; <em>P</em> &lt; .05), respectively. In the venous group, relative fibrinogen γ’ levels tended to be lower in cases (<em>P</em> = .07) and were associated with a lower risk of recurrent thrombosis (odds ratio, 0.82; 95% CI, 0.62, 1.08).</div></div><div><h3>Conclusion</h3><div>In the arterial group, absolute and relative fibrinogen γ’ levels were positively associated with the risk of recurrent thrombosis. In the venous group, relative fibrinogen γ’ levels and recurrent thrombosis were inversely associated, but not significant.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 10","pages":"Pages 3679-3686"},"PeriodicalIF":5.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extended anticoagulation with edoxaban in chronic thromboembolic pulmonary hypertension: reassuring real-world data, but can direct oral anticoagulants systematically replace vitamin K antagonists?","authors":"Laurent Bertoletti,&nbsp;Céline Chapelle","doi":"10.1016/j.jtha.2026.07.022","DOIUrl":"10.1016/j.jtha.2026.07.022","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 10","pages":"Pages 3450-3452"},"PeriodicalIF":5.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149078491","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":"Translating molecular thrombus imaging into clinical practice: scientific promise, practical barriers, and pragmatic solutions","authors":"Yimin Li,&nbsp;James D. McFadyen,&nbsp;Karlheinz Peter","doi":"10.1016/j.jtha.2026.07.014","DOIUrl":"10.1016/j.jtha.2026.07.014","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 10","pages":"Pages 3432-3437"},"PeriodicalIF":5.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149078537","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":"Low temperature, air pollutants, and onset of pulmonary embolism","authors":"Pier Mannuccio Mannucci,&nbsp;Jecko Thachil","doi":"10.1016/j.jtha.2026.07.002","DOIUrl":"10.1016/j.jtha.2026.07.002","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 10","pages":"Pages 3443-3445"},"PeriodicalIF":5.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149078540","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":"Peptide-mediated inhibition of surface-initiated thrombogenesis","authors":"Adam Hansen,&nbsp;Bernard Essuman,&nbsp;Georgios Kementzidis,&nbsp;Nabila Jaman Tripti,&nbsp;Fubao Lin,&nbsp;Volodymyr Chernyshenko,&nbsp;Richard A.F. Clark,&nbsp;Yuefan Deng,&nbsp;Miriam Rafailovich,&nbsp;Dennis K. Galanakis","doi":"10.1016/j.jtha.2026.06.029","DOIUrl":"10.1016/j.jtha.2026.06.029","url":null,"abstract":"<div><h3>Background</h3><div>Surface-induced fibrinogen misfolding drives thrombogenesis at hydrophobic material interfaces, as demonstrated in our prior mechanistic model. Extending this concept to pathophysiological settings, viral infection creates a clinically relevant prothrombotic environment by promoting lipid droplet release and elevating circulating fibrinogen levels, generating vascular interfaces that favor aberrant fibrin assembly. Targeted peptide inhibitors may provide a selective strategy to interrupt this surface-mediated process. P12, a fibronectin-derived peptide previously shown to attenuate burn progression, is a promising candidate for modulating surface-driven thrombogenesis.</div></div><div><h3>Objectives</h3><div>To evaluate whether P12 disrupts surface-initiated thrombogenesis on biomaterial surfaces and prothrombotic endothelium and to define its mechanism of action.</div></div><div><h3>Methods</h3><div>P12–fibrin(ogen) interactions were assessed by immunofluorescence and supported by molecular dynamics simulations. Effects on fibrin(ogen) assembly, from molecular interactions to macroscopic clot formation, were analyzed using complementary multiscale microscopy techniques.</div></div><div><h3>Results</h3><div>P12 selectively bound fibrin(ogen) within the αC-domain, specifically the N-terminal subdomain (Aα392-503), with preferential interaction spanning residues Aα476-496. Binding inhibited intermolecular interactions among surface-bound fibrin(ogen) and disrupted protofibril formation, thereby limiting fibrin assembly. P12 also bound soluble fibrin, reducing both its surface adsorption and ability to aggregate into fibers. Consistent with these effects, platelet accumulation was markedly reduced and thrombogenesis suppressed. Importantly, these inhibitory effects were preserved in a pathological context involving viral infection.</div></div><div><h3>Conclusion</h3><div>A targeted peptide can effectively inhibit surface-initiated thrombogenesis without directly impairing physiological clotting mechanisms. These findings support the translational potential of P12 for treating pathological thrombosis and inform the rational design of antithrombotic surfaces and therapeutics.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 10","pages":"Pages 3588-3602"},"PeriodicalIF":5.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148339024","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 natural mutation Arg221aTrp in human α-thrombin abrogates physiological Na+ binding and preferentially hinders the protease anticoagulant functions","authors":"Laura Acquasaliente,&nbsp;Andrea Pierangelini,&nbsp;Federico Uliana,&nbsp;Anna Pagotto,&nbsp;Alberto Covallero,&nbsp;Daniele Peterle,&nbsp;Serena Toffanin,&nbsp;Cristiana Bulato,&nbsp;Elena Campello,&nbsp;Antonella Ciancetta,&nbsp;Paolo Simioni,&nbsp;Vincenzo De Filippis","doi":"10.1016/j.jtha.2026.06.033","DOIUrl":"10.1016/j.jtha.2026.06.033","url":null,"abstract":"<div><h3>Background</h3><div>Natural mutations in the prothrombin gene, involving the substitution of Arg596 with polar/apolar amino acids, represent an important risk factor for thrombosis. Notably, Arg596 in prothrombin corresponds to position 221a in the Na⁺-binding loop of mature α-thrombin (αT). Patients carrying these mutations (Arg221a→Gln/Leu/Trp) share a common clinical phenotype, characterized by a moderately reduced procoagulant function in coagulation tests and resistance of αT variants to inactivation by antithrombin III (ATIII). However, the biochemical mechanisms linking these mutations to the increased thrombotic risk remain elusive.</div></div><div><h3>Objectives</h3><div>To provide quantitative data on the effect that the recombinant Arg221aTrp αT mutant (αT-PD2) has on the activation of procoagulant and anticoagulant pathways and elucidate the structural basis of the observed functional changes.</div></div><div><h3>Methods</h3><div>A multipronged approach was used, integrating recombinant DNA techniques, clotting/fibrinolytic and enzymatic assays, microscopy, proteomics, spectroscopic, mass spectrometry, and molecular modeling techniques.</div></div><div><h3>Results</h3><div>Arg221aTrp mutation abrogates physiological Na⁺ binding and reduces the proportion of the fully active αT conformation. αT-PD2 affects procoagulant pathways by less efficiently generating fibrin (7-fold) and activating platelets (10-fold). The mutation potently affects anticoagulant pathways, as αT-PD2 is less efficiently inhibited by ATIII (3-fold), binds heparin less tightly (10-fold), and much less efficiently (41-fold) activates protein C.</div></div><div><h3>Conclusion</h3><div>Our data indicate that the procoagulant phenotype, observed in Arg221aTrp mutation carriers, may result from opposing inhibitory effects on both procoagulant and anticoagulant pathways, with the impact on anticoagulant pathways being predominant and shifting the natural anticoagulant↔procoagulant equilibrium <em>in vivo</em> toward thrombosis.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 10","pages":"Pages 3603-3618"},"PeriodicalIF":5.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148352342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relapsed/refractory immune thrombocytopenia—moving past the toxicity profile of spleen tyrosine kinase inhibitors with TQB3473","authors":"Surbhi Shah","doi":"10.1016/j.jtha.2026.07.021","DOIUrl":"10.1016/j.jtha.2026.07.021","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 10","pages":"Pages 3453-3454"},"PeriodicalIF":5.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149078492","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":"TQB3473, a novel spleen tyrosine kinase inhibitor for primary immune thrombocytopenia: a single-arm, open-label, multicenter phase 1 study","authors":"Bingjie Ding,&nbsp;Tiejun Gong,&nbsp;Xiangzhou Du,&nbsp;Xiaoming Li,&nbsp;Yinghui Lai,&nbsp;Zhenyu Yan,&nbsp;Rong Fu,&nbsp;Xin Du,&nbsp;Anqi Yang,&nbsp;Jiajia Zhu,&nbsp;Yiran Wang,&nbsp;Hu Zhou","doi":"10.1016/j.jtha.2026.04.012","DOIUrl":"10.1016/j.jtha.2026.04.012","url":null,"abstract":"<div><h3>Background</h3><div>Effective treatments for relapsed/refractory immune thrombocytopenia (ITP) remain limited.</div></div><div><h3>Objectives</h3><div>TQB3473, a novel oral spleen tyrosine kinase inhibitor, was evaluated to address this unmet need.</div></div><div><h3>Methods</h3><div>This phase 1 study enrolled patients aged 18 to 75 years with relapsed/refractory ITP from 6 centers in China. Patients received oral TQB3473 (400, 600, or 800 mg once daily) for 24 weeks during the dose escalation and expansion phases. The primary endpoints were safety and determination of the recommended phase 2 dose.</div></div><div><h3>Results</h3><div>The overall response rate (platelet count ≥ 50 × 10⁹/L at least once within 12 weeks) was 56.8%. Response rates were 0% (400 mg), 60.7% (600 mg), and 66.7% (800 mg). The durable response rate (platelet count ≥ 50 × 10⁹/L in ≥4 of the last 6 visits within 14-24 weeks) was 25% with a 600 mg dose. Treatment-related adverse events occurred in 72.9% of patients and were mostly grade 1 to 2. The most frequent treatment-related adverse events in the 600 mg cohort were increased lactate dehydrogenase (32.1%), increased aspartate aminotransferase (28.6%), increased alanine aminotransferase (25.0%), and hypertriglyceridemia (21.4%). Hypertension (3.6%) and gastrointestinal toxicity were infrequent. No thrombotic events or deaths were reported. Based on a favorable benefit-risk profile, including a longer response duration and better tolerability, 600 mg once daily was established as the recommended phase 2 dose.</div></div><div><h3>Conclusion</h3><div>The promising efficacy and favorable safety profile of TQB3473, particularly its minimal hypertension and gastrointestinal toxicity, support 600 mg once daily as the recommended dose and underscore its potential as a new treatment option for relapsed/refractory ITP, a premise currently under evaluation in a phase 3 trial.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 10","pages":"Pages 3711-3722"},"PeriodicalIF":5.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prepartum acquired hemophilia A: managing a double challenge for mother and child","authors":"Audrey Hochart,&nbsp;Bénédicte Wibaut,&nbsp;Louis Terriou,&nbsp;Benoit Guillet,&nbsp;Nicolas Belhomme,&nbsp;Nicolas Schleinitz,&nbsp;Mélanie Y. Daniel,&nbsp;Sophie Susen,&nbsp;Annabelle Dupont,&nbsp;Sophie Bayart,&nbsp;Céline Falaise,&nbsp;Audrey F. Petit","doi":"10.1016/j.jtha.2026.07.004","DOIUrl":"10.1016/j.jtha.2026.07.004","url":null,"abstract":"<div><div>Acquired hemophilia A during pregnancy is exceptionally rare and poses significant risks to both mother and fetus, including maternal hemorrhage and neonatal bleeding due to transplacental transfer of factor (F)VIII inhibitors. We report four cases of antenatally diagnosed acquired hemophilia A to provide insights into management and outcomes. All patients received corticosteroids during pregnancy, with individualized peripartum hemostatic strategies using bypassing agents when indicated. Transplacental FVIII inhibitor transfer occurred in three neonates, leading to transient low FVIII levels; only one mild bleeding event was observed, and all infants achieved spontaneous remission within weeks. Postpartum escalation of immunosuppressive therapy, including rituximab, was required in selected mothers to achieve remission. Our series highlights the critical importance of prepartum diagnosis, allowing optimized maternal hemostatic management, avoidance of traumatic delivery, and structured neonatal surveillance to prevent severe bleeding complications.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 10","pages":"Pages 3538-3543"},"PeriodicalIF":5.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422116","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":"Joint effect of muscle strength and physical inactivity on risk of incident venous thromboembolism: the Tromsø Study","authors":"Oda G.R. Leknessund,&nbsp;John-Bjarne Hansen,&nbsp;Sigrid K. Brækkan","doi":"10.1016/j.jtha.2026.06.037","DOIUrl":"10.1016/j.jtha.2026.06.037","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 10","pages":"Pages 3797-3800"},"PeriodicalIF":5.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387837","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}