Journal of Thrombosis and Haemostasis最新文献

{"title":"Carbon tetrachloride (CCl4)-induced liver injury activates hepatocyte-independent tissue factor-driven coagulation","authors":"Amish K. Patel,&nbsp;Gina E. Capece,&nbsp;Bianca Hazel,&nbsp;Tayana Roychowdhury,&nbsp;Noah A. Mac,&nbsp;Daniel Hu,&nbsp;Kevin S. Baker,&nbsp;Maria T. Fernandes-Fonseca,&nbsp;Zimu Wei,&nbsp;Ana T.A. Sachetto,&nbsp;Michael J. Goedken,&nbsp;James P. Luyendyk,&nbsp;Nigel Mackman,&nbsp;Lauren G. Poole","doi":"10.1016/j.jtha.2026.07.017","DOIUrl":"10.1016/j.jtha.2026.07.017","url":null,"abstract":"<div><h3>Background</h3><div>Liver injury is associated with activation of the blood coagulation cascade. Hepatocytes express low levels of tissue factor (TF), the transmembrane receptor and cofactor for coagulation factor VIIa (FVIIa). The TF-FVIIa complex activates the extrinsic coagulation pathway and plays an essential role in hemostasis.</div></div><div><h3>Objectives</h3><div>This study tested the hypothesis that hepatocyte TF drives coagulation activation after toxicant-induced liver injury.</div></div><div><h3>Methods</h3><div>Wild-type mice, mice with whole-body TF deficiency (LowTF), and mice lacking TF specifically in hepatocytes (HPC^ΔTF) were challenged once with carbon tetrachloride (CCl₄, 1 mL/kg, intraperitoneally). Liver injury and coagulation parameters were evaluated 2 to 96 hours after challenge. In separate studies, mice were challenged twice weekly for 4 to 6 weeks, and samples were collected 24 to 72 hours after the final challenge.</div></div><div><h3>Results</h3><div>Acute CCl₄ challenge caused hepatic injury and robust coagulation activation. Whole-body TF deficiency significantly reduced coagulation activation and attenuated peak hepatocellular necrosis, whereas hepatocyte TF deficiency had no effect on coagulation activation or acute liver injury. <em>In situ</em> hybridization identified cells in inflammatory foci expressing TF (<em>F3</em>) transcripts in the necrotic region of the CCl₄-challenged liver. After chronic CCl₄ challenge, whole-body TF deficiency significantly reduced coagulation activation and modestly decreased fibrosis by means of reduced hepatic stellate cell activation, but hepatocyte TF deficiency did not affect coagulation activation or liver fibrosis.</div></div><div><h3>Conclusion</h3><div>These data suggest that TF-expressing nonparenchymal cells mediate coagulation activation during CCl₄-induced liver injury. Our findings provide the foundation for future work to identify TF-expressing cell types and their underlying contributions to liver injury pathogenesis.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 10","pages":"Pages 3687-3701"},"PeriodicalIF":5.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584710","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":"Development of a new disseminated intravascular coagulation score tailored for patients with chronic liver disease: a prospective observational study","authors":"Ecaterina Scarlatescu,&nbsp;Ton Lisman","doi":"10.1016/j.jtha.2026.05.024","DOIUrl":"10.1016/j.jtha.2026.05.024","url":null,"abstract":"<div><h3>Background</h3><div>Diagnosing disseminated intravascular coagulation (DIC) in patients with chronic liver disease is challenging because cirrhosis-related hemostatic abnormalities mimic DIC laboratory features, leading to frequent overdiagnosis using conventional DIC scoring systems.</div></div><div><h3>Objectives</h3><div>This study aimed to evaluate the performance of existing DIC scores in patients with cirrhosis and develop a tailored diagnostic prediction tool.</div></div><div><h3>Methods</h3><div>We prospectively enrolled 80 consecutive patients with cirrhosis admitted to a single intensive care unit. Clinical manifestations of DIC, conventional DIC scores, routine hemostatic parameters, and advanced coagulation biomarkers were assessed. Machine learning techniques combining random forest, logistic regression, and extreme gradient boosting with the Synthetic Minority Oversampling Technique were used to develop a DIC prediction model using 4 routinely available parameters: chronic liver failure—sequential organ failure assessment score, platelet count, fibrinogen, and D-dimer levels.</div></div><div><h3>Results</h3><div>Conventional DIC scores (the International Society on Thrombosis and Haemostasis, the Japanese Association for Acute Medicine, and the Japanese Ministry of Health, Labour, and Welfare) were positive in &gt;50% of patients at study inclusion despite only 1.3% having clinical DIC manifestations, demonstrating substantial overdiagnosis. During follow-up, 10 patients (12.5%) developed clinical DIC with 90% mortality, while positive DIC scores did not predict outcomes. The newly developed ensemble prediction model achieved 100% sensitivity and 87% specificity, accurately discriminating clinical DIC from cirrhosis-related hemostatic abnormalities. Coagulation activation marker levels were elevated universally, while progressive fibrin monomer level depletion distinguished overt DIC from compensated hemostatic imbalance.</div></div><div><h3>Conclusion</h3><div>The proposed prediction tool showed excellent internal performance in identifying DIC risk in patients with cirrhosis using readily available parameters, and its implementation in a freely accessible web-based application may facilitate future clinical use after external validation.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 10","pages":"Pages 3474-3488"},"PeriodicalIF":5.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148150166","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":"Transfer of emicizumab into breast milk in postpartum acquired hemophilia A","authors":"Simon Alexander Krooss,&nbsp;Tim Halling,&nbsp;Dirk Varnholt,&nbsp;Annika Klingberg,&nbsp;Korbinian Brand,&nbsp;Sonja Werwitzke,&nbsp;Heiner Wedemeyer,&nbsp;Christiane Dobbelstein,&nbsp;Andreas Tiede,&nbsp;Olga Oleshko","doi":"10.1016/j.jtha.2026.07.001","DOIUrl":"10.1016/j.jtha.2026.07.001","url":null,"abstract":"<div><h3>Background</h3><div>Acquired hemophilia A (AHA) is a rare, potentially life-threatening autoimmune bleeding disorder caused by neutralizing autoantibodies against factor (F)VIII. The postpartum period is a recognized risk factor for AHA. Emicizumab is increasingly used for hemostatic prophylaxis in AHA, including in women who may wish to continue breastfeeding. However, data on transfer of emicizumab into breast milk are lacking. This limits evidence-based counseling and shared decision-making.</div></div><div><h3>Objective</h3><div>To assess whether emicizumab is detectable in the breast milk of a patient with postpartum AHA.</div></div><div><h3>Methods</h3><div>Plasma and breast milk samples were collected from a woman who developed AHA 4 months after delivery and was treated with emicizumab while breastfeeding. Samples were analyzed for emicizumab using a modified one-stage clot assay and for anti-FVIII immunoglobulin (Ig)G and IgA antibodies using immunoassays.</div></div><div><h3>Results</h3><div>Emicizumab was measurable in breast milk shortly after treatment initiation and reached concentrations of up to 20 μg/mL. The steady-state plasma concentration of emicizumab was 42 μg/mL. Anti-FVIII IgG and IgA were detected in plasma but not in breast milk samples.</div></div><div><h3>Conclusion</h3><div>In this patient with postpartum AHA, emicizumab was detectable in breast milk, whereas FVIII inhibitors were not. These findings are relevant for counseling breastfeeding women receiving emicizumab. Further studies are needed to determine the extent and clinical relevance of infant exposure.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 10","pages":"Pages 3531-3537"},"PeriodicalIF":5.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148404114","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":"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}