Journal of Thrombosis and Haemostasis最新文献

{"title":"Bleeding risk prediction models in varied clinical scenarios","authors":"Mark Goldin , Ermioni Oikonomou , Alex C. Spyropoulos","doi":"10.1016/j.jtha.2025.10.010","DOIUrl":"10.1016/j.jtha.2025.10.010","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 2","pages":"Pages 368-371"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102417","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":"Reduced vs full-dose direct oral anticoagulants for extended treatment of cancer-associated venous thromboembolism: a systematic review and meta-analysis of randomized trials","authors":"Larissa A. de Lucena ,&nbsp;Amanda G. Duarte ,&nbsp;Larissa C. Hespanhol ,&nbsp;Juliana Muniz ,&nbsp;Nicole Félix ,&nbsp;Kleyton Medeiros ,&nbsp;C. Michael Gibson","doi":"10.1016/j.jtha.2025.09.026","DOIUrl":"10.1016/j.jtha.2025.09.026","url":null,"abstract":"<div><h3>Background</h3><div>Patients with cancer-associated venous thromboembolism (VTE) are at high risk of recurrent thrombosis and bleeding during prolonged anticoagulation. While full-dose direct oral anticoagulants (DOACs) are widely used, the safety and efficacy of reduced-dose regimens for extended treatment remain uncertain.</div></div><div><h3>Objectives</h3><div>This study compared the safety and efficacy of reduced-dose vs full-dose DOACs in the extended treatment of cancer-associated VTE.</div></div><div><h3>Methods</h3><div>We conducted a systematic review and meta-analysis of randomized controlled trials comparing reduced- and full-dose DOACs in adults with active cancer and VTE. Searches were performed in PubMed, Embase, and the Cochrane Library. The primary outcomes were a composite of VTE recurrence, major bleeding, or clinically relevant nonmajor bleeding, and the combined risk of major or clinically relevant nonmajor bleeding.</div></div><div><h3>Results</h3><div>Three randomized controlled trials comprising 2361 patients were included. Two trials evaluated apixaban 2.5 mg vs 5 mg twice daily, and 1 evaluated rivaroxaban 10 mg vs 20 mg once daily. Reduced-dose DOACs were associated with a lower risk of the composite outcome (relative risk, 0.77; 95% CI, 0.64-0.93; <em>P</em> = .006) and reduced bleeding (relative risk, 0.76; 95% CI, 0.62-0.93; <em>P</em> = .008) than full-dose DOACs. No significant differences were observed in major bleeding, clinically relevant nonmajor bleeding, VTE recurrence, or all-cause mortality when analyzed individually.</div></div><div><h3>Conclusions</h3><div>Reduced-dose DOACs appear as effective as full-dose regimens for extended treatment of cancer-associated VTE, with a lower risk of bleeding. These findings support their use as a safer long-term anticoagulation strategy in selected patients.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 2","pages":"Pages 573-582"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318393","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":"Lipoprotein(a) prolongs ex vivo plasma clot lysis times through effects on clot formation rate and fibrin structure","authors":"Justin R. Clark ,&nbsp;Frances S. Sutherland ,&nbsp;Julia M. Assini ,&nbsp;Luke Daichedt ,&nbsp;Robert Szabla ,&nbsp;Murray W. Junop ,&nbsp;Marlys L. Koschinsky ,&nbsp;Michael B. Boffa","doi":"10.1016/j.jtha.2025.10.009","DOIUrl":"10.1016/j.jtha.2025.10.009","url":null,"abstract":"<div><h3>Background</h3><div>Elevated levels of lipoprotein(a) (Lp[a]) are a causal risk factor for atherosclerotic cardiovascular disease. Similarities between the apolipoprotein(a) (apo[a]) component of Lp(a) and plasminogen suggest that antifibrinolytic properties may account for the pathological effects of Lp(a). However, the antifibrinolytic effects of apo(a) do not appear to be retained by the complete Lp(a) particle.</div></div><div><h3>Objectives</h3><div>We evaluated the effects of Lp(a), apo(a), and various apo(a) variants on clot formation and lysis times, thrombin generation, plasminogen activation, and fibrin architectures in <em>ex vivo</em> plasma clots. We also constructed predictive protein models to gain insight into the apo(a)-plasminogen interaction.</div></div><div><h3>Results</h3><div>Apo(a) strongly inhibited fibrinolysis, an effect dependent on the presence of the apo(a) protease domain and mediated by Lys216 in this domain. Modeling of apo(a) suggests that Lys216 is blocked from binding to plasminogen in the Lp(a) particle by the presence of the apoB-containing lipoprotein. Lp(a) and apo(a) shortened plasma clot formation times, and accounting for this revealed a small but significant prolongation of fibrinolysis by Lp(a). The procoagulant effects involved the development of lysis-resistant clot architectures and were mediated through the strong lysine-binding site in apo(a) kringle IV type 10. In addition, Lp(a) (but not apo[a]) accelerated thrombin generation.</div></div><div><h3>Conclusions</h3><div>The strong antifibrinolytic effects of apo(a) do not appear to be retained in the complete Lp(a) particle. However, Lp(a) and apo(a) displayed procoagulant effects, in part dependent on the kringle 4–like lysine-binding site. Further analysis is required to determine whether these reported procoagulant effects of Lp(a) impact thrombosis <em>in vivo</em>.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 2","pages":"Pages 701-715"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145431440","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":"Higher citrullinated histone H3 is associated with postthrombotic syndrome: a cohort study","authors":"Julia Krupa-Zabiegała ,&nbsp;Patryk Stanisław Michel ,&nbsp;Konrad Stępień ,&nbsp;Maciej Polak ,&nbsp;Joanna Natorska ,&nbsp;Anetta Undas","doi":"10.1016/j.jtha.2025.10.013","DOIUrl":"10.1016/j.jtha.2025.10.013","url":null,"abstract":"<div><h3>Background</h3><div>Postthrombotic syndrome (PTS) is a serious complication of deep vein thrombosis (DVT), linked to persistent inflammation and impaired thrombus resolution. Enhanced formation of neutrophil extracellular traps (NETs) is involved in DVT pathogenesis.</div></div><div><h3>Objectives</h3><div>We investigated whether increased NET formation, associated with an unfavorable fibrin clot phenotype, predisposes to the development of PTS.</div></div><div><h3>Methods</h3><div>We studied 179 patients with DVT. Three months after diagnosis and initiation of anticoagulant therapy, citrullinated histone H3 (H3cit), thrombin generation, clot permeability, clot lysis time, and inflammatory markers were measured. PTS severity was assessed at 12 to 14 months by the Villalta score. During a median 53-month follow-up, we recorded recurrent venous thromboembolism and venous ulcers.</div></div><div><h3>Results</h3><div>Patients with PTS (<em>n</em> = 43, 24.0%) had 68.8% higher H3cit levels compared with those without PTS (<em>P</em> &lt; .001). In the whole group, H3cit showed a positive association with Villalta scores (R = .596; <em>P</em> &lt; .001). Higher H3cit was linked to denser fibrin clots (ie, clot permeability; R = −.352; <em>P</em> &lt; .001), slower fibrinolysis (ie, clot lysis time; R = .287; <em>P</em> &lt; .001), and higher interleukin 6 (R = .429; <em>P</em> &lt; .001), but not C-reactive protein or thrombin generation. In multivariable analysis, higher H3cit per 1 ng/mL at 3 months was independently associated with PTS (odds ratio, 5.50; 95% CI, 2.52-12.01). Patients with recurrent venous thromboembolism (<em>n</em> = 43, 24.0%) had 37.8% higher H3cit concentrations compared with those without recurrence (<em>P</em> &lt; .001). Venous ulcer formation was not related to this marker.</div></div><div><h3>Conclusion</h3><div>This study is the first to show that enhanced NET formation following DVT may contribute to PTS and its severe forms, at least in part through unfavorable fibrin clot properties.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 2","pages":"Pages 633-643"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145452089","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":"Potential utility of the new ISTH overt disseminated intravascular coagulation scoring system for mortality risk assessment of patients with sepsis, hematopoietic neoplasms, and solid cancers: a nation-wide database study in Japan","authors":"Akane Shinkai ,&nbsp;Takashi Ito ,&nbsp;Ema Hashiguchi ,&nbsp;Michiko Katsuno ,&nbsp;Yutaka Umemura ,&nbsp;Kazuma Yamakawa ,&nbsp;Kohji Okamoto ,&nbsp;LOCOMOCO Study Group","doi":"10.1016/j.jtha.2025.10.006","DOIUrl":"10.1016/j.jtha.2025.10.006","url":null,"abstract":"<div><h3>Background</h3><div>Disseminated intravascular coagulation (DIC) is characterized by systemic activation of coagulation pathways within the microvasculature, ultimately resulting in multiorgan dysfunction. The International Society on Thrombosis and Haemostasis (ISTH) subcommittee has recently introduced the 2025 overt DIC scoring system for clinical diagnosis.</div></div><div><h3>Objectives</h3><div>This study aimed to evaluate the clinical relevance of the 2025 ISTH overt DIC scoring system and its proposed cutoff values for the mortality risk assessment in patients with diverse underlying diseases.</div></div><div><h3>Methods</h3><div>Patient data were extracted from the Japan Medical Data Center database, focusing on individuals diagnosed with sepsis, hematopoietic neoplasms, or solid cancers. Patients were included only if baseline levels of fibrinogen, platelets, prothrombin time (PT), and fibrin-related markers were available on the day of admission. Restricted cubic spline models were applied to evaluate nonlinear associations between coagulation parameters and in-hospital death.</div></div><div><h3>Results</h3><div>Data from 8181 patients with sepsis, 7548 patients with hematopoietic neoplasms, and 11 614 with solid cancers revealed a marked increase in mortality associated with fibrinogen &lt; 2 g/L, platelets &lt; 100 × 10⁹/L, PT &gt;14 seconds, and D-dimer &gt; 3 mg/L. Among these, PT prolongation and elevated D-dimer demonstrated the strongest associations with mortality. Across all 3 disease groups, in-hospital mortality showed a consistent positive correlation with the ISTH DIC sum score.</div></div><div><h3>Conclusion</h3><div>These findings support the prognostic utility of the 2025 ISTH overt DIC scoring system and its proposed cutoff values in evaluating mortality risk among patients with sepsis, hematopoietic malignancies, and solid cancers.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 2","pages":"Pages 608-617"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145431411","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":"Insights from a genome-wide association study of factor IX activity","authors":"Paul S. de Vries","doi":"10.1016/j.jtha.2025.10.025","DOIUrl":"10.1016/j.jtha.2025.10.025","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 2","pages":"Pages 381-383"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102413","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":"Frail older patients and direct oral anticoagulants: trouble in paradise?","authors":"Fabienne J.H. Magdelijns ,&nbsp;Melanie J. de Jong ,&nbsp;Kristien Winckers ,&nbsp;Dionne C.W. Braeken ,&nbsp;Hugo ten Cate","doi":"10.1016/j.jtha.2025.10.034","DOIUrl":"10.1016/j.jtha.2025.10.034","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 2","pages":"Pages 781-783"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102419","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":"When hydrophobic surfaces rewrite the chorography of fibrinogen","authors":"Lydia Lillian Mireles ,&nbsp;Jason Patrick Flynn ,&nbsp;Mehmet Sen","doi":"10.1016/j.jtha.2025.10.026","DOIUrl":"10.1016/j.jtha.2025.10.026","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 2","pages":"Pages 375-377"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102418","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":"Development and validation of risk models for hospital-acquired bleeding in medical inpatients: the Medical Inpatients Thrombosis and Hemostasis (MITH) study","authors":"Neil A. Zakai ,&nbsp;Katherine Wilkinson ,&nbsp;Andrew D. Sparks ,&nbsp;Ryan T. Packer ,&nbsp;Nicholas S. Roetker ,&nbsp;Allen B. Repp ,&nbsp;Mansour Gergi ,&nbsp;Chris Holmes ,&nbsp;Mary Cushman ,&nbsp;Timothy B. Plante ,&nbsp;Hanny Al-Samkari ,&nbsp;Allyson M. Pishko ,&nbsp;William A. Wood ,&nbsp;Camila Masias ,&nbsp;Radhika Gangaraju ,&nbsp;Ang Li ,&nbsp;David Garcia ,&nbsp;Kerri L. Wiggins ,&nbsp;Jordan K. Schaefer ,&nbsp;Nicholas L. Smith ,&nbsp;Leslie A. McClure","doi":"10.1016/j.jtha.2025.07.007","DOIUrl":"10.1016/j.jtha.2025.07.007","url":null,"abstract":"<div><h3>Background</h3><div>Hospital-acquired (HA) bleeding in medical inpatients is a serious complication with limited tools to predict risk.</div></div><div><h3>Objectives</h3><div>This study aimed to develop and validate risk assessment models (RAMs) for anatomic location-specific HA bleeding in medical inpatients using objective and routinely available risk factors.</div></div><div><h3>Methods</h3><div>Patients aged ≥18 years admitted to medical hospital services from 6 health systems and 15 hospitals in the United States between 2016 and 2020 for at least 1 midnight and without bleeding at admission were eligible for inclusion. Two health systems (10 hospitals) formed the development cohort, and 4 systems (5 hospitals) constituted the validation cohort. Bayesian Least absolute shrinkage and selection operator was used to develop anatomic site-specific RAMs.</div></div><div><h3>Results</h3><div>Among the development (153 707 admissions) and validation (137 460 admissions) cohorts, 5999 (3.9%) and 3282 (2.4%) HA bleeds occurred. RAMs had varied risk factors by anatomic bleeding location; for instance, older age was associated with genitourinary bleeding in men but not in women. Different cancer types were associated with different anatomic bleeding locations such as genitourinary cancers associated with genitourinary bleeding and gynecologic bleeding. The RAMs demonstrated good predictive performance for most anatomical bleeding locations; the C-statistic was ≥0.67 for all anatomic location bleeding in the development and validation cohorts and generally higher in the anatomic location specific RAMs.</div></div><div><h3>Conclusion</h3><div>These RAMs provide anatomic location-specific and sex-specific HA-bleeding risk stratification, addressing a critical gap in individualized risk assessment. Integration into clinical workflows could enhance patient safety and outcomes. Implementation studies are essential to maximize their clinical utility.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 2","pages":"Pages 418-430"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667838","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":"Bleeding risk and performance of bleeding risk assessment models in patients with venous thromboembolism on anticoagulation: results from the prospective observational bleeding and assess long-term outcomes on health in patients with venous thromboembolism (BACH-VTE) study","authors":"Timothy Hoberstorfer ,&nbsp;Stephan Nopp ,&nbsp;Daniel Steiner ,&nbsp;Julia Deinsberger ,&nbsp;Oliver Schlager ,&nbsp;Ingrid Pabinger ,&nbsp;Benedikt Weber ,&nbsp;Cihan Ay","doi":"10.1016/j.jtha.2025.05.005","DOIUrl":"10.1016/j.jtha.2025.05.005","url":null,"abstract":"<div><h3>Background</h3><div>Patients with venous thromboembolism (VTE) are at risk of bleeding during anticoagulation.</div></div><div><h3>Objectives</h3><div>This study aimed to assess bleeding risk and the performance of risk assessment models (RAMs) VTE-PREDICT, HAS-BLED, RIETE, and VTE-BLEED in patients with acute VTE initiating anticoagulation.</div></div><div><h3>Methods</h3><div>We used data from a prospective observational cohort study (BACH-VTE) including patients with acute VTE who initiated anticoagulation with a follow-up period of up to 2 years. Exclusion criteria were active cancer, pregnancy, and postpartum period. Major bleeding, clinically relevant nonmajor bleeding (CRNMB), and minor bleeding were recorded and their frequencies calculated. RAM performance was evaluated by discrimination and calibration. Predictors associated with clinically relevant bleeding (CRB; composite of major and CRNMB) were assessed.</div></div><div><h3>Results</h3><div>In total, 308 patients (median age, 55 years; 42% women, 47% pulmonary embolism, 62% unprovoked VTE) were included. During a median follow-up time of 12.6 months, we observed 2 major bleedings, 41 CRNMBs, and 66 minor bleedings, corresponding to 2-year cumulative incidences (95% CI) of 0.9% (0%-2.1%), 16.2% (10.7%-21.3%), and 20.6% (15.1%-25.8%), respectively, and of 33.4% (26.7-39.5) for any bleeding. RAM discrimination was poor to moderate with C-statistics (95% CI) for CRB of 0.71 (0.61-0.80) for VTE-PREDICT, 0.59 (0.49-0.68) for HAS-BLED, 0.52 (0.41-0.62) for RIETE, and 0.56 (0.45-0.68) for VTE-BLEED. Calibration analysis revealed underestimation of bleeding risk. Female sex, lower hemoglobin, and bleeding history were associated with CRB in a univariable but not in a multivariable model.</div></div><div><h3>Conclusion</h3><div>In patients treated with anticoagulants for VTE, we found high rates of CRB. Only the VTE-PREDICT model showed acceptable discrimination, but poor calibration.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 2","pages":"Pages 498-507"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086312","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}