{"title":"High-sensitivity thrombin generation profiling identifies divergent coagulation states across peripheral artery disease severity","authors":"Yosuke Morodomi , Shinichiro Yoshino , Koichi Morisaki , Yuichi Kamikubo , Rina Inoue , Yusuke Fujioka , Kentaro Inoue , Sachiko Kanaji , Taisuke Kanaji , Kenta Ishimoto , Zheng Situo , Seiichiro Kizaki , Noriko Yasuda-Yoshihara , Yui Harada , Tomoharu Yoshizumi , Yoshikazu Yonemitsu","doi":"10.1016/j.tru.2026.100235","DOIUrl":"10.1016/j.tru.2026.100235","url":null,"abstract":"<div><h3>Background</h3><div>Factor Xa inhibition has demonstrated clinical benefit in peripheral artery disease (PAD), yet the mechanisms underlying this effect remain poorly defined. Uncertainty also persists regarding which patient subgroups derive net benefit, particularly given concerns about bleeding risk. Conventional thrombin generation assays primarily capture late and amplified coagulation phases and may overlook subtle abnormalities in the early-phase. We therefore investigated stage-specific profiles of the initial activated Factor II (FIIa) generation (ITG) during the early phase of coagulation in PAD using two high-sensitivity thrombin generation assays.</div></div><div><h3>Methods</h3><div>TF-driven ITG (TF-ITG) and FVIIIa/FIXa-dependent ITG (FVIIIa/FIXa-ITG) were measured in plasma samples from patients with intermittent claudication (IC), chronic limb-threatening ischemia (CLTI), and healthy controls. Tissue factor pathway inhibitor (TFPI) activity levels were also assessed.</div></div><div><h3>Results</h3><div>Distinct early-phase coagulation phenotypes emerged across PAD severity. Patients with IC showed selective intrinsic coagulation pathway hypercoagulability with significantly elevated FVIIIa/FIXa-ITG compared to controls (<em>p</em> < 0.005), while TF-ITG remained normal. Conversely, patients with CLTI demonstrated paradoxical suppression of both TF-ITG and FVIIIa/FIXa-ITG (<em>p</em> < 0.005), accompanied by elevated TFPI activity levels. The TFPI levels correlated negatively with both TF-ITG (r = −0.696, <em>p</em> = 0.0057) and FVIIIa/FIXa-ITG (r = −0.535, <em>p</em> = 0.049) only in CLTI.</div></div><div><h3>Conclusions</h3><div>Early-phase thrombin generation differs fundamentally between IC and CLTI. These exploratory findings provide hypothesis-generating mechanistic insights for the variable clinical effects of Factor Xa inhibition in PAD. Prospective studies are warranted to determine whether early-phase thrombin generation profiling can inform biomarker-guided antithrombotic strategies.</div></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"22 ","pages":"Article 100235"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147750635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thrombosis UpdatePub Date : 2026-03-01Epub Date: 2026-01-14DOI: 10.1016/j.tru.2026.100232
Denise Abbel , Dieuwke Luijten , Suzanne C. Cannegieter , Jeroen Eikenboom , Paul L. den Exter , Frederikus A. Klok , Bas de Groot , Jacobijn Gussekloo , Menno V. Huisman , Thijs E. van Mens , Lara Tahir , Johanneke E.A. Portielje , Stella Trompet , Simon P. Mooijaart
{"title":"Geriatric characteristics and outcomes of older patients diagnosed with acute pulmonary embolism in the emergency department","authors":"Denise Abbel , Dieuwke Luijten , Suzanne C. Cannegieter , Jeroen Eikenboom , Paul L. den Exter , Frederikus A. Klok , Bas de Groot , Jacobijn Gussekloo , Menno V. Huisman , Thijs E. van Mens , Lara Tahir , Johanneke E.A. Portielje , Stella Trompet , Simon P. Mooijaart","doi":"10.1016/j.tru.2026.100232","DOIUrl":"10.1016/j.tru.2026.100232","url":null,"abstract":"<div><h3>Introduction</h3><div>Knowledge on characteristics and outcomes of older patients with pulmonary embolism (PE) fuels decision making on PE management, but data are scarce. We aimed to describe geriatric characteristics and outcomes of older patients diagnosed with PE in the Emergency Department (ED).</div></div><div><h3>Methods</h3><div>We used two ED-cohorts from the Leiden University Medical Center in the Netherlands: 229 patients (≥70 years) diagnosed with PE in the ED between 2015 and 2022, and 751 control patients (≥70 years) who visited the ED in 2014 for any indication. We compared baseline cognition and physical functioning, and outcomes including mortality and hospitalization between the two cohorts.</div></div><div><h3>Results</h3><div>At ED presentation the median age was 76 years (IQR = 72–81) for PE patients and 78 years (IQR = 74–83) for control patients (p < 0.001). PE patients had similar cognitive impairment (23 % vs 25 %, p = 0.84) and functional impairment (37 % vs 40 %, p = 0.67) compared to the control patients. PE patients were more often hospitalized (OR: 4.1; 95 %CI: 2.9–5.7), and had a higher 7 days mortality (HR: 3.2; 95 %CI: 1.5–6.9), 3 months mortality (HR: 1.7; 95 %CI: 1.1–2.6) and 12 months mortality (HR: 1.6; 95 %CI: 1.2–2.2). The 56 of 229 (24 %) PE patients with an active cancer diagnosis had a fourfold higher 3 months mortality risk compared to PE patients without cancer.</div></div><div><h3>Conclusion</h3><div>Older PE patients and general older patients are comparable in terms of cognitive and physical functioning at ED presentation. PE is associated with higher mortality among other ED presentations, particularly in patients with underlying cancer.</div></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"22 ","pages":"Article 100232"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146190550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mathematical modeling of cross-mixing test dynamics in adult-onset lupus Anticoagulant–Associated hypoprothrombinemia syndrome","authors":"Noriko Seno , Takafumi Ohama , Natsuko Morita , Akiyoshi Takami , Masahiro Ieko , Kazuhiro Ikegame","doi":"10.1016/j.tru.2026.100239","DOIUrl":"10.1016/j.tru.2026.100239","url":null,"abstract":"<div><div>Lupus anticoagulant–associated hypoprothrombinemia syndrome (LAHPS) is a rare acquired bleeding disorder, and interpretation of coagulation mixing tests can be challenging, particularly in the presence of direct oral anticoagulants (DOACs).</div><div>We report an adult-onset case of LAHPS associated with Sjögren's syndrome and aimed to clarify discrepant cross-mixing test results using a mathematical modeling approach.</div><div>Cross-mixing tests were performed twice during the diagnostic workup: first using a single-centrifuged plasma sample obtained 2 days after initiating DOAC therapy, and the second using a double-centrifuged sample collected on day 7. Mixing test patterns were evaluated morphologically and using quantitative indices, including the index of circulating anticoagulant (ICA), mixing test–specific cutoffs, and %C indices. A mathematical model incorporating features of coagulation factor deficiency and lupus anticoagulant–type inhibition was constructed to aid interpretation.</div><div>The first test showed an almost linear activated partial thromboplastin time–patient plasma ratio curve in immediate and delayed reactions. The second test demonstrated convex upward curves in both reactions, consistent with an inhibitor-type pattern. Quantitative indices supported inhibitor-type reactions in both tests, whereas additional parameters (ICAwi–ICAwo, ICAwi/ICAwo, and WaS–ALD50) indicated a lupus anticoagulant–like profile rather than a coagulation factor–specific inhibitor. The model reproduced these patterns and discrepancies by accounting for DOAC effects and centrifugation differences.</div><div>We present a simple, robust mathematical framework for interpreting cross-mixing test results. This approach may improve differentiation between factor deficiency and lupus anticoagulant–type inhibition, particularly in complex clinical settings involving DOAC therapy.</div></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"22 ","pages":"Article 100239"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147750636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thrombosis UpdatePub Date : 2026-03-01Epub Date: 2026-03-17DOI: 10.1016/j.tru.2026.100234
Yi-Jie Lu , Shi-Yu Tang , Meng Hao , Shu-Ya Tang , Hui Zhang , Serick Duysenbi , Najiahai Jinsihan , Bo Yu , Jing-Dong Tang , Shuai Jiang , Bing-bing Pu , Ying Deng
{"title":"Baseline low-grade systemic inflammation and risk of hospitalized venous thromboembolism: A UK Biobank cohort study","authors":"Yi-Jie Lu , Shi-Yu Tang , Meng Hao , Shu-Ya Tang , Hui Zhang , Serick Duysenbi , Najiahai Jinsihan , Bo Yu , Jing-Dong Tang , Shuai Jiang , Bing-bing Pu , Ying Deng","doi":"10.1016/j.tru.2026.100234","DOIUrl":"10.1016/j.tru.2026.100234","url":null,"abstract":"<div><h3>Background</h3><div>Venous thromboembolism (VTE) is a major vascular disease associated with substantial morbidity and mortality worldwide. Chronic low-grade systemic inflammation has been implicated in thrombus formation, yet its long-term association with incident VTE in the general population remains incompletely understood using routinely available biomarkers.</div></div><div><h3>Methods</h3><div>We conducted a prospective cohort analysis of 473,717 participants from the UK Biobank to examine associations between baseline inflammatory biomarkers—including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI)—and incident hospitalized VTE. Inflammatory biomarkers were measured at baseline (2006–2010), and hospitalized VTE events were identified through linked hospital inpatient records using ICD-10 codes during follow-up. Cox proportional hazards regression models were used to estimate associations between inflammatory biomarkers and incident hospitalized VTE, with hazard ratios (HRs) calculated per unit increase, based on baseline blood cell counts.</div></div><div><h3>Results</h3><div>During a median follow-up of 14.6 years, 13,709 participants developed hospitalized VTE, including 12,291 pulmonary embolism events, 1168 deep vein thrombosis events, and 250 cases with both conditions. Higher baseline neutrophil count, monocyte count, and NLR were independently associated with incident hospitalized VTE after multivariable adjustment. Associations for composite indices such as SII and SIRI were attenuated after accounting for shared cellular components and clinical confounders. The observed VTE incidence was lower than population-based estimates, reflecting reliance on hospital inpatient records that preferentially capture clinically significant events.</div></div><div><h3>Conclusion</h3><div>Baseline low-grade systemic inflammation is associated with the long-term risk of hospitalized VTE in the general population. Despite conservative event ascertainment, routinely measured inflammatory biomarkers—particularly NLR and monocyte count—remained independently associated with future events, supporting their potential role as complementary markers for long-term VTE risk stratification and prevention.</div></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"22 ","pages":"Article 100234"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147539023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thrombosis UpdatePub Date : 2026-03-01Epub Date: 2026-01-14DOI: 10.1016/j.tru.2026.100233
Bengt Zöller , Mark Jonas Haastrup , Niels Tækker Foged , Gunnar Engström
{"title":"Prothrombin concentrations in middle-aged men and women – stability over time and correlations with cardiovascular risk factors","authors":"Bengt Zöller , Mark Jonas Haastrup , Niels Tækker Foged , Gunnar Engström","doi":"10.1016/j.tru.2026.100233","DOIUrl":"10.1016/j.tru.2026.100233","url":null,"abstract":"<div><h3>Background</h3><div>Prothrombin is a vitamin K-dependent glycoprotein synthesized in the liver and circulating in blood as an inactive zymogen. The corresponding activated thrombin enzyme is a central player in hemostasis and thrombosis. Still, little is known about the individual variation over time of the prothrombin concentration in plasma in the general population.</div></div><div><h3>Objectives</h3><div>This study aimed to establish the prothrombin plasma level and its correlation with cardiovascular risk factors in the general population.</div></div><div><h3>Methods</h3><div>A novel aptamer-based electrochemical biosensor, which in a single, direct incubation step and within 5 min quantifies the prothrombin concentration in molar amounts, was used for analysis of plasma samples from 141 non-anticoagulated individuals in the Swedish cardiopulmonary bioimage study (SCAPIS). Plasma samples from baseline and from re-examination after one year of follow-up were tested.</div></div><div><h3>Results</h3><div>The study population consisted of 141 individuals with a mean age of 57.3 (standard deviation 3.79) years, and 66 (47 %) were females. The mean (±standard deviation) prothrombin concentrations in plasma were 1565 nM (±249) and 1526 nM (±319) at baseline and one-year follow-up, respectively. There was a strong correlation between the individual prothrombin concentration at baseline and one year later, r = 0.658, p < 0.001. Baseline prothrombin plasma levels correlated positively and weakly with weight (r = 0.183, p = 0.030), waist (r = 0.213, p = 0.011), waist-hip-ratio (r = 0.191, p = 0.023), body mass index (r = 0.244, p = 0.004), cholesterol (r = 0.281, p < 0.001), LDL-cholesterol (r = 0.220, p = 0.009), triglycerides (r = 0.257, p = 0.002), and thrombocytes (r = 0.170, p = 0,046).</div></div><div><h3>Conclusions</h3><div>Plasma levels of prothrombin are stable over time in most individuals and are positively and weakly correlated with cardiovascular risk factors.</div></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"22 ","pages":"Article 100233"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146001777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thrombosis UpdatePub Date : 2025-12-01Epub Date: 2025-11-13DOI: 10.1016/j.tru.2025.100228
L. Talon , B. Pereira , J. Douxfils , A.F. Sapin , T. Dureng , V. Fourneyron , M. Maugis , S. Senectaire , M. Tardieu , M. Tillier , A. Trapani , A. Trayaud , T. Sinegre , A. Lebreton
{"title":"Analytical performance of the quantitative point-of-care PATHFAST D-dimer assay","authors":"L. Talon , B. Pereira , J. Douxfils , A.F. Sapin , T. Dureng , V. Fourneyron , M. Maugis , S. Senectaire , M. Tardieu , M. Tillier , A. Trapani , A. Trayaud , T. Sinegre , A. Lebreton","doi":"10.1016/j.tru.2025.100228","DOIUrl":"10.1016/j.tru.2025.100228","url":null,"abstract":"<div><h3>Background</h3><div>In the diagnosis of venous thromboembolism (VTE), the use of point-of-care (POC) D-dimer testing is emerging as a promising alternative to laboratory-based D-dimer assays. These POC devices, easier to use, raise the question of their analytical and clinical performances. We evaluated the analytical performances of the POC Pathfast D-dimer chemiluminescence assay and compared its results with two laboratory-based D-dimer assays: Vidas D-dimer Exclusion II and STA-Liatest D-Di Plus.</div></div><div><h3>Methods</h3><div>Within- and between-run imprecision were evaluated using low-and high-level quality control plasma samples and healthy controls and patients’ whole blood. Limit of quantification and linearity were determined according to the Clinical and Laboratory Standards Institute (CLSI). Comparisons were performed using the Passing-Bablok and Bland-Altman analysis, using fresh citrated whole blood and plasma samples collected from 150 consecutive routine samples.</div></div><div><h3>Results</h3><div>The within- and between-run imprecision of the assay did not exceed 4.4 % and 5.8 %, respectively. Our study found higher D-Dimer results with the Pathfast D-dimer assay (whole blood) than with the Vidas D-dimer Exclusion II and STA-Liatest D-Di Plus assays (plasma) with mean bias of 1.16 and 1.20 μg/mL FEU, respectively. Around the most clinically relevant area (<1 μg/mL FEU), bias was smallest, from 0.07 to 0.15 μg/mL FEU.</div></div><div><h3>Conclusion</h3><div>The Pathfast D-dimer assay is a rapid POC test for determination of D-dimer with good analytical performance. However, these results may be further investigated by a well-designed prospective clinical evaluation in a context of VTE suspicion and appropriate scoring.</div></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"21 ","pages":"Article 100228"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thrombosis UpdatePub Date : 2025-12-01Epub Date: 2025-11-21DOI: 10.1016/j.tru.2025.100227
Arturo D. Mora , David Alejandro Pantoja , Wikler Bernal Torres , Saulo Andrés Quiñones-Cañaveral , Hoover León-Giraldo , María Camila Naranjo-Ramírez , Clara Isabel Marín Chaves , Judith Andrea Rivas Amaris , Maribel Ñañez Jauregui , Carlos E. Durán-Rebolledo , Juan Esteban Gómez-Mesa
{"title":"Anticoagulation in renal impairment: Indications, clinical profiles, and complications from a colombian high-complexity hospital","authors":"Arturo D. Mora , David Alejandro Pantoja , Wikler Bernal Torres , Saulo Andrés Quiñones-Cañaveral , Hoover León-Giraldo , María Camila Naranjo-Ramírez , Clara Isabel Marín Chaves , Judith Andrea Rivas Amaris , Maribel Ñañez Jauregui , Carlos E. Durán-Rebolledo , Juan Esteban Gómez-Mesa","doi":"10.1016/j.tru.2025.100227","DOIUrl":"10.1016/j.tru.2025.100227","url":null,"abstract":"<div><h3>Background</h3><div>Anticoagulation in patients with renal impairment (RI) carries an increased risk of complications. This study aimed to assess clinical and therapeutic differences among anticoagulated patients across stages of renal dysfunction.</div></div><div><h3>Methods</h3><div>An observational study was conducted in patients receiving anticoagulation with creatinine clearance <60 mL/min. Based on creatinine clearance, patients were classified as G3a, G3b, G4, or G5. Baseline characteristics, treatment regimens, and complications were evaluated.</div></div><div><h3>Results</h3><div>A total of 802 patients were included in the study (median age 79.5 years [IQR 70.1–86.5]; 53.2 % female): G3a (n = 418), G3b (n = 244), G4 (n = 100), and G5 (n = 40). Among atrial fibrillation (AF) patients (n = 314), direct oral anticoagulants (DOAC) were preferred, with apixaban the most frequently used therapy; reduced-dose regimens predominated in advanced RI (G4: 65.8 %, G5: 94.4 %). In venous thromboembolism (VTE) patients (n = 294), low-molecular-weight heparin (LMWH) was the predominant therapy (70.6 % in G5). For other indications (n = 181), LMWH and warfarin were the most frequently used. Hemorrhagic events occurred in 78 patients (10.1 %), including 36 patients with major bleeds (4.5 %), numerically higher rates in were found in G4–G5. Thromboembolic events were observed in 36 patients (4.9 %), mainly cerebral ischemia. The overall cohort showed a median HASBLED score of 3, consistent with a high bleeding risk.</div></div><div><h3>Conclusion</h3><div>In RI patients, DOAC were preferred in the AF group, often at reduced doses in advanced stages, whereas LMWH was mostly used for VTE. This elderly, multimorbid population showed high bleeding and thrombotic event rates, underscoring the need for individualized anticoagulant strategies and close monitoring.</div></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"21 ","pages":"Article 100227"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}