Thrombosis and haemostasis最新文献

{"title":"Factor XI Measurement in Acute Coronary Syndrome.","authors":"Diana A Gorog, Young-Hoon Jeong","doi":"10.1055/a-2546-2581","DOIUrl":"https://doi.org/10.1055/a-2546-2581","url":null,"abstract":"","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754440","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":"Tissue Factor Pathway-Driven Initial Thrombin Generation is Associated with Hypercoagulability in Obesity.","authors":"Yuichi Kamikubo, Satomi Nagaya, Rina Inoue, Koichi Yamaguchi, Riyo Morimoto-Kamata, Kenichi Inoue, Eriko Morishita, Fahumiya Samad, Naoki Ohkura","doi":"10.1055/a-2552-2050","DOIUrl":"10.1055/a-2552-2050","url":null,"abstract":"<p><p>Initial thrombin (FIIa) generated via the tissue factor (TF) pathway plays a crucial role in amplifying coagulation. There is growing evidence that the TF pathway might contribute to hypercoagulation in obesity. However, it is unclear if the initial generation of FIIa (TG) is associated with hypercoagulation in obesity due to the lack of appropriate assays. This study aims to evaluate association between TF pathway-driven initial TG and hypercoagulability in obesity.We measured the initial TG levels in plasma from male Tsumura Suzuki obese diabetes (TSOD) mice and overweight subjects using the highly sensitive TG assay. To induce initial TG, TF was added to the plasma and incubated at 37°C for up to 3 minutes. After quenching the TG, we quantified the generated FIIa by kinetically monitoring its amidolytic activity with a fluorogenic substrate.We observed that initial TG levels were significantly higher in TSOD mice (<i>n</i> = 31) compared with non-obese mice (<i>n</i> = 32). Even in the absence of exogenous TF, initial TG levels in obese mice and overweight individuals were elevated when procoagulant phospholipids were added alone. Moreover, the increased initial TG that the inhibitory anti-TF antibody abolished was detectable in reconstituted plasma including pellets prepared by high-speed centrifugation of plasma from obese mice, not in plasma supernatant. We attributed the promotion of the initial TG to the increase in procoagulant TF-bearing microvesicles in circulation. Based on the findings, measuring TF pathway-driven initial TG could be a valuable method for assessing hypercoagulability in obesity.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573753","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":"Estimated Glomerular Filtration Rate Decline is Causally Associated with Acute Pulmonary Embolism: A Nested Case-Control and Mendelian Randomization Study.","authors":"Yanshuang Lyu, Haobo Li, Xin Liu, Xiaomeng Zhang, Yinong Chen, Guohui Fan, Hong Zhang, Zhifa Han, Zhuangjie Guo, Haoyi Weng, Huiyuan Hu, Xincheng Li, Zhu Zhang, Yu Zhang, Feiya Xu, Chen Wang, Dingyi Wang, Peiran Yang, Zhenguo Zhai","doi":"10.1055/a-2439-5200","DOIUrl":"10.1055/a-2439-5200","url":null,"abstract":"<p><p>Renal dysfunction is highly prevalent among patients with pulmonary embolism (PE). This study combined population-based study and Mendelian randomization (MR) to observe the relationship between renal function and PE.A nested case-control study were performed using data of PE patients and controls were from two nationwide cohorts, the China pUlmonary thromboembolism REgistry Study (CURES) and China Health and Retirement Longitudinal Survey (CHARLS). Baseline characteristics were balanced using propensity score matching and inverse probability of treatment weighting. Restricted cubic spline models were applied for the relationship between estimated glomerular filtration rate (eGFR) decline and the risk of PE. Bidirectional two-sample MR analyses were performed using genome-wide association study summary statistics for eGFR involving 1,201,909 individuals and for PE from the FinnGen consortium.The nested case-control study including 17,547 participants (6,322 PE patients) found that eGFR distribution was significantly different between PE patients and controls (<i>p</i> < 0.001), PE patients had a higher proportion of eGFR < 60 mL/min/1.73 m². eGFR below 88 mL/min/1.73 m² was associated with a steep elevation in PE risk. MR analyses indicated a potential causal effect of eGFR decline on PE (odds ratio = 4·26, 95% confidence interval: 2·07-8·79), with no evidence of horizontal pleiotropy and reverse causality.Our findings support the hypothesis that renal function decline contributes to an elevated PE risk. Together with the high prevalence of chronic kidney diseases globally, there arises the necessity for monitoring and modulation of renal function in effective PE prevention.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475431","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":"Antithrombotic Therapy in People with Hemophilia-A Narrative Review.","authors":"Azusa Nagao, Shinichi Goto, Shinya Goto","doi":"10.1055/a-2548-4192","DOIUrl":"10.1055/a-2548-4192","url":null,"abstract":"<p><p>As the life expectancy of individuals with hemophilia continues to increase, the complexity of balancing bleeding risks and thrombotic management has become increasingly critical in people with hemophilia with or at a high risk of thrombosis. Advances in hemophilia therapies such as extended half-life coagulation factors, non-factor therapies, rebalancing agents, and gene therapy have expanded treatment options for a variety of people with hemophilia. The thrombotic risk of people with hemophilia in general are relatively low as compared to those without hemophilia. However, antithrombotic therapy for prevention and treatment for thrombosis should still be considered in some situations, even in hemophilia. This clinical focus highlights the use of antithrombotic therapy in the management of thrombosis in people with hemophilia. A multidisciplinary, personalized approach is essential for optimizing the safety and efficacy of antithrombotic therapy in people with hemophilia with or at a high risk of thrombosis. High performance computer based multidimensional data analysis may help in establishing the personalized antithrombotic therapy in the future.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531883","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":"Inhibitor Formation in the Era of Novel Haemophilia Treatment-A Humanized Mouse Model to Answer Our Questions?","authors":"Lize F D van Vulpen, Simon C Mastbergen","doi":"10.1055/a-2551-8561","DOIUrl":"10.1055/a-2551-8561","url":null,"abstract":"","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573741","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":"Hyperfibrinolysis Is Associated With Complement Activation Following Trauma.","authors":"Christopher D Barrett, Elizabeth Maginot, Ernest E Moore, Collin M White, Hunter B Moore, Isabella M Bernhardt, Trace Moody, James G Chandler, Flobater I Gawargi, Reynold Henry, Dominik Draxler, Martin Schreiber, Robert Medcalf, Angela Sauaia","doi":"10.1055/a-2565-2449","DOIUrl":"https://doi.org/10.1055/a-2565-2449","url":null,"abstract":"<p><strong>Background: </strong>Complement is activated after trauma, but the activation mechanism is unknown. Plasmin can directly activate C3 and C5, and four distinct fibrinolytic phenotypes have now been recognized after injury - hyperfibrinolysis, fibrinolysis shutdown, hypofibrinolysis, and non-pathologic/physiologic.</p><p><strong>Objectives: </strong>We set out to investigate whether a relationship between complement activation and fibrinolysis was present in adult trauma patients (n=56).</p><p><strong>Methods: </strong>Rapid and tPA-challenged thromboelastography (TEG) were performed in the emergency department with IRB approval, and plasma obtained for C3a, C4a, C5a, Ba, sC5b-9, Factor I, Factor H, active PAI-1, alpha-2 antiplasmin (A2AP), plasmin-antiplasmin complex (PAP), and tPA activity measurement via multiplex, ELISA and activity assays. Data were analyzed using ANOVA and Spearman's correlations. Significance was set at p<0.05.</p><p><strong>Results: </strong>C3a and sC5b-9 were significantly higher in patients with hyperfibrinolysis than with physiologic or hypofibrinolysis (p<0.05). Elevations in C3a, C4a, and SC5b9, along with depletion of Factors H and I, were significantly associated with massive transfusion within 6 hours and post-injury death. There were significant positive correlations between multiple markers of fibrinolysis and complement activation markers, and significant negative correlations with Factors H and I. Significant negative correlations between fibrinolytic inhibitors and complement activation were also observed.</p><p><strong>Conclusions: </strong>Our findings suggest that fibrinolysis may play a direct role in complement activation in trauma through plasmin-mediated cleavage of C3 and C5.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711331","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":"Homophilic interactions of platelet F11R/JAM-A with its surface-bound counterpart facilitate thrombus formation.","authors":"Piotr Kamola, Boguslawa Luzak, Patrycja Przygodzka, Cezary Watala, Moro O Salifu, Anna Babinska, Tomasz Przygodzki","doi":"10.1055/a-2565-9496","DOIUrl":"https://doi.org/10.1055/a-2565-9496","url":null,"abstract":"<p><strong>Background: </strong>F11Receptor/Junctional Adhesion Molecule-A (F11R/JAM-A) is a transmembrane protein expressed in endothelial cells, epithelial cells and in blood platelets. In blood platelets F11R/JAM-A participates in adhesion of platelets under static conditions, suppresses the activation of the platelet αIIbβ3 integrin and was shown to activate blood platelets as soluble form via homophilic interaction.</p><p><strong>Objectives: </strong>The purpose of presented study was to evaluate whether F11R/JAM-A is involved in platelet adhesion under flow conditions and in thrombus formation.</p><p><strong>Methods: </strong>F11R/JAM-A contribution to platelet adhesion under flow conditions was assessed using flow chamber assay. Monoclonal antibodies and recombinant F11R/ JAM-A were used to assess the effects of F11R/JAM-A blockade on platelet aggregation and thrombus formation using total thrombus formation analysis system. Effects of F11R/JAM-A blockade on thrombus formation in vivo were evaluated in murine models of carotid artery injury.</p><p><strong>Results: </strong>F11R/JAM-A was not capable of capturing flowing blood platelets alone but enhanced platelet adhesion to fibrinogen under flow conditions. Blocking of F11R/JAM-A homophilic interactions with specific monoclonal antibodies or with recombinant F11R/JAM-A impaired thrombus formation in vitro in human blood and in vivo in the models of thrombosis in mice.</p><p><strong>Conclusion: </strong>Interactions of F11R/JAM-A located on flowing platelets with its surface-bound counterpart enhance platelets binding to fibrinogen under high shear-stress conditions. Blocking of these homophilic interactions compromises thrombus formation. While previously published studies pointed at a significant role of soluble F11R/JAM-A in priming platelets during thrombus formation, our results highlight the role of surface-bound F11R/JAM-A in this process.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711328","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":"Optimal Long-term Antiplatelet Regimen for Patients with High Ischaemic and Bleeding Risks After Percutaneous Coronary Intervention.","authors":"Jeong Yoon Jang, Ga-In Yu, Jongwha Ahn, Jae-Suck Bae, Yun-Ho Cho, Min-Gyu Kang, Jin-Sin Koh, Young-Hoon Jeong, Sang Yeup Lee, Byeong-Keuk Kim, Hyung Joon Joo, Do-Sun Lim, Kiyuk Chang, Young Bin Song, Sung Gyun Ahn, Jung-Won Suh, Jung Rae Cho, Ae-Young Her, Jee-Hoon Kang, Hyo-Soo Kim, Moo Hyun Kim, Eun-Seok Shin, Yongwhi Park","doi":"10.1055/a-2499-5458","DOIUrl":"10.1055/a-2499-5458","url":null,"abstract":"<p><p>To assess an optimal long-term antiplatelet strategy in patients at both high ischaemic and bleeding risks after percutaneous coronary intervention (PCI).Patients at high risks of both ischaemia and bleeding were eligible for inclusion. We excluded patients with any ischaemic and major bleeding complications during the mandatory period of dual antiplatelet therapy (DAPT). Clinical outcomes were evaluated in three groups of regimens, namely, clopidogrel monotherapy (CLPD), aspirin monotherapy (ASA), and DAPT group. The primary endpoint was a composite of all-cause death, myocardial infarction, stroke, or major bleeding for 12-month follow-up period. To balance characteristics according to antiplatelet strategies, stabilized inverse probability treatment weighting (IPTW) was conducted. After IPTW adjustment, CLPD group (<i>N</i> = 916) showed significantly lower rate of primary endpoint than DAPT group (<i>N</i> = 949) (hazard ratio [HR] = 2.09, 95% confidence interval [CI] = 1.22-3.60, <i>p</i> = 0.008), but there was no statistical difference between CLPD and ASA groups (<i>N</i> = 838) (HR = 1.46, 95% CI = 0.83-2.54, <i>p</i> = 0.187). Clinical benefits of CLPD over DAPT was mainly driven by the lower incidence of ischemic events (HR = 2.51, 95% CI 1.37-4.61; <i>p</i> = 0.003). Incidence of major bleeding did not differ among groups, but there was an increased bleeding tendency in DAPT group compared to CLPD group (HR = 2.51, 95% CI = 0.85-7.41, <i>p</i> = 0.096).For patients at high bleeding and ischaemic risk, especially undergoing complex PCI, clopidogrel monotherapy demonstrated a significant net clinical benefit compared to DAPT. Clopidogrel monotherapy showed numerical reductions of bleeding and ischaemic event rates compared to aspirin monotherapy.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808212","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":"Modifications of the Prothrombin Active Site S4 Subpocket Confer Resistance to Dabigatran.","authors":"Viola J F Strijbis, Ka Lei Cheung, Dejvid Veizaj, Tessa Rutten, Boris de Bruin, Pieter H Reitsma, Daniël Verhoef, Mettine H A Bos","doi":"10.1055/a-2537-6037","DOIUrl":"10.1055/a-2537-6037","url":null,"abstract":"<p><p>Direct anticoagulants inhibit coagulation serine proteases by reversibly engaging their active site with high affinity. By modifying the S4 active site subpocket of factor (F)Xa, we introduced inhibitor resistance while preserving catalytic activity. Given the homology between FXa and thrombin in active site architecture and direct anticoagulant binding, we have targeted the S4 subsite to introduce inhibitor resistance in (pro)thrombin.Recombinant prothrombin variants were generated in which I174 was substituted or sequence R92-N98 was exchanged with that of human kallikrein-3.Specific prothrombin clotting activity of the variants was 6-fold (intrinsic clotting) to 10-fold (extrinsic clotting) reduced relative to wild-type prothrombin. Further analyses revealed that modification of the S4 subsite hampers fibrinogen and thrombomodulin-mediated protein C conversion by thrombin. Consistent with this, the thrombin variants displayed a reduced catalytic efficiency toward the peptidyl substrate used in thrombin generation assessments. The variants displayed a 2-fold reduced sensitivity for dabigatran relative to wild-type prothrombin, while argatroban inhibition was unaffected. Analyses using a purified component system revealed an up to 24-fold and 4-fold reduced IC₅₀ for inhibition of thrombin by dabigatran and argatroban, respectively. Molecular dynamics (MD) simulations of both dabigatran-bound and unbound (apo) modified thrombin variants indicated these to comprise a larger inhibitor binding pocket relative to wild-type thrombin and display reduced inhibitor binding. As a net effect, (pro)thrombin variants with S4 subsite modifications supported detectable fibrin formation at therapeutic dabigatran concentrations.Our findings provide proof-of-concept for the engineering of thrombin variants that are resistant to direct thrombin inhibitors by modulating the S4 subsite.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410848","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":"Impact of Obesity and Overweight on Heparin Dosing and Clinical Outcomes in Pediatric Patients with Venous Thromboembolism.","authors":"Alexandra Larouche, Valérie Dollo, Gabriel Mercier, Narcisse Singbo, Chantal Éthier, Marie-Christine Boulanger, Marie-Claude Pelland-Marcotte","doi":"10.1055/a-2544-6183","DOIUrl":"https://doi.org/10.1055/a-2544-6183","url":null,"abstract":"<p><p>Dosing guidance for anticoagulation, the mainstay of venous thromboembolism (VTE) treatment, is lacking for obese children. We aimed to compare unfractionated heparin (UFH) and low-molecular-weight heparins (LMWH) dosing requirements and clinical outcomes between obese/overweight and nonobese children.This monocentric retrospective cohort study included patients aged < 18 years old receiving anticoagulation for VTE. The outcomes were: (1) number of dose adjustments to reach therapeutic levels, (2) variation from initial dose, (3) thrombotic progression/recurrence, and (4) clinically relevant bleeding. Characteristics and dosing requirements of obese/overweight and nonobese children were compared using Pearson chi-square, Fisher exact, and Wilcoxon Mann-Whitney tests. Kaplan-Meier estimator compared the cumulative incidence of thrombotic recurrence/progression and clinically relevant bleeding between groups.We included 212 patients (median age: 6.2 years, 23.6% obese/overweight) having 258 anticoagulation encounters (LMWH: 82.6%, UFH: 17.4%). Most children had therapeutic levels following one dosage (66.7% in obese/overweight vs. 51.8% in nonobese, <i>p</i> = 0.201). Dosing requirements significantly differed between obese/overweight and nonobese children (average increase from initial dose: 3.2 vs. 11.3%, <i>p</i> < 0.001). In obese/overweight children, 11.1% of patients required ≥ 10% dose reduction versus 2.1% in nonobese children (<i>p</i> < 0.001). The cumulative incidence of thrombotic progression/recurrence was comparable between groups (obese/overweight: 12.0%, nonobese: 10.5%, <i>p</i> = 0.786). Similarly, clinically significant bleeding was rare for both groups (obese/overweight: 2.0%, nonobese: 3.1%, <i>p</i> = 0.609).In children treated for VTE, obesity/overweight was associated with lower anticoagulation requirements. Further prospective work is urgently needed to explore alternate regimens, such as dose capping, reduced initial dosing, or the use of fat-free mass.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701646","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}