Journal of Thrombosis and Thrombolysis最新文献

{"title":"The factor XI/XIa antibody abelacimab combined with enoxaparin inhibits filter clotting in hemodialysis circuits ex vivo.","authors":"Juergen Grafeneder, Gesche Langer, Christian Schoergenhofer, Farsad Eskandary, Bernd Jilma, Yasser Khder, Katarina D Kovacevic Miljevic","doi":"10.1007/s11239-024-03059-x","DOIUrl":"10.1007/s11239-024-03059-x","url":null,"abstract":"<p><p>Drugs targeting factor XI may offer an alternative to heparin for preventing blood clotting in extracorporeal circulation. We investigated the effects of abelacimab, a novel monoclonal antibody targeting factor XI. We collected whole blood samples into two bags (each 240 ml, control group: enoxaparin 1.2 mg, treatment group: enoxaparin 1.2 mg plus abelacimab 5 mg) and circulated in a hemodialysis device for up to 3 h. We performed whole blood aggregation and thromboelastometry at several time points. Time to filter clotting was the primary endpoint. We included 10 volunteers. Each volunteer's blood was split into two bags (containing enoxaparin +/- abelacimab) and used simultaneously on two hemodialysis devices. The treatment group's time to filter clotting was significantly prolonged (treatment: 180 min, IQR 180-180 vs. control: 120 min, IQR 97-147, p < 0.001), and the transmembrane pressure was significantly lower at the end of the circuit flow (treatment: 13 mmHg vs. control: 65 mmHg, p = 0.001). Fibrinogen levels and median platelet counts were preserved. Platelet aggregation was better preserved in the treatment group for ristocetin (p = 0.015), thrombin receptor activating peptide (p = 0.015), and arachidonic acid (p = 0.001). Thromboelastometry showed prolonged clotting times in the treatment group at the end of the experiment (INTEM, p < 0.001; HEPTEM, p = 0.001). Abelacimab prolonged the time to filter clotting in this ex vivo model of hemodialysis. This is an aggressive model due to the frequent re-circulation of blood and a lack of endothelial cells. These data provide support for testing abelacimab in patients on hemodialysis.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"1339-1348"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential role of factor XI inhibitors in managing long COVID.","authors":"Chia Siang Kow, Dinesh Sangarran Ramachandram, Syed Shahzad Hasan, Kaeshaelya Thiruchelvam","doi":"10.1007/s11239-024-03031-9","DOIUrl":"10.1007/s11239-024-03031-9","url":null,"abstract":"","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"1363-1364"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel antithrombotic approaches in cardiovascular disease - what is on the horizon?","authors":"Geoffrey D Barnes, Diana A Gorog","doi":"10.1007/s11239-024-03062-2","DOIUrl":"10.1007/s11239-024-03062-2","url":null,"abstract":"","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"1281-1282"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142729734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factor XIa inhibition as a therapeutic strategy for atherothrombosis.","authors":"Eric Bailey, Renato D Lopes, C Michael Gibson, John W Eikelboom, Sunil V Rao","doi":"10.1007/s11239-024-03023-9","DOIUrl":"10.1007/s11239-024-03023-9","url":null,"abstract":"<p><p>When selecting an anticoagulant, clinicians consider individual patient characteristic, the treatment indication, drug pharmacology, and safety and efficacy as demonstrated in randomized trials. An ideal anticoagulant prevents thrombosis with little or no increase in bleeding. Direct oral anticoagulants represent a major advance over traditional anticoagulants (e.g., unfractionated heparin, warfarin) but still cause bleeding, particularly from the gastrointestinal tract which can limit their use. Epidemiological studies indicate that patients with congenital factor XI (FXI) deficiency have a lower risk of venous thromboembolism (VTE) and ischemic stroke (IS) than non-deficient individuals, and do not have an increased risk of spontaneous bleeding, even with severe deficiency. These observations provide the rationale for targeting FXI as a new class of anticoagulant. Multiple FXI inhibitors have been introduced and several are being evaluated in Phase III trials. In this review, we explain why drugs that target FXI may be associated with a lower risk of bleeding than currently available anticoagulants and summarize the completed and ongoing trials.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"1297-1307"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness and safety of non-vitamin K antagonist oral anticoagulants in low-weight patients with atrial fibrillation.","authors":"Kuan-Hsuan Chen, Yeh-Yun Hsu, Chian-Ying Chou, Chia-Chen Hsu, Shih-Lin Chang, Wen-Chung Yu, Yuh-Lih Chang","doi":"10.1007/s11239-024-03016-8","DOIUrl":"10.1007/s11239-024-03016-8","url":null,"abstract":"<p><p>It remains unclear whether non-vitamin K antagonist oral anticoagulants (NOACs) are more effective and safer than warfarin in low-weight patients with atrial fibrillation (AF). Here, we retrospectively compared the effectiveness and safety of NOACs with those of warfarin in low-weight patients with AF. We extracted the July 2011-September 2022 data of patients with AF treated with a NOAC (dabigatran, rivaroxaban, apixaban, or edoxaban) or warfarin at a tertiary hospital. The patients were divided into low-weight (body weight ≤ 60 kg) and non-low-weight (body weight = 60-100 kg) groups. The primary outcomes were hospitalization for ischemic stroke (IS) or systemic embolism (SE) and major bleeding, whereas the secondary outcomes were any ischemic and bleeding events. We used the inverse probability of treatment weighting to balance the baseline characteristics between the groups. In total, 5,044 patients (mean age = 73.7 years, mean CHA2DS2-VASc score = 3.0, mean HAS-BLED score = 2.3) were enrolled and divided into low-weight and non-low-weight groups-containing 1,666 (1,406 NOAC users, 260 warfarin users) and 3,378 (2,978 NOAC users, 400 warfarin users) patients, respectively. NOACs were associated with a lower risk of any bleeding event in the low-weight group (adjusted hazard ratio = 0.61, 95% confidence interval = 0.51-0.73). The between-group differences in the risks of IS/SE, any ischemic event, major bleeding, and any bleeding event were nonsignificant. Thus, the use of NOACs (specifically dabigatran or edoxaban) is associated with a lower risk of any bleeding event than warfarin use in low-weight patients with AF.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"1268-1280"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intravenous thrombolysis versus dual antiplatelet therapy in minor ischemic stroke within the thrombolytic window (TAMIS): a multicenter cohort study.","authors":"Dan Wang, Qianru Wen, Kewei Liu, Yan Ding, Lu Xiao, Wei Li, Xiaoyun Lei, Siqi Zhang, Peijie Du, Huan Zhou, Yimin Chen, Hong Zhang, Ying Zhao, Thanh N Nguyen, Anding Xu, Jia Xiao, Heng Meng","doi":"10.1007/s11239-024-03032-8","DOIUrl":"10.1007/s11239-024-03032-8","url":null,"abstract":"<p><p>Intravenous thrombolysis (IVT) and dual antiplatelet therapy (DAPT) have been widely used in minor ischemic stroke (MIS) treatment. However, the clinical outcomes and safety of these two treatments have not been compared within the early thrombolytic time window. Here, we conducted a multicenter, ambispective cohort study involving patients with MIS presenting within 4.5 h of symptom onset at 3 affiliated hospitals of Jinan University from 2018-2022. The patients were divided into the IVT group and DAPT group. The primary outcome was a 90-day excellent outcome (mRS ≤ 1). A total of 1,026 patients were enrolled, of whom 492 were assigned to the IVT group and 534 were assigned to the DAPT group. The IVT group had better 90-day excellent outcomes (mRS ≤ 1) than the DAPT group (OR 1.69, 95% CI 1.14-2.52, P = 0.010). Among the 623 patients with nondisabling stroke, the proportion of mRS ≤ 1 in the IVT group was higher than the DAPT group (P = 0.009). In the subtypes of MIS with large vessel occlusion/stenosis and with isolated symptoms, the 90-day outcomes of the IVT group and DAPT group were not different (P > 0.05). In conclusion, compared with DAPT, IVT was associated with better 90-day clinical outcomes in patients with MIS (in particular, for those with mRS > 1), including earlier clinical improvement.IVT also benefited the early neurological improvement of patients with severe stenosis/occlusion of intracranial large vessels, nondisabling mild stroke, nondisabling mild stroke with isolated symptoms.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"1172-1182"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated plasma protein carbonylation increases the risk of ischemic cerebrovascular events in patients with atrial fibrillation: association with a prothrombotic state.","authors":"Karol Nowak, Michal Zabczyk, Joanna Natorska, Jaroslaw Zalewski, Anetta Undas","doi":"10.1007/s11239-024-03003-z","DOIUrl":"10.1007/s11239-024-03003-z","url":null,"abstract":"<p><strong>Introduction: </strong>Plasma protein carbonylation that reflects oxidative stress has been demonstrated to be associated with the prothrombotic fibrin clot phenotype. However, the role of protein carbonyls (PC) in predicting ischemic stroke in atrial fibrillation (AF) is largely unknown. This study aimed to investigate whether PC increase the risk of stroke in anticoagulated AF patients during follow-up.</p><p><strong>Methods: </strong>In 243 AF patients on anticoagulation (median age 69 years; median CHA₂DS₂-VASc of 4), we measured plasma PC using the assay by Becatti, along with plasma clot permeability (K_s), clot lysis time (CLT), thrombin generation, and fibrinolytic proteins, including plasminogen activator inhibitor type 1 (PAI-1) and thrombin activatable fibrinolysis inhibitor (TAFI). Ischemic stroke, major bleeding, and mortality were recorded during a median follow-up of 53 months.</p><p><strong>Results: </strong>Plasma PC levels (median, 3.16 [2.54-3.99] nM/mg protein) at baseline showed positive associations with age (P < 0.001), CHA₂DS₂-VASc (P = 0.003), and N-terminal B-type natriuretic peptide (P = 0.001), but not with type of AF or comorbidities except for heart failure (P = 0.007). PC levels were correlated with CLT (r = 0.342, P < 0.001), endogenous thrombin potential (r = 0.217, P = 0.001) and weakly with Ks (r = -0.145, P = 0.024), but not with fibrinogen, PAI-1, or TAFI levels. Stroke was recorded in 20 patients (1.9%/year), who had at baseline 36% higher PC levels (P < 0.001). Elevated PC (P = 0.003) at baseline were independently associated with stroke risk.</p><p><strong>Conclusion: </strong>Our findings suggest that in patients with AF enhanced protein carbonylation is associated with increased \"residual\" risk of stroke despite anticoagulation, which is at least in part due to unfavorably altered fibrin clot phenotype.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"1206-1215"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The journal of thrombosis and thrombolysis: commemorating the written word in science and medicine: three decades and counting.","authors":"Richard C Becker","doi":"10.1007/s11239-024-03012-y","DOIUrl":"10.1007/s11239-024-03012-y","url":null,"abstract":"","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"1103-1108"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Initial hemodynamic status and Acute Mortality in Cancer patients with Acute Pulmonary Embolism: from the COMMAND VTE Registry.","authors":"Wei Xiong, Yugo Yamashita, Takeshi Morimoto, Toru Takase, Seiichi Hiramori, Kitae Kim, Maki Oi, Masaharu Akao, Yohei Kobayashi, Po-Min Chen, Koichiro Murata, Yoshiaki Tsuyuki, Yuji Nishimoto, Jiro Sakamoto, Kiyonori Togi, Hiroshi Mabuchi, Kensuke Takabayashi, Takao Kato, Koh Ono, Takeshi Kimura","doi":"10.1007/s11239-024-03009-7","DOIUrl":"10.1007/s11239-024-03009-7","url":null,"abstract":"<p><strong>Background: </strong>Initial hemodynamic status in patients with acute pulmonary embolism (PE) concerns their acute clinical outcomes. Nevertheless, the characteristics of initial hemodynamic dysfunction and acute mortality in PE patients with active cancer is still controversial.</p><p><strong>Methods: </strong>We analyzed the data of 1715 PE patients in the COMMAND VTE Registry to compare initial hemodynamic dysfunction, management strategies, and mortality outcomes at 30 days after PE diagnosis between patients with and without active cancer (N = 393 and N = 1322).</p><p><strong>Results: </strong>The patients with active cancer showed lower prevalence of right ventricular dysfunction (35.4% vs. 49.5%, P < 0.001), shock (6.4% vs. 11.6%, P = 0.003), and cardiac arrest (1.8% vs. 5.5%, P = 0.002) at PE diagnosis, compared with those without. The patients with active cancer less frequently received systemic thrombolysis (4.1% vs. 12.6%, P < 0.001) than those without. There was no significant difference in the cumulative 30-day incidence of PE-related death between patients with and without active cancer (4.1% vs. 4.2%, P = 0.89). The cumulative 30-day incidence of all-cause death was significantly higher in patients with active cancer than in those without (11.5% vs. 4.9%, P < 0.001).</p><p><strong>Conclusions: </strong>PE patients with active cancer less frequently present with initial hemodynamic dysfunction at PE diagnosis, compared with those without. Nevertheless, PE patients with active cancer still show a similar risk of PE-related death and a higher risk of all-cause death at 30 days after PE diagnosis, suggesting the importance of prudent management for this patient population even if their initial hemodynamic status are not compromised.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"1183-1192"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth differentiation factor-15 predicts all-cause death and major adverse cardiovascular events in patients with coronary heart disease: a prospective cohort study.","authors":"Lyu Lyu, Cui Xv, Juan Xu, Zhenzhen Liu, Yanru He, Wenjing Zhu, Lin Lin, Qiang Yang, Yun Wei, Jinda Wang, Taoke Huang, Benchuan Hao, Hongbin Liu","doi":"10.1007/s11239-024-03019-5","DOIUrl":"10.1007/s11239-024-03019-5","url":null,"abstract":"<p><p>The prognostic value of growth differentiation factor-15 (GDF-15) in predicting long-term adverse outcomes in coronary heart disease (CHD) patients remains limited. Our study examines the association between GDF-15 and adverse outcomes over an extended period in CHD patients and firstly assesses the incremental prognostic effect of incorporating GDF-15 into the Framingham risk score (FRS)-based model. This single-center prospective cohort study included 3,321 patients with CHD categorized into 2,479 acute coronary syndrome (ACS) (74.6%) and 842 non-ACS (25.4%) groups. The median age was 61.0 years (range: 53.0-70.0), and 917 (27.6%) were females. Mortality and major adverse cardiovascular events (MACEs) included cardiovascular mortality, myocardial infarction (MI), stroke, and heart failure (HF) (inclusive of HF episodes requiring outpatient treatment and/or hospital admission). Cox regression models assessed the associations between GDF-15 and the incidence of all-cause mortality and MACEs. Patients were stratified into three groups based on GDF-15 levels: the first tertile group (< 1,370 ng/L), the second tertile group (1,370-2,556 ng/L), and the third tertile group (> 2,556 ng/L). The C-index, integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA) were used to assess incremental value. Over a median 9.4-year follow-up, 759 patients (22.9%) died, and 1,291 (38.9%) experienced MACEs. The multivariate Cox model indicated that GDF-15 was significantly associated with all-cause mortality (per ln unit increase, HR = 1.49, 95% CI: 1.36-1.64) and MACEs (per ln unit increase, HR = 1.29, 95% CI: 1.20-1.38). These associations persisted when GDF-15 was analyzed as an ordinal variable (p for trend < 0.05). Subgroup analysis of ACS and non-ACS for the components of MACEs separately showed a significant association between GDF-15 and both cardiovascular mortality and HF, but no association was observed between GDF-15 and MI /stroke in both ACS and non-ACS patients. The addition of GDF-15 to the FRS-based model enhanced the discrimination for both all-cause mortality (∆ C-index = 0.009, 95% CI: 0.005-0.014; IDI = 0.030, 95% CI: 0.015-0.047; continuous NRI = 0.631, 95% CI: 0.569-0.652) and MACEs (∆ C-index = 0.009, 95% CI: 0.006-0.012; IDI = 0.026, 95% CI: 0.009-0.042; continuous NRI = 0.593, 95% CI: 0.478-0.682). DCA suggested that incorporating GDF-15 into the FRS-based model demonstrated higher net benefits compared to FRS-based models alone (All-cause mortality: FRS-based model: area under the curve of DCA (AUDC) = 0.0903, FRS-based model + GDF-15: AUDC = 0.0908; MACEs: FRS-based model: AUDC = 0.1806, FRS-based model + GDF-15: AUDC = 0.1833). GDF-15 significantly associates with the long-term prognosis of all-cause mortality and MACEs in CHD patients and significantly improves the prognostic accuracy of the FRS-based model for both outcomes.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"1109-1121"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}