Journal of Thrombosis and Thrombolysis最新文献

{"title":"Intravenous thrombolysis or dual antiplatelet therapy for minor ischemic stroke?","authors":"Li Zhou, Mingxin Wang","doi":"10.1007/s11239-024-03046-2","DOIUrl":"10.1007/s11239-024-03046-2","url":null,"abstract":"","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"157-158"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372209","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":"Correction: Ghrelin may protect against vascular endothelial injury in acute traumatic coagulopathy by mediating the RhoA/ROCK/MLC2 pathway.","authors":"Chengjian He, Xiaojing Song, Zigui Zhu, Yan Xiao, Jiacheng Chen, Hongyi Yao, Rongjun Xie","doi":"10.1007/s11239-024-03058-y","DOIUrl":"10.1007/s11239-024-03058-y","url":null,"abstract":"","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"96"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710580","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":"Factor XI as a new target for prevention of thromboembolism in cardiovascular disease: a meta-analysis of randomized controlled trials.","authors":"Ahmed E Ali, Mohamed K Awad, Karim Ali, Mohamed Riad Abouzid, Marwan H Ahmed, Muhammad S Mazroua","doi":"10.1007/s11239-024-02986-z","DOIUrl":"10.1007/s11239-024-02986-z","url":null,"abstract":"<p><p>Anticoagulant therapy is a mainstay in the management of patients with cardiovascular disease. The use of conventional anticoagulants carries potential side effects, mainly bleeding. Drugs targeting Factor XI (FXI) have been investigated in randomized controlled trials as a new option with more favorable outcomes. A comprehensive literature search was conducted to identify relevant studies comparing FXI inhibitors to placebo or standard therapy. The primary outcomes were incidence of all bleeding events, major bleeding, and thromboembolism. Secondary outcomes included incidence of all adverse events (AE), serious AE, and all-cause mortality. A total of 11 studies involving 10,536 patients were included. FXI inhibitors were associated with a trend toward reduction of bleeding events and incidence of thromboembolism compared to the control group (placebo/standard therapy). There was no statistically significant difference between both groups in terms of adverse events and all-cause mortality. When compared to enoxaparin, FXI inhibitors significantly reduced the risk of bleeding events (RR = 0.42, 95% CI: 0.23-0.76, P = 0.004) and thromboembolism (RR = 0.59, 95% CI: 0.44-0.77, P = 0.001). On the other hand, when compared to DOACs, FXI inhibitors were associated with a significant reduction in bleeding events but not thromboembolism. Whereas, compared to placebo, FXI inhibitors did not increase the risk of bleeding events, adverse events, or all-cause mortality (P > 0.05). FXI inhibitors could be a safer and more potent option for prevention of thromboembolism than conventional therapy.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"1-14"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958305","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":"Eosinopenia in patients with acute myocardial infarction- longitudinal imaging insights from the CAPRI study.","authors":"Bilal Bawamia, Ashish Gupta, Muntaser Omari, Mohamed Farag, Ioakim Spyridopoulos, Mohammad Alkhalil","doi":"10.1007/s11239-024-03042-6","DOIUrl":"10.1007/s11239-024-03042-6","url":null,"abstract":"<p><p>Eosinophils are recruited to the heart during acute myocardial infarction (MI) and are considered part of the inflammatory response associated with adverse clinical outcomes. We assessed the impact of eosinopenia on cardiac imaging biomarkers in patients presenting with ST-segment elevation MI. This is a post-hoc analysis of the Evaluating the effectiveness of intravenous Ciclosporin on reducing reperfusion injury in pAtients undergoing PRImary percutaneous coronary intervention (CAPRI) trial. Patients underwent cardiac MRI within 1 week and 12 weeks and low eosinophil was defined as less than 40 cells/ml. The study included 52 patients and 38% had low eosinophil. Ciclosporin administration was comparable between patients with low versus normal eosinophils. The ischaemia time was significantly longer in low eosinophil patients [262 (205-325) vs. 138 (102-195) minutes, P < 0.001]. At 12 weeks, patients with eosinopenia had larger infarct size [9.8% (5.7-18.4) vs. 7.4% (1.9-10.2), P = 0.045], larger left ventricle (LV) end systolic volume (89 ± 28 vs. 68 ± 23, P = 0.02), and lower LV ejection fraction (EF) (49 ± 9 vs. 58 ± 7, P < 0.001). After adjustments for significant predictors, including ischaemia time, low eosinophil count was an independent predictor of worse LVEF at 12 weeks [-5.78, 95% CI (-11.22 to -0.34), P = 0.038] but not infarct size [1.83, 95% CI (-2.77 to 6.43), P = 0.43]. Patients with low eosinophil count had larger infarct size and LV volumes and worse adverse remodeling compared to those with normal eosinophil count. At 12 weeks, eosinopenia was an independent predictor of worse LVEF but not infarct size.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"136-144"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290148","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":"Risk of incident venous thromboembolism in patients with atopic dermatitis: systematic analysis of the literature and meta-analysis.","authors":"Yifei Wang, Zhiqiang Chen, Ting He, Changzheng Huang, Chen Shen","doi":"10.1007/s11239-024-03038-2","DOIUrl":"10.1007/s11239-024-03038-2","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease. While various inflammatory conditions have been linked to venous thromboembolism (VTE), the risk of VTE among patients with AD remains unclear. We sought to systematically review and meta-analyze population-based studies to determine the association between AD and incident VTE. A systematic review was performed of published studies in PubMed, Web of Science, Embase and Cochrane library from their inception to 27 May 2024. At least two reviewers conducted title/abstract, full-text review and data extraction. Cohort studies examining the association of AD with incident VTE were included. Quality of evidence was assessed using the Newcastle-Ottawa Scale. Six cohort studies, encompassing a total of 10,186,861 participants, were included. The meta-analysis revealed a significantly increased risk for incident VTE among AD patients (pooled hazard ratio (HR), 1.10; 95% CI, 1.00-1.21), with an incidence rate of VTE at 3.35 events per 1000 patient-years. Individual outcome analyses suggested that AD was associated with higher risks of deep vein thrombosis (pooled HR, 1.15; 95% CI, 1.04-1.27) but not pulmonary embolism (pooled HR, 0.99; 95% CI, 0.87-1.13). This systematic review and meta-analysis indicated an increased risk of incident VTE among patients with AD. Future studies are necessary to elucidate the underlying pathophysiology of the association between AD and VTE.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"126-135"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145908","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":"Finding individualised treatment in obese needing enoxaparin (FIT ONE): a multicentre study of therapeutic enoxaparin and the role of anti-factor Xa monitoring.","authors":"Marcelle Appay, Justine Lai, Justine Hay, Connie Calvisi, Geoffrey Wills, Shreyas Kharadi, Sajani Nanayakkara, Ji Sang Ryu, Rozanna Alameddine, Sarah Jupp, Margaretta Lin, Jessica Nguyen, Tammy Nguyen, Nicholas Harrison, Fady Gad, Sakura Kagaya, Liam Nguyen, Sharma Piyush, Vicky Shion, Advait Pandya, Mustafa Emin, Ewe Shen Lim, Urna Rahman, Farhad Hayat, Chamali Gajaweera, Nashwa Sheriff, Asad E Patanwala, Leonardo Pasalic, Jan-Willem Alffenaar","doi":"10.1007/s11239-024-03033-7","DOIUrl":"10.1007/s11239-024-03033-7","url":null,"abstract":"<p><p>Enoxaparin is dosed according to actual body weight in treatment of arterial and venous thrombosis. Due to its hydrophilic nature, it distributes according to lean body mass which may be problematic when dosing obese patients as this may increase the risk of bleeding events in this population. The aim was to evaluate current therapeutic enoxaparin dosing strategies, including Antifactor Xa (AFXa) level monitoring, in obese patients and to identify factors that contribute to treatment failure and excess anticoagulation. A retrospective cohort study was conducted reviewing patients administered therapeutic enoxaparin between May 2020 and April 2021. Data were collected on patient characteristics, enoxaparin therapy, AFXa monitoring, and outcomes. Regression models were constructed to assess variables of interest to estimate any association with AFXa levels. In total 762 patients were included in the analysis. The mean initial weight-based dose was 0.95 mg/kg twice daily (SD: ± 0.12, IQR 0.92-1.01) and 1.04 mg/kg once daily (SD: ± 0.26, IQR 0.93-1.12) and 14.4% of patients had AFXa monitoring. Treatment failure was experienced by 2.2%, 5% experienced bleeding. There was no association between the mean actual milligram per kilogram weight-based twice daily doses and subtherapeutic, therapeutic and supratherapeutic AFXa levels (P = 0.135). Obesity was not included in the final regression models due to lack of significance. At a mean therapeutic enoxaparin dose of 0.95 mg/kg twice daily and 1.04 mg/kg once daily no excess in treatment failure or bleeding events were observed in obese patients compared to the product information. Obesity was not an independent variable that affected the achievement of target AFXa levels.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"109-119"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073176","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":"Clinical outcomes of patients with atrial fibrillation in relation to multimorbidity status changes over time and the impact of ABC pathway compliance: a nationwide cohort study.","authors":"Rungroj Krittayaphong, Arjbordin Winijkul, Komsing Methavigul, Ply Chichareon, Gregory Y H Lip","doi":"10.1007/s11239-024-03007-9","DOIUrl":"10.1007/s11239-024-03007-9","url":null,"abstract":"<p><p>Patients with atrial fibrillation (AF) commonly have associated comorbidities. The primary aim was to determine the effect of increasing numbers of comorbidity on clinical outcomes. The secondary aims were (1) the association of comorbidities with oral anticoagulants (OAC) discontinuation, and quality control, (2) the impact of holistic care based on the ABC pathway on clinical outcomes. The primary outcome was the composite of all-cause death, ischemic stroke/systemic embolism, major bleeding, and heart failure. A total of 3405 patients were enrolled; mean age 67.8 ± 11.3 years, 41.8% female. Compared to low comorbidity group [n = 897 (26.3%)], hazard ratios (HR) and 95% confidence intervals (CI) for the composite outcome in the high [n = 929 (27.3%)] and moderate comorbidity [n = 1579 (46.4%)] groups were 5.40 (4.20-6.94) and 2.54 (1.97-3.27), respectively. ABC pathway adherence was associated with reduction of the composite outcome overall (HR 0.63; 0.54-0.74). High comorbidity adversely impacted on OAC use, OAC discontinuation, and quality of warfarin control. If quality of anticoagulation control was included as part of the ABC pathway adherence, the reduction in composite outcome risk was greater (HR 0.46; 0.36-0.58). During 3-year follow-up, 33.9% changed from low- to the moderate-high comorbidity groups and 22.3% changed from moderate- to the high comorbidity group. In conclusion, comorbidity burden in AF patients is an important determinant of clinical outcomes, and changed over time. OAC use, OAC discontinuation, and quality of OAC control were impacted by comorbidity burden. ABC pathway adherence was associated with a reduced risk of adverse clinical outcomes.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"97-108"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563656","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":"Heparin-like effect of a dual antiplatelet and anticoagulant (APAC) agent on red blood cell deformability and aggregation in an experimental model.","authors":"Adam Attila Matrai, Adam Varga, Barbara Bedocs-Barath, Erzsebet Vanyolos, Rita Orban-Kalmandi, Linda Loczi, Zsuzsa Bagoly, Annukka Jouppila, Riitta Lassila, Norbert Nemeth, Adam Deak","doi":"10.1007/s11239-024-03040-8","DOIUrl":"10.1007/s11239-024-03040-8","url":null,"abstract":"<p><p>Treatments with different antithrombotic agents can affect micro-rheological variables, such as red blood cell (RBC) deformability and aggregation. Since the effect of dual antiplatelet and anticoagulant (APAC) treatment on micro-rheology is unknown, we aimed to investigate the effect of different intravenous doses of APAC on hematological and micro-rheological variables in a porcine model. Two groups were formed (APAC group, Control group), and blood was collected from the animals at preset intervals. Hematological variables, RBC deformability, and aggregation were measured. We observed an improvement in the RBC deformability measured at a low shear stress range (< 3 Pa). However, after both doses, a decrease in the maximal elongation index of RBC values occurred in the APAC group. RBC aggregation increased after APAC bolus dose, while it gradually and dose-dependently decreased. Supposedly, the improvement in RBC deformability that was observed at a lower shear rate could facilitate aggregation. Administration of APAC and unfractionated heparin (UFH) caused comparable changes in hematological and hemorheological variables. Signs of thrombosis or bleeding did not occur. APAC and UFH had comparable micro-rheological effects.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"1329-1338"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133088","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":"RNAi targeting LMAN1-MCFD2 complex promotes anticoagulation in mice.","authors":"Siqian Ma, Boyan Liu, Hong Du, Fei Yang, Jingjing Han, Xinqi Huang, Minyang Zhang, Shundong Ji, Miao Jiang","doi":"10.1007/s11239-024-03034-6","DOIUrl":"10.1007/s11239-024-03034-6","url":null,"abstract":"<p><p>Combined deficiency of coagulation factor V (FV) and factor VIII (FVIII) is a rare bleeding disease caused by variants in either lectin mannose binding 1 (LMAN1) or multiple coagulation factor deficiency 2 (MCFD2) gene. Reducing the level of FVIII by inhibiting the LMAN1-MCFD2 complex may become a new anticoagulant approach. We aimed to find a new therapeutic option for anticoagulation by RNA interference (RNAi) targeting LMAN1 and MCFD2. siRNA sequences with cross-homology between mice and humans were designed based on LMAN1 or MCFD2 transcripts in NCBI and were screened with the Dual-Luciferase reporter assay. The optimal siRNAs were chemically modified and conjugated with three N-acetylgalactosamine molecules (GalNAc-siRNA), promoting their targeted delivery to the liver. The expression of LMAN1 and MCFD2 in cell lines or mice was examined by RT-qPCR and western blotting. For the mice administered with siRNA, we assessed their coagulation function by measuring APTT and the activity of FVIII factor. After administration, siRNAs GalNAc-LMAN1 and GalNAc-MCFD2 demonstrated effective and persistent LMAN1 and MCFD2 inhibition. 7 days after injection of 3mg/kg GalNAc-LMAN1, the LMAN1 mRNA levels reduced to 19.97% ± 3.78%. MCFD2 mRNA levels reduced to 32.22% ± 13.14% with injection of 3mg/kg GalNAc-MCFD2. After repeated administration, APTT was prolonged and the FVIII activity was remarkably decreased. The tail bleeding test of mice showed that the amount of bleeding in the treated group did not significantly increase compared with the control group. Our study confirms that therapy with RNAi targeting LMAN1-MCFD2 complex is effective and can be considered a viable option for anticoagulation drugs. However, the benefits and potential risk of bleeding in thrombophilic mice model needs to be evaluated.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"1349-1362"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108795","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":"Discovery of a new lead molecule to develop a novel class of human factor XIIa inhibitors.","authors":"Anthony Dumas, Navneet Goyal, Madhusoodanan Mottamal, Daniel K Afosah, Rami A Al-Horani","doi":"10.1007/s11239-024-03054-2","DOIUrl":"10.1007/s11239-024-03054-2","url":null,"abstract":"<p><p>Factor XIIa (FXIIa) is a plasma serine protease within the contact activation pathway. Inhibiting FXIIa could offer a viable therapeutic approach for achieving effective and safer anticoagulation without the bleeding risks that accompany the use of existing anticoagulants. Therefore, we investigated the anticoagulant properties of an amidine-containing molecule (inhibitor 1) to identify a potential lead molecule for subsequent development of FXIIa inhibitors. Results indicated that inhibitor 1 primarily inhibits human FXIIa with an IC₅₀ value of ~30 µM. The inhibitor demonstrated variable selectivity against thrombin, factor IXa, factor Xa, factor XIa, and activated protein C. Michaelis-Menten kinetics indicated that the molecule is an active site inhibitor of FXIIa. Molecular modeling studies revealed that the molecule recognizes residues His57, Asp189, and Ala190 in FXIIa's active site. The inhibitor selectively and concentration-dependently prolonged the clotting time of human plasma under activated partial thromboplastin time assay conditions. The inhibitor did not exhibit significant cytotoxicity in human HEK293 cells and the in silico pharmacokinetics and toxicology data were comparable to known anticoagulants. This study introduces inhibitor 1 as a lead platform for further development as an anticoagulant to provide a more effective and safer approach to preventing and treating thromboembolic diseases.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"1308-1314"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564452","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}