Thrombosis and haemostasis最新文献

{"title":"Risk of Major Bleeding with Antiplatelet and/or Anticoagulation Therapy in Inherited Factor XI Deficiency: Insights from Real-World Observations.","authors":"Shanni Vaismann, Nili Stein, Liat Dizengoff, Amir Warwar, Shoshan Perek, Ibraheem Zoabi, Walid Saliba, Meir Preis","doi":"10.1055/a-2347-4338","DOIUrl":"10.1055/a-2347-4338","url":null,"abstract":"","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421098","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 a nomogram for predicting sepsis-induced coagulopathy in septic patients: mixed cohort study.","authors":"Yuting Li, Liying Zhang, Youquan Wang, Meng Gao, Chaoyang Zhang, Yuhan Zhang, Dong Zhang","doi":"10.1055/a-2359-2563","DOIUrl":"https://doi.org/10.1055/a-2359-2563","url":null,"abstract":"<p><strong>Background: </strong>Sepsis-induced coagulopathy (SIC) is a common cause of poor prognosis in critically ill patients in the intensive care unit (ICU). This study aimed to develop a predictive nomogram incorporating clinical markers and scoring systems to individually predict the probability of SIC in septic patients.</p><p><strong>Methods: </strong>Patients consecutively recruited in the stage between January 2022 and April 2023 constituted the development cohort for retrospective analysis to internally test the nomogram, and patients in the stage between May 2023 to November 2023 constituted the validation cohort for prospective analysis to external validate the nomogram. The nomogram was validated in an independent external validation cohort, involving discrimination and calibration. A decision curve analysis was also performed to evaluate the net benefit of the insertion decision with this nomogram.</p><p><strong>Results: </strong>A total of 548 and 245 patients were included in the development and validation cohort, respectively. Predictors contained in the prediction nomogram included shock, platelets and INR. Patients with shock (OR, 4.499; 95% CI, 2.730-7.414; P < 0.001) , higher INR (OR, 349.384; 95% CI, 62.337-1958.221; P < 0.001) and lower platelet (OR, 0.985; 95% CI, 0.982-0.988; P < 0.001) had higher probabilities of SIC. The development model showed good discrimination, with an AUROC of 0.879（95%CI, 0.850-0.908）and good calibration. Application of the nomogram in the validation cohort also gave good discrimination with an AUROC of 0.872（95%CI,0.826-0.917）and good calibration.</p><p><strong>Conclusions: </strong>By incorporating shock, platelets and INR in the model, this useful nomogram could be accessibly utilized to predict SIC occurrence in septic patients.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499059","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":"Heterozygous Prothrombin Mutation-Associated Thrombophilia.","authors":"Xi Wu, Lei Li, Zhengjing Lu, Xiaobo Hu, Yeling Lu, Yu Liu, Guanqun Xu, Qiulan Ding, Xuefeng Wang, Wenman Wu, Peipei Jin, Jing Dai","doi":"10.1055/a-2350-8338","DOIUrl":"10.1055/a-2350-8338","url":null,"abstract":"<p><strong>Background: </strong> Venous thromboembolism (VTE) is predisposed by thrombotic mutations in patients with hereditary thrombophilia. Although prothrombin deficiencies caused by homozygous or compound heterozygous mutations are associated with bleeding diathesis, rare cases have shown a correlation between heterozygous prothrombin mutations and thrombosis.</p><p><strong>Materials and methods: </strong> We surveyed genetic variants involved in thrombosis and hemostasis in 347 patients with unprovoked VTE or having a positive family history of thrombosis. For patients identified with heterozygous prothrombin mutations, we conducted family investigations and performed a thrombin generation test (TGT) to elucidate the thrombotic risk. Novel mutants were expressed and subjected to functional assays to clarify the underlying thrombotic mechanisms.</p><p><strong>Results: </strong> Heterozygous prothrombin mutations were identified in 3.5% of patients (12/347), including three novel mutations Phe382Ser, Phe382Leu, and Asp597Tyr found in one patient each, as well as previously reported Arg541Trp mutation in four patients and Arg596Gln mutation in five patients. A total of 42 mutation carriers were identified within the 12 pedigrees, among whom 64.3% (27/42) had experienced thrombotic events. TGT results demonstrated hypercoagulability for carriers of the five mutations, with Arg596Gln showing the highest thrombin generation potential followed by Arg541Trp. The Phe382-associated mutations severely impaired thrombomodulin-binding ability of thrombin, resulting in obviously reduced protein C (PC) activation. The Asp597Tyr mutation exhibited a mild reduction in both inactivation by antithrombin and PC activation reactions.</p><p><strong>Conclusion: </strong>The presence of heterozygous prothrombin mutations represents a potential genetic predisposition for VTE. All thrombosis-associated mutations potentiate coagulation activity by either conferring antithrombin resistance and/or impairing PC pathway activity.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447174","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":"2024 Chinese Expert Consensus Guidelines on the Diagnosis and Treatment of Atrial Fibrillation in the Elderly, Endorsed by Geriatric Society of Chinese Medical Association (Cardiovascular Group) and Chinese Society of Geriatric Health Medicine (Cardiovascular branch): Executive Summary.","authors":"Yutang Wang, Yutao Guo, Mingzhao Qin, Jin Fan, Ming Tang, Xinjun Zhang, Hao Wang, Xiaoying Li, Gregory Y H Lip","doi":"10.1055/a-2325-5923","DOIUrl":"10.1055/a-2325-5923","url":null,"abstract":"<p><p>The consensus guidelines of the Geriatric Society of Chinese Medical Association on the management of atrial fibrillation (AF) in the elderly was first published in 2011 and updated in 2016, with endorsement by Chinese Society of Geriatric Health Medicine. Since then, many important studies regarding the screening and treatment in the elderly population have been reported, necessitating this updated expert consensus guideline. The writing committee members comprehensively reviewed updated evidence pertaining to elderly patients with AF, and formulated this 2024 update. The highlighted issues focused on the following: screening for AF, geriatric comprehensive assessment, use of the Atrial fibrillation Better Care (ABC) pathway for the elderly patients, and special clinical settings related to elderly patients with AF. New recommendations addressing smart technology facilitated AF screening, ABC pathway based management, and optimal anticoagulation were developed, with a focus on the elderly.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923250","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":"Binding promiscuity of therapeutic factor VIII.","authors":"Alejandra Reyes Ruiz, Aishwarya Sudam Bhale, Krishnan Venkataraman, Jordan D Dimitrov, Sebastien Lacroix-Desmazes","doi":"10.1055/a-2358-0853","DOIUrl":"https://doi.org/10.1055/a-2358-0853","url":null,"abstract":"<p><p>The binding promiscuity of proteins defines their ability to indiscriminately bind multiple unrelated molecules. Binding promiscuity is implicated, at least in part, in the off-target reactivity, non-specific biodistribution, immunogenicity and/or short half-life of potentially efficacious protein drugs, thus affecting their clinical use. In this review, we discuss the current evidence for the binding promiscuity of factor VIII (FVIII), a protein used for the treatment of hemophilia A, which cumulates poor pharmacokinetics, and elevated immunogenicity. We summarize the different canonical and non-canonical molecular interactions that FVIII may establish in the circulation and that could be responsible for its therapeutic liabilities. We also provide information suggesting that the FVIII light chain, and notably its C1 and C2 domains, could play an important role in binding promiscuity. We believe that the knowledge accumulated over years of FVIII usage could be exploited for the development of tools that predict drug efficacy and toxicity and open a mutational space to reduce the binding promiscuity of newly generated protein drugs while conserving their therapeutic efficacy.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477498","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 Prophylaxis with Rivaroxaban in Patients with Prehospital COVID-19: A Meta-analysis of Two Placebo-Controlled Trials.","authors":"Judith Hsia, Alex C Spyropoulos, Gregory Piazza, Stephen Weng, Michael W Dunne, Concetta Lipardi, Elliot S Barnathan, Marc P Bonaca","doi":"10.1055/a-2216-5848","DOIUrl":"10.1055/a-2216-5848","url":null,"abstract":"<p><strong>Background: </strong> We conducted a prespecified meta-analysis of two randomized, placebo-controlled trials of rivaroxaban 10 mg daily in prehospital patients with acute coronavirus disease 2019 (COVID-19). Individually, the trials had limited power to detect a treatment effect due to recruitment stopping ahead of plan.</p><p><strong>Material and methods: </strong> The statistical analysis plan for the meta-analysis was finalized before unblinding of PREVENT-HD, the larger of the two trials. Pooled risk ratios and pooled risk differences along with the two-sided 95% confidence intervals were calculated using random-effect models.</p><p><strong>Results: </strong> Rivaroxaban did not reduce the occurrence of either the primary prespecified endpoint, a composite of symptomatic arterial and venous thromboembolism, myocardial infarction, ischemic stroke, acute limb ischemia, all-cause hospitalization, and all-cause mortality (risk difference: 0.0044; 95% confidence interval: -0.0263, 0.0175; <i>p</i> = 0.69 for pooled risk difference) or the secondary endpoint of all-cause hospitalization (<i>p</i> = 0.76). Although thrombotic events were infrequent, pooled analysis did reveal that rivaroxaban reduced arterial and venous thrombotic events (placebo 6 events, rivaroxaban 0 events; pooled risk difference: -0.0068; 95% confidence interval: -0.0132, -0.0006; <i>p</i> = 0.03). In the pooled studies, only one major bleeding event was observed in a rivaroxaban-allocated patient with no critical site or fatal bleeding events.</p><p><strong>Conclusion: </strong> Although this meta-analysis does not support antithrombotic prophylaxis with rivaroxaban in a broad prehospital population with acute COVID-19, the prevention of arterial and venous thrombotic events among rivaroxaban-allocated patients is consistent with the known thromboprophylactic effect of the drug in medically ill patients.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11199042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138300097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycosaminoglycans: Participants in Microvascular Coagulation of Sepsis.","authors":"Nanxi Li, Ruolin Hao, Peng Ren, Jingya Wang, Jiahui Dong, Tong Ye, Danyang Zhao, Xuan Qiao, Zhiyun Meng, Hui Gan, Shuchen Liu, Yunbo Sun, Guifang Dou, Ruolan Gu","doi":"10.1055/a-2250-3166","DOIUrl":"10.1055/a-2250-3166","url":null,"abstract":"<p><p>Sepsis represents a syndromic response to infection and frequently acts as a common pathway leading to fatality in the context of various infectious diseases globally. The pathology of severe sepsis is marked by an excess of inflammation and activated coagulation. A substantial contributor to mortality in sepsis patients is widespread microvascular thrombosis-induced organ dysfunction. Multiple lines of evidence support the notion that sepsis induces endothelial damage, leading to the release of glycosaminoglycans, potentially causing microvascular dysfunction. This review aims to initially elucidate the relationship among endothelial damage, excessive inflammation, and thrombosis in sepsis. Following this, we present a summary of the involvement of glycosaminoglycans in coagulation, elucidating interactions among glycosaminoglycans, platelets, and inflammatory cells. In this section, we also introduce a reasoned generalization of potential signal pathways wherein glycosaminoglycans play a role in clotting. Finally, we discuss current methods for detecting microvascular conditions in sepsis patients from the perspective of glycosaminoglycans. In conclusion, it is imperative to pay closer attention to the role of glycosaminoglycans in the mechanism of microvascular thrombosis in sepsis. Dynamically assessing glycosaminoglycan levels in patients may aid in predicting microvascular conditions, enabling the monitoring of disease progression, adjustment of clinical treatment schemes, and mitigation of both acute and long-term adverse outcomes associated with sepsis.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11199054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139502633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Insights into the Aortic Mechanical Properties of Mice Modeling Hereditary Aortic Diseases.","authors":"Nicolo Dubacher, Kaori Sugiyama, Jeffrey D Smith, Vanessa Nussbaumer, Máté Csonka, Szilamér Ferenczi, Krisztina J Kovács, Sylvan M Caspar, Lisa Lamberti, Janine Meienberg, Hiromi Yanagisawa, Mary B Sheppard, Gabor Matyas","doi":"10.1055/s-0044-1787957","DOIUrl":"https://doi.org/10.1055/s-0044-1787957","url":null,"abstract":"<p><strong>Objective: </strong> Hereditary aortic diseases (hADs) increase the risk of aortic dissections and ruptures. Recently, we have established an objective approach to measure the rupture force of the murine aorta, thereby explaining the outcomes of clinical studies and assessing the added value of approved drugs in vascular Ehlers-Danlos syndrome (vEDS). Here, we applied our approach to six additional mouse hAD models.</p><p><strong>Material and methods: </strong> We used two mouse models (<i>Fbn1C1041G</i> and <i>Fbn1mgR</i> ) of Marfan syndrome (MFS) as well as one smooth-muscle-cell-specific knockout (SMKO) of <i>Efemp2</i> and three CRISPR/Cas9-engineered knock-in models (<i>Ltbp1</i>, <i>Mfap4</i>, and <i>Timp1</i>). One of the two MFS models was subjected to 4-week-long losartan treatment. Per mouse, three rings of the thoracic aorta were prepared, mounted on a tissue puller, and uniaxially stretched until rupture.</p><p><strong>Results: </strong> The aortic rupture force of the SMKO and both MFS models was significantly lower compared with wild-type mice but in both MFS models higher than in mice modeling vEDS. In contrast, the <i>Ltbp1</i>, <i>Mfap4</i>, and <i>Timp1</i> knock-in models presented no impaired aortic integrity. As expected, losartan treatment reduced aneurysm formation but surprisingly had no impact on the aortic rupture force of our MFS mice.</p><p><strong>Conclusion: </strong> Our read-out system can characterize the aortic biomechanical integrity of mice modeling not only vEDS but also related hADs, allowing the aortic-rupture-force-focused comparison of mouse models. Furthermore, aneurysm progression alone may not be a sufficient read-out for aortic rupture, as antihypertensive drugs reducing aortic dilatation might not strengthen the weakened aortic wall. Our results may enable identification of improved medical therapies of hADs.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477499","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":"Anticoagulation in Patients with Mechanical Heart Valves: Less Is More?","authors":"Daniela Poli, Alessandro Squizzato, Alberto Tosetto","doi":"10.1055/s-0044-1786176","DOIUrl":"10.1055/s-0044-1786176","url":null,"abstract":"","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852861","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":"Platelet-Derived TGF-β1 Promotes Deep Vein Thrombosis.","authors":"Sixuan Zhang, Yingying Li, Jie Zhang, Yueyue Sun, Xiang Chu, Xiang Gui, Huan Tong, Yangyang Ding, Wen Ju, Mengdi Xu, Zhenyu Li, Lingyu Zeng, Kailin Xu, Jianlin Qiao","doi":"10.1055/a-2235-7485","DOIUrl":"10.1055/a-2235-7485","url":null,"abstract":"<p><strong>Background: </strong> Transforming growth factor-β1 (TGF-β1) modulates multiple cellular functions during development and tissue homeostasis. A large amount of TGF-β1 is stored in platelet α-granules and released upon platelet activation. Whether platelet-derived TGF-β1 plays a role in venous thrombosis remains unclear. This study intends to assess the role of platelet-derived TGF-β1 in the development of venous thrombosis in mice.</p><p><strong>Material and methods: </strong> TGF-β1^flox/flox and platelet-specific TGF-β1^-/- mice were utilized to assess platelet function in vitro, arterial thrombosis induced by FeCl₃, tail bleeding time, prothrombin time (PT), activated partial thromboplastin time (APTT), and deep vein thrombosis induced through ligation of the inferior vena cava (IVC). The IVC sample was collected to measure accumulation of neutrophils, monocytes, and the formation of neutrophil extracellular traps (NETs) by immunofluorescence staining.</p><p><strong>Results: </strong> TGF-β1 deficiency in platelets did not affect the number of circulating platelets, platelet aggregation, adenosine triphosphate release, and integrin αIIbβ3 activation. Meanwhile, TGF-β1 deficiency did not alter the arterial thrombus formation, hemostasis, and coagulation time (PT and APTT), but significantly impaired venous thrombus formation, inhibited the recruitment and accumulation of neutrophils and monocytes in thrombi, as well as reduced formation of NETs and platelet-neutrophil complex. In addition, adoptive transfer of TGF-β1^flox/flox platelets to TGF-β1^-/- mice rescued the impaired venous thrombus formation, recruitment of leukocytes and monocytes, as well as the NETs formation.</p><p><strong>Conclusion: </strong>In conclusion, platelet-derived TGF-β1 positively modulates venous thrombus formation in mice, indicating that targeting TGF-β1 might be a novel approach for treating venous thrombosis without increasing the risk of bleeding.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139049349","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}