Journal of Thrombosis and Haemostasis最新文献

{"title":"Low thrombin inactivation capacity is associated with an increased risk of recurrent ischemic events after ischemic stroke at a young age.","authors":"Janneke P Spiegelenberg, Romy De Laat-Kremers, Mark Roest, Bas de Laat, Marleen M H J van Gelder, Anil M Tuladhar, Saskia Middeldorp, Frank-Erik de Leeuw, Jenneke Leentjens","doi":"10.1016/j.jtha.2024.12.002","DOIUrl":"10.1016/j.jtha.2024.12.002","url":null,"abstract":"<p><strong>Background: </strong>Patients with ischemic stroke at a young age (18-50 years) have an increased long-term risk of recurrent ischemic events. Hypercoagulability may contribute to this high risk.</p><p><strong>Objectives: </strong>To investigate the associations between in vivo and ex vivo hemostatic parameters and recurrent ischemic events after an ischemic stroke or transient ischemic attack (TIA) at a young age.</p><p><strong>Methods: </strong>We included patients with ischemic stroke or TIA between 1980 and 2010 from the prospective FUTURE cohort. Blood samples were collected in 2010, and patients were followed for recurrent ischemic events from 2010 to 2023. Pro- and anticoagulant markers and thrombin generation assay were measured. Thrombin dynamic analysis was used to study underlying pro- and anticoagulant processes. Hazard ratios (HRs) per standard deviation increase were assessed with cause-specific hazard models.</p><p><strong>Results: </strong>Of the initial cohort of 581 patients, 332 were eligible. The median time between the index event and 2010 was 7.6 years. During a mean follow-up of 6.5 years, 70 of 332 (21.1%) patients experienced a recurrent ischemic event. Lower antithrombin levels (adjusted HR, 0.77; 95% CI, 0.60-0.98) and higher fibrinogen levels (HR, 1.35; 95% CI, 1.04-1.73) were associated with higher risk of recurrent ischemic events. Plasma thrombin generation was not associated with recurrence. However, the thrombin decay constant (HR, 0.67; 95% CI, 0.51-0.87) was associated with a lower risk of recurrent ischemic events.</p><p><strong>Conclusion: </strong>After an ischemic stroke or TIA at a young age, the thrombin decay constant, which reflects reduced protection against thrombin (low antithrombin) and decreased potential to inhibit thrombin (high fibrinogen), is associated with recurrent ischemic events.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822217","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":"Intercellular synergy between protease-activated receptors 1 and 4 during mouse development.","authors":"Rahul Rajala, Courtney T Griffin","doi":"10.1016/j.jtha.2024.11.022","DOIUrl":"10.1016/j.jtha.2024.11.022","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818496","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":"Therapeutic potential of DNases in immunothrombosis: promising succor or uncertain future?","authors":"Sara Zalghout, Kimberly Martinod","doi":"10.1016/j.jtha.2024.11.028","DOIUrl":"10.1016/j.jtha.2024.11.028","url":null,"abstract":"<p><p>Sepsis, a life-threatening condition characterized by systemic inflammation and multiorgan dysfunction, is closely associated with the excessive formation of neutrophil extracellular traps (NETs) and the release of cell-free DNA. Both play a central role in sepsis progression, acting as major contributors to immunothrombosis and associated complications. Endogenous DNases play a pivotal role in degrading NETs and cell-free DNA, yet their activity is often dysregulated during thrombotic disease. Although exogenous DNase1 administration has shown potential in reducing NET burden and mitigating the detrimental effects of immunothrombosis, its therapeutic efficacy upon intravenous administration remains uncertain. The development of engineered DNase formulations and combination therapies may further enhance its therapeutic effectiveness by modifying its pharmacodynamic properties and avoiding the adverse effects associated with NET degradation, respectively. Although NETs are well-established targets of DNase1, it remains uncertain whether the positive effects of DNase1 on immunothrombosis are exclusively related to it's targeting of NETs or if other components contributing to immunothrombosis are also affected. This review examines the endogenous regulation of NETs in circulation and the therapeutic potential of DNases in immunothrombosis, underscoring the necessity for further investigation to optimize their clinical application.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818467","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":"Safe and effective anticoagulation use: case studies in anticoagulation stewardship.","authors":"Jori E May, Arthur L Allen, Bethany T Samuelson Bannow, Carlee O'Connor, Katelyn W Sylvester, Scott Kaatz","doi":"10.1016/j.jtha.2024.11.024","DOIUrl":"10.1016/j.jtha.2024.11.024","url":null,"abstract":"<p><p>Anticoagulant use is prevalent and associated with significant potential for harm. Anticoagulation stewardship practice has emerged to address care gaps and promote safe, effective, and cost-conscious anticoagulation use across health care systems. We present 4 patient cases describing common challenges in anticoagulation management: inappropriate dosing of direct oral anticoagulants, the diagnosis and management of heparin-induced thrombocytopenia, periprocedural anticoagulation management, and heavy menstrual bleeding on anticoagulation. We discuss available examples of successful stewardship programs that can address the challenges of each case, demonstrating how an investment in anticoagulation stewardship can improve patient outcomes.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818466","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":"FVIIa-PAR2 signaling facilitates immune escape by reducing phagocytic potential of macrophages in breast cancer.","authors":"Arnab Ghosh, Avinandan Bhoumick, Subhojit Paul, Akash Chatterjee, Subhasis Mandal, Abhimanyu Basu, Soma Mukhopadhyay, Kaushik Das, Prosenjit Sen","doi":"10.1016/j.jtha.2024.11.027","DOIUrl":"10.1016/j.jtha.2024.11.027","url":null,"abstract":"<p><strong>Background: </strong>Treatment of breast cancers with immunotherapy has so far achieved limited success. Traditional immunotherapies focusing on cytotoxic T cells have attained modest success, while the approval of phagocytic checkpoint blockers is still pending. Coagulation proteases are crucial to cancer growth and proliferation, but their relevance in altering the immunologic topography in tumors remains largely unknown.</p><p><strong>Objectives: </strong>In this study, we aimed to examine whether factor VIIa (FVIIa)-driven protease-activated receptor 2 (PAR2) activation and its subsequent signaling pathways assist cancer cells in evading phagocytic macrophages.</p><p><strong>Methods: </strong>Peripheral blood mononuclear cell- or THP-1-derived macrophages were cocultured with MDA-MB-468 cells that were pretreated with or without FVIIa. The phagocytic activity of macrophages was assessed through flow cytometry and immunofluorescence. Additionally, an allograft model using wild-type and PAR2-deleted 4T1 cells was employed to investigate the impact of PAR2 activation on immune escape from macrophages in vivo.</p><p><strong>Results: </strong>We found evidence that FVIIa-induced PAR2 cleavage activates downstream signaling cascades and augments cellular levels of microRNA221, which transcriptionally activates both CD47 and stanniocalcein 1 expression, thereby assisting the escape from phagocytosis by macrophages. Stanniocalcein 1 decreases the surface expression of calreticulin, a dominant prophagocytic signal, thereby tilting it in favor of phagocytic evasion. Mouse models using PAR2-depleted cells displayed smaller tumor volumes and corresponding greater phagocytic events when combined with anti-CD47/anti-PD-L1 antibodies.</p><p><strong>Conclusion: </strong>PAR2 signaling initiates an intrinsic mechanism of immune escape by diminishing phagocytosis of cancer cells.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818494","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":"Out-of-hospital cardiac arrest associated with venous thromboembolism-a Swedish population-based cohort study.","authors":"Emma Bendz, Anna Oksanen, Susanna Larsson, Joel Ohm, Therese Djärv, Maria Bruzelius","doi":"10.1016/j.jtha.2024.11.021","DOIUrl":"10.1016/j.jtha.2024.11.021","url":null,"abstract":"<p><strong>Background: </strong>Venous thromboembolism (VTE) is a common and preventable cardiovascular disease but is potentially fatal if it presents as pulmonary embolism. There are few population-based studies on out-of-hospital cardiac arrest (OHCA) associated with VTE.</p><p><strong>Objectives: </strong>We aimed to investigate the prevalence and survival of VTE-associated OHCA in relation to sex, age, and presenting rhythm.</p><p><strong>Methods: </strong>This population-based cohort included all individuals over 15 years registered with a medical OHCA in Sweden 2008-2018. Data from national registers were used. Association with presenting rhythm, 30-day survival, and sex was estimated using adjusted multinomial and binary logistic regression for odds ratios (ORs) with 95% CI.</p><p><strong>Results: </strong>OHCA was associated with VTE in 852 (2.0%) of 41 813 individuals. The median age for VTE-associated OHCA was 69, compared to 73 for the entire cohort, with a higher female prevalence (45% vs 34%). Younger women had a proportionally higher incidence of VTE-associated OHCA than men of the same age. Pulseless electrical activity and asystole had adjusted ORs of 17.2 (95% CI, 11.3-26.0) and 9.59 (95% CI, 6.37-14.4) for VTE-associated OHCA compared with the entire cohort. The 30-day survival was substantially lower in the VTE group compared with the overall medical OHCA group, 2.0% vs 12%, adjusted OR 0.25 (95% CI, 0.13-0.47).</p><p><strong>Conclusion: </strong>This nationwide study confirms that VTE-associated OHCA is uncommon and almost always fatal. Despite fewer women experiencing OHCA, a higher proportion had VTE-associated OHCA, especially younger women. Our findings highlight the need for better prevention and identification of VTE-associated OHCA, particularly in women.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813643","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":"A novel automated chemiluminescent enzyme immunoassay for ADAMTS-13 activity enables accompanying measurements of the inhibitory autoantibodies.","authors":"Masayuki Kubo, Kazuyasu Konko, Emi Kinoshita, Satoshi Uemae, Katsushi Kobayashi, Yoshinori Hayashi, Akihiko Kan, Yoshihiro Fujimura, Masanori Matsumoto","doi":"10.1016/j.jtha.2024.11.020","DOIUrl":"10.1016/j.jtha.2024.11.020","url":null,"abstract":"<p><strong>Background: </strong>Thrombotic thrombocytopenic purpura (TTP) is a fatal disease caused by severe deficiency in ADAMTS-13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs 13) activity. ADAMTS-13 activity measurement is essential for the diagnosis of TTP, but conventional standard assays are manual and time-consuming. Automated ADAMTS-13 activity assays have recently become available; however, their accuracy remains challenging.</p><p><strong>Objectives: </strong>We here developed a novel chemiluminescent enzyme immunoassay (CLEIA) for ADAMTS-13 activity that is fully automated, highly sensitive, and has a short reaction time (17 minutes). We evaluated the utility of our fully automated CLEIA for measuring ADAMTS-13 activity and inhibitory antibodies and compared it with conventional manual assays.</p><p><strong>Methods: </strong>We compared our CLEIA for ADAMTS-13 activity and inhibitory antibodies with an in-house FRETS-VWF73 assay and commercial enzyme-linked immunosorbent assay (ELISA) using samples from 100 patients and 50 healthy donors. Agreement between assays was evaluated using a cutoff value of 10 international units/dL for ADAMTS-13 activity and 0.5 Bethesda units/mL for inhibitory antibodies.</p><p><strong>Results: </strong>The CLEIA and conventional assays for ADAMTS-13 activity correlated well. The CLEIA showed high agreement with the FRETS-VWF73 assay (kappa = 0.96) and ELISA (kappa = 1.0) in classifying patients with a cutoff value of 10 international units/dL for ADAMTS-13 activity. Furthermore, in classifying patients with the cutoff value of 0.5 Bethesda units/mL for inhibitory antibodies, the CLEIA agreed strongly with the FRETS-VWF73 assay (kappa = 0.95) and ELISA (kappa = 0.98). Its diagnostic performance for TTP was satisfactory.</p><p><strong>Conclusion: </strong>The high-performance and fully automated CLEIA enables rapid in-hospital diagnosis and follow-up of TTP, as well as detection of inhibitory ADAMTS-13 autoantibodies.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813639","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":"Disseminated intravascular coagulation and cirrhotic coagulopathy: overlap and differences. The current state of knowledge. Communication from the SSC of the ISTH.","authors":"Ecaterina Scarlatescu, Jerrold H Levy, Hunter Moore, Jecko Thachil, Toshiaki Iba, Lara N Roberts, Ton Lisman","doi":"10.1016/j.jtha.2024.11.019","DOIUrl":"10.1016/j.jtha.2024.11.019","url":null,"abstract":"<p><p>Patients with disseminated intravascular coagulation (DIC) have decreasing plasma levels of coagulation factors and platelet counts with increased levels of D-dimer. Standard laboratory tests are used clinically to diagnose DIC and quantify the severity of the disease. In patients with cirrhosis, liver-derived plasma coagulation factor levels are reduced due to decreased hepatic synthesis, further exacerbated by extravascular redistribution of these proteins, causing prolongation of routine diagnostic coagulation tests. Platelets are often decreased in cirrhosis due to reduced production and portal hypertension, resulting in hypersplenism and sequestration. Patients with cirrhosis frequently have elevated fibrin/fibrinogen degradation product levels without having acute medical decompensation. As a result, these patients commonly meet the laboratory criteria of DIC. However, it has been debated whether laboratory-assessed DIC is present in patients with cirrhosis and if it has clinical relevance. In this communication, we review hemostatic features in cirrhosis and DIC, examine published studies that evaluate the activation of hemostasis in patients with cirrhosis, and highlight future directions for research.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813641","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":"Endothelial colony-forming cells in the spotlight: insights into the pathophysiology of von Willebrand disease and rare bleeding disorders","authors":"Sebastiaan N.J. Laan ,&nbsp;Britte G. Lenderink ,&nbsp;Jeroen C.J. Eikenboom ,&nbsp;Ruben Bierings ,&nbsp;SYMPHONY consortium","doi":"10.1016/j.jtha.2024.08.011","DOIUrl":"10.1016/j.jtha.2024.08.011","url":null,"abstract":"<div><div>Endothelial cells deliver a vital contribution to the maintenance of hemostasis by constituting an anatomical as well as functional barrier between the blood and the rest of the body. Apart from the physical barrier function, endothelial cells maintain the hemostatic equilibrium by their pro- and anticoagulant functions. An important part of their procoagulant contribution is the production of von Willebrand factor (VWF), which is a carrier protein for coagulation factor VIII and facilitates the formation of a platelet plug. Thus, VWF is indispensable for both primary and secondary hemostasis, which is exemplified by the bleeding disorder von Willebrand disease that results from qualitative or quantitative deficiencies in VWF. A cellular model that was found to accurately reflect the endothelium and its secretory organelles are endothelial colony-forming cells, which can be readily isolated from peripheral blood and constitute a robust <em>ex vivo</em> model to investigate the donor’s endothelial cell function. This review summarizes some of the valuable insights on biology of VWF and pathogenic mechanisms of von Willebrand disease that have been made possible using studies with endothelial colony-forming cells derived from patients with bleeding disorders.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"22 12","pages":"Pages 3355-3365"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145869","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":"Estimation of gestational age-specific reference intervals for coagulation assays in a neonatal intensive care unit using real-world data","authors":"Natasha Lalos ,&nbsp;Zachary Vesoulis ,&nbsp;Carly Maucione ,&nbsp;Charles Eby ,&nbsp;Dennis J. Dietzen ,&nbsp;Stephen M. Roper ,&nbsp;Nicholas C. Spies","doi":"10.1016/j.jtha.2024.08.017","DOIUrl":"10.1016/j.jtha.2024.08.017","url":null,"abstract":"<div><h3>Background</h3><div>Interpretation of coagulation testing in neonates currently relies on reference intervals (RIs) defined from older patient cohorts. Direct RI studies are difficult, but indirect estimation may allow us to infer normative neonatal distributions from routinely collected clinical data.</div></div><div><h3>Objective</h3><div>Assess the utility of indirect reference interval methods in estimating coagulation reference intervals in critically ill neonates.</div></div><div><h3>Methods</h3><div>We analyzed first-in-life coagulation testing results from all patients admitted to a level IV neonatal intensive care unit between January 1, 2018, and January 1, 2024. Results obtained after transfusion of any blood product were excluded. Indirect RIs were estimated across gestational age groups using <em>refineR</em> and compared with currently reported intervals for patients less than 1 year of age.</div></div><div><h3>Results</h3><div>Prothrombin times (PTs) and international normalized ratios (INRs) were available for 1128 neonates, while activated partial thromboplastin times (APTTs) were available for 790 neonates. The indirect RI was 10 to 25 seconds in preterm, 10 to 22 seconds in term, and 10 to 24 seconds in all neonates for PT; 0.7 to 2.1 in preterm, 0.8 to 1.8 in term, and 0.8 to 1.9 in all neonates for INR; and 25 to 68 seconds in preterm, 25 to 58 seconds in term, and 25 to 62 seconds in all neonates for APTT. Compared with our current intervals, the indirect RIs would flag 58% fewer PT, 43% fewer INR, and 17% fewer APTT results as abnormal.</div></div><div><h3>Conclusion</h3><div>Indirectly estimated RIs in neonates admitted to intensive care show substantial divergence from current, first-year-of-life RIs, leading to an abundance of abnormal flags. The associations between these flags and provider behavior, transfusion practice, or clinical outcomes are areas of future exploration.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"22 12","pages":"Pages 3473-3478"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142251213","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}