Journal of Thrombosis and Haemostasis最新文献

{"title":"Myocardial infarction and short- or long-term risk of a subsequent cancer diagnosis: A Danish Nationwide Cohort Study.","authors":"Jens Sundbøll, Katalin Veres, Frederikke S Troelsen, Morten Würtz, Hans Erik Bøtker, Henrik Toft Sørensen","doi":"10.1016/j.jtha.2024.12.008","DOIUrl":"https://doi.org/10.1016/j.jtha.2024.12.008","url":null,"abstract":"<p><strong>Background: </strong>Growing evidence suggests that myocardial infarction (MI) may be a marker of cancer risk, but many aspects of this relation are poorly understood. We therefore examined the short- and long-term risk of incident cancer in patients presenting with MI.</p><p><strong>Methods: </strong>Using nationwide population-based Danish health registries, we identified all patients with a first-time diagnosis of MI (1995-2021) and followed them for up to 28 years for any subsequent diagnosis of cancer. We computed risks and standardized incidence ratios with 95% confidence intervals (CIs) as the observed number of cancers relative to the expected number based on national cancer incidence rates by sex, age, and calendar year.</p><p><strong>Results: </strong>Among 185,065 patients diagnosed with MI, we observed 25,315 subsequent cancers. The risk of any cancer was 2.4% after 1 year of follow-up, increasing to 25.8% after 28 years, taking the competing risks of death into account. During the first year of follow-up, the standardized incidence ratio of any cancer was 1.67 (95% CI: 1.62-1.73). The standardized incidence ratio remained moderately elevated during 2-5 years (1.03, 95% CI: 1.01-1.05) and beyond 5 years (1.07, 95% CI: 1.05-1.09). The strongest associations were found for hematological as well as obesity- and smoking-related cancers during the first year of follow-up, whereas primarily the risk of smoking-related cancers remained elevated throughout the entire follow-up period.</p><p><strong>Conclusion: </strong>MI was associated with subsequent risk of cancer, driven by hematological, obesity- and smoking-related cancers in the short term and smoking-related cancers in the long term.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864745","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":"Molecular signatures associated with venous thromboembolism in children with acute lymphoblastic leukemia.","authors":"Marie-Claude Pelland-Marcotte, Anas Belaktib, Arnaud Droit, Meredith Michelle Remy, Jeyani George Clement, Stéphanie Bianco, Yan Ma, Jessica Liu, Lara Herrmann, Virgile Raufaste-Cazavieille, Charles Joly-Beauparlant, Loïc Mangnier, Mickael Leclercq, Thomas Sontag, Maxime Caron, Pascal St-Onge, Sylvie Langlois, Victoria Koch, Yael Flamand, Daniel Sinnett, Lewis Silverman, Thai Hoa Tran, Raoul Santiago","doi":"10.1016/j.jtha.2024.12.007","DOIUrl":"https://doi.org/10.1016/j.jtha.2024.12.007","url":null,"abstract":"<p><strong>Background: </strong>Venous thromboembolism (VTE) is a frequent complication of childhood acute lymphoblastic leukemia (ALL).</p><p><strong>Objectives: </strong>We aimed to identify molecular markers and signatures of leukemia microenvironment associated with VTE in childhood ALL, by dual-omics approach of gene expression (GEP) and DNA-methylation profiling.</p><p><strong>Patients/methods: </strong>Eligible children were aged 1-21 years old with newly diagnosed ALL enrolled on the Dana Farber Cancer Institute 16-001 trial with available RNA sequencing data from bone marrow at diagnosis. Primary outcome was VTE requiring medical intervention, divided between early events (ET), within 6 weeks from ALL diagnosis, or late (LT) otherwise. We compared differential gene expression and DNA-methylation in children with and without VTE and in the subgroup of children with ETs. The DNA-methylation cis-regulation was explored by dual-omics integration. Functional gene set enrichment analyses were performed to assess dysregulated pathways associated with thrombosis. GEP-based signature for thrombosis-free interval was determined using Kaplan-Meier estimator and log-rank tests.</p><p><strong>Results: </strong>We included 248 patients (median age: 7.5 years, 78% precursor B-cell ALL), of whom 56 (23%) developed VTE. Genes and metabolic pathways involved in coagulation, platelet activation and neutrophil extracellular trap formation (NETosis) were associated with ETs. Dual-omics analysis indicated that methylation reprogramming might be responsible for the over-expression of genes involved in NETosis and coagulation in patients with ETs. A prothrombotic gene signature, based on VWF, PF4 and CXCL8 expression, predicted thrombosis-free interval.</p><p><strong>Conclusions: </strong>This suggests that gene markers and epigenetic regulation of the leukemic microenvironment are drivers of VTE, notably early events, in childhood ALL.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854438","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":"Transfusion Biomaterials for Hemostasis.","authors":"Ethan Pozy, Ashley C Brown","doi":"10.1016/j.jtha.2024.11.030","DOIUrl":"https://doi.org/10.1016/j.jtha.2024.11.030","url":null,"abstract":"<p><p>Bleeding is a leading cause of trauma deaths and surgical complications. Excessive bleeding has traditionally been treated with the transfusion of donated blood. However, the complicated logistics of sourcing and storing donated blood increases the cost and reduces the accessibility of treatment, particularly as rates of blood donation decline. Advances in biomaterials for targeted drug delivery have presented the opportunity for alternative synthetic injectable hemostats. Among these leading technologies are lipid and polymeric particles and polymer platforms that bind to ligands present at wound sites and amplify hemostatic pathways. As leading hemostatic biomaterials advance towards clinical application, we review current preclinical research models and findings as well as future research directions for next-generation biomaterial injectable hemostatic technologies.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829158","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":"New Targets for Antithrombotic Medications: Seeking to Decouple Thrombosis from Hemostasis.","authors":"Geoffrey D Barnes","doi":"10.1016/j.jtha.2024.12.003","DOIUrl":"https://doi.org/10.1016/j.jtha.2024.12.003","url":null,"abstract":"<p><p>Arterial and venous thromboses are leading causes of morbidity and mortality worldwide. Numerous antithrombotic agents are currently available with antiplatelet, thrombolytic/fibrinolytic, and anticoagulant activity. However, all the currently available antithrombotic agents carry a risk of bleeding that often prevents their use. This unfavorable risk-benefit profile is particularly challenging for patients with cancer-associated venous thromboembolism, patients with atrial fibrillation at a high risk of bleeding, and for patients with end-stage renal disease. Patients with ischemic stroke and acute coronary syndromes have not yet found a favorable risk-benefit profile with anticoagulant therapy to help reduce the residual thromboembolic risk that remains after antiplatelet and lipid therapy. Two emerging classes of antithrombotic agents, factor XI/XIa inhibitors and glycoprotein VI inhibitors, have shown promise in their ability to prevent pathologic thrombosis without increasing the risk of hemostatic-related bleeding in phase 2 studies. Among the factor XI/XIa inhibitors of coagulation, a parenterally administered monoclonal antibody (abelacimab) and two orally administered small molecule inhibitors (asundexian, milvexian) are collectively being studied in patients with atrial fibrillation, cancer-associated venous thromboembolism, acute coronary syndrome, and ischemic stroke. One parenterally administered glycoprotein VI antiplatelet agent (glenzocimab) is currently being studied in patients with ischemic stroke. If shown to be efficacious and safe in ongoing phase 3 studies, both classes of emerging antithrombotic agents have the potential to greatly improve outcomes for patients with challenging thrombotic conditions.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829154","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":"The history of women and hemophilia: a narrative review of evolving beliefs and testing practices.","authors":"Megan Chaigneau, Mackenzie Bowman, Pamela Wilton, Robert Card, Man-Chiu Poon, David Lillicrap, Michelle Sholzberg, Paula James","doi":"10.1016/j.jtha.2024.12.004","DOIUrl":"https://doi.org/10.1016/j.jtha.2024.12.004","url":null,"abstract":"<p><p>The history of hemophilia is well-documented, yet reports focus heavily on the male-perspective and severe forms of the disease. Although hemophilia was initially believed to only affect men with women seen as silent carriers, it is now universally acknowledged that women and girls can also be affected. In this narrative review, we track the progression of beliefs about women and hemophilia as documented in the literature from pre-1800's to the present time. We present a timeline of evolving beliefs and testing practices and identify nine distinct time periods when key shifts occurred related to various scientific discoveries. Our review highlights how women affected by hemophilia experienced complete dismissal of their health issues despite evidence of bleeding symptoms as early as the 1900's. We identify 1990 as a major timepoint for shifting beliefs when large scale acknowledgement that hemophilia also affects women is documented and systematic testing for bleeding risk is first suggested. Women evolve from being seen as unaffected genetic transmitters only to being recognized as a population affected by hemophilia in unique ways requiring timely testing and effective treatment. Yet despite documented progress, recent publications document many persistent issues such as delayed diagnosis, untreated symptoms, and barriers to care. Ongoing research and advocacy efforts are required to improve knowledge translation until real-world outcomes are seen in screening, diagnosis, treatment and prevention of bleeding.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829156","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":"Evaluation of the MRX PT DOAC assay for detection of clinically relevant factor Xa inhibitor drug levels.","authors":"Brittany Salter, Karen Moffat, Stephen Carlino, Jackie Dobson-Storr, Lee Beckett, Emma Broomhead, Liselotte Onelöv, Sarah Ge, Marina Atalla, Raymond Melika, Saumya Bansal, Steven Kitchen, Mark Crowther, Siraj Mithoowani","doi":"10.1016/j.jtha.2024.12.005","DOIUrl":"https://doi.org/10.1016/j.jtha.2024.12.005","url":null,"abstract":"<p><strong>Background: </strong>Although routine monitoring is not needed for DOACs, knowing if a clinically relevant DOAC level is present can be critical, especially in cases of severe bleeding or urgent surgery. Rapid assays to exclude these levels are necessary but not widely available.</p><p><strong>Methods: </strong>The MRX PT DOAC assay measures the functional effect of DOACs using the clot-time ratio; a ratio between DOAC-sensitive prothrombin time (PT) and DOAC-insensitive PT. We conducted a multi-center retrospective study of 152 samples from 151 patients with known DOAC levels to assess whether the MRX PT DOAC assay could exclude clinically relevant drug levels of >50 ng/mL, and whether test performance differed across coagulation analyzers. To assess generalizability, the assay was run on four coagulation analyzers: Werfen ACLTOP 750, Diagnostica Stago STACompact MAX, Sysmex CS2500, and Sysmex CN-6000.</p><p><strong>Results: </strong>The MRX PT DOAC assay had a sensitivity of 100% with a confidence interval (CI) of 70-100% and negative predictive value (NPV) of 100% (CI:57-100%) for edoxaban drug levels >50 ng/mL. For rivaroxaban, sensitivity was 100% (CI:61-100%) and NPV was 100% (CI:5-100%). For apixaban, sensitivity ranged from 59% to 83% (CI:41-93%) and NPV ranged from 0% to 50% (CI:0-69%). The specificity of the assay ranged from 61% to 86% (CI:39-93%) for apixaban, 36% to 50% (CI:3-95%) for edoxaban, and 75% to 100% (CI:30-100%) for rivaroxaban.</p><p><strong>Conclusion: </strong>The MRX PT DOAC assay reliably excludes clinically relevant DOAC levels edoxaban and rivaroxaban, across multiple analyzers, but not for apixaban.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829152","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":"Impaired Hemostatic and Immune Functions of Platelets After Acute Thrombocytopenia.","authors":"Anita Pirabe, Waltraud C Schrottmaier, Dino Mehic, Hubert Hackl, Sabine Frühwirth, Anna Schmuckenschlager, Sarah Beck, Johanna Gebhart, Karoline Gleixner, Wolfgang Sperr, Alice Assinger","doi":"10.1016/j.jtha.2024.11.029","DOIUrl":"https://doi.org/10.1016/j.jtha.2024.11.029","url":null,"abstract":"<p><strong>Background: </strong>Platelets are pivotal in maintaining vascular integrity, hemostasis, and immune modulation, with newly generated, immature platelets being the most responsive in fulfilling these tasks. Therefore, the immature platelet fraction provides insights into thrombopoiesis dynamics and clinical prognostication. However, it is currently unclear how immature platelet functions change in settings of acute thrombocytopenia.</p><p><strong>Objectives: </strong>We aimed to investigate the functional consequences of acute thrombocytopenia on newly generated immature platelets in various mouse models and human subjects.</p><p><strong>Methods: </strong>To examine platelet functionality after acute thrombocytopenia, we depleted either megakaryocytes using a PF4-specific iDTR transgenic mouse model or platelets via antibody-mediated depletion in mice, and collected blood from acute myeloid leukemia (AML) patients before and after consolidation or induction chemotherapy. Chemotherapy treatment was further repeated in an animal model. We assessed surface receptor expression of activation markers (CD62P, active GPIIb/IIIa, CD40L, CD63, CD107a) and toll-like receptors (TLR2, TLR4, TLR9) on immature and mature platelets following activation. Additionally, we investigated procoagulant platelet formation and platelet-leukocyte interactions in mouse models and AML patients.</p><p><strong>Results: </strong>In murine models, acute thrombocytopenia led to impaired hemostatic function and altered surface receptor expression in newly generated immature platelets. Similarly, AML patients during regeneration post-chemotherapy exhibited reduced platelet activation and procoagulant function, alongside altered receptor expression and diminished platelet-leukocyte interactions.</p><p><strong>Conclusions: </strong>After acute thrombocytopenia platelet-mediated hemostasis and immune modulation by newly generated platelets are impaired, underscoring the clinical relevance of understanding platelet function alterations in (post)thrombocytopenic conditions for therapeutic optimization.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829153","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":"Assessment of a next generation sequencing gene panel strategy in 133 patients with negative thrombophilia screening.","authors":"Pierre Suchon, Omar Soukarieh, Clara Bernard, Antoine Mariotti, Vincent Ernest, Marie-Christine Barthet, Noémie Saut, Alexandre Theron, Christine Biron-Andréani, Mélanie Y Daniel, Judith Catella, Pierre-Simon Rohrlich, Florence Blanc-Jouvan, Véronique Le Cam Duchez, Loubna Dari, David-Alexandre Trégouët, Pierre-Emmanuel Morange","doi":"10.1016/j.jtha.2024.12.006","DOIUrl":"https://doi.org/10.1016/j.jtha.2024.12.006","url":null,"abstract":"<p><strong>Background: </strong>Although heritability of venous thromboembolism (VTE) is high, the thrombophilia screening appears to be positive only in a minority of VTE patients. Adding rare variants screening to identify VTE missing heritability still requires further assessment.</p><p><strong>Objective: </strong>We report the results of a panel strategy after 3 years of application.</p><p><strong>Patients/methods: </strong>We performed the sequencing of 28 genes related to coagulation cascade and/or VTE using high-throughput sequencing in133 unrelated patients with a personal history of VTE and negative thrombophilia screening. Only variants with minor allele frequency <0.1% were classified according to ACMG recommendations. We recorded Class 3, 4 and 5 variants.</p><p><strong>Results and conclusions: </strong>We identified Class 3, 4 or 5 variants in 46 patients resulting in an identification rate of 35%. Out of the 45 recorded variants, 35 were considered as Class 3 (78%), 9 were Class 4 (20%) and 1 was Class 5 (2%). Four genes accounted for nearly two-thirds (27/45) of the identified variants: SERPINC1, PROS1, F2 and F5. We observed a high rate of recurrent variants in the SERPINC1 and PROS1 genes, including the Cambridge II (SERPINC1 p.A416S), Dublin (SERPINC1 p.V30E), and Heerlen (PROS1 p.S501P) variants. The elevated frequency of these variants in a symptomatic population, compared to their frequency in the general population, provides strong support for their association with VTE risk. We identified 4 (likely) pathogenic variants in F2: p.R596Q (F2 Belgrade), p.R541W, p.P386T and p.R425L.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829151","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":"Clinical and Genetic Characteristics of 40 Patients with Non-Muscle Myosin Heavy Chain 9-Related Disease (MYH9-RD) Misdiagnosed as ITP: A Retrospective Analysis in China.","authors":"Abdul Rehman Arif, Hu Zhou, Yongjun Fang, Yunfeng Cheng, Jieyu Ye, Wenlan Chen, Yajie Ding, Li Cai, Mei Xue, Heng Mei, Yadan Wang","doi":"10.1016/j.jtha.2024.12.001","DOIUrl":"https://doi.org/10.1016/j.jtha.2024.12.001","url":null,"abstract":"<p><strong>Background: </strong>Myosin Heavy Chain 9-related diseases (MYH9-RD) are rare autosomal dominant platelet disorders characterised by macrothrombocytopaenia and leukocyte inclusion bodies. They can manifest with non-haematological complications, including deafness, nephropathy, or cataracts. Due to its rarity and its similar clinical presentation with immune thrombocytopaenia (ITP), MYH9-RD is often misdiagnosed as ITP, leading to inappropriate treatment and delayed management of complications.</p><p><strong>Objective: </strong>The study aimed to evaluate clinical, therapeutic, and genetic aspects of patients with MYH9-RD misdiagnosed with ITP, comparing differences between Chinese paediatric and adult cases of this condition.</p><p><strong>Methods: </strong>This multi-centre retrospective study included data obtained from Chinese patients diagnosed with MYH9-RD between January 2014 and December 2023 at five centres.</p><p><strong>Results: </strong>Adults exhibited significantly longer median misdiagnosis (9 years vs. 0.2 years, p < 0.001) and treatment durations (1.5 years vs. 0.1 years, p < 0.001) than children. Non-haematological manifestations were exclusive to adults (10/21). All patients received inappropriate ITP treatments, with adults receiving more different treatments. Genetic analysis revealed 21 spontaneous mutations (52.5%), 12 familial mutations, and 7 mutations of unknown inheritance patterns. Two novel mutations (p.G1517V and p.K1674Q) were identified. Patients with p.R702C mutation demonstrated early-stage kidney injury and hearing loss.</p><p><strong>Conclusion: </strong>Adult patients with MYH9-RD face elevated risks of misdiagnosis, prolonged inappropriate treatment, and non-haematological complications than paediatric patients. Enhanced awareness, consideration of mean platelet volume, family history, and genetic screening are crucial for accurate MYH9-RD diagnosis and management. The prevalence of spontaneous mutations and identified genotype-phenotype correlations warrant further investigation in the Chinese population.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822211","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":"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":"https://doi.org/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 associations between in and ex vivo hemostatic parameters and recurrent ischemic events after an ischemic stroke or transient ischemic attack 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 (HR) 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; 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; 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, thrombin decay constant, reflecting 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":"2024-12-11","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}