Thrombosis and haemostasis最新文献

{"title":"Distinct Platelet Phenotype and Reactivity in Individuals with Permanent Atrial Fibrillation Treated with Direct Oral Anticoagulants: A Pilot Study.","authors":"Marzia Miglionico, Francesca Maiorca, Annamaria Sabetta, Ludovica Lombardi, Tania D'amico, Alessandro Cincione, Giovanni Buoninfante, Marin Pecani, Marco Proietti, Giulio Francesco Romiti, Roberto Cangemi, Stefania Basili, Valeria Raparelli, Lucia Stefanini","doi":"10.1055/a-2632-3100","DOIUrl":"10.1055/a-2632-3100","url":null,"abstract":"<p><p>Atrial fibrillation (AF) is linked to an elevated risk of thromboembolic events. Despite the use of guideline-recommended direct anticoagulants (DOACs), a significant proportion of AF patients show a residual risk of thromboembolic events, driven by mechanisms that are not fully understood.We conducted a pilot study to characterize the platelet function in DOACs-treated AF patients, to explore whether an association between platelets and the residual thromboembolic risk exists.Within the Age-It project of the National Recovery and Resilience Plan, we examined by flow cytometry the platelet phenotype, reactivity, and mitochondrial function and quantified 12 inflammatory cytokines of individuals with DOACs-treated permanent AF without a history of stroke (<i>n</i> = 18, 66 ± 13 years, 39% females), compared with an age-, sex-, and comorbidity-matched control group without AF (<i>n</i> = 18, 65 ± 11 years, 39% females).Unstimulated circulating platelets of DOACs-treated AF displayed a low-adhesive phenotype compared with matched controls. Upon stimulation, platelets of DOACs-treated AF were hyporeactive to ADP and PAR1 stimulation, but hyper-reactive to GPVI stimulation (adjusted <i>p</i> < 0.01). The lower responsiveness to ADP correlated with increased plasmatic concentrations of IFN-γ (r = - 0.539; <i>p</i> < 0.05) and TNF-α (r = - 0.472; <i>p</i> < 0.05). The higher reactivity to GPVI associated with an increased mitochondrial function, which positively correlated with TNF-α levels.Individuals with AF treated with DOACs exhibit low-grade inflammation and an altered platelet reactivity, suggesting a potential mechanism behind their residual thromboembolic risk. Further well-powered studies are warranted to test whether the observed platelet phenotype is implicated with the residual thromboembolic events in DOACs-treated AF patients.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275995","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":"Venous Thromboembolism Outcomes by Geographic Region and Self-Reported Race: Insights from the RIETE Registry.","authors":"Alfonso J Tafur, Benjamin Brenner, Pablo Demelo-Rodríguez, Leticia Guirado, José María Pedrajas, Lucia Mazzolai, Ana Cristina Montenegro, Raimundo Tirado, Aurora Villalobos, Manuel Monreal","doi":"10.1055/a-2615-4591","DOIUrl":"10.1055/a-2615-4591","url":null,"abstract":"<p><p>Venous thromboembolism (VTE) outcomes are influenced by various factors, including race and geographic location. This study aimed to evaluate the associations between race, geographic location, and VTE-related outcomes using real-world data.We analyzed data from 42,206 patients with acute VTE enrolled in the RIETE registry between June 2016 and June 2024. Patients were categorized by self-reported race/ethnicity: White (40,258), Arab (995), Asian (689), and Black (264). Baseline characteristics, comorbidities, treatment strategies, and outcomes (including recurrences, major bleeding, and mortality) were compared across groups and regions. Multivariable analyses were performed to adjust for confounders, including geographic location and comorbidities.Arabic and Asian patients were generally younger, had fewer comorbidities, and were more likely to receive direct oral anticoagulants than White patients. In unadjusted analysis, non-White patients had higher rates of deep vein thrombosis (DVT) recurrence and mortality. After multivariable adjustment, most differences disappeared. Notably, White patients enrolled in Asian centers had higher DVT recurrence (4.54 vs. 1.10/100 patient-years, respectively) and mortality rates (27.9 vs. 8.88/100 patient-years, respectively) than those in European centers, and Arab patients in Asia had higher mortality compared to those in Europe (24.1 vs. 8.26/100 patient-years, respectively).Geographic location, likely representing healthcare infrastructure, had a greater influence on VTE outcomes than self-reported race alone.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102499","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":"Left Atrial Appendage Closure after Ablation for Atrial Fibrillation: A Real-World Propensity Score-Matched Study.","authors":"Laurent Fauchier, Lisa Lochon, Thibault Lenormand, Bertrand Pierre, Arnaud Bisson","doi":"10.1055/a-2633-0069","DOIUrl":"10.1055/a-2633-0069","url":null,"abstract":"","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144286577","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":"HMGB1-Platelet Interactions: Mechanisms and Targeted Therapy Strategies.","authors":"Xiyuan Fang, Xianghui Zhou, Xin Zhou, Zhipeng Cheng, Yu Hu","doi":"10.1055/a-2622-0074","DOIUrl":"https://doi.org/10.1055/a-2622-0074","url":null,"abstract":"<p><p>Platelets serve not only as crucial hemostatic components but also as pivotal regulators of inflammatory responses, capable of interacting with diverse cell types and secreting abundant extracellular factors. Accumulating evidence demonstrates that high mobility group box 1 (HMGB1), a DNA-binding protein and critical inflammatory mediator, plays multifaceted roles in disease progression, with platelets being one cellular source of circulating HMGB1. Under pathological conditions, platelets release HMGB1 into the extracellular matrix, establishing bidirectional communication between platelets and other immune cells. Moreover, HMGB1 reciprocally activates platelets through Toll-like receptors (TLRs) and receptor for advanced glycation end-products (RAGE), facilitating platelet activation and subsequent release of regulatory factors that drive inflammation-associated pathological thrombosis. In this review, we systematically characterize the HMGB1-platelet axis and elucidate its context-dependent roles in specific disease states. The mechanistic interplay between HMGB1 signaling and platelet pathophysiology is discussed, particularly its implications for disease progression. Furthermore, we critically evaluate therapeutic strategies targeting HMGB1 developed over the past decade, while proposing future directions for dual-target interventions that simultaneously modulate HMGB1 and platelet activity to combat inflammation-driven thrombotic disorders.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294882","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":"Human Platelets Internalize Pregnancy-Specific Glycoprotein-1 (PSG1).","authors":"Ejaife O Agbani, Lorraine Chow, Joshua Nicholas, Ibukun Akinrinade, Nancy Soliman, Donna M Slater, Pavel Davizon-Castillo, Gabriela Dveksler","doi":"10.1055/a-2618-4817","DOIUrl":"https://doi.org/10.1055/a-2618-4817","url":null,"abstract":"<p><p>It has been long suggested that the placenta \"educates\" maternal platelets to contribute to a healthy pregnancy. Several studies have also demonstrated unique changes in platelet function and ultrastructure during pregnancy, some of which may drive hypertensive complications of pregnancy. One of the few proteins that are differentially found in the plasma of pregnant females when compared with non-pregnant females and males are the members of the pregnancy-specific glycoprotein (PSG) family, and PSG1 is one of the highest expressed and best characterized of all human PSGs. Because PSGs are secreted into the maternal circulation (by the trophoblast cells of the placenta), platelets may be picking up placental exosomes containing PSGs. Also, platelets may directly incorporate circulating PSGs, which are found in high concentration, as has been shown for other serum proteins, including fibrinogen. In this image report, we have utilized a state-of-the-art high-resolution imaging approach to examine the interactions of labeled recombinant PSG1 with non-permeabilized human platelets. Strikingly, we observed that human platelets internalize PSG1 and express PSGs during pregnancy.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267282","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":"Landscape and Spectrum of VWF Variants in Type 2 Von Willebrand Disease: Insights from a German Patient Cohort.","authors":"Hamideh Yadegari, Susan Halimeh, Alexander Krahforst, Anna Pavlova, Behnaz Pezeshkpoor, Jens Müller, Bernd Pötzsch, Arijit Biswas, Natascha Marquardt, Ute Scholz, Heinrich Richter, Heiner Trobisch, Karin Liebscher, Martin Olivieri, Karolin Trautmann-Grill, Oliver Tiebel, Ralf Knöfler, Johannes Oldenburg","doi":"10.1055/a-2616-5161","DOIUrl":"10.1055/a-2616-5161","url":null,"abstract":"<p><p>von Willebrand disease (VWD) type 2 arises from variants in von Willebrand factor (VWF) that disrupt its essential hemostatic functions. As per ISTH guidelines, it is classified as type 2A, 2B, 2M, and 2N based on the affected VWF roles.This population-based study aims to uncover the genotype and laboratory phenotypes in type 2 VWD, providing insights into underlying genetics and genotype-phenotype associations.Our cohort included 247 patients from 196 families. Patients were characterized through multiple VWF phenotypic assays and genetic analyses, including DNA sequencing, copy number variation evaluations, and bioinformatic assessments.A total of 86 index patients (IPs, 44%) were diagnosed with type 2A, the most prevalent subtype. Additionally, 27 IPs (14%) were diagnosed with type 2N, 24 IPs (12%) with type 2B, 17 IPs (9%) with type 2M, and 42 IPs categorized as type U VWD carried VWD-associated variants but could not be assigned to a specific subtype. VWF variants were detected in 187 out of 196 (95%) individuals. A total of 222 VWF variants were identified: 187 missense (84%), 22 null alleles (10%), 5 regulatory (2%), 6 gene conversions (3%), and 2 silent variants (1%). Many variants were recurrent in our cohort, resulting in 114 distinct variants. Of these, 45 (39%) were novel.Our data expands the spectrum of disease-associated variants in VWF, including many newly identified variants. This provides valuable insights for accurate diagnosis and personalized treatment. Additionally, the significant genetic heterogeneity among type 2 patients highlights the challenges in sub-classification.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111976","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":"Association of Fibrinogen Variants with Severity of Obesity and Metabolic Liver Disease: 2-Year Follow-up after Bariatric Surgery.","authors":"Nadja B Pedersen, Anna-Marie Bloch Münster, Mette Munk Lauridsen, Yaseelan Palarasah, Charlotte W Wernberg, Lea Ladegaard Grønkjær, Birgitte G Jacobsen, Elise Jonasson, Moniek P M de Maat, Else-Marie Bladbjerg","doi":"10.1055/a-2615-4682","DOIUrl":"10.1055/a-2615-4682","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is the hepatic manifestation of obesity. Studies in mice link fibrinogen variation to obesity and MASLD, but how naturally occurring fibrinogen variants associate with obesity and MASLD in humans is unknown.To investigate associations of fibrinogen variants (fibrinogen γ', fibrinogen α_E, and sialylated fibrinogen) with obesity, MASLD, and fibrosis severity and examine changes in variants 2 years after bariatric surgery.We included 195 individuals with a body mass index (BMI) > 35 kg/m². A subgroup of 93 individuals, who underwent bariatric surgery (<i>n</i> = 35) or served as nonsurgical control group (<i>n</i> = 58), were followed for 2 years. Hepatic tissue samples were scored for MASLD and fibrosis. Fibrinogen variants were measured using enzyme-linked immunosorbent assay.Absolute levels of fibrinogen variants tended to be higher in individuals with BMI > 45 kg/m² compared with BMI < 40 kg/m² (Δγ': 70 [95% confidence interval: -19, 160] µg/mL; Δα_E: 0.85 [-0.36, 2.06] µg/mL; Δsialylated: 0.09 [-0.05, 0.24] arbitrary units [AU]). Absolute and relative fibrinogen α_E levels increased with MASLD (Δα_E: 2.04 [0.74, 3.35] µg/mL; Δα_E ratio: 0.05 [0.02, 0.08] %) and fibrosis (Δα_E: 1.79 [0.48, 3.11] µg/mL; Δα_E ratio: 0.05 [0.02, 0.07] %), whereas relative fibrinogen γ' levels decreased with fibrosis (Δγ' ratio: -2.52 [-4.70, -0.35] %). After bariatric surgery, sialylated fibrinogen levels were lower (Δsialylated: -0.22 [-0.32, -0.11] AU), but relative levels of the fibrinogen variants were higher (Δγ': 1.7 [0.03, 3.30] %; Δα_E: 0.03 [0.001, 0.06] %; Δsialylated: 0.02 [0.002, 0.04] AU/g/L) compared with the control group.Obesity, MASLD, and fibrosis alter fibrinogen variant profiles in plasma suggesting that fibrinogen variation plays a role in these inflammatory conditions.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102443","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":"Major Bleeding Risk Assessment in Patients with Cancer-Associated Venous Thromboembolism Treated with DOACs: Data from a Multicenter Cohort.","authors":"Maria Cristina Vedovati, Rosa Talerico, Clara Sacco, Matteo Mazzetti, Elena Campello, Simone Birocchi, Sofia Beccatini, Angelo Porfidia, Rachele Caprari, Corrado Lodigiani, Paolo Simioni, Gian Marco Podda, Isabella Mastandrea, Cecilia Becattini, Roberto Pola","doi":"10.1055/a-2605-9015","DOIUrl":"https://doi.org/10.1055/a-2605-9015","url":null,"abstract":"<p><p>In cancer-associated venous thromboembolism (CAT), extended anticoagulation should be considered when the risk-benefit profile is favorable. However, optimal predictors of major bleeding (MB) remain unclear.This multicenter observational study included CAT patients treated with direct oral anticoagulants (DOACs). Study objectives were: (i) assess the performance of nine bleeding risk scores (ATRIA, CAT-BLEED, CHAP, DOAC, HAS-BLED, Kuijer, ORBIT, RIETE, VTE-BLEED), (ii) identify predictors of MB (ISTH definition), and (iii) propose an improved bleeding risk model (Perform score).Overall, 823 patients were followed (mean 1.6 years). MB occurred in 44 cases (3.4% per patient-year). The predictive performance of bleeding risk scores was modest (c-statistics range 0.513-0.606). Risk factors included increasing age (HR 1.04, 95% CI 1.00-1.07), use of steroids (HR 2.69, 95% CI 1.34-5.40), antimetabolites (HR 2.51, 95% CI 1.28-4.93), and unresected gastrointestinal cancer (HR 7.30, 95% CI 1.70-31.30). Conversely, prior cancer surgery (HR 0.41, 95% CI 0.20-0.82) and anticancer hormones (HR 0.22, 95% CI 0.05-0.92) showed a possible protective effect toward MB risk. The Perform score provided a slight enhancement in risk prediction (c-statistics 0.678), but remained suboptimal.In this real-world cohort of CAT patients treated with DOACs, unresected gastrointestinal cancer and use of steroids or antimetabolites were associated with increased MB risk, while prior cancer surgery and anticancer hormones were linked to a lower risk. These factors, not considered in current bleeding risk scores, may refine bleeding prediction. Further studies should clarify their role in guiding anticoagulation decisions and improving personalized risk assessment.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216942","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":"Ticagrelor Therapy Modifications after Acute Coronary Syndrome: An Ever-Evolving Issue.","authors":"Felice Gragnano, Dominick J Angiolillo","doi":"10.1055/a-2448-7029","DOIUrl":"10.1055/a-2448-7029","url":null,"abstract":"","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"607-609"},"PeriodicalIF":5.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508515","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":"Treatment Modifications in Acute Coronary Syndrome Patients Treated with Ticagrelor: Insights from the FORCE-ACS Registry.","authors":"Niels M R van der Sangen, Jaouad Azzahhafi, Dean R P P Chan Pin Yin, Lucas J G Zaaijer, Wout W A van den Broek, Ronald J Walhout, Melvyn Tjon Joe Gin, Ron Pisters, Deborah M Nicastia, Jorina Langerveld, Georgios J Vlachojannis, Rutger J van Bommel, Yolande Appelman, José P S Henriques, Wouter J Kikkert, Jurriën M Ten Berg","doi":"10.1055/a-2421-8866","DOIUrl":"10.1055/a-2421-8866","url":null,"abstract":"<p><p>Patients presenting with acute coronary syndrome (ACS) are frequently treated with the P2Y₁₂-inhibitor ticagrelor. Some patients prematurely discontinue ticagrelor, but the incidence of reasons for and clinical implications of treatment modification are relatively unknown.Data from 4,278 ACS patients (mean age: 63.6 years, 26.1% women) who were discharged on ticagrelor and enrolled in the FORCE-ACS registry between 2015 and 2020 were used. Treatment modifications were categorized as physician-recommended discontinuation, alteration, interruption, or disruption and occurred in 26.7, 20.1, 2.8, and 3.1% of patients within 12 months of follow-up (VISUAL SUMMARY: ). Underlying reasons for treatment modification differed per type of modification. Overall, the rate of ischemic events defined as all-cause death, myocardial infarction, or stroke was 6.6% at 12 months of follow-up. Cox regression analysis using time-updated modification variables as independent variables showed that treatment interruption (adjusted hazard ratio [HR]: 2.93, 95% confidence interval [CI]: 1.48-5.79, <i>p</i> < 0.01) and disruption (adjusted HR: 2.33, 95% CI: 1.07-5.07, <i>p</i> = 0.03) were associated with an increased risk of ischemic events even after adjustment for relevant confounders. Discontinuation and alteration were not associated with increased ischemic risk.In clinical practice, treatment modifications in ACS patients discharged on ticagrelor are common, although type and reasons for modification are heterogeneous. Treatment interruption and disruption are associated with excess cardiovascular risk.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"597-606"},"PeriodicalIF":5.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547628","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}