{"title":"Implications of Soluble C-type Lectin-Like Receptor 2 Levels in Patients with Coronavirus Disease 2019-Associated with Thrombosis.","authors":"Hideo Wada, Katsuya Shiraki, Yuhuko Ichikawa, Nobuo Ito, Hidekazu Inoue, Isao Moritani, Jun Masuda, Akitaka Yamamoto, Masaki Tomida, Masamichi Yoshida, Masahide Kawamura, Motomu Shimaoka, Toshiaki Iba, Hideto Shimpo","doi":"10.1055/a-2572-1170","DOIUrl":"10.1055/a-2572-1170","url":null,"abstract":"<p><p>Coronavirus disease 2019 (COVID-19) is often associated with thrombosis. Elevated levels of soluble C-type lectin-like receptor 2 (sCLEC-2), a biomarker for platelet activation, have been reported in COVID-19. Therefore, we examined the behavior of sCLEC-2 levels and their relationship with thrombosis.The clinical course of inflammatory and thrombotic biomarkers was assessed in 271 patients with COVID-19.Inflammatory biomarkers such as C-reactive protein, procalcitonin, and presepsin levels were significantly increased in patients with COVID-19, and these behaviors differed among the clinical course or stages. The plasma D-dimer levels increased slightly and gradually. Platelet counts were within the normal range, and plasma sCLEC-2 levels were markedly increased in most patients with COVID-19. There were 17 patients with thrombosis in this study. Although there was no significant difference in various biomarkers between COVID-19 patients with and without thrombosis, the super formula of sCLEC-2xD-dimer/platelet count in patients with thrombosis was significantly higher than in those without thrombosis. Furthermore, this super formula was significantly higher in COVID-19 patients with severe or critical illness than in those with mild or moderate illness.Elevation of the super formula of sCLEC-2xD-dimer/platelet count was associated with the thrombosis in patients with COVID-19 suggesting the thrombosis in COVID-19 may be caused by the development of microthrombosis.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773332","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":"Navigating Anticoagulation in Ischemic Left Ventricular Aneurysms: Lessons from Cardiac Magnetic Resonance Imaging.","authors":"Ashkan Hashemi, Behnood Bikdeli","doi":"10.1055/a-2576-8009","DOIUrl":"10.1055/a-2576-8009","url":null,"abstract":"","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812388","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":"Asn384Ser Mutation in Protein C is Associated with Multiple-Site Thrombosis in a Young Heterozygous Male.","authors":"Junwei Yuan, Shijie Zhou, Xi Wu, Fang Li, Zhe Lai, Qiulan Ding, Wenman Wu, Xuefeng Wang, Jing Dai, Xiaobo Hu, Yeling Lu","doi":"10.1055/a-2569-6439","DOIUrl":"https://doi.org/10.1055/a-2569-6439","url":null,"abstract":"<p><p>Protein C (PC) is an important physiological anticoagulant factor in humans. Activated protein C (APC) is generated from the PC zymogen through proteolytic activation by thrombin. APC inhibits thrombin generation by inactivating activated factors V and VIII via limited proteolysis. In addition to its anticoagulant function, APC also exhibits potent cytoprotective and anti-inflammatory properties. We have identified a young male with multiple-site thrombosis, who carries a heterozygous mutation c.1151A > G,p.Asn384Ser(N384S) in PC. Although this mutation has been previously documented, limited functional research has been conducted to elucidate its pathogenesis.To elucidate the functional alternations of the N384S mutant protein C and delineate the molecular mechanism underlying thrombosis in the patient carrying this mutation.We expressed the recombinant PC-N384S in mammalian cells and characterized its properties in established coagulation and anti-inflammatory assay systems.The expression level of the PC-N384S was reduced to approximately 7% of that observed for PC-WT. The activation of PC-N384S by thrombin or thrombin-thrombomodulin (TM) complex was significantly impaired, although the addition of TM exhibited a slight enhancement in the activation process. In terms of cleaving a chromogenic substrate, the catalytic efficiency reduced to approximately 50% of that observed in the wild type. In addition, in comparison with APC-WT, APC-N384S demonstrated a pronounced decline in amidolytic activity following an extended incubation period at 37°C. APC-N384S exhibited slightly impaired anticoagulant activity in either FVa inhibition assay or plasma-based assay systems. Furthermore, anti-inflammatory activity of APC-N384S was dramatically impaired as determined by evaluating the barrier-protective effect.The Asn384Ser mutation impairs both the anticoagulant and barrier-protective activities of protein C, thereby increasing the thrombosis risk in the heterozygous young male.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038162","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}
Piotr Kamola, Boguslawa Luzak, Patrycja Przygodzka, Cezary Watala, Moro O Salifu, Anna Babinska, Tomasz Przygodzki
{"title":"Homophilic Interactions of Platelet F11R/JAM-A with Its Surface-Bound Counterpart Facilitate Thrombus Formation.","authors":"Piotr Kamola, Boguslawa Luzak, Patrycja Przygodzka, Cezary Watala, Moro O Salifu, Anna Babinska, Tomasz Przygodzki","doi":"10.1055/a-2565-9496","DOIUrl":"10.1055/a-2565-9496","url":null,"abstract":"<p><p>F11Receptor/junctional adhesion molecule-A (F11R/JAM-A) is a transmembrane protein expressed in endothelial cells, epithelial cells, and in blood platelets. In blood platelets, F11R/JAM-A participates in adhesion under static conditions, suppresses the activation of the platelet α<sub>IIb</sub>β<sub>3</sub> integrin and was shown to activate blood platelets as soluble form via homophilic interactions.The purpose of presented study was to evaluate whether F11R/JAM-A is involved in platelet adhesion under flow conditions and in thrombus formation.F11R/JAM-A contribution to platelet adhesion under flow conditions was assessed using flow chamber assay. Monoclonal antibodies and recombinant F11R/ JAM-A were used to assess the effects of F11R/JAM-A blockade on platelet aggregation and thrombus formation using total thrombus formation analysis system. Effects of F11R/JAM-A blockade on thrombus formation in vivo were evaluated in murine models of carotid artery injury.F11R/JAM-A was not capable of capturing flowing blood platelets alone but enhanced platelet adhesion to fibrinogen under flow conditions. Blocking of F11R/JAM-A homophilic interactions with specific monoclonal antibodies or with recombinant F11R/JAM-A impaired thrombus formation in vitro in human blood and in vivo in the models of thrombosis in mice.Interactions of F11R/JAM-A located on flowing platelets with its surface-bound counterpart enhance platelet binding to fibrinogen under high shear stress conditions. Blocking of these homophilic interactions compromises thrombus formation. While previously published studies pointed at a significant role of soluble F11R/JAM-A in priming platelets during thrombus formation, our results highlight the role of surface-bound F11R/JAM-A in this process.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711328","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}
Yating Zhao, Longting Du, Shaobin Lin, Lu Bai, Yao Chen, Manman Ye, Shihong Zhang, Chang Su, Xiaohe Zheng
{"title":"Clinical Phenotype and Genetic Analysis of a Family with Hereditary Antithrombin Deficiency Caused by SERPINC1 Gene Mutation.","authors":"Yating Zhao, Longting Du, Shaobin Lin, Lu Bai, Yao Chen, Manman Ye, Shihong Zhang, Chang Su, Xiaohe Zheng","doi":"10.1055/a-2558-8193","DOIUrl":"10.1055/a-2558-8193","url":null,"abstract":"<p><p>Inherited deficiency of the antithrombin (hereditary antithrombin deficiency, AT deficiency, OMIM #613118) is a relatively rare (1:2,000-3,000) autosomal-dominant disorder with high risk of venous thromboembolism. The molecular basis of this condition has not yet fully understood, highlighting the need for further research to elucidate the underlying pathological mechanisms.This study aimed to investigate coagulation parameters and genetic phenotypes in a proband with hereditary antithrombin deficiency and her family members. Additionally, the investigation sought to provide preliminary insights for the molecular pathogenesis of this condition.Blood coagulation parameters, including plasma antithrombin activity (AT:A), antithrombin antigen (AT:Ag), protein C activity (PC:A), and protein S activity (PS:A) were measured in the peripheral blood of each family member by a Stago instrument. Peripheral blood was also extracted and sequenced to identify possible genetic mutation sites. The functional impact of variants on protein was subsequently analyzed by bioinformatics software.The proband, her mother, and brother all exhibited decreased activity and antigen of AT but normal PC and PS activity. The proband's father had normal activity and antigen levels of AT, PC, and PS. Sequencing revealed the proband's mother inherited the SERPINC1:c.661T > C,p.(Trp221Arg) heterozygous variant and her father harbored PROC:c.572_574del,p.(Lys193del) heterozygous variant while the proband as well as her brother carried both. Conservation analysis revealed that Trp221 is highly conserved across homologous species. Bioinformatics tools consistently classify the p.Trp221Arg mutation as \"pathogenic\" or \"deleterious.\" Protein modeling indicated that the p.Trp221Arg variant does not alter the protein structure but may modify glycosylation sites to affect its function.The proband and family members exhibited varying degrees of decreased levels of AT and thrombosis, which were closely associated with inheritance of SERPINC1:c.661T > C,p.(Trp221Arg).</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650922","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}
Rungroj Krittayaphong, Sukrit Treewaree, Ahthit Yindeengam, Chulalak Komoltri, Gregory Y H Lip
{"title":"Latent Class Analysis for the Identification of Phenotypes Associated with Increased Risk in Atrial Fibrillation Patients: The COOL-AF Registry.","authors":"Rungroj Krittayaphong, Sukrit Treewaree, Ahthit Yindeengam, Chulalak Komoltri, Gregory Y H Lip","doi":"10.1055/a-2559-9994","DOIUrl":"10.1055/a-2559-9994","url":null,"abstract":"<p><p>Patients with atrial fibrillation (AF) often have clinical complexity phenotypes. Latent class analysis (LCA) is based on the concept of modeling of both observed and unobserved (latent) variables. We hypothesized that LCA can help in identification of AF patient groups with different risk profiles and identify patients who benefit most from the Atrial fibrillation Better Care (ABC) pathway.We studied non-valvular AF patients in the prospective multicenter COOL-AF registry. The outcomes were all-cause death, ischemic stroke/systemic embolism (SSE), major bleeding, and heart failure. Components of CHA<sub>2</sub>DS<sub>2</sub>-VASc score, HAS-BLED score, and ABC pathway were recorded.A total of 3,405 patients were studied. We identified 3 LCA groups from 42 variables: LCA class 1 (<i>n</i> = 1,238), LCA class 2 (<i>n</i> = 1,790), and LCA class 3 (<i>n</i> = 377). Overall, the incidence rates of composite outcomes, death, SSE, major bleeding, and heart failure were 8.69, 4.21, 1.51, 2.27, and 2.84 per 100 person-years, respectively. When compared to LCA class 1, hazard ratios (HR) of composite outcome of LCA classes 3 and 2 were 3.86 (3.06-4.86) and 2.31 (1.91-2.79), respectively. ABC pathway compliance was associated with better outcomes in LCA classes 2 and 3 with the HR of 0.63 (0.51-0.76) and 0.57 (0.39-0.84), but not in LCA class 1.LCA can identify patients who are at risk of developing adverse clinical outcomes. The implementation of holistic management based on the ABC pathway was associated with a reduction in the composite outcomes as well as the individual outcomes.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658690","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}
Karin Janata, Alexandra Julia Lipa, Anne Merrelaar, Marieke Merrelaar, Ursula Azizi-Semrad, Harald Herkner, Michael Schwameis, Juergen Grafeneder
{"title":"Enhancing Pulmonary Embolism Risk Stratification: The National Early Warning Score and Its Integration into the European Society of Cardiology Classification.","authors":"Karin Janata, Alexandra Julia Lipa, Anne Merrelaar, Marieke Merrelaar, Ursula Azizi-Semrad, Harald Herkner, Michael Schwameis, Juergen Grafeneder","doi":"10.1055/a-2544-3626","DOIUrl":"10.1055/a-2544-3626","url":null,"abstract":"<p><p>Pulmonary embolism (PE) requires accurate risk assessment. We investigated the prognostic performance of the National Early Warning Score (NEWS) in emergency department patients with PE.We included patients ≥ 18 years from our PE registry (2017 to 2021), excluding patients after cardiac arrest or intubation before admission. The primary outcome was a composite of 30-day all-cause mortality or the need for advanced therapy (i.e., systemic or catheter-directed thrombolysis). We used logistic regression and the Cox proportional hazards models to estimate associations. The Pulmonary Embolism Severity Index (PESI) and the European Society of Cardiology (ESC) classification served as covariates. The overall score performances were quantified using receiver operating characteristic analysis.We included 524 patients. Each increase in NEWS points increased the odds of the primary outcome by 69% (odds ratio: 1.69, 95% confidence interval [CI]: 1.51-1.89, <i>p</i> < 0.001) and 30-day mortality by 44% (hazard ratio: 1.44, 95% CI: 1.30-1.60, <i>p</i> < 0.001). Within the ESC intermediate-high and high-risk group, the 30-day mortality rate was higher in patients with a NEWS ≥ 7 compared with NEWS < 7 (24 vs. 1%, <i>p</i> < 0.001). With a NEWS ≥ 7, 30-day mortality was lower in patients who received advanced therapy (18 vs. 39%) but not significantly. The NEWS predicted the primary outcome better than the PESI (area under the curve: 0.853 vs. 0.752, <i>p</i> < 0.001).The NEWS was associated with 30-day mortality and the need for advanced therapy. Incorporating the NEWS into the ESC classification could help to assess patient outcomes early and thus support timely treatment decisions.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493619","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}
Eva K Kempers, Chantal Visser, Eric C T Geijteman, Jamilla Goedegebuur, Johanneke E A Portielje, Mette Søgaard, Anne Gulbech Ording, Carline van den Dries, Denise Abbel, Geert-Jan Geersing, Sarah J Aldridge, Kate J Lifford, Ashley Akbari, Sjef J C M van de Leur, Melchior C Nierman, Isabelle Mahé, Simon P Mooijaart, Sebastian Szmit, Michelle Edwards, Simon I R Noble, Frederikus A Klok, Qingui Chen, Suzanne C Cannegieter, Marieke J H A Kruip
{"title":"Discontinuation of Anticoagulants and Occurrence of Bleeding and Thromboembolic Events in Vitamin K Antagonist Users with a Life-limiting Disease.","authors":"Eva K Kempers, Chantal Visser, Eric C T Geijteman, Jamilla Goedegebuur, Johanneke E A Portielje, Mette Søgaard, Anne Gulbech Ording, Carline van den Dries, Denise Abbel, Geert-Jan Geersing, Sarah J Aldridge, Kate J Lifford, Ashley Akbari, Sjef J C M van de Leur, Melchior C Nierman, Isabelle Mahé, Simon P Mooijaart, Sebastian Szmit, Michelle Edwards, Simon I R Noble, Frederikus A Klok, Qingui Chen, Suzanne C Cannegieter, Marieke J H A Kruip","doi":"10.1055/a-2524-5334","DOIUrl":"10.1055/a-2524-5334","url":null,"abstract":"<p><p>Data on risks and benefits of long-term anticoagulants in patients with a life-limiting disease are limited. This cohort study aims to describe (dis)continuation of anticoagulants and incidences of bleeding and thromboembolic events in vitamin K antagonist (VKA) users with a life-limiting disease.Data from five Dutch anticoagulation clinics were linked to data from Statistics Netherlands and the Netherlands Cancer registry. Prevalent VKA users diagnosed with a pre-specified life-limiting disease between January 1, 2013 and December 31, 2019 were included and followed until December 31, 2019. Bleeding and thromboembolic events were identified by hospitalization data. Cumulative incidences of anticoagulant discontinuation, accounting for death as competing risk, and event rates for both anticoagulant exposed and unexposed person-years (PYs) were determined.Among 18,145 VKA users (median age 81 years [IQR: 74-86], 49% females, median survival time 2.03 years [95%CI: 1.97-2.10]), the most common life-limiting diseases were heart disease (60.0%), hip fracture (18.1%), and cancer (13.5%). One year after diagnosis, the cumulative incidence of anticoagulant discontinuation was 14.0% (95%CI: 13.5-14.6). Over 80% of patients continued anticoagulant therapy until the last month before death, with median 14 days between discontinuation and death. Event rates per 100 PYs (95%CI) were comparable during anticoagulant use and after discontinuation for bleeding 2.6 (2.4-2.8) versus 2.1 (1.5-2.8), venous thromboembolism 0.2 (0.1-0.2) versus 0.4 (0.2-0.7), and arterial thromboembolism 3.1 (2.9-3.3) versus 3.3 (2.6-4.2).Most VKA users with a life-limiting disease continued anticoagulant treatment during their last phase of life, with similar rates of bleeding and thromboembolic events during use and after discontinuation.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042051","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}