Laura S. Duarte , Neil Blumberg , Joshua Marvald , Tanzy Love , Jeffrey R. Andolina , Suzie A. Noronha , Laurie A. Steiner , Kelly Henrichs , Richard John Looney , Majed A. Refaai , Akua Asante
{"title":"Differences in outcomes associated with ABO blood groups in recipients of IVIG","authors":"Laura S. Duarte , Neil Blumberg , Joshua Marvald , Tanzy Love , Jeffrey R. Andolina , Suzie A. Noronha , Laurie A. Steiner , Kelly Henrichs , Richard John Looney , Majed A. Refaai , Akua Asante","doi":"10.1016/j.bvth.2025.100075","DOIUrl":"10.1016/j.bvth.2025.100075","url":null,"abstract":"","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 3","pages":"Article 100075"},"PeriodicalIF":0.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144588417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thomas E. Plate ∗ , Asaad Trabolsi ∗ , Rachel S. Kronenfeld , Leticia E. Campoverde , Dan Morgenstern-Kaplan , Alyssa J. Mercadel , Michael Caballero , Wei Zhao , Gerald A. Soff
{"title":"Association of risk factors for venous thromboembolism and overall survival in lung cancer","authors":"Thomas E. Plate ∗ , Asaad Trabolsi ∗ , Rachel S. Kronenfeld , Leticia E. Campoverde , Dan Morgenstern-Kaplan , Alyssa J. Mercadel , Michael Caballero , Wei Zhao , Gerald A. Soff","doi":"10.1016/j.bvth.2025.100074","DOIUrl":"10.1016/j.bvth.2025.100074","url":null,"abstract":"<div><h3>Abstract</h3><div>Venous thromboembolism (VTE) is a frequent complication in patients with lung cancer, but the risk factors and incidence in different lung cancer subtypes have not been fully characterized. Despite multiple studies supporting the use of VTE prophylaxis in patients with cancer at increased risk of VTE based on the Khorana score (KS), routine use of VTE prophylaxis is uncommon in clinical practice. This study further characterizes the risk factors and incidence of VTE in patients with lung cancer at a university cancer center. Furthermore, we assessed the association of KS and its individual components with overall survival in this same group of patients. Using natural language processing and human review to detect thrombotic events in the electronic medical record, a 12-month incidence of 10.1% was identified in the 632 patients with lung cancer analyzed. Significant risk factors included age <60 years and white blood cell (WBC) count ≥11 × 10<sup>9</sup>/L, but KS itself was not significantly associated with VTE. The median overall survival was 12 months with VTE. The KS, age ≥60 years, stage III to IV, WBC count ≥11 × 10<sup>9</sup>/L, hemoglobin <10 g/dL, body mass index, surgery, and VTE were identified as significant predictors of death. These findings warrant further validation, because the KS and 2 of its individual components in this study of lung cancer were significantly associated with reduced overall survival.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 3","pages":"Article 100074"},"PeriodicalIF":0.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144654934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NaShea C. Kendrick , Grace H. Huang , Germaine J. Harvey , Marvin T. Nieman
{"title":"From theory to platelets: unraveling the history and complexities of biased signaling","authors":"NaShea C. Kendrick , Grace H. Huang , Germaine J. Harvey , Marvin T. Nieman","doi":"10.1016/j.bvth.2025.100073","DOIUrl":"10.1016/j.bvth.2025.100073","url":null,"abstract":"<div><h3>Abstract</h3><div>Biased signaling refers to a phenomenon where a ligand preferentially activates 1 signaling pathway over another at the same receptor. It is best described for ligands that selectively activate G protein–coupled receptors through G protein or β-arrestin pathways. The concept of biased signaling has a rich history that has been experimentally characterized in the past 40 years. As early as the 1970s, models of biased signaling suggested that ligand-bound receptors have a rigid structure, whereas free receptors are fluid proteins with multiple potential active states. Recent cell signaling studies demonstrate that ligands block select signaling pathways but amplify others. This suggests that each ligand can stabilize a unique active conformation supporting the proposed model. Additional studies expanded our understanding of biased signaling to include biased receptors and system bias, which consider the impact of genetic differences and cellular context in which the signal is being studied. This is exemplified in platelet biology. Platelets are nonnucleated cells that rely on membrane receptors such as protease-activated receptor 1 (PAR1), PAR4, and Toll-like receptor 4 (TLR4) to facilitate platelet activation. There is now evidence of biased signaling through PAR1, PAR4, and TLR4 in platelets, making them attractive therapeutic targets. Here, we describe the origins of biased signaling theory and explore the concepts of biased agonists and systems through the lens of platelet activation.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 3","pages":"Article 100073"},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144588724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jerrold H. Levy , Peta M. A. Alexander , Alisa S. Wolberg , Owen J. T. McCarty , Anthony E. Pusateri , Raquel R. Bartz , Wolfgang Bergmeier , Mitchell J. Cohen , Jean M. Connors , James H. Morrissey , Matthew D. Neal , Elisabeth T. Tracy , Keith McCrae , Bruce A. Sullenger
{"title":"ECMO-induced coagulopathy: strategic initiatives for research and clinical practice (a workshop report of the NHLBI)","authors":"Jerrold H. Levy , Peta M. A. Alexander , Alisa S. Wolberg , Owen J. T. McCarty , Anthony E. Pusateri , Raquel R. Bartz , Wolfgang Bergmeier , Mitchell J. Cohen , Jean M. Connors , James H. Morrissey , Matthew D. Neal , Elisabeth T. Tracy , Keith McCrae , Bruce A. Sullenger","doi":"10.1016/j.bvth.2025.100064","DOIUrl":"10.1016/j.bvth.2025.100064","url":null,"abstract":"<div><h3>Abstract</h3><div>In May 2024, the Division of Blood Diseases and Resources of the National Heart, Lung, and Blood Institute (NHLBI) hosted a hybrid workshop on “Extracorporeal membrane oxygenation (ECMO)-induced coagulopathy: strategic initiatives for research and clinical practice.” The event brought together clinicians, scientists, bioengineers, and policymakers to address the challenges of ECMO-associated coagulopathy and explore novel therapeutic approaches. Through expert presentations and collaborative discussions, the workshop focused on innovative anticoagulation strategies, precision medicine, and advanced diagnostics to enhance patient care. The discussions also identified critical research gaps and opportunities for future interdisciplinary collaboration. This summary reviews the current state of knowledge and outlines future research directions for improving ECMO-induced coagulopathy management.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 2","pages":"Article 100064"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bender MT, Aggarwal A, Godwin M, et al. Cellular and enzymatic features of thrombi in humans are vascular bed dependent. Blood Vessels Thromb Hemost. 2025;2(1):100029.","authors":"","doi":"10.1016/j.bvth.2025.100057","DOIUrl":"10.1016/j.bvth.2025.100057","url":null,"abstract":"","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 2","pages":"Article 100057"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143894832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alicia S. Eustes , Meena Kumari Palani Kumar , Julie A. Peterson , Alan E. Mast , Steven R. Lentz , Sanjana Dayal
{"title":"Elevated tissue factor pathway inhibitor delays thrombin generation in COVID-19 but is not associated with clinical outcomes","authors":"Alicia S. Eustes , Meena Kumari Palani Kumar , Julie A. Peterson , Alan E. Mast , Steven R. Lentz , Sanjana Dayal","doi":"10.1016/j.bvth.2025.100071","DOIUrl":"10.1016/j.bvth.2025.100071","url":null,"abstract":"<div><h3>Abstract</h3><div>Plasma levels of tissue factor pathway inhibitor (TFPI) are elevated in many patients with COVID-19 but the role of TFPI in COVID-19 coagulopathy remains elusive. We sought to determine the contribution of TFPI to thrombin generation in patients with COVID-19 and assess its association with thrombosis and other clinical outcomes. We used blood samples from an early COVID-19 clinical trial of adult patients hospitalized with acute COVID-19 from April 2020 to January 2021 (<span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> identifier: NCT04360824). Plasma TFPI was measured by enzyme-linked immunosorbent assay, and thrombin generation potential was measured in the presence or absence of TFPI neutralizing antibodies. Thromboelastography was performed with whole-blood samples. We found that plasma TFPI was elevated in patients with COVID-19 compared with healthy individuals. Thrombin generation triggered by exogenous TF and phospholipids was increased in COVID-19, reflected by greater peak thrombin, velocity index, and endogenous thrombin potential; however, the time to initiation of thrombin generation (lag time) was delayed. Addition of a neutralizing anti-TFPI antibody significantly shortened the lag time in COVID-19 and normalized the difference in lag time between those with COVID-19 and healthy individuals. Plasma TFPI was positively associated with lag time, time to peak thrombin, and time to initial clot formation in thromboelastography. Multivariate analysis demonstrated that TFPI correlated with lag time and time to reach peak thrombin but not with 30-day mortality, thrombosis, or other adverse clinical outcomes. We conclude that elevated plasma TFPI delays the initiation of thrombin generation and clot formation but is not associated with thrombosis in patients hospitalized with COVID-19.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 3","pages":"Article 100071"},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144571320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparison of genotypes and phenotypes for von Willebrand factor gene variants using Japanese genome database","authors":"Takafumi Akimoto , Hiroshi Inaba , Soichi Ogishima , Kazuki Kumada , Ayano Mitsuhashi , Ryui Miyashita , Tomoko Yamaguchi , Masato Bingo , Yushi Chikasawa , Keiko Shinozawa , Takeshi Hagiwara , Kagehiro Amano , Eiichi N. Kodama , Ei Kinai","doi":"10.1016/j.bvth.2025.100070","DOIUrl":"10.1016/j.bvth.2025.100070","url":null,"abstract":"<div><h3>Abstract</h3><div>von Willebrand disease (VWD) is a common inherited bleeding disorder. The aim of this study was to determine the predicted disease states associated with various pathogenic von Willebrand factor (VWF) variants and their phenotypes using the largest Japanese whole-genome database. Of the 5857 <em>VWF</em> gene variants registered in the Japanese Multi-Omics Reference Panel (jMorp), variants with the following criteria were extracted: (1) caused protein abnormalities due to genetic alterations; (2) have already been detected and included in a database, including known association with VWD; and (3) highly likely pathogenic by in silico analysis. We measured VWF activity, antigen, propeptide, and collagen binding activity in stored plasma samples obtained from heterozygous carriers of the selected variants. A total of 29 <em>VWF</em> variants (26 single nucleotide and 3 small insertions/deletions) were detected, and 6 of these were found in Leiden Open Mutation Database. We obtained 43 plasma samples from individuals carrying these 29 variants as heterozygous. For the 43 variant carriers, their mean age was 43.0 years, and blood group was type O in 17 (39.5%). Analysis of these plasma samples showed low VWF levels (<50%) in 6 (14.0%). Low VWF levels were found in 2 of 8 of the nonsense (25%) and 4 of 31 of the missense variants (12.9%). Taking into consideration the limitation of using stored plasma samples, analysis of the jMorp indicated that most <em>VWF</em> gene variants with predicted pathogenic potential did not correlate with phenotypic expression. Our results supported incomplete penetrance and variable expressivity of the <em>VWF</em> gene variants.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 3","pages":"Article 100070"},"PeriodicalIF":0.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jessica Wu , Veronica Bochenek , Kandace Gollomp , Andrea H. Roe
{"title":"C-reactive protein and the menstrual cycle in females with sickle cell disease","authors":"Jessica Wu , Veronica Bochenek , Kandace Gollomp , Andrea H. Roe","doi":"10.1016/j.bvth.2025.100067","DOIUrl":"10.1016/j.bvth.2025.100067","url":null,"abstract":"<div><h3>Abstract</h3><div>Females with sickle cell disease (SCD) experience more frequent and severe vaso-occlusive episodes (VOEs) than males. Many also report perimenstrual timing of VOEs, suggesting cyclic variation in pain risk. C-reactive protein (CRP) is a robust inflammatory marker that is elevated at baseline in patients with SCD and rises during VOEs. Cyclic patterns of inflammatory markers in female patients with SCD have not been previously examined. This study examined the relationship between CRP and menstrual cycle phase in female patients with SCD. Frozen plasma samples from reproductive-aged adult patients with SCD were analyzed. Estradiol, progesterone, and luteinizing hormone levels were measured in female patient samples to estimate menstrual cycle phase at time of collection. CRP levels were compared by SCD genotype, hydroxyurea treatment, female vs male sex, and menstrual cycle phase in the female subgroup. CRP levels did not differ significantly by SCD genotype (SS vs SC), hydroxyurea use, or sex. However, in females with SCD, median CRP levels were significantly higher during the follicular phase than the luteal phase (8.80 mg/L [2.7-10.5] vs 0.82 mg/L [0.6-2.1]; <em>P</em> = .03). Although there were no differences in CRP levels in patients with SCD by sex, genotype, or hydroxyurea use, our results suggest that female patients have cyclicity in inflammation across the menstrual cycle that may predispose them to VOEs during the follicular phase. Further study is needed to validate these findings prospectively and to correlate biomarker patterns with clinical symptoms.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 3","pages":"Article 100067"},"PeriodicalIF":0.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144261372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jingnan Huang , Federico Marini , Fiorella A. Solari , Frauke Swieringa , Bas de Laat , Ilaria De Simone , Luigi Grassi , Xiang Gui , Kunpeng Li , Elizabeth A. Middleton , Neil V. Morgan , Isabella Provenzale , Carina Santos , Saskia Schols , Sarah Westbury , Albert Sickmann , Matthew T. Rondina , Wolfram Ruf ∗ , Mattia Frontini ∗ , Johan W. M. Heemskerk ∗
{"title":"Human and mouse platelet transcriptomes and proteomes for phenotyping 3474 genes with hemostatic and platelet traits","authors":"Jingnan Huang , Federico Marini , Fiorella A. Solari , Frauke Swieringa , Bas de Laat , Ilaria De Simone , Luigi Grassi , Xiang Gui , Kunpeng Li , Elizabeth A. Middleton , Neil V. Morgan , Isabella Provenzale , Carina Santos , Saskia Schols , Sarah Westbury , Albert Sickmann , Matthew T. Rondina , Wolfram Ruf ∗ , Mattia Frontini ∗ , Johan W. M. Heemskerk ∗","doi":"10.1016/j.bvth.2025.100068","DOIUrl":"10.1016/j.bvth.2025.100068","url":null,"abstract":"<div><h3>Abstract</h3><div>The hemostatic process relies on platelet and coagulation activation, with additional roles of red blood cells and the vessel wall. By systematic screening of databases for gene-linked information on hemostasis, we collected phenotypic profiles of 3474 orthologous human and mouse genes regarding bleeding, arterial thrombosis, thrombophilia, platelet traits, coagulation, and erythrocytes. Comparisons showed that defects in 252 mouse genes led to increased bleeding combined with platelet dysfunction or thrombocytopenia, in addition to 150 human orthologs that are registered for familial bleeding disorders, based on panel sequencing. Additionally, 139 mouse genes contributed to arterial thrombosis without bleeding phenotype. To further investigate the role of platelets in hemostasis, we integrated multiple genome-wide RNA-sequencing transcriptomes and proteomes from healthy subjects and C57BL/6 mice. This provided reference levels for 54 790 (54 247) transcripts and 6379 (4563) proteins in human (mouse) platelets. Orthologous transcripts in human and mouse platelets correlated with <em>R=</em>0.75, whereas orthologous platelet proteins correlated with <em>R=</em>0.87. Comparison with the phenotypic analysis revealed the following: (i) overall high qualitative similarity of human and mouse platelets regarding composition and function; (ii) presence of transcripts in platelets for most of the 3474 phenotyped genes; (iii) preponderance of syndromic platelet-expressed genes; and (iv) 20-40% overlap with genes from genome-wide association studies. For 42 mouse genes, among which receptors, signaling proteins, and transcription regulators (ASXL1, ERG, GATA2, MEIS1, NFE2, and TAL1), we confirmed novel links with human platelet function or count. This interspecies comparison can serve as a valuable resource for researchers and clinicians studying the genetics of blood-borne hemostasis and thrombosis.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 3","pages":"Article 100068"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}