Zhuqing Shi , Ashley J. Mulford , Huy Tran , Michal Filipczak , Song Gao , Stevie Xie , Jason Lobel , Jun Wei , Andrew S. Rifkin , Annabelle Ashworth , Siqun Lilly Zheng , Clay Wiske , David Duggan , Brian T. Helfand , Arman Qamar , Alan R. Sanders , Alfonso J. Tafur , Jianfeng Xu
{"title":"Development and validation of a genetic probability for venous thromboembolism","authors":"Zhuqing Shi , Ashley J. Mulford , Huy Tran , Michal Filipczak , Song Gao , Stevie Xie , Jason Lobel , Jun Wei , Andrew S. Rifkin , Annabelle Ashworth , Siqun Lilly Zheng , Clay Wiske , David Duggan , Brian T. Helfand , Arman Qamar , Alan R. Sanders , Alfonso J. Tafur , Jianfeng Xu","doi":"10.1016/j.rpth.2025.102876","DOIUrl":"10.1016/j.rpth.2025.102876","url":null,"abstract":"<div><h3>Background</h3><div>Factor V Leiden (FVL) and prothrombin gene mutations (PGMs), as well as recently developed polygenic scores (PGSs), have been consistently associated with venous thromboembolism (VTE) risk in European ancestry populations.</div></div><div><h3>Objectives</h3><div>This study aimed to develop an optimized risk-assessment tool combining mutations and PGS for diverse ancestry populations.</div></div><div><h3>Methods</h3><div>The association of VTE risk with FVL/PGM and PGS was tested using multivariable analyses in the UK Biobank. A genetic probability for VTE (GenProb-VTE) combining PGS and FVL/PGM was developed. Its discriminative and reclassification performances over FVL/PGM alone were assessed using observed VTE rate and the continuous net reclassification index, respectively. Results were validated in the Genomic Health Initiative of Endeavor Health, an ancestry-diverse health care system–based biobank.</div></div><div><h3>Results</h3><div>Among 432,831 participants in the UK Biobank, FVL, PGM, and PGS were significantly and independently associated with VTE risk (<em>P</em> < .001). Compared with FVL/PGM alone, GenProb-VTE identified 1.5 times more high-risk subjects whose observed VTE rates exceeded those of FVL/PGM carriers. GenProb-VTE also significantly reclassified VTE risk from the model with FVL/PGM alone, with continuous net reclassification index of 0.10 (<em>P</em> < .001). VTE risk was reclassified in FVL/PGM heterozygous carriers (51%) and homozygous/compound heterozygous carriers (46%) as well as noncarriers (14%). These results were validated among 16,341 participants in the Genomic Health Initiative, in participants of both European and non-European ancestry.</div></div><div><h3>Conclusion</h3><div>GenProb-VTE, an optimized tool combining PGS with FVL/PGM, significantly improves VTE risk assessment compared with FVL/PGM alone in diverse ancestry populations. It provides a novel tool for genetic risk assessment of VTE.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 4","pages":"Article 102876"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144105625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laura Calderon-Lugo , Litzalee Camacho-Vega , Jennifer Crowley , Marina Babilonia-Leon
{"title":"104 To Prescribe or Deprescribe: Antiplatelet Discontinuation versus Proton Pump Inhibitor (PPI) Addition in Veterans with Combined Antithrombotic Therapy","authors":"Laura Calderon-Lugo , Litzalee Camacho-Vega , Jennifer Crowley , Marina Babilonia-Leon","doi":"10.1016/j.rpth.2025.102805","DOIUrl":"10.1016/j.rpth.2025.102805","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 ","pages":"Article 102805"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144202998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"128 Evaluation of Heparin-Induced Thrombocytopenia Testing to Improve Anticoagulation Stewardship in an Acute Care Setting","authors":"Yelena Samofalova PharmD , Nicole Thurnherr PharmD , Micaela Powner PharmD, BCPS , Jillian Searle PharmD, BCPS, BCACP , Michelle Byram BS, Pharm, CACP","doi":"10.1016/j.rpth.2025.102783","DOIUrl":"10.1016/j.rpth.2025.102783","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 ","pages":"Article 102783"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144203007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"185 The Youth is our Future, and the Future is Here","authors":"Omkar Garud , Naga Sahithi Rajuladevi , Sonika Tatipalli , Atul Laddu , Jawed Fareed","doi":"10.1016/j.rpth.2025.102834","DOIUrl":"10.1016/j.rpth.2025.102834","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 ","pages":"Article 102834"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144203533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nghi Ha , Liza Renner , Erin Mouland , Denise Sutter-Long , Anisa Bici
{"title":"161 Evaluation of a Pharmacist-led Perioperative Antithrombotic Management Service","authors":"Nghi Ha , Liza Renner , Erin Mouland , Denise Sutter-Long , Anisa Bici","doi":"10.1016/j.rpth.2025.102794","DOIUrl":"10.1016/j.rpth.2025.102794","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 ","pages":"Article 102794"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144203746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Corinne M. Bertolaccini , Collin J. Culbertson , Yixin Kong , Zhibang Lin , Tara K. Lech
{"title":"132 Antithrombotic Prescribing Practices in Patients with Atrial Fibrillation Presenting with Acute Ischemic Stroke while on Oral Anticoagulation","authors":"Corinne M. Bertolaccini , Collin J. Culbertson , Yixin Kong , Zhibang Lin , Tara K. Lech","doi":"10.1016/j.rpth.2025.102771","DOIUrl":"10.1016/j.rpth.2025.102771","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 ","pages":"Article 102771"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144203807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Meng-Ni Fan , Tangliang Shen , Barbara A. Konkle , Xiaohe Cai , Ting-Yen Chao , Marilyn Manco-Johnson , Anna V. Faino , Junping Zhang , Shumin Bao , Weidong Xiao , Lei Li , Carol H. Miao
{"title":"Exploration of biomarkers for inhibitor development in persons with hemophilia A","authors":"Meng-Ni Fan , Tangliang Shen , Barbara A. Konkle , Xiaohe Cai , Ting-Yen Chao , Marilyn Manco-Johnson , Anna V. Faino , Junping Zhang , Shumin Bao , Weidong Xiao , Lei Li , Carol H. Miao","doi":"10.1016/j.rpth.2025.102877","DOIUrl":"10.1016/j.rpth.2025.102877","url":null,"abstract":"<div><h3>Background</h3><div>Inhibitor development remains a significant challenge for hemophilia A (HA) treatment. Cytokines and glycosylation play crucial roles in inducing and regulating immune responses. Cytokine and altered N-glycan profiles have the potential to be biomarkers in association with the presence of inhibitors in persons with HA.</div></div><div><h3>Objectives</h3><div>We investigated the association of cytokine and plasma N-glycan profiles with inhibitor presence.</div></div><div><h3>Methods</h3><div>In 60 persons with HA and 23 controls, we analyzed 10 cytokines and used multivariable regression to assess their association with inhibitor presence. Given the challenges of validating these findings in previously untreated patients, we employed an HA mouse model to explore the association between cytokine levels and inhibitors. We also examined the correlation between plasma N-glycan profiles and inhibitors in persons with HA, analyzing adult and pediatric groups separately due to age-dependent glycosylation.</div></div><div><h3>Results</h3><div>Elevated granulocyte colony-stimulating factor and interleukin (IL) 6 levels, coupled with decreased IL-10, were significantly associated with inhibitor presence in multivariable regression analysis. High-titer inhibitor was observed in factor (F)VIII-treated mice experiencing chronic inflammation with increased levels of granulocyte colony-stimulating factor, IL-6, and macrophage inflammatory protein-1β, a murine IL-8 homolog, but not in those receiving FVIII alone, consistent with our clinical observations. Inhibitor-positive adult patients exhibited higher biantennary <em>N</em>-glycan and reduced multiantennary <em>N</em>-glycan ratios compared with inhibitor-negative adults. Conversely, inhibitor-positive pediatric patients displayed decreased sialic acid ratios.</div></div><div><h3>Conclusion</h3><div>These findings highlight the association of inhibitor presence with altered plasma cytokine levels and <em>N-</em>glycosylation patterns. Prospective validation is crucial to confirm these associations, develop robust biomarkers, and improve inhibitor risk assessment for persons with HA.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 4","pages":"Article 102877"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zikou Liu , Orr Zaacks , Be’eri Niego , Robert L. Medcalf
{"title":"Halo fluorescence fibrinolysis test: a novel quantitative assay to evaluate fibrinolysis on established plasma clots","authors":"Zikou Liu , Orr Zaacks , Be’eri Niego , Robert L. Medcalf","doi":"10.1016/j.rpth.2025.102874","DOIUrl":"10.1016/j.rpth.2025.102874","url":null,"abstract":"<div><h3>Background</h3><div>Fibrinolysis is essential for dissolving blood clots and maintaining hemostasis. This process is primarily mediated by tissue-type plasminogen activator, which converts plasminogen into plasmin, thereby breaking down fibrin clots. Traditional amidolytic assays often measure plasmin generation without directly assessing fibrin degradation, while thromboelastography frequently overlooks clot maturation, which significantly influences fibrinolysis resistance.</div></div><div><h3>Objectives</h3><div>To address these limitations, we present a novel quantitative assay for analyzing fibrinolysis on established clots, termed the halo fluorescence fibrinolysis (HoFF) test.</div></div><div><h3>Methods</h3><div>The HoFF test used fluorophore-conjugated fibrinogen to form halo-shaped plasma clots. Fibrinolysis was induced with tissue-type plasminogen activator or its variant tenecteplase, and clot breakdown was monitored via real-time fluorescence detection by a microplate reader. The fluorescence signal was analyzed to calculate a fibrinolysis index, indicating fibrinolytic capacity. Its specificity for fibrinolysis over plasmin generation was validated against traditional amidolytic assays using a plasmin substrate.</div></div><div><h3>Results</h3><div>Fluorescence-labeled fibrinogen was confirmed as a reliable marker of fibrin degradation. The HoFF test exhibited strong linear correlations between the fibrinolysis index and plasminogen activator concentrations, with robust reproducibility. It also effectively evaluated tenecteplase-induced fibrinolysis and demonstrated versatility across clot types, including mouse plasma and human whole-blood models. Furthermore, the test distinguished fibrinolysis from plasmin generation, demonstrated by the differential effects of tranexamic acid inhibition.</div></div><div><h3>Conclusion</h3><div>The HoFF test offers a sensitive, reliable, and high-throughput tool for quantitatively evaluating fibrinolysis on established human and mouse plasma and whole blood clots.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 4","pages":"Article 102874"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144166401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aidan R. Campbell , Cole J. Florio , Grace V. Heringer , Sara T. Woldemariam , Scott D. Casey , William B. Stubblefield , Lauren M. Westafer , Edward Qiao , Cydney E. Middleton , Lara Zekar , Nachiketa Gupta , Madeline J. Somers , Mary E. Reed , Nareg H. Roubinian , Ashok P. Pai , Jeffrey D. Sperling , David R. Vinson
{"title":"Corrigendum to ‘Preemptive anticoagulation during antenatal pulmonary embolism diagnostics in a community setting: retrospective cohort study’","authors":"Aidan R. Campbell , Cole J. Florio , Grace V. Heringer , Sara T. Woldemariam , Scott D. Casey , William B. Stubblefield , Lauren M. Westafer , Edward Qiao , Cydney E. Middleton , Lara Zekar , Nachiketa Gupta , Madeline J. Somers , Mary E. Reed , Nareg H. Roubinian , Ashok P. Pai , Jeffrey D. Sperling , David R. Vinson","doi":"10.1016/j.rpth.2025.102892","DOIUrl":"10.1016/j.rpth.2025.102892","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 4","pages":"Article 102892"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144166402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}