Research and Practice in Thrombosis and Haemostasis最新文献

{"title":"Reply to a letter from Miesbach and Srivastava: response to hemophilia B gene therapy based on adeno-associated virus serotype 5 antibody status","authors":"Robert Klamroth , Paul E. Monahan , Sandra Le Quellec","doi":"10.1016/j.rpth.2026.103448","DOIUrl":"10.1016/j.rpth.2026.103448","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 3","pages":"Article 103448"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147712878","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":"Andexanet alfa for the reversal of anticoagulation: Dutch practice data","authors":"Jurjen F. Krommenhoek ,&nbsp;Wendy Beekman ,&nbsp;Flip Kor ,&nbsp;Pim Gal ,&nbsp;Willemijn E.M. Berkhout ,&nbsp;Karina Meijer ,&nbsp;Dionne C.W. Braeken ,&nbsp;Frederikus A. Klok ,&nbsp;Hugo ten Cate ,&nbsp;Renske H. Olie","doi":"10.1016/j.rpth.2026.103438","DOIUrl":"10.1016/j.rpth.2026.103438","url":null,"abstract":"<div><h3>Background</h3><div>Andexanet alfa is a reversal agent for factor Xa (FXa) inhibitors (rivaroxaban and apixaban) and is available for the treatment of severe FXa inhibitor-associated bleeding. However, an increase in thrombotic events after administration has been reported.</div></div><div><h3>Objectives</h3><div>This multicenter Dutch observational study aimed to provide insights into the characteristics, usage patterns, and clinical outcomes of the Dutch patient population treated with andexanet alfa.</div></div><div><h3>Methods</h3><div>We included all patients treated with on- and off-label andexanet alfa from 6 of the 11 hospitals in the Netherlands that prescribed andexanet alfa between June 2019 and December 2023. Data were collected by LOGEX, a Dutch healthcare data company, using healthcare administrative data and questionnaires completed by clinicians at participating centers. Patient characteristics, details related to andexanet alfa administration, and 30-day clinical outcomes, including thrombotic events and all-cause mortality, were collected.</div></div><div><h3>Results</h3><div>A total of 217 patients received andexanet alfa, including 192 treated on-label and 25 off-label. In the on-label group, the median age was 77 years (IQR, 69-82 years), and intracranial hemorrhage was the most common indication for reversal (61%). Most patients received a low dose (≤1000 mg) and were administered andexanet alfa within 4 hours of hospital admission (79%). The overall 30-day cumulative incidence of thrombotic events was 4.6%, and no thrombotic events occurred after anticoagulation was reinitiated. All-cause mortality was 34%, with similar rates between the on- and off-label groups.</div></div><div><h3>Conclusion</h3><div>Andexanet alfa was primarily prescribed for the reversal of FXa inhibitors in patients with intracerebral hemorrhage. We observed a lower incidence of thrombotic events than reported in clinical trials.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 3","pages":"Article 103438"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147803604","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":"Oral contraceptives and tissue factor expression. Comments on “Do combined oral contraceptives induce formation of tissue factor?”: reply","authors":"Søren Risom Kristensen ,&nbsp;Jette Nybo ,&nbsp;Jesper Strandberg","doi":"10.1016/j.rpth.2026.103444","DOIUrl":"10.1016/j.rpth.2026.103444","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 3","pages":"Article 103444"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147859627","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":"Response to hemophilia B gene therapy based on adenoassociated virus serotype 5 antibody status","authors":"Wolfgang Miesbach ,&nbsp;Alok Srivastava","doi":"10.1016/j.rpth.2026.103447","DOIUrl":"10.1016/j.rpth.2026.103447","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 3","pages":"Article 103447"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147712442","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":"Oral contraceptives and tissue factor expression. Comments on “Do combined oral contraceptives induce formation of tissue factor?”","authors":"Bjarne Østerud","doi":"10.1016/j.rpth.2026.103445","DOIUrl":"10.1016/j.rpth.2026.103445","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 3","pages":"Article 103445"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147712877","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":"Improving bleeding and thrombosis in patients with extracorporeal life support: could hematology help?","authors":"Heidi J. Dalton","doi":"10.1016/j.rpth.2026.103422","DOIUrl":"10.1016/j.rpth.2026.103422","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 3","pages":"Article 103422"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147712879","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":"Hemophilia and hereditary angioedema: parallel therapeutic advances in genetic diseases of serine protease pathways","authors":"Massimo Cugno ,&nbsp;Pier Mannuccio Mannucci","doi":"10.1016/j.rpth.2026.103456","DOIUrl":"10.1016/j.rpth.2026.103456","url":null,"abstract":"<div><div>Hemophilia and hereditary angioedema (HAE) are rare monogenic disorders characterized by the dysregulation of serine protease-based biological pathways, that is, blood coagulation and the kallikrein–kinin system. Although clinical manifestations differ profoundly (bleeding vs angioedema), both diseases have recently undergone parallel therapeutic revolutions, shaped by advances in molecular biology and biotechnology. Early management in the 1970s relied for both diseases on the episodic administration of plasma-derived products, subsequently replaced by recombinant products that improved safety and feasibility of prophylaxis regimens. In the last 20 years, the development of nonreplacement products, such as emicizumab and rebalancing agents in hemophilia and kallikrein/bradykinin pathway inhibitors in HAE, shifted clinical practice from the episodic management of clinical events to their prevention. More recently, gene and RNA-based therapies are further transforming both diseases toward curative attempts: in hemophilia, adeno-associated virus vector-mediated gene therapy and lentiviral stem-cell approaches; in HAE, antisense oligonucleotide–mediated kallikrein suppression. Emerging genome-editing approaches and biomarker- and genotype-driven strategies are poised to further improve and personalize treatment. The therapeutic trajectories of rare diseases such as hemophilia and HAE illustrate how mechanistic insights enable the transition from the episodic management of acute events to long-term disease control, offering prospects for curative interventions.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 3","pages":"Article 103456"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147712881","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":"Toward improved thrombolysis in ischemic stroke: targeting nonfibrin components","authors":"Simon F. De Meyer","doi":"10.1016/j.rpth.2026.103434","DOIUrl":"10.1016/j.rpth.2026.103434","url":null,"abstract":"<div><div>A State of the Art lecture titled “Targeting nonfibrin components in ischemic stroke” was presented at the International Society on Thrombosis and Haemostasis Congress in 2025. Fibrinolysis using recombinant tissue plasminogen activators remains the primary pharmacologic approach for reperfusion therapy in ischemic stroke. Its clinical benefit has been well established over the past 3 decades. However, fibrinolytic therapy is not universally effective, and its limitations have become increasingly apparent. Recent research has provided deeper insights into acute ischemic stroke thrombus composition and architecture, revealing complex structures containing not only fibrin but also cellular and extracellular components that contribute to fibrinolysis resistance. These findings have led to the development of novel strategies aimed at targeting nonfibrin components to enhance overall thrombolysis and overcome fibrinolysis resistance. This review highlighted the current evidence from studies on ischemic stroke thrombi that underpin emerging thrombolytic strategies that target nonfibrin components and discusses their potential clinical implications. Finally, relevant new data on this topic presented during the 2025 International Society on Thrombosis and Haemostasis Congress were summarized.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 3","pages":"Article 103434"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147745138","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":"Identification of novel PROS1 variants through systematic analysis of patients with suspected hereditary protein S deficiency","authors":"Malte M. Bartylla,&nbsp;Susanne Achenbach,&nbsp;Holger Hackstein,&nbsp;Sabine Schneider","doi":"10.1016/j.rpth.2026.103432","DOIUrl":"10.1016/j.rpth.2026.103432","url":null,"abstract":"<div><h3>Background</h3><div>Protein S (PS) is an important, nonenzymatic cofactor with clinical relevance in coagulation disorders. Hereditary deficiency of PS is caused by pathogenic variants in the <em>PROS1</em> gene, which encodes this protein. Identifying the presence and assessing the pathogenicity of <em>PROS1</em> variants is essential for the effective management of patients with hereditary PS deficiency.</div></div><div><h3>Objectives</h3><div>The aim of this study was to identify <em>PROS1</em> variants in patients with suspected hereditary PS deficiency and to evaluate their pathogenicity.</div></div><div><h3>Methods</h3><div>The <em>PROS1</em> coding sequence, including adjacent intron–exon boundaries, was analyzed in 276 patients with suspected hereditary PS deficiency using next-generation sequencing. Identified variants were evaluated based on existing literature, when available, or using bioinformatic prediction tools. The predicted pathogenicity was then compared with the patients’ PS activity levels.</div></div><div><h3>Results</h3><div>Forty-eight distinct variants were identified in 101 patients. Twenty-seven of these variants have been previously described in the literature, and their pathogenicity was categorized based on all available evidence. Of the remaining 21 variants, 11 are listed in ClinVar and/or dbSNP; 10 are novel. The potential pathogenicity of these variants, as well as possible explanations for PS deficiency in patients without an identified variant, are discussed.</div></div><div><h3>Conclusion</h3><div><em>In silico</em> prediction tools are useful for a first assessment of pathogenicity for novel <em>PROS1</em> variants. For a final evaluation of whether a variant is causative for hereditary PS deficiency, a comprehensive characterization is indispensable.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 3","pages":"Article 103432"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147750612","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":"The effects of recombinant human activated factor VII and tranexamic acid on traumatic bleeding and mortality in mice","authors":"Bilgimol Chumappumkal Joseph ,&nbsp;Juan Andres De Pablo-Moreno ,&nbsp;Nicca Falah ,&nbsp;Abraham Wentzel ,&nbsp;Mia Lora Cacho ,&nbsp;Eduardo Frias-Anaya ,&nbsp;Miguel A. Lopez-Ramirez ,&nbsp;Annette von Drygalski","doi":"10.1016/j.rpth.2026.103436","DOIUrl":"10.1016/j.rpth.2026.103436","url":null,"abstract":"<div><h3>Background</h3><div>Tranexamic acid (TXA) and recombinant human activated factor (F)VII (rhFVIIa) both control severe traumatic bleeding, with mortality benefit only demonstrated for TXA.</div></div><div><h3>Objectives</h3><div>To compare the effects of rhFVIIa and TXA on bleeding, trauma-induced coagulopathy (TIC), inflammation, and survival in a murine trauma model.</div></div><div><h3>Methods</h3><div>Liver laceration (LL) was employed to induce TIC. C57BL/6J mice were pretreated intravenously with saline, rhFVIIa (3 mg/kg), or TXA (10 mg/kg). Blood loss, coagulopathy (activated partial thromboplastin time [aPTT], FII, FV, FVIII, FX, thrombin-antithrombin [TAT], and fibrinogen), and fibrinolysis (tissue-type plasminogen activator, plasmin-α2-antiplasmin complexes, and D-dimer) were analyzed 60 minutes after LL. Cytokines were measured at 60 minutes and 6 hours. Pulmonary fibrin deposition and survival were evaluated for up to 7 days.</div></div><div><h3>Results</h3><div>Both rhFVIIa and TXA reduced blood loss compared with saline-treated mice after LL. Saline-treated mice developed TIC (prolonged aPTT, increased TAT complex formation, and selective depletion of FV, FVIII, and fibrinogen). rhFVIIa overcorrected the aPTT and increased TAT complex levels, whereas TXA normalized these parameters. Both agents reduced tissue-type plasminogen activator and plasmin-α2-antiplasmin complex formation; however, rhFVIIa failed to suppress D-dimer formation and exacerbated interleukin-6 formation. Pulmonary fibrin deposition and microthrombi occurred exclusively in rhFVIIa-treated mice (days 1, 2, and 7), accompanied by reduced survival (∼50%) compared with TXA (∼80%).</div></div><div><h3>Conclusion</h3><div>While both agents reduced bleeding, rhFVIIa promoted prothrombotic and inflammatory responses, which were associated with increased mortality. Our findings highlight the unmet need for targeted interventions to reduce TIC while minimizing thromboinflammatory risk.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 3","pages":"Article 103436"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147712454","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}