Research and Practice in Thrombosis and Haemostasis最新文献

{"title":"Thiol isomerase ERp18 enhances platelet activation and arterial thrombosis","authors":"Chao He ,&nbsp;Aizhen Yang ,&nbsp;Keyu Lv ,&nbsp;Yuxin Zhang ,&nbsp;Zhenzhen Zhao ,&nbsp;Yi Lu ,&nbsp;Chao Fang ,&nbsp;Yue Han ,&nbsp;Depei Wu ,&nbsp;Miao Jiang ,&nbsp;Jingyu Zhang ,&nbsp;Yi Wu","doi":"10.1016/j.rpth.2025.102706","DOIUrl":"10.1016/j.rpth.2025.102706","url":null,"abstract":"<div><h3>Background</h3><div>Thiol isomerases regulate the thiol-disulfide exchange of functional proteins in cells. Using genetically modified mouse models and inhibitors, we and others demonstrated that 7 thiol isomerases (ERp57, protein diisulfide isomerase, ERp72, ERp46, ERp5, TMX4, and TMX1) participate in thrombosis. There are 21 thiol isomerases in mammals, but whether other enzymes of this family also contribute to thrombosis remains unknown.</div></div><div><h3>Objectives</h3><div>Investigate whether and how ERp18 participates in arterial thrombosis.</div></div><div><h3>Methods</h3><div>ERp18 knockout mice and arterial thrombosis models were used to determine the role of ERp18 in thrombosis. Platelets from ERp18 knockout mice were used to detect aggregation, activation, spreading, and clot retraction. Finally, flow cytometry and immunoprecipitation were used to detect the binding between ERp18 and α_IIbβ₃.</div></div><div><h3>Results</h3><div>The mice lacking ERp18 exhibited a prolonged tail bleeding time and decreased platelet thrombus formation in FeCl₃-induced carotid arterial injury and laser-induced cremaster artery injury models. ERp18 deficiency inhibited platelet aggregation, adenosine triphosphate release, integrin α_IIbβ₃ activation, P-selectin expression, platelet adhesion, as well as clot retraction. Flow cytometry and coimmunoprecipitation analyses revealed that ERp18 binds to the platelet surface via interaction with integrin α_IIbβ₃. Moreover, the ERp18 protein promoted the binding of integrin α_IIbβ₃ to fibrinogen and platelet aggregation. Furthermore, the recombinant ERp18 protein exhibited reductase activity and cleaved integrin α_IIbβ₃ disulfides.</div></div><div><h3>Conclusion</h3><div>ERp18 participates in platelet activation and thrombosis. Its function is, at least in part, through the regulation of integrin α_IIbβ₃ function. This finding expands our understanding of the role of thiol isomerases in the redox regulation of thrombosis and platelet function.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102706"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a novel gene editing lexicon for hemophilia: methodology and results","authors":"Craig M. Kessler ,&nbsp;Leonard A. Valentino ,&nbsp;Courtney D. Thornburg ,&nbsp;Carmen Unzu ,&nbsp;Mark A. Kay ,&nbsp;Flora Peyvandi ,&nbsp;Penni Smith ,&nbsp;Wolfgang Miesbach ,&nbsp;William McKeown ,&nbsp;Glenn F. Pierce ,&nbsp;Kate Khair ,&nbsp;Katarina Starcevic ,&nbsp;Monisha Pillai ,&nbsp;Micheala Jones ,&nbsp;Anil Sindhurakar ,&nbsp;Lauren Whyte ,&nbsp;Virginie Delwart ,&nbsp;Megan Chiao ,&nbsp;David E. Gutstein ,&nbsp;Ilia Antonino ,&nbsp;Steven W. Pipe","doi":"10.1016/j.rpth.2025.102710","DOIUrl":"10.1016/j.rpth.2025.102710","url":null,"abstract":"<div><h3>Background</h3><div>Clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9)-based targeted gene editing platforms are being developed to treat genetic diseases like hemophilia. Such novel therapy involves complex concepts and terminology that require aligned language to engage key stakeholders in the hemophilia community. Thus, a globally aligned gene editing lexicon – a consistent language to communicate the fundamentals of gene editing in hemophilia, designed to be credible and accessible for people with hemophilia and caregivers while avoiding unnecessary complexity – is required to address this need.</div></div><div><h3>Objectives</h3><div>To establish an aligned language and communications framework that facilitates informed consent and shared decision-making regarding gene editing and treatment considerations in hemophilia.</div></div><div><h3>Methods</h3><div>Through an innovative partnership with global experts in hemophilia, gene editing, and biotechnology, initial insights were gathered via interviews, workshops, and analysis of existing language within the hemophilia community. Qualitative research involving lived experience experts (people with hemophilia and caregivers; <em>n</em> = 43) and hematologists (<em>n</em> = 24) informed the lexicon development, which was further validated by a steering committee of global experts in the hemophilia and gene editing fields. Finally, optimized language recommendations were developed for a clear, consistent gene editing lexicon.</div></div><div><h3>Results</h3><div>Key themes included insights into audience mindsets, guiding language principles, and optimized terminology for key topics like gene editing concepts and posttreatment considerations. Audience mindsets revealed cautious optimism around gene therapy, with more skepticism around gene editing. Guiding language principles indicated a preference for plainspoken over technical language, definitions that link to patient benefits, and explanations that highlight the precise nature of gene editing.</div></div><div><h3>Conclusion</h3><div>This collaborative approach ensures broad adoption of the lexicon within the hemophilia community and readiness for beta testing.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102710"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global patterns of hemophilia drug trials, hemophilia care, and health care measures","authors":"Stacey A. Fedewa ,&nbsp;Leonard A. Valentino ,&nbsp;Andee Koo ,&nbsp;Lorraine Cafuir ,&nbsp;Theresa W. Gillespie ,&nbsp;Tyler W. Buckner ,&nbsp;Duc Q. Tran ,&nbsp;Ana Antun ,&nbsp;Christine L. Kempton","doi":"10.1016/j.rpth.2025.102714","DOIUrl":"10.1016/j.rpth.2025.102714","url":null,"abstract":"<div><h3>Background</h3><div>Drug trials are vital to establish safe and effective treatments for congenital hemophilia, a bleeding disorder that affects about 800,000 males worldwide. The global distribution of hemophilia drug trials (HDTs) and their alignment with hemophilia care is unknown.</div></div><div><h3>Objectives</h3><div>This study aimed to evaluate the global distribution of HDTs and its association with hemophilia care.</div></div><div><h3>Methods</h3><div>In this cross-sectional study, HDTs conducted between 2007 and 2022 were selected from the <span><span>clinicaltrials.gov</span><svg><path></path></svg></span> database. The density of trials per 1000 expected males with hemophilia (eMwH) was assessed according to hemophilia care measures (factor VIII and IX utilization per 1000 eMwH) derived from World Federation of Hemophilia data.</div></div><div><h3>Results</h3><div>Among 124 trials, 55 countries were represented, with an average of 7.9 countries per trial. Most HDT sites were in high-income (74.4%) or upper middle (20.1%)–income countries. The number of sites in lower-middle–income countries doubled, from 12 in 2007-2011 to 30 in 2017-2022—a nonsignificant increase from 5.8% to 7.0% (<em>P</em> = .53). Factor utilization was substantially reduced in lower-middle (0.4 international units [IUs] per 1000 eMwH) and upper middle (2.8 IUs per 1000 eMwH) compared with high (6.8 IUs per 1000 eMwH) income countries. HDT density was moderately correlated with factor usage (<em>r</em> = 0.436; <em>P</em> ≤ .001).</div></div><div><h3>Conclusion</h3><div>Most HDT sites were located in high-income countries, although a substantial proportion were in upper middle–income countries. A small but increasing number of trials were conducted in lower-middle–income countries, where factor usage is relatively low. This study provides evidence on the global distribution of HDT and raises questions regarding the generalizability, barriers, opportunities, and ethics of trials for a rare bleeding disorder.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102714"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between genetic risk and adherence to the Dietary Approaches to Stop Hypertension diet for developing venous thromboembolism","authors":"Si Li ,&nbsp;Minghui Jiang ,&nbsp;Yunlong Guan ,&nbsp;Xi Cao ,&nbsp;Zhonghe Shao ,&nbsp;Jun Deng ,&nbsp;Xingjie Hao","doi":"10.1016/j.rpth.2025.102731","DOIUrl":"10.1016/j.rpth.2025.102731","url":null,"abstract":"<div><h3>Background</h3><div>The relationship between diet and venous thromboembolism (VTE) remains unclear, and the joint effects of diet patterns and genetic susceptibility on VTE risk are unknown.</div></div><div><h3>Objectives</h3><div>Investigate the independent and joint effects of Dietary Approaches to Stop Hypertension (DASH) diet adherence and polygenic risk scores (PRS) on VTE risk.</div></div><div><h3>Methods</h3><div>A total of 411,539 UK Biobank participants were included. DASH scores were calculated using Food Frequency Questionnaires, and PRS quantified genetic risk. Cox proportional hazard models estimated hazard ratios (HRs) for VTE, assessing interactions between the DASH diet and genetic susceptibility.</div></div><div><h3>Results</h3><div>During a median follow-up of 13.4 years, 10,543 participants were diagnosed with VTE. Higher DASH scores were associated with a lower VTE risk (HR, 0.87; 95% CI, 0.82-0.92). A low-adherent DASH diet combined with high-genetic risk had the highest VTE risk (HR, 2.78; 95% CI, 2.47-3.14). High DASH scores reduced VTE risk in high-genetic-risk individuals (HR, 0.84; 95% CI, 0.76-0.92). Sex-specific associations were detected in the joint effect and interaction of DASH scores and PRS. Notably, high DASH scores can offset moderate genetic risk among men (HR, 0.79; 95% CI, 0.67-0.94). There were additive interactions between DASH scores and high genetic risk in total subjects and men, while not observed in women.</div></div><div><h3>Conclusion</h3><div>The DASH diet is associated with reduced VTE risk and can partially offset genetic predisposition. Low adherence to the DASH diet increases VTE risk, particularly in high-genetic-risk individuals. The protective effect of high DASH scores against genetic risks for VTE is more pronounced in males. Precision medicine should consider both diet and genetics for VTE prevention.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102731"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stepwise response-guided treatment protocol superior to thrombopoietin receptor agonist-based second-line therapy for severe persistent/chronic immune thrombocytopenia: a multicenter prospective study from China","authors":"Lingling Fu ,&nbsp;Xi Lin ,&nbsp;Zhenping Chen ,&nbsp;Zhifa Wang ,&nbsp;Yan Liu ,&nbsp;Lijuan Wang ,&nbsp;Yu Hu ,&nbsp;Jingyao Ma ,&nbsp;Nan Wang ,&nbsp;Xiaoling Cheng ,&nbsp;Jie Ma ,&nbsp;Runhui Wu","doi":"10.1016/j.rpth.2025.102702","DOIUrl":"10.1016/j.rpth.2025.102702","url":null,"abstract":"<div><h3>Background</h3><div>The first second-line international recommendation for children with severe persistent/chronic immune thrombocytopenia is thrombopoietin receptor agonist (TPO-RA)-based treatment; however, &lt;30% can achieve sustained response off-treatment (SRoT), leading to a heavy medical burden.</div></div><div><h3>Objectives</h3><div>This study aimed to confirm the efficacy of the stepwise response-guided treatment protocol compared with TPO-RA–based second-line therapy for children with severe P/CITP.</div></div><div><h3>Methods</h3><div>The stepwise response-guided treatment protocol is an individualized stratified immune thrombocytopenia treatment starting with high-dose dexamethasone, then adding rituximab and TPO-RAs in sequential order according to treatment response. A prospective, multicenter clinical cohort study enrolled severe P/CITP children with a 1-year follow-up. We compared the treatment outcome response of platelet count, bleeding control, and treatment-related side effects and cost outcomes (escalation status, SRoT, and treatment costs) between the stepwise group and the TPO-RA–based second-line treatment group (TPO-RA group).</div></div><div><h3>Results</h3><div>The study enrolled 143 cases of severe P/CITP children with a 12-month follow-up period. There were no differences in baseline characteristics between the stepwise and TPO-RA groups (<em>P</em> &gt; .05). Response/remission rates and bleeding grades showed no differences (<em>P</em> &gt; .05), but there were fewer side effects related to treatment in the stepwise group (9.0%; <em>P</em> &lt; .00). A total of 74% in the stepwise group achieved SRoT while none in the TPO-RA group did. The cost of treatment was significantly lower in the stepwise group compared with the TPO-RA group over the 12-month follow-up period (USD 68.26/kg vs USD 384.76/kg, <em>P</em> &lt; .00).</div></div><div><h3>Conclusion</h3><div>The stepwise response-guided treatment protocol effectively stratifies children with severe P/CITP based on treatment response, enabling individualized treatment strategies. This protocol achieves comparable efficacy and safety while reducing the treatment burden compared with TPO-RA–based second-line therapy, making it a preferable option for children with severe P/CITP.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102702"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elderly patients are hyperresponsive to potent P2Y12 inhibitors","authors":"David Mutschlechner ,&nbsp;Maximilian Tscharre ,&nbsp;Patricia Pia Wadowski ,&nbsp;Silvia Lee ,&nbsp;Joseph Pultar ,&nbsp;Constantin Weikert ,&nbsp;Simon Panzer ,&nbsp;Thomas Gremmel","doi":"10.1016/j.rpth.2025.102704","DOIUrl":"10.1016/j.rpth.2025.102704","url":null,"abstract":"<div><h3>Background</h3><div>Aging has recently been associated with increased basal platelet activation and platelet hyperreactivity in response to adenosine diphosphate (ADP) but with decreased platelet response to thrombin receptor stimulation in individuals without antiplatelet therapy.</div></div><div><h3>Objectives</h3><div>To investigate platelet response to agonist stimulation in elderly patients (≥70 years) on dual antiplatelet therapy with potent P2Y12 inhibitors.</div></div><div><h3>Methods</h3><div>Platelet aggregation in response to arachidonic acid (AA), ADP, collagen, the protease-activated receptor-1 agonist SFLLRN, and the protease-activated receptor-4 agonist AYPGKF was assessed by multiple electrode aggregometry in 79 prasugrel- and 77 ticagrelor-treated patients 3 days after acute percutaneous coronary intervention.</div></div><div><h3>Results</h3><div>In the overall study population (<em>N</em> = 156), patients aged ≥70 years (<em>n</em> = 33) had lower platelet aggregation in response to AA, ADP, and SFLLRN than younger patients (all <em>P</em> &lt; .05). In prasugrel-treated patients (<em>n</em> = 79), those aged ≥70 years (<em>n</em> = 13) showed lower platelet aggregation in response to all agonists than younger patients (all <em>P</em> &lt; .05). In contrast, in ticagrelor-treated patients (<em>n</em> = 77), those aged ≥70 years (<em>n</em> = 20) only had lower ADP-inducible platelet aggregation than younger patients (<em>P</em> = .03), whereas platelet aggregation in response to AA, collagen, SFLLRN, and AYPGKF was similar between elderly and younger patients (all <em>P</em> &gt; .05). Among patients aged ≥70 years, prasugrel-treated patients showed lower platelet aggregation in response to AA, collagen, and AYPGKF than those receiving ticagrelor (all <em>P</em> &lt; .05).</div></div><div><h3>Conclusion</h3><div>Patients aged ≥70 years on potent P2Y12 inhibitors exhibit increased inhibition of ADP-inducible platelet aggregation. In addition, elderly patients on prasugrel show a lower response to AA, collagen, SFLLRN and AYPGKF than younger patients.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102704"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical outcomes of cancer-associated isolated distal deep vein thrombosis: a comparison between asymptomatic and symptomatic thrombosis—findings from the ONCO DVT Study","authors":"Yoshito Ogihara ,&nbsp;Yugo Yamashita ,&nbsp;Takeshi Morimoto ,&nbsp;Nao Muraoka ,&nbsp;Michihisa Umetsu ,&nbsp;Yuji Nishimoto ,&nbsp;Takuma Takada ,&nbsp;Tatsuya Nishikawa ,&nbsp;Nobutaka Ikeda ,&nbsp;Kazunori Otsui ,&nbsp;Daisuke Sueta ,&nbsp;Yukari Tsubata ,&nbsp;Masaaki Shoji ,&nbsp;Ayumi Shikama ,&nbsp;Yutaka Hosoi ,&nbsp;Yasuhiro Tanabe ,&nbsp;Ryuki Chatani ,&nbsp;Kengo Tsukahara ,&nbsp;Naohiko Nakanishi ,&nbsp;Kitae Kim ,&nbsp;Kaoru Dohi","doi":"10.1016/j.rpth.2025.102722","DOIUrl":"10.1016/j.rpth.2025.102722","url":null,"abstract":"<div><h3>Background</h3><div>The risk of recurrent venous thromboembolism (VTE) in patients with isolated distal deep vein thrombosis (IDDVT) is generally low, particularly when IDDVT is asymptomatic. However, cancer patients with IDDVT, even asymptomatic IDDVT, may be at a higher risk of recurrent VTE.</div></div><div><h3>Objectives</h3><div>To compare the clinical outcomes of cancer patients with asymptomatic and symptomatic IDDVT.</div></div><div><h3>Methods</h3><div>The ONCO DVT trial is a randomized clinical trial that compared 12-month versus 3-month edoxaban treatment regimens in cancer patients with IDDVT. In this post hoc analysis, 601 patients were categorized into the asymptomatic (<em>n</em> = 479) and symptomatic (<em>n</em> = 122) groups based on IDDVT-related symptoms at diagnosis. The primary outcome was the composite of symptomatic recurrent VTE or VTE-related death at 12 months, while the major secondary outcome was major bleeding at 12 months.</div></div><div><h3>Results</h3><div>The cumulative 12-month incidence of the primary outcome was lower in the asymptomatic group than that in the symptomatic group (2.9% vs 13.4%; <em>P</em> &lt; .001; hazard ratio, 0.21; 95% CI, 0.10-0.47). Among the 12 patients with symptomatic recurrent VTE in the asymptomatic group, 8 (67%) had recurrent IDDVT, and 11 (92%) experienced recurrence after discontinuing anticoagulation therapy. The cumulative 12-month incidence of major bleeding was lower in the asymptomatic group than that in the symptomatic group (7.8% and 13.2%; <em>P</em> = .048).</div></div><div><h3>Conclusion</h3><div>The risk of recurrent symptomatic VTE was lower in cancer patients with asymptomatic IDDVT than in those with symptomatic IDDVT. Most recurrent VTE events were recurrent IDDVT, with the majority occurring after discontinuing anticoagulation therapy.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102722"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid signatures of immunothrombosis: insights from VITT","authors":"Tamam Bakchoul,&nbsp;Madhumita Chatterjee","doi":"10.1016/j.rpth.2025.102725","DOIUrl":"10.1016/j.rpth.2025.102725","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102725"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factor XI localization in human deep venous thrombus and function of activated factor XI on venous thrombus formation and hemostasis","authors":"Nobuyuki Oguri ,&nbsp;Toshihiro Gi ,&nbsp;Eriko Nakamura ,&nbsp;Kazunari Maekawa ,&nbsp;Eiji Furukoji ,&nbsp;Hoshimi Okawa ,&nbsp;Sho Kouyama ,&nbsp;Saki Horiuchi ,&nbsp;Akira Sawaguchi ,&nbsp;Tatefumi Sakae ,&nbsp;Minako Azuma ,&nbsp;Yujiro Asada ,&nbsp;Atsushi Yamashita","doi":"10.1016/j.rpth.2025.102720","DOIUrl":"10.1016/j.rpth.2025.102720","url":null,"abstract":"<div><h3>Background</h3><div>Novel anticoagulants targeting coagulation factor (F)XI/activated FXI (FXIa) are currently under development. However, whether FXI is present in human deep vein thrombosis (DVT) and whether FXIa and activated FX (FXa) play different roles in venous thrombus formation and hemostasis remain unclear.</div></div><div><h3>Objectives</h3><div>To determine the presence of FXI in DVT and the effects of direct oral FXIa and FXa inhibitors on venous thrombus formation and hemostasis in rabbits and on <em>in vitro</em> thrombus formation.</div></div><div><h3>Methods</h3><div>We immunohistochemically assessed FXI localization in human-aspirated DVT (<em>n</em> = 15). Additionally, we compared thrombus formation induced by endothelial denudation and stenosis or stasis in the jugular vein and skin bleeding time and volume between rabbits treated with direct FXIa inhibitors (ONO-1600586) and FXa inhibitors (rivaroxaban). <em>Ex vivo</em> rabbit and human blood were perfused in a flow chamber under low-shear rates (70/s).</div></div><div><h3>Results</h3><div>FXI was localized in all DVT, predominantly in fibrin-rich areas. The FXI immunopositive area in the nonorganizing area was greater than that in the organizing area. Although FXIa and FXa inhibitors comparably inhibited venous thrombus formation, FXIa inhibitors did not affect bleeding time or volume in rabbits. FXIa or FXa inhibitors mildly or strongly inhibited fibrin formation at low-shear rates, respectively. Furthermore, the FXIa inhibitor suppressed human FXIa activity, thrombin generation, and fibrin formation during perfusion.</div></div><div><h3>Conclusion</h3><div>The pathologic findings of human DVT suggest FXI’s role in human DVT. FXIa inhibitors may inhibit less fibrin formation than FXa inhibitors and may explain the minor role of FXIa in hemostasis.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102720"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic factors for recurrence in acquired hemophilia A-results from a long-term observational study","authors":"Lisa Reich,&nbsp;Florian Gatzke,&nbsp;Steffen Rauchfuss,&nbsp;Stefanie Roth,&nbsp;Wolfgang Miesbach","doi":"10.1016/j.rpth.2025.102707","DOIUrl":"10.1016/j.rpth.2025.102707","url":null,"abstract":"<div><h3>Objectives</h3><div>Acquired hemophilia A (AHA) is a rare autoimmune disease caused by autoantibodies against factor (F)VIII (FVIII), potentially leading to life-threatening bleeding. While predictors for remission have been analyzed, data on recurrence is lacking.</div></div><div><h3>Methods</h3><div>This study investigated predictors of AHA recurrence in 41 patients. Patients were divided into 2 groups: those with recurrence (<em>n</em> = 18) and those in stable long-term remission (<em>n</em> = 23) with at least 1 year of follow-up.</div></div><div><h3>Results</h3><div>All relapses occurred within 1 year of initial remission. The median follow-up period was 3.8 years (IQR, 1.8-6.4) for all included patients. Multivariate Cox regression analysis revealed that initial FVIII activity &lt;1 IU/dL and failure to achieve initial complete remission (CR) were significant predictors of relapse. Kaplan–Meier curves showed significantly different relapse-free survival rates for patients with initial FVIII activity &lt;1 IU/dL vs ≥1 IU/dL (χ²[1] = 5.950, <em>P</em> = .015), and for those achieving initial CR vs partial remission (χ²[1] = 6.570, <em>P</em> = .010).</div><div>Other factors such as inhibitor titer, gender, age, World Health Organization scale, underlying disorder, controlled disorder, initial immunosuppressive therapy, immunosuppressive therapy escalation, and partial remission at day 21 showed no significant relation to recurrences. Overall survival did not differ significantly between relapsing and nonrelapsing patients (χ²[1] = .896, <em>P</em> = .344).</div></div><div><h3>Conclusion</h3><div>Initial FVIII &lt;1 IU/dL and failure to achieve initial CR are identified as risk factors for recurrence in AHA. Patients with these characteristics should be closely monitored for at least 1 year after initial remission due to increased recurrence risk.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102707"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}