Journal of Thrombosis and Haemostasis最新文献

{"title":"Navigating the waters of acute minor stroke therapies: a systematic review and network meta-analysis.","authors":"Xuefan Yao, Aini He, Benke Zhao, Wei Sun, Xiao Wu, Xue Wang, Chengyu Song, Haiqing Song, Yuan Wang","doi":"10.1016/j.jtha.2025.02.017","DOIUrl":"10.1016/j.jtha.2025.02.017","url":null,"abstract":"<p><strong>Background: </strong>Although acute minor stroke often presents with mild symptoms, such as unilateral limb weakness, mild aphasia, dizziness, or mild cognitive impairment, untreated outcomes could be poor, and optimal treatment methods are still debated.</p><p><strong>Objectives: </strong>We aimed to identify the optimum treatment for minor strokes with a network meta-analysis.</p><p><strong>Methods: </strong>Studies from Embase, Ovid, and Cochrane Library were considered. Randomized controlled trials and prospective cohort studies on ischemic stroke with a National Institutes of Health Stroke Scale score no more than 5, explicit intravenous thrombolysis, or antiplatelet therapy were included. Efficacy outcome was measured by 3-month modified Rankin scale (mRS), with primary outcome defined as mRS score of 0 to 1 and secondary outcome defined as mRS score of 0 to 2. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality at 3 months.</p><p><strong>Results: </strong>Nine studies encompassing 10 665 patients were meta-analyzed. Aspirin plus clopidogrel (n = 4283) was more strongly associated with primary outcome than aspirin (n = 2128; odds ratio [OR], 1.26; 95% CI, 1.04∼1.54) and recombinant tissue plasminogen activator (rt-PA; n = 1840; OR, 1.23; 95% CI, 1.00∼1.50). Aspirin plus clopidogrel (n = 3933) also had a lower sICH risk than rt-PA (n = 2538; OR, 0.11; 95% CI, 0.04∼0.30) and tenecteplase (n = 194; OR, 0.15; 95% CI, 0.03∼0.68), as well as a lower mortality than aspirin alone (n = 830; OR, 0.27; 95% CI, 0.10∼0.71). Patients treated with aspirin (n = 815) also had a lower sICH risk than rt-PA (n = 2538; OR, 0.20; 95% CI, 0.04∼0.95).</p><p><strong>Conclusion: </strong>Dual antiplatelet therapy based on aspirin and clopidogrel offers balanced efficacy and safety, positioning it as a potentially optimal treatment for minor stroke. rt-PA showed comparable efficacy, while its associated risks were more pronounced.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515931","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":"Corrigendum to 'FRONTIER1: a partially randomized phase 2 study assessing the safety, pharmacokinetics, and pharmacodynamics of Mim8, a factor VIIIa mimetic': [Journal of Thrombosis and Haemostasis Volume 22, Issue 4, April 2024, Pages 990-1000].","authors":"Steven R Lentz, Pratima Chowdary, Lidia Gil, Francisco J Lopez-Jaime, Johnny Mahlangu, Irina Matytsina, Anne Louise Nielsen, Jerzy Windyga","doi":"10.1016/j.jtha.2025.02.008","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.02.008","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472661","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":"Sedentary behaviors and venous thromboembolism risk among older women: the Objective Physical Activity and Cardiovascular Health study.","authors":"Laura B Harrington, Kara L Cushing-Haugen, Steve Nguyen, John Bellettiere, Michael J LaMonte, Charles B Eaton, Matthew A Allison, Robert B Wallace, JoAnn E Manson, Majken K Jensen, Christopher Kabrhel, Gregory A Wellenius, I-Min Lee, Kenneth J Mukamal, Andrea Z LaCroix","doi":"10.1016/j.jtha.2025.02.014","DOIUrl":"10.1016/j.jtha.2025.02.014","url":null,"abstract":"<p><strong>Background: </strong>Venous stasis, which can occur with prolonged sedentary behavior (SB), is associated with venous thromboembolism (VTE) risk, but VTE risk associated with accelerometer-measured SB has not been quantified.</p><p><strong>Objectives: </strong>To evaluate accelerometer-based measures of SB in relation to incident VTE.</p><p><strong>Methods: </strong>We included 5591 participants, aged 63 to 99 years, of the Women's Health Initiative Objective Physical Activity and Cardiovascular Health cohort study without prior VTE. Between May 2012 and April 2014, participants wore the ActiGraph GT3X+ accelerometer at the hip for 7 days. Three SB measures were classified using the Convolutional Neural Network Hip Accelerometer Posture algorithm: total sitting time, mean sitting bout duration, and total time spent in prolonged (≥30 minutes) sitting bouts. VTE events were centrally adjudicated. Multivariable-adjusted Cox models estimated hazard ratios for each SB and VTE risk. Women were censored at first VTE, death, loss to follow-up, or February 2023. Mediation by body mass index (BMI) was evaluated.</p><p><strong>Results: </strong>Over a mean follow-up of 8.2 years, 229 women experienced a VTE. In adjusted models, longer mean sitting bout duration was associated with greater incident VTE risk (hazard ratio per 5-minute increase, 1.15; 95% CI, 1.04-1.28). BMI mediated approximately 30% of this association (P < .01). We found no significant evidence that total sitting time or total time spent in prolonged sitting bouts were associated with VTE.</p><p><strong>Conclusion: </strong>Longer mean sitting bout duration was associated with greater VTE risk, with substantial mediation by BMI. Behavioral efforts to reduce sedentary bout length in older women may reduce their VTE risk.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476716","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":"Functional disability after clinically significant extracranial bleeding: a secondary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) Trial.","authors":"Darrick K Li, David Cheng, Anna Parks, Meghan L Rieu-Werden, Galina Polekhina, Suzanne E Mahady, M Maria Glymour, Andrew T Chan, Sachin J Shah","doi":"10.1016/j.jtha.2025.02.013","DOIUrl":"10.1016/j.jtha.2025.02.013","url":null,"abstract":"<p><strong>Background: </strong>Clinically significant extracranial bleeding, defined as bleeding at any site other than the brain or spinal cord requiring either a hospital admission >24 hours, red blood cell transfusion, surgery for hemostasis, or resulting in death, is a common side effect of antithrombotic agents. Compared to intracranial bleeding, the impact of clinically significant extracranial bleeding on long-term outcomes, including functional independence, has been poorly studied.</p><p><strong>Objectives: </strong>To determine if clinically significant extracranial bleeding impacts the development of functional disability in healthy older adults.</p><p><strong>Methods: </strong>We performed a secondary analysis of the Aspirin in Reducing Events in the Elderly trial. The primary outcome of this study was incident dependence in the Katz Activities of Daily Living (ADLs), defined as being unable to perform or requiring assistance with any ADLs or being admitted to a long-term care facility.</p><p><strong>Results: </strong>A total of 18 982 participants were included in the analysis, of which 547 (2.9%) developed clinically significant extracranial bleeding during study follow-up. In adjusted analyses, clinically significant extracranial bleeding was significantly associated with the development of incident ADL dependence (hazard ratio [HR], 2.46; 95% CI, 1.97-3.07). This finding was similar for gastrointestinal (HR, 2.29; 95% CI, 1.72-2.08) and nongastrointestinal extracranial bleeds (HR, 2.68; 95% CI, 1.96-3.69). The association with increased risk of incident ADL dependence remained significant in secondary analysis of groups randomized to either aspirin (HR, 2.15; 95% CI, 1.57-2.94) or placebo (HR, 2.84; 95% CI, 2.09-3.86).</p><p><strong>Conclusion: </strong>Clinically significant extracranial bleeding was associated with the development of incident ADL dependence in otherwise healthy older adults.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476713","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":"Results of an international survey on the management of therapeutic intensity unfractionated heparin: communication from the SSCs of the ISTH.","authors":"Isabelle Gouin-Thibault, Lana A Castellucci, Jean M Connors, Michael Hardy, Alexandre Mansour, Virginie Siguret, Corinne Frere, Jerrold H Levy, Adam Cuker, Thomas Lecompte, François Mullier","doi":"10.1016/j.jtha.2025.02.012","DOIUrl":"10.1016/j.jtha.2025.02.012","url":null,"abstract":"<p><strong>Background: </strong>Unfractionated heparin (UFH) remains the anticoagulant of choice in critically ill patients. However, its laboratory monitoring and clinical management are particularly challenging.</p><p><strong>Objectives: </strong>Our objective was to describe current practices and variations among centers of the ISTH.</p><p><strong>Methods: </strong>Between November 2023 and February 2024, we surveyed 142 clinicians and laboratory medicine specialists from 15 countries involved in the care of patients receiving therapeutic-intensity UFH.</p><p><strong>Results: </strong>UFH monitoring was based on an anti-Xa assay or on activated partial thromboplastin time in 54% and 46% of respondents, respectively. Different therapeutic ranges were used depending on local protocols and indications; the 0.3 to 0.7 IU/mL anti-Xa range was commonly used, except for patients on mechanical circulatory support with a lower range, mostly 0.3 to 0.5 IU/mL. Most respondents managed therapeutic UFH administration with weight-based dosing (88%), while fewer used a nomogram (57%) for dose adjustment. When a nomogram was used, it was primarily based on anti-Xa monitoring (86%). The situations when respondents administered antithrombin varied widely; 22% reported using it when antithrombin levels were below 60 IU/dL(%) and 20% reported never using it.</p><p><strong>Conclusion: </strong>Our survey results revealed considerable heterogeneity in UFH management approaches, reflecting a knowledge gap and a paucity of evidence to guide decision-making. Key issues requiring well-designed up-to-date studies were identified that include optimal approaches to heparin monitoring, assays and reagents to be used, therapeutic range based on indications, the use of weight-adjusted nomograms for initial dosing and titrating of UFH infusion, and indications for antithrombin supplementation. Survey results provide a strong rationale for the development of international guidance addressing these issues.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472673","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":"Intravenous immunoglobulin prevents thrombosis in an endothelialized disease model of heparin-induced thrombocytopenia.","authors":"Andreas Witzemann, Günalp Uzun, Nina Wolska, Meltem Avci-Adali, Jean Amiral, Karina Althaus, Tamam Bakchoul, Jan Zlamal","doi":"10.1016/j.jtha.2025.02.011","DOIUrl":"10.1016/j.jtha.2025.02.011","url":null,"abstract":"<p><strong>Background: </strong>Heparin-induced thrombocytopenia (HIT) is a serious adverse reaction to heparin, associated with increased risk of thromboembolic complications. Intravenous immunoglobulins (IVIGs) have been used as a therapeutic for HIT and are believed to alleviate thrombocytopenia and reduce thrombosis risk. Yet the antithrombotic effects of IVIG in HIT remain underexplored.</p><p><strong>Objective: </strong>To investigate the effect of IVIG on thrombus formation in an ex vivo model of HIT-IgG-induced thrombosis.</p><p><strong>Methods: </strong>Microfluidic channels were coated with a confluent monolayer of human umbilical vein endothelial cells that were primed with TNF-α to induce an activated, inflammatory state. Whole blood was exposed to unfractionated heparin, with or without IVIG before subjecting to treatment with a monoclonal HIT-like antibody (K070), or HIT-patient-IgG. Recalcified blood was perfused over human umbilical vein endothelial cells at venous shear stress. Thrombus structure and dynamics were investigated by immunofluorescence microscopy.</p><p><strong>Results: </strong>HIT-patient-IgGs and K070 induced thrombus formation in the presence of prophylactic heparin exposure, over TNF-α treated, inflamed endothelial cells. HIT thrombi were enriched in fibrin, phosphatidylserine-bearing platelets, and leukocyte aggregates. We observed thrombi being formed on adherent platelets, which gradually recruited leukocytes into a three-dimensional thrombus structure. Pretreatment of blood with IVIG significantly reduced cellular adhesions and prevented thrombus formation.</p><p><strong>Conclusion: </strong>Our endothelialized ex vivo flow chamber system effectively recapitulates the immunothrombotic phenotype of HIT and offers a reliable tool to urgently validate the efficacy of IVIG intervention against HIT-IgG-induced thrombosis in patients.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472665","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":"Identification of multiple novel procoagulant plasma ligands for stabilin-2.","authors":"Mary Underwood, Felipe Da Veiga Leprevost, Venkatesha Basrur, Alexey I Nesvizhskii, Orla Rawley, Krista Golden, Brian Emmer, David Lillicrap, Karl Desch","doi":"10.1016/j.jtha.2025.01.023","DOIUrl":"10.1016/j.jtha.2025.01.023","url":null,"abstract":"<p><strong>Background: </strong>Damaging STAB2 gene variants are associated with increased venous thromboembolic risk. STAB2 encodes stabilin-2, a clearance receptor, expressed by the liver and spleen. Given its function, it is likely that the prothrombotic state associated with stabilin-2 deficiency is due to reduced procoagulant protein clearance, but the identity of these ligands is unknown.</p><p><strong>Objectives: </strong>To identify plasma stabilin-2 ligands using proximity biotinylation proteomics.</p><p><strong>Methods: </strong>Cells stably expressing stabilin-2-TurboID were incubated with human plasma and biotin to initiate TurboID labeling of plasma ligands in endocytic vesicles. Biotinylated proteins were purified and identified using mass spectrometry. Candidate plasma ligands with roles in hemostasis were fluorescently labeled and incubated with stabilin-2 expressing and control cells. Flow cytometry assessed ligand surface binding and confocal microcopy assessed colocalization with stabilin-2 and lysosomes. Furthermore, plasma levels of ligands were measured in Stab2-deficient mice and littermate controls.</p><p><strong>Results: </strong>Twenty-eight stabilin-2 specific ligands were identified. Interactions with von Willebrand factor, fibrinogen, pro(thrombin), heparin cofactor II, high molecular weight kininogen, plasminogen, and C4b-binding protein were probed. Heparin cofactor II, high molecular weight kininogen, plasminogen, and fibrinogen showed binding to stabilin-2 using flow cytometry (>2-fold higher than controls). Confocal microscopy demonstrated stabilin-2 dependent colocalization of all ligands with lysosomes. In Stab2-deficient mice, ligand levels were not significantly increased, suggesting in mice stabilin-2 is not their main clearance receptor.</p><p><strong>Conclusion: </strong>These results confirm the value of proximity labeling proteomics in identifying receptor ligands and suggest damaging STAB2 variants may increase venous thromboembolic risk potentially through altered hemostatic protein clearance.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458374","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":"Single-cell transcriptomic analysis reveals distinct plasma cell populations in chronic thromboembolic pulmonary hypertension.","authors":"Rui Zhang, Yunlong Zhang, Huiting Li, Jing Zhang, Qiao Feng, Yitong Lei, Sihan Liu, Qinhua Zhao, Jing He, Cijun Luo, Hongling Qiu, Jianfeng Zhang, Sugang Gong, Lan Wang","doi":"10.1016/j.jtha.2025.02.010","DOIUrl":"10.1016/j.jtha.2025.02.010","url":null,"abstract":"<p><strong>Background: </strong>Chronic thromboembolic pulmonary hypertension (CTEPH) presents challenges due to its complex pathobiology. Although numerous studies have reported heterogeneous cell types by single-cell RNA sequencing, the atlas and characteristics of plasma cells remain poorly understood.</p><p><strong>Objectives: </strong>To identify the altered phenotype and differentiation patterns of plasma cells in CTEPH.</p><p><strong>Methods: </strong>We performed single-cell RNA sequencing on pulmonary endarterectomy tissue from 5 patients and 6 normal pulmonary arteries. Serum immunoglobulins (Igs) were measured using protein electrophoresis among 273 CTEPH patients, 259 idiopathic pulmonary arterial hypertension (IPAH) patients, and 251 healthy controls.</p><p><strong>Results: </strong>The percentage of plasma cells was significantly increased from less than 1% in healthy controls to 15% in CTEPH patients. We identified 1 B cell cluster and 5 distinct mature plasma cell clusters, including IGHG1, HSPA1A, AHNAK, IGLC3, and IGKV4. Notably, the AHNAK and IGLC3 subclusters are newly identified. GeneSwitches analysis indicated early activation of IGHG1 and early deactivation of HLA-DPA1. The trajectory of AHNAK cluster was earlier than that of IGLC3 cluster, with an enrichment for pathways responsive to lipopolysaccharide. The IGLC3 cluster revealed lower differentiation potential and was predominantly associated with Ig production. Furthermore, Igα2 levels in CTEPH patients were lower than in controls but higher than in IPAH patients. Significantly, Igγ levels were markedly elevated in CTEPH patients compared with IPAH patients and controls, better distinguishing CTEPH patients from controls and IPAH patients.</p><p><strong>Conclusion: </strong>Plasma cells of CTEPH had a distinctive landscape and heterogeneity. The newly identified clusters represented excessive Ig production but lacked immune response function. These findings highlight that targeted plasma cells can be used to develop novel CTEPH treatments.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449480","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":"Body height and risk of venous thromboembolism in men vs women.","authors":"Carl Arne Løchen Arnesen, Kristian Hveem, Maiken E Gabrielsen, John-Bjarne Hansen, Sigrid K Brækkan","doi":"10.1016/j.jtha.2025.02.006","DOIUrl":"10.1016/j.jtha.2025.02.006","url":null,"abstract":"<p><strong>Background: </strong>Body height is associated with venous thromboembolism (VTE) and may contribute to differences in VTE risk in men vs women.</p><p><strong>Objectives: </strong>To investigate the risk of VTE according to body height in men and women and assess VTE risk in men vs women after adjustment for height in young, middle-aged, and elderly individuals.</p><p><strong>Methods: </strong>Participants of the Tromsø Study (1994-2020) and the Nord-Trøndelag Health Study (1995-2019) formed the study cohort (N = 114 567). Cox regression was used to estimate hazard ratios (HRs) with 95% CIs of VTE per 10 cm increase in body height in men and women. VTE risk in men vs women was estimated in the age groups 19 to 49, 50 to 74, and ≥75 years before and after adjustment for height.</p><p><strong>Results: </strong>Taller stature was associated with increased VTE risk in both men (HR, 1.34; 95% CI: 1.25-1.44) and women (HR, 1.23; 95% CI, 1.13-1.33). In the middle-aged, the risk was higher in men than in women (HR, 1.45; 95% CI, 1.32-1.60) but diminished after adjustment for height (HR, 0.98; 95% CI, 0.85-1.13). In the young (HR, 0.87; 95% CI, 0.70-1.08) and elderly (HR, 1.08; 95% CI, 0.97-1.20), there was no difference in VTE risk in men vs women before adjustment, while the risk was higher in women after height adjustment (HR, 0.60; 95% CI, 0.44-0.83 and HR, 0.83; 95% CI, 0.71-0.97, respectively).</p><p><strong>Conclusion: </strong>Taller stature was a risk factor for VTE in men and women. The risk of VTE in men vs women was substantially affected by adjustment for body height in all age groups.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432537","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":"Preventative and therapeutic effects of a novel humanized anti-glycoprotein Ibα fragment of antigen-binding region in a murine model of thrombotic thrombocytopenic purpura.","authors":"Liang Zheng, Reheman Adili, Zhijian Wu, Quan Zhang, Guangheng Zhu, Xi Lei, Zhenze Liu, Miguel A D Neves, Wenjing Ma, Sladjana Slavkovic, Xiaohong Ruby Xu, Heyu Ni, X Long Zheng","doi":"10.1016/j.jtha.2025.02.009","DOIUrl":"10.1016/j.jtha.2025.02.009","url":null,"abstract":"<p><strong>Background: </strong>Thrombotic thrombocytopenic purpura (TTP) is a potentially fatal blood disorder resulting from severe deficiency of plasma ADAMTS-13 activity. Current treatment for immune-mediated TTP includes daily therapeutic plasma exchange plus caplacizumab and immunosuppressives. For hereditary TTP resulting from mutations of ADAMTS-13, plasma infusion or recombinant ADAMTS-13 is the treatment of choice. However, there are still unmet needs for an effective alternative therapy for TTP.</p><p><strong>Objectives: </strong>The present study aimed to evaluate the therapeutic efficacy of a novel humanized antibody fragment of antigen binding against platelet glycoprotein Ibα (CA1001) in a murine model of TTP.</p><p><strong>Methods: </strong>Platelet agglutination profiles, microfluidic shear-based assay, intravital microscopy thrombosis model, and lysine histone-induced murine \"TTP-like\" model were employed.</p><p><strong>Results: </strong>CA1001 exhibited potent inhibition of botrocetin-induced murine platelet agglutination in a dose- and time-dependent manner. CA1001 also significantly inhibited shear-dependent adhesion and aggregation of murine platelets to endothelial von Willebrand factor (VWF) released from calcium ionophore-activated cremaster venules in Adamts-13 null mice and blocked the formation of platelet-VWF rich thrombosis. More importantly, CA1001 appeared to be efficacious in preventing and treating a histone-induced \"TTP-like\" syndrome in Adamts-13 null mice, demonstrated by the alleviation of thrombocytopenia, prerenal injury, and formation of microvascular thrombosis in major organ tissues.</p><p><strong>Conclusion: </strong>CA1001 can effectively inhibit VWF-platelet interaction and thrombus formation under various (patho)physiological conditions. Thus, CA1001 may be a potential candidate for further development as a novel therapeutic for immune-mediated and hereditary TTP and perhaps for other inflammatory thrombotic disorders such as ischemic stroke.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433051","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}