Research and Practice in Thrombosis and Haemostasis最新文献

{"title":"Illustrated capsules from the Advanced Course in Platelet Research","authors":"Christian Andrea Di Buduo ,&nbsp;Vittorio Abbonante ,&nbsp;Alessandro Malara ,&nbsp;Alessandra Balduini ,&nbsp;Amie K. Waller ,&nbsp;Steve P. Watson ,&nbsp;Eleyna M. Martin ,&nbsp;Lloyd Bridge ,&nbsp;Jonathan Gibbins ,&nbsp;Ingeborg Hers ,&nbsp;Claire Masson ,&nbsp;Anita Eckly ,&nbsp;Natalie S. Poulter ,&nbsp;Beatriz Martínez-García ,&nbsp;Sonia Aguila ,&nbsp;Paolo Gresele ,&nbsp;Stefania Momi ,&nbsp;Paul Amstrong ,&nbsp;Matthew Rondina ,&nbsp;Sara Troitiño ,&nbsp;Chris Ward","doi":"10.1016/j.rpth.2025.102715","DOIUrl":"10.1016/j.rpth.2025.102715","url":null,"abstract":"<div><div>This series of illustrated capsules summarizes the presentations made by the speakers at the first International Advanced Course in Platelet Research held in Murcia (Spain) from 27 to 28 September, 2024. This is the first course to receive a Fundamental Research Workshop Grant from the International Society on Thrombosis and Haemostasis (ISTH) and was also supported administratively and scientifically by the Spanish Society of Thrombosis and Haemostasis (SETH). This unique course focused on new methodologies applied in platelet research and how these are increasing our understanding of platelet formation, their multifunctionality in different physiological and pathological contexts, and contributing to the development of new platelet-targeted therapies to improve the management of hemostatic/thrombotic pathologies. It aligns with the objectives of several Scientific and Standardization Committees of the ISTH, including Platelet Physiology and Genomics in Thrombosis and Haemostasis, as well as with the academic objectives of the ISTH and SETH. The program was designed by the coordinator (J. Rivera), and the scientific advisory board (SAB: S.P. Watson, K. Freson, A. Balduini, and J. Di Paola) and comprised 9 scientific sessions with 25 presentations, each with time for extensive open discussion. Additionally, 33 abstract posters were presented, with the 3 highest scoring selected as oral presentations. The course was held in a single location and with an informal atmosphere to facilitate networking among participants. The course received very positive feedback from the 140 attendees. The course was supported by the ISTH, SETH, University of Murcia, CIBERER-ISCIII, Fundación Séneca (22426/OC/24), the United Kingdom Platelet Society and various pharmaceutical companies. We believe that the extraordinary scientific and human experience of this course may act as a stimulus for future courses.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102715"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642969","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":"Comparison of 7 artificial intelligence models in predicting venous thromboembolism in COVID-19 patients","authors":"Indika Rajakaruna ,&nbsp;Mohammad Hossein Amirhosseini ,&nbsp;Mike Makris ,&nbsp;Mike Laffan ,&nbsp;Yang Li ,&nbsp;Deepa J. Arachchillage","doi":"10.1016/j.rpth.2025.102711","DOIUrl":"10.1016/j.rpth.2025.102711","url":null,"abstract":"<div><h3>Background</h3><div>An artificial intelligence (AI) approach can be used to predict venous thromboembolism (VTE).</div></div><div><h3>Objectives</h3><div>To compare different AI models in predicting VTE using data from patients with COVID-19.</div></div><div><h3>Methods</h3><div>We used feature ranking through recursive feature elimination with AI algorithms (logistic regression and random forest classifier) and standard statistical methods to identify the significant factors that contribute to developing VTE in COVID-19 patients using a large dataset from “Coagulopathy associated with COVID-19,” a multicenter observational study. We developed 7 AI models (Multilayer perceptron classifier, Artificial neural network with backpropagation, eXtreme gradient boosting, Support vector classifier, Stochastic gradient descent classifier, Random forest classifier and Logistic regression classifier) using the selected significant features to predict the development of VTE during hospitalization and used K-fold cross-validation and hyperparameter tuning to validate and optimize the models. The models’ predictive power was tested on 2649 (33% of 8027 overall patients), which were previously separated and not used during model training and validation stages.</div></div><div><h3>Results</h3><div>Age, female sex, white ethnicity, comorbidities (diabetes, liver disease, autoimmune disease), and laboratory features (increased hemoglobin, white cell count, D-dimer, lactate dehydrogenase, ferritin), and presence of multiorgan failure were major factors associated with the development of thrombosis. Support vector classifier (SVC) model outperformed all other models, achieving an accuracy of 97%. The SVC model also led in precision (0.98), recall (0.97), and F1 score (0.97), and recorded the lowest log-loss score (0.112 on the test dataset), reflecting better model convergence and an improved fit to the data. Additionally, it achieved the highest area under the curve score (0.983).</div></div><div><h3>Conclusion</h3><div>The SVC model delivered the best overall performance outperforming similar studies that developed deep learning and machine-learning models for COVID-19.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102711"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683443","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":"Concizumab prophylaxis in people with hemophilia A or B without inhibitors: patient-reported outcome results from the phase 3 explorer8 study","authors":"Pantep Angchaisuksiri ,&nbsp;Sylvia von Mackensen ,&nbsp;Shashikant Apte ,&nbsp;Gary Benson ,&nbsp;Hermann Eichler ,&nbsp;Amy Findley ,&nbsp;Tadashi Matsushita ,&nbsp;Camila M. Mazini Tavares ,&nbsp;Morten Puggaard Ravn ,&nbsp;Jameela Sathar ,&nbsp;Laura Villarreal Martinez ,&nbsp;Guy Young","doi":"10.1016/j.rpth.2025.102705","DOIUrl":"10.1016/j.rpth.2025.102705","url":null,"abstract":"<div><h3>Background</h3><div>Patient-reported outcomes (PROs) can provide useful insights into patient perception of concizumab, an anti–tissue factor pathway inhibitor monoclonal antibody intended for once-daily, subcutaneous prophylaxis for hemophilia A (HA) or hemophilia B (HB), with and without inhibitors.</div></div><div><h3>Objectives</h3><div>To evaluate PROs from the phase 3 explorer8 study (NCT04082429).</div></div><div><h3>Methods</h3><div>Male patients aged ≥12 years with HA/HB without inhibitors were enrolled and randomized 1:2 to no prophylaxis/on-demand treatment (arm 1) or concizumab prophylaxis (arm 2) or allocated to concizumab prophylaxis (arms 3 and 4). PRO questionnaires included the 36-item short-form health survey version 2, Haemophilia Quality of Life Questionnaire for Adults, Hemophilia Treatment Experience Measure, and Haemophilia Patient Preference Questionnaire.</div></div><div><h3>Results</h3><div>Estimated treatment difference for change in 36-item short-form health survey version 2 “bodily pain” and “physical functioning” from baseline to week 24 between patients in arms 1 and 2 was 9.5 points (95% CI, 2.4 to 16.7) and 0.3 points (95% CI, −5.1 to 5.6), respectively. Estimated treatment difference at week 24 between patients in arms 1 and 2 was −18.0 points (95% CI, −26.4 to −9.5) for Haemophilia Quality of Life Questionnaire for Adults “total score” and −16.8 points (95% CI, −32.2 to −1.4) for “physical health.” Hemophilia Treatment Experience Measure and Haemophilia Patient Preference Questionnaire results favored concizumab prophylaxis over no prophylaxis or previous treatment.</div></div><div><h3>Conclusion</h3><div>PRO data from the phase 3 explorer8 study provided additional support for concizumab prophylaxis compared with no prophylaxis as a treatment option for patients with HA/HB.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102705"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620576","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":"Identification and characterization of factor XI autoantibodies in 2 patients with systemic lupus erythematosus: insights into mechanisms of acquired factor XI deficiency","authors":"Priyanka Srivastava ,&nbsp;Amy Zhou ,&nbsp;Christine Fuja ,&nbsp;Charles S. Eby ,&nbsp;Gail Baxter ,&nbsp;Anton Matafonov ,&nbsp;Serena Fedorov ,&nbsp;Miriam Brown ,&nbsp;Michael Pettit ,&nbsp;Benjamin F. Tillman ,&nbsp;David Gailani ,&nbsp;Jeremy W. Jacobs","doi":"10.1016/j.rpth.2025.102703","DOIUrl":"10.1016/j.rpth.2025.102703","url":null,"abstract":"<div><h3>Background</h3><div>Factor (F)XI is a zymogen that contributes to thrombin generation through activation of FIX. Patients with a complete absence of FXI are prone to developing alloantibody inhibitors after replacement therapy. Acquired FXI autoantibodies are less common, and data regarding their mechanisms of action are lacking.</div></div><div><h3>Objectives</h3><div>We describe 2 patients with severe acquired FXI deficiency and identify the FXI domains to which the autoantibodies bind.</div></div><div><h3>Methods</h3><div>FXI and prekallikrein (PK) are homologs with similar structures. We prepared recombinant human FXI and PK, as well as chimeric molecules in which individual domains within FXI or PK are replaced with the corresponding domain from the other protein. Patient plasma and normal plasma were used as antibody sources, and their capacities to recognize recombinant proteins on Western blots were compared.</div></div><div><h3>Results</h3><div>Patients 1 and 2 were females with systemic lupus erythematous and no bleeding history. FXI activity in both cases was undetectable by one-stage clotting assay, with autoantibody titers of 64 Bethesda Units and 11.4 Bethesda Units, respectively. In both cases, the autoantibody appeared to clear FXI protein from plasma. Immunoglobulin G in patient 1 targeted the FXI catalytic domain, while the autoantibody in patient 2 was likely oligoclonal with components that recognized the FXI apple 2 and apple 3 domains.</div></div><div><h3>Conclusion</h3><div>These autoantibodies inhibited FXI function and promoted its clearance. The inhibitors targeted the 2 most important FXIa domains for FIX activation and demonstrated properties similar to those described in patients with FXI alloantibody inhibitors.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102703"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549335","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":"Ex vivo lentiviral gene therapy for severe hemophilia A: an alternative to recombinant adeno-associated viral-based strategies?","authors":"Benjamin J. Samelson-Jones","doi":"10.1016/j.rpth.2025.102716","DOIUrl":"10.1016/j.rpth.2025.102716","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102716"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683527","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":"No correlation between thrombin generation and emicizumab levels: implications for monitoring emicizumab therapy","authors":"Konrad van der Zwet ,&nbsp;Mark Roest ,&nbsp;Dana Huskens ,&nbsp;Roger E.G. Schutgens ,&nbsp;Lize F.D. van Vulpen ,&nbsp;Kathelijn Fischer ,&nbsp;Rolf T. Urbanus","doi":"10.1016/j.rpth.2024.102658","DOIUrl":"10.1016/j.rpth.2024.102658","url":null,"abstract":"<div><h3>Background</h3><div>Emicizumab, a bispecific antibody that mimics factor (F)VIII, has significantly improved hemophilia A management. Although emicizumab levels can be measured, tools for estimating the hemostatic efficacy of emicizumab are lacking. Thrombin generation (TG) assays can distinguish bleeding phenotypes in persons with hemophilia A on FVIII prophylaxis and may also be used during emicizumab therapy.</div></div><div><h3>Objectives</h3><div>To assess the association between TG parameters, emicizumab levels, and bleeding in patients on emicizumab therapy.</div></div><div><h3>Methods</h3><div>A single-center longitudinal cohort study was conducted, with samples collected during the steady-state phase of emicizumab therapy. TG was measured using tissue factor (TF; TF-TG, 1 pM) and FXIa (FXIa-TG, 200 pM). Emicizumab concentrations were determined with mass spectrometry. Only treated bleeds were recorded. Pearson correlations (rho, <em>r</em>) were reported.</div></div><div><h3>Results</h3><div>Eighty-five samples from 49 patients were analyzed during a median of 1 year of emicizumab therapy. Most bleeds were traumatic (97%; <em>n</em> = 30), whereas 1 bleed was spontaneous. At 12 months, TF-TG (<em>r</em> = 0.42) showed a borderline correlation, and FXIa-TG (<em>r</em> = 0.15) showed no correlation with emicizumab concentrations. Although FXIa-TG showed a 9% higher endogenous thrombin potential in patients with zero vs ≥1 treated bleed (endogenous thrombin potential: 957 vs 878 nM/min, <em>P</em> = .045), neither the FXIa-peak height nor TF-TG showed any association with traumatic bleeding.</div></div><div><h3>Conclusion</h3><div>TG parameters showed no clinically relevant correlations with emicizumab plasma concentrations, were not associated with traumatic bleeding, and showed considerable intrapatient variability. Therefore, TG was not considered useful for monitoring coagulation potential in patients on steady-state emicizumab prophylaxis.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102658"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029455","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":"A cell-based model to study mechanisms of endothelial-dependent thrombin generation in response to inflammation and its modulation by hydroxychloroquine","authors":"Deepa J. Arachchillage ,&nbsp;Golzar Mobayen ,&nbsp;Mike Laffan ,&nbsp;Anna M. Randi ,&nbsp;Josefin Ahnström ,&nbsp;Charis Pericleous","doi":"10.1016/j.rpth.2024.102665","DOIUrl":"10.1016/j.rpth.2024.102665","url":null,"abstract":"<div><h3>Background</h3><div>Inflammation is a driver of thrombosis, but the phenomenon of thromboinflammation has been defined only recently, bringing together the multiple pathways involved. <em>In vitro</em> models can support the development of new therapeutics targeting the endothelium and also assess the existing immunomodulatory drugs, such as hydroxychloroquine, in modulating the inflammation-driven endothelial prothrombotic phenotype.</div></div><div><h3>Objectives</h3><div>To develop a model for thrombin generation (TG) on the surface of human endothelial cells (ECs) to assess pro/antithrombotic properties in response to inflammation. Furthermore, to elucidate the mechanisms of TG regulation and its modulation by immunomodulatory therapies.</div></div><div><h3>Methods</h3><div>Cytokine-induced (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, and interferon-γ) effects on ECs isolated from umbilical veins or human aortic tissue were assessed using calibrated automated thrombography in platelet-poor plasma. The expression of key coagulant and inflammatory regulators was measured at the mRNA level. Tissue factor (TF) protein levels were further assessed by flow cytometry.</div></div><div><h3>Results</h3><div>Endothelial stimulation with TNF-α or IL-1β caused ECs to trigger TG without the addition of exogenous TF, with higher TG observed after 6 hours of stimulation than 24 hours. IL-1β induced higher peak thrombin (170 ± 5.9 nM vs 115 ± 4.9 nM), endogenous thrombin potential (1632 ± 35 nM ∗ min vs 1370 ± 23 nM ∗ min) presented as mean ± SD, and TF expression (∼2.8-fold higher) compared with TNF-α at 6 hours. Interferon-γ stimulation failed to induce TG and TF expression. The immunomodulatory drug, hydroxychloroquine, reduced cytokine-induced TG and downregulated TF expression.</div></div><div><h3>Conclusion</h3><div>We provide detailed optimization of a robust <em>in vitro</em> model to assess the induction of an inflammation-driven endothelial prothrombotic phenotype that is also sensitive to immunomodulatory therapies, providing a tool for investigating mechanisms of disease and new drugs.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102665"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060628","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":"Carbon dioxide alleviates platelet storage lesions via stimulating fatty acid metabolism and reducing platelet glucose consumption","authors":"Shunli Gu,&nbsp;Jinmei Xu,&nbsp;Erxiong Liu,&nbsp;Xuejia Hou,&nbsp;Ning An,&nbsp;Yaozhen Chen,&nbsp;Zhixin Liu,&nbsp;Wenting Wang,&nbsp;Xingbin Hu,&nbsp;Wen Yin","doi":"10.1016/j.rpth.2025.102681","DOIUrl":"10.1016/j.rpth.2025.102681","url":null,"abstract":"<div><h3>Background</h3><div>The timely administration of platelet transfusions is critical for patient survival, and the clinical demand for platelet transfusions has been steadily increasing. However, platelet storage lesions (PSLs) that develop during <em>in vitro</em> preservation exacerbate these shortages. The PSL is significantly influenced by various factors, including temperature, gas composition, and buffering systems. Strategies to mitigate PSLs and improve platelet storage have been actively explored in recent years.</div></div><div><h3>Objectives</h3><div>This study aimed to investigate whether elevated carbon dioxide (CO₂) levels improve platelet quality and functionality during storage.</div></div><div><h3>Methods</h3><div>Platelet concentrates from 28 donors were stored under control or 3% CO₂ conditions at 22 ± 2 °C for up to 7 days. Platelet quality was evaluated through scanning electron microscopy, adhesion, aggregation, clot contraction, activation, apoptosis assays, blood gas, adenosine triphosphate, metabolomics analyses, and <em>in vivo</em> thrombosis and survival tests.</div></div><div><h3>Results</h3><div>Our findings indicate that increasing the CO₂ concentration in the storage environment mitigates PSLs and improves platelet quality.</div></div><div><h3>Conclusion</h3><div>Our study highlights the potential benefits of utilizing a high CO₂ storage environment to improve platelet preservation, offering a promising method to address clinical platelet shortages.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102681"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387615","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":"Measurement of factor XIII for the diagnosis and management of deficiencies: insights from a retrospective review of 10 years of data on consecutive samples and patients","authors":"Mohammed Abdullah Al Sharif ,&nbsp;Natalie Mathews ,&nbsp;Subia Tasneem ,&nbsp;Karen A. Moffat ,&nbsp;Stephen A. Carlino ,&nbsp;Siraj Mithoowani ,&nbsp;Catherine P.M. Hayward","doi":"10.1016/j.rpth.2025.102689","DOIUrl":"10.1016/j.rpth.2025.102689","url":null,"abstract":"<div><h3>Background</h3><div>Factor XIII (FXIII) deficiency is a challenge in the diagnosis of rare bleeding disorders with inherited and acquired causes.</div></div><div><h3>Objectives</h3><div>We evaluated consecutive cases tested for FXIII deficiency for insights on diagnosis.</div></div><div><h3>Methods</h3><div>With ethics approval, we retrospectively reviewed FXIII tests performed between 2013 and 2023 and local patient records for insights into causes and presentations of FXIII deficiency.</div></div><div><h3>Results</h3><div>Two thousand one hundred ninety-one samples from 1915 patients (ages: 0-90 years; 38% local) were tested. The FXIII activity (FXIII:Act; Berichrom FXIII, Siemens Healthcare) was low in 14%/9.7% of tested samples/patients. FXIII subunit A antigen (FXIII-A:Ag; Werfen HemosIL FXIII antigen; low in 45% of 251 samples) helped characterize FXIII deficiency severity and identify type 2 deficiencies from acquired FXIII inhibitors. Urea clot solubility tests (18.2% requested without FXIII:Act) were largely noninformative as all abnormal samples (<em>n</em> = 7) had undetectable FXIII-A:Ag levels. Excluding FXIII inhibitor patients, FXIII:Act showed strong correlation with FXIII-A:Ag (<em>R</em>² = 0.84, <em>P</em> &lt; .001) and weak correlation with plasma fibrinogen (<em>R</em>² = .005, <em>P</em> &lt; .001). Some patients had combined acquired FXIII and fibrinogen deficiencies from consumption or major bleeding. FXIII-deficient and nondeficient patients had similar bleeding except for more umbilical and gastrointestinal bleeding among deficient patients (<em>P</em> &lt; .05). Most FXIII deficiencies were acquired (92%), and although several were autoimmune, most were from consumption, major bleeds, or severe infections or had uncertain significance, with bleeding sometimes attributable to other causes.</div></div><div><h3>Conclusion</h3><div>Congenital and acquired FXIII deficiency are associated with bleeding. Local practices were changed to ensure that FXIII:Act is used to screen for FXIII deficiency and that deficient patients have FXIII:Act and FXIII-A:Ag quantified and compared.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102689"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387616","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":"Immune tolerance induction for inhibitor eradication in nonsevere hemophilia A: a case series","authors":"Sanober Nusrat ,&nbsp;Niveditha Popuri ,&nbsp;Vishnu Nagalapuram ,&nbsp;Osman Khan","doi":"10.1016/j.rpth.2024.102637","DOIUrl":"10.1016/j.rpth.2024.102637","url":null,"abstract":"<div><h3>Background</h3><div>Persons with hemophilia A are at risk of inhibitor development with repeated exposures to factor (F)VIII concentrates. When persons with nonsevere hemophilia A (NSHA) develop inhibitors, they are at risk of developing severe bleeding manifestations like persons with severe hemophilia A (SHA). Evidence to guide inhibitor eradication in this population is limited as opposed to persons with SHA who develop inhibitors. Hence, inhibitor eradication strategies in NSHA are based on observational and retrospective data and are largely adopted from evidence derived from SHA with inhibitors.</div></div><div><h3>Key Clinical Question</h3><div>Can immune tolerance induction be used for patients with NSHA who develop inhibitors?</div></div><div><h3>Clinical Approach</h3><div>In this case series, we describe our single institutional experience with the management of 5 persons with NSHA who developed FVIII inhibitors, leading to significant bleeding complications, and underwent successful immune tolerance induction with eradication of FVIII inhibitor.</div></div><div><h3>Conclusion</h3><div>More research specific to persons with NSHA with inhibitors is warranted to develop guidelines regarding indications and strategies for inhibitor eradication therapy.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102637"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080790","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}