Research and Practice in Thrombosis and Haemostasis最新文献

{"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":"Fibrinogen levels and bleeding risk in adult extracorporeal cardiopulmonary resuscitation: multicenter observational study subanalysis","authors":"Seiya Kanou ,&nbsp;Eiji Nakatani ,&nbsp;Tetsumei Urano ,&nbsp;Hatoko Sasaki ,&nbsp;Akihiko Inoue ,&nbsp;Toru Hifumi ,&nbsp;Tetsuya Sakamoto ,&nbsp;Yasuhiro Kuroda ,&nbsp;Yoshihiro Tanaka","doi":"10.1016/j.rpth.2025.102700","DOIUrl":"10.1016/j.rpth.2025.102700","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102700"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563802","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":"Addressing the perimenopause: what’s blood got to do with it?","authors":"Briony A. Cutts ,&nbsp;Kristy Fennessy","doi":"10.1016/j.rpth.2025.102698","DOIUrl":"10.1016/j.rpth.2025.102698","url":null,"abstract":"<div><div>A state of the art lecture titled, “Addressing the Perimenopause: What’s Blood Got to Do with It?” was presented at the International Society on Haemostasis and Thrombosis (ISTH) Congress in 2024. Perimenopause is when fluctuations of previously cyclically regulated hormones occur prior to menopause, resulting in a number of symptoms that can negatively impact a woman’s quality of life. Thrombosis and hemostasis experts are often approached to help investigate and manage clinical issues associated with perimenopause. This includes the safety of using menopause hormonal therapy in a past history or family history of venous thromboembolism, arterial thrombosis or thrombophilia, heavy menstrual bleeding, and iron deficiency anemia. A review of recent literature and clinical practice guidelines was undertaken to help determine the role of iron deficiency anemia in perimenopause, thrombotic risk in the setting of using menopause hormonal therapy, and indications for thrombophilia testing prior to commencing menopause hormonal therapy. Finally, we summarize relevant new data on this topic presented during the ISTH 2024 Congress.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102698"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143580128","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":"Major bleeding and thromboembolism risks of antithrombotic treatment in patients with incident atrial fibrillation/flutter and a history of cancer","authors":"Nienke van Rein ,&nbsp;Gordon Chu ,&nbsp;Menno V. Huisman ,&nbsp;Lars Pedersen ,&nbsp;Henrik T. Sørensen ,&nbsp;Frederikus A. Klok ,&nbsp;Suzanne C. Cannegieter","doi":"10.1016/j.rpth.2025.102679","DOIUrl":"10.1016/j.rpth.2025.102679","url":null,"abstract":"<div><h3>Background</h3><div>Literature shows that atrial fibrillation (AF) patients with a history of cancer have a higher risk of thromboembolism (TE) and major bleeding (MB) compared to patients without. However, cancer type and time between cancer and AF diagnosis is often lacking in such analyses.</div></div><div><h3>Objectives</h3><div>To examine MB and TE rates of AF patients with a prior cancer diagnosis, stratified by cancer type and interval between cancer and AF diagnosis.</div></div><div><h3>Methods</h3><div>This Danish population-based cohort study included all patients aged ≥50 years with incident AF between January 1, 1995, and December 31, 2016, and identified those who had cancer before the AF diagnosis. From hospital and drug prescription databases, data on cancer type, time interval between cancer and AF diagnosis (ie, &lt;1, 1-3, or &gt;3 years), outcomes, and antithrombotic exposure were collected. Follow-up started from the AF diagnosis until the occurrence of an outcome or the end of the 2-year follow-up. Incidence rates (IRs) per 100 patient-years and adjusted hazard ratios (aHRs) with corresponding 95% CIs were calculated using Cox regression.</div></div><div><h3>Results</h3><div>We identified 39,178 patients with incident AF and a prior cancer diagnosis. These patients demonstrated higher MB (IR, 3.35 [3.25-3.45] vs 2.23 [2.29-2.35]) and TE rates (IR, 3.21 [3.11-3.31] vs 2.53 [2.50-2.56]) than those without prior cancer. The higher MB risk in AF patients with a prior cancer diagnosis was observed in all examined time intervals, while a higher TE risk was only observed in those with a cancer diagnosis &lt;1 year prior (aHR, 1.27 [1.16-1.40]). Prior respiratory cancer was associated with increased MB (aHR, 1.37 [1.26-1.48]) and TE risks (aHR, 1.26 [1.15-1.38]).</div></div><div><h3>Conclusion</h3><div>A prior cancer diagnosis confers additional MB and, to a lesser extent and in certain conditions, thromboembolic risks in patients with AF. The type and timing of the prior cancer diagnosis determines the degree of risk.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102679"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610930","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":"Major bleeding and thromboembolic complications associated with antithrombotic treatment in patients with atrial fibrillation/flutter and incident cancer","authors":"Gordon Chu ,&nbsp;Nienke van Rein ,&nbsp;Menno V Huisman ,&nbsp;Lars Pedersen ,&nbsp;Henrik T. Sørensen ,&nbsp;Suzanne C. Cannegieter ,&nbsp;Frederikus A. Klok","doi":"10.1016/j.rpth.2025.102697","DOIUrl":"10.1016/j.rpth.2025.102697","url":null,"abstract":"<div><h3>Background</h3><div>Anticoagulant management of patients with atrial fibrillation with active cancer is complex because cancer increases the risk of thrombosis as well as bleeding. Previous studies have investigated the impact of any type of cancer, while outcomes may differ per specific type. We performed the present study to provide more insight into the impact of specific types of cancer on clinical outcomes.</div></div><div><h3>Objectives</h3><div>We examined major bleeding (MB) and thromboembolism (TE) rates associated with antithrombotic treatment in patients with atrial fibrillation/flutter (AF) who develop cancer and examined whether cancer type affected MB and TE risks.</div></div><div><h3>Methods</h3><div>This Danish population-based cohort study included all patients aged ≥ 50 years discharged with incident AF between January 1, 1995, and December 31, 2016, and identified those who subsequently developed cancer. Data on cancer type, outcomes, and antithrombotic exposure were obtained from hospital and drug prescription databases. Follow-up continued from the time of cancer diagnosis until the occurrence of an outcome or the end of the 2-year follow-up. Incidence rates (IRs) per 100 patient-years and adjusted hazard ratios with corresponding 95% CIs were calculated using Cox regression.</div></div><div><h3>Results</h3><div>A total of 22,996 patients with AF with subsequent incident cancer were identified. These patients had higher MB (IR, 5.36 [95% CI, 5.09-5.64] vs 2.27 [95% CI, 2.22-2.32]) and TE (IR, 3.91 [95% CI, 3.68-4.15] vs 2.71 [95% CI, 2.66-2.76]) rates than those without cancer. The higher MB rate was observed across all antithrombotic exposure categories. Urogenital (IR, 6.43 [95% CI, 5.94-6.95]) and intracranial cancer (IR, 6.36 [95% CI, 3.85-9.76]) demonstrated the highest MB rates; hematologic (IR, 4.92 [95% CI, 4.12-5.82]) and gastrointestinal cancer (IR, 4.82 [95% CI, 4.31-5.36]) had the highest TE rates. A particularly high MB rate was observed in patients with AF with gastrointestinal cancer and triple antithrombotic therapy (IR, 39.0 [95% CI, 15.5-79.1]).</div></div><div><h3>Conclusion</h3><div>Patients with AF with certain incident cancer types experienced higher rates of MB and TE than those without cancer. Dual/triple antithrombotic therapy in patients with AF with incident cancer was associated with high bleeding rates, particularly with gastrointestinal cancer.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102697"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592077","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":"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":"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}