Platelets最新文献

{"title":"Xanthone impairs platelet activation and thrombus formation.","authors":"Hui Zhu, Ruoyi Shen, Chenyue Wang, Xiaoyue Zu, Yanlong Zhou, Long Yang, Yueyue Sun, Ping Fu, Jun Lu","doi":"10.1080/09537104.2025.2597777","DOIUrl":"https://doi.org/10.1080/09537104.2025.2597777","url":null,"abstract":"<p><p>Xanthone, a naturally occurring oxygenated heterocyclic compound from the Garcinia family with known anti-cancer, antimicrobial, antioxidant, anti-inflammatory, and antiviral properties, has an unclear role in platelet function. This study investigated its effects by incubating human platelets with xanthone at doses of 0, 5, 10, and 20 μM for 1 hour to analyze platelet aggregation, granule release, activation, receptor expression, spreading, and clot retraction, while also administering xanthone (10 mg/kg) to mice to evaluate its impact on hemostasis, arterial, and venous thrombosis. Our findings demonstrated that xanthone dose-dependently reduced platelet aggregation and granule release induced by collagen-related peptide (CRP) or thrombin without altering the surface expression of receptors αIIbβ3, GPIbα, and GPVI; it also significantly inhibited platelet spreading on collagen or fibrinogen, thrombin-mediated clot retraction, and decreased phosphorylation of c-Src and PLCγ2 in treated platelets. In vivo, xanthone-administered mice exhibited prolonged tail bleeding time and impaired arterial and venous thrombosis. Mechanistically, xanthone inhibited NF-κB activation, phosphorylation of ERK1/2 and p38, calcium mobilization, and platelet procoagulant activity. These findings indicate that xanthone impairs platelet activation and both arterial and venous thrombus formation, suggesting its potential as a novel agent for treating thrombotic or cardiovascular diseases.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"36 1","pages":"2597777"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145763661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clopidogrel monotherapy is associated with higher mortality risk compared to aspirin: a retrospective analysis of NHANES 1999-2018.","authors":"Tieshi Zhu, Yong He, Yuzhang Bei, Hui Mai, Le Zhao","doi":"10.1080/09537104.2025.2532454","DOIUrl":"https://doi.org/10.1080/09537104.2025.2532454","url":null,"abstract":"<p><strong>Background: </strong>Clopidogrel and aspirin are widely used antiplatelet agents. Although clopidogrel resistance is more prevalent in Asian populations, a Korean study suggested that clopidogrel was superior to aspirin in patients who completed standard dual antiplatelet therapy following percutaneous coronary intervention. However, the comparative effectiveness of clopidogrel versus aspirin in populations with lower levels of clopidogrel resistance remains to be further investigated.</p><p><strong>Methods: </strong>This study included 1,007 participants from NHANES 1999-2018 who were receiving aspirin or clopidogrel monotherapy. Cox proportional hazards regression and Kaplan-Meier survival analyses were used to compare the risks of mortality between the two groups. Sensitivity analyses were conducted by excluding individuals who died within the first 6 months of follow-up.</p><p><strong>Results: </strong>Across all Cox models, clopidogrel use was associated with significantly higher risks of all-cause mortality (Model 1, HR1.47, 95%CI 1.20-1.79, <i>p</i> < .01; Model 2, HR1.25, 95%CI 1.02-1.54, <i>p</i> = .03; Model 3, HR 1.33, 95%CI 1.08-1.64, <i>p</i> = .01; Model 4, HR1.31, 95%CI 1.06-1.63, <i>p</i> = .01), stroke and cardiac mortality (Model 1, HR1.76, 95%CI 1.27-2.43, <i>p</i> < .01; Model 2, HR1.41, 95%CI 1.01-1.97, <i>p</i> = .04; Model 3, HR 1.54, 95%CI 1.10-2.17, <i>p</i> = .01; Model 4, HR1.47, 95%CI 1.03-2.08, <i>p</i> = .03) compared with aspirin. These associations remained consistent in sensitivity analyses. Kaplan-Meier survival curves also indicated higher risks of all-cause mortality, stroke and cardiac mortality in the clopidogrel group relative to the aspirin group.</p><p><strong>Conclusion: </strong>In this community-based population, clopidogrel monotherapy was associated with higher risks of all-cause mortality, stroke and cardiac mortality compared with aspirin.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"36 1","pages":"2532454"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The NLRP3 inflammasome in platelets - form, functions, and future of the complex.","authors":"Matthew S Hindle, Martin Berger, Khalid M Naseem","doi":"10.1080/09537104.2025.2562267","DOIUrl":"https://doi.org/10.1080/09537104.2025.2562267","url":null,"abstract":"<p><p>Platelets are anucleate cells that primarily facilitate thrombosis and hemostasis but can also act as mediators of vascular inflammation in disease. Platelets are typically understood to do this through the release of pre-formed chemokines coupled with direct heterotypic interactions with a variety of immune cells. However, an alternative mode of action has been described where platelets are able to undertake <i>de novo</i> synthesis of the cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). The primary mechanism to produce these inflammatory mediators is the activation of the NACHT leucine-rich repeat pyrin domain-containing protein 3 (NLRP3) inflammasome, a multi-protein complex that processes IL-1β and IL-18 through caspase activation. The presence and characteristics of the NLRP3 inflammasome have been widely described in a variety of nucleated cells, although its role in anucleate platelets is less clear. In the last decade, the presence of the inflammasome has been reported in platelets and linked to several diseased states including sickle cell disease, acute coronary syndrome, sepsis, and viral hemorrhagic fever. This emerging new biology of platelets, its role in platelet function, vascular inflammation, and other related areas of exploration are critically reviewed here.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"36 1","pages":"2562267"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-28-5p targeted Rap1b attenuates splenic inflammation infiltration in immune thrombocytopenia.","authors":"Rongqing Yu, Lizhen Cen, Xinyu Wu, Huaiyuan Liu, Xuejun Zhai, Qiong Bin","doi":"10.1080/09537104.2025.2487756","DOIUrl":"10.1080/09537104.2025.2487756","url":null,"abstract":"<p><p>Immune thrombocytopenia (ITP) is an autoimmune disease with isolated platelet count decrease. A subset of patients responds inferiorly to the first-line therapies including glucocorticoid and intravenous immunoglobulins (IVIG), of which the underlying mechanisms have not been fully elucidated. We first found that expression of miR-28-5p was obviously increased in complete responders, and decreased to substantially low levels in partial or non-responders. In the passive ITP model, upregulation of miR-28-5p by injecting agomir slightly improved thrombocytopenia, and obviously inhibited the <i>Rap1b</i> gene expression. Luciferase reporter assay demonstrated there was significant decrease of luciferase activity in 293T cells co-transfected with miR-28-5p mimics and plasmids with <i>Rap1b</i> wide-type sequence. Upregulation of miR-28-5p, and downregulation of <i>Rap1b</i> played a favorable role in reducing B cell infiltration in the marginal zone of spleen in mice. However, miR-28-5p exhibited no significant influence on megakaryocyte maturation in ITP both in vitro and in vivo studies. Finally, we confirmed that miR-28-5p upregulation was associated with superior early treatment response in ITP, and possibly functioned by targeting <i>Rap1b</i> gene to inhibit humoral immunity.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"36 1","pages":"2487756"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complement C3 inhibition reduces complement activation in clinical platelet concentrates but does not counteract platelet storage lesions.","authors":"Linnea I Andersson, Per Sandgren, Dick J Sjöström, Camilla Mohlin, Kim Hägerström, Ivar Tjernberg, Tom Eirik Mollnes, Per H Nilsson","doi":"10.1080/09537104.2025.2513298","DOIUrl":"https://doi.org/10.1080/09537104.2025.2513298","url":null,"abstract":"<p><p>Platelet storage is associated with storage lesions, including platelet morphological changes and a gradual functional loss. We investigated the impact of complement C3 inhibition on complement activation and platelet storage lesions in clinical platelet concentrates. Platelet concentrates (<i>n</i> = 8) were prepared in PAS-E and stored for seven days at 22°C. Each concentrate was split in two, with the C3 inhibitor compstatin Cp40 added to one part, and the other serving as the control. Complement and platelet activation markers, platelet function, and metabolic measures were analyzed every second day. Cp40 significantly reduced C3bc and sC5b-9 levels, but not C4c, indicating inhibition of complement activation at the level of C3. However, Cp40 did not affect platelet-specific or metabolic measures. Surface expression of CD62P and NAP-2 release increased significantly over the storage time, whereas CD63 expression and PF4 and TSP-1 release remained stable. Platelet responses to TRAP-6 mediated PAR-1 activation and U46619 mediated TXA₂R stimulation decreased over time, recorded as CD62P and CD63 expression and release of soluble factors. No drop in platelet count was observed, and metabolic markers remained within their critical limits. While C3 inhibition effectively reduced complement activation in stored platelet concentrates, it did not mitigate platelet storage lesions.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"36 1","pages":"2513298"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacodynamic effects of early aspirin withdrawal after percutaneous coronary intervention in patients with atrial fibrillation treated with ticagrelor or prasugrel.","authors":"Mark A Sammut, Mohammed E F Rahman, Claire Bridge, Jessica Hanson, Heather Judge, Bethany Lynch, Emily Maz, Hannah McMellon, Janet Middle, Georgia Williamson, William A E Parker, Justin Lee, Robert F Storey","doi":"10.1080/09537104.2025.2507037","DOIUrl":"10.1080/09537104.2025.2507037","url":null,"abstract":"<p><p>Dual antithrombotic therapy (DAT) without aspirin reduces bleeding compared with triple antithrombotic therapy (TAT) in patients with atrial fibrillation who have undergone percutaneous coronary intervention, without apparently increasing ischemic events. A prospective pharmacodynamic study was performed to investigate the impact of aspirin on bleeding time, platelet function and fibrin clot analysis in this population. Patients receiving TAT (<i>n</i> = 16), comprising aspirin, ticagrelor/prasugrel and a direct-acting oral anticoagulant (DOAC), were compared with those receiving DAT without aspirin (<i>n</i> = 18). Bleeding time was reduced with DAT compared with TAT (median 27.8 vs 30.0 minutes, <i>p</i> = .005). Assessed by light transmission aggregometry, median platelet aggregation was significantly increased with DAT compared with TAT in response to arachidonic acid (63 vs 3%, <i>p</i> = .002) and collagen (72 vs 37%, <i>p</i> < .001) but not 5-μmol/L adenosine diphosphate (25 vs 27%, <i>p</i> = .966) or thrombin-receptor-activating peptide (37 vs 24%, <i>p</i> = .086). VerifyNow P2Y₁₂ assay showed > 70% inhibition in all patients. Fibrin clot lysis time and maximum turbidity were similar between groups. Using P2Y₁₂ inhibitors of consistent potency, DAT improves hemostasis through sparing cyclooxygenase-1-mediated platelet activation but has a comparable effect to TAT on other pathways and fibrin clot properties. DAT with ticagrelor/prasugrel and DOAC may provide sufficient antithrombotic effect without excessive anti-hemostatic effect.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"36 1","pages":"2507037"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128529","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":"Differential effects of dual antiplatelet and dual antithrombotic therapy on hemostasis in chronic coronary syndrome patients: the DEFINE CCS study.","authors":"Tony Haddad, Osama Elkhateeb, Lawrence Title, Ata Quraishi, Wan Cheol Kim, Ali Hillani, Scott Grandy, Stefan S Heinze, Finn Eichhorn, Hannah Harquail, John Sapp, William Parker, Shamir R Mehta, Robert F Storey, Wael Sumaya","doi":"10.1080/09537104.2025.2524624","DOIUrl":"10.1080/09537104.2025.2524624","url":null,"abstract":"<p><p>Optimal long term antithrombotic treatment in high-risk chronic coronary syndrome (CCS) patients remains uncertain. Both ticagrelor (60 mg BID) and low-dose rivaroxaban (2.5 mg BID) in addition to low-dose aspirin resulted in significant reductions in major cardiovascular events in high-risk patients at the expense of increased bleeding risk. We aimed to compare the effects of both strategies on bleeding time, fibrin clot lysis time and inflammatory biomarkers in CCS patients with history of acute coronary syndrome. Twenty aspirin-treated patients were recruited into a randomized crossover study to receive ticagrelor 60 mg BID in 1 week and rivaroxaban 2.5 mg BID in the other with a 2-week washout period in between. Outcome measures were determined at the start and end of each treatment week. Two-way ANOVA was used to determine difference in treatment effect. Data are presented as mean ± SD. At baseline, there was no significant difference in any studied outcome measure. Bleeding time was significantly longer with ticagrelor compared to rivaroxaban (Ticagrelor: 897 ± 481secs vs. Rivaroxaban: 440 ± 184 secs; <i>p</i> = .0001). Fibrin clot lysis time was not impacted by ticagrelor but significantly dropped post treatment with rivaroxaban (Ticagrelor: 5743 ± 2590 secs vs. Rivaroxaban: 4309 ± 2308 secs; <i>p</i> = .0049). Neither treatment had an impact on levels of high-sensitivity CRP or white cell count. In conclusion, ticagrelor 60 mg BID has greater impact on bleeding time compared to rivaroxaban 2.5 mg BID. Whereas rivaroxaban, positively modulates fibrin clots, rendering them more prone to lysis.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"36 1","pages":"2524624"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144554275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of platelet dense granules by transmission electron microscopy in healthy pediatric donors and pediatric patients with suspected platelet disorders.","authors":"Jacob R Greenmyer, Dong Chen, Kyle G Howell, Karen M Fischer, Brandi Johnson, Noelle Drapeau, Lindsay R Stromback, Jon E Charlesworth, Susan C Gossman, Jeffrey D Gamez, Rajiv K Pruthi, Deepti M Warad","doi":"10.1080/09537104.2025.2590752","DOIUrl":"https://doi.org/10.1080/09537104.2025.2590752","url":null,"abstract":"<p><strong>Background: </strong>Whole mount (WM) platelet transmission electron microscopy (PTEM) is a standard method for evaluating platelet dense granules (DG). However, because of the lack of a pediatric/adolescent mean DG/platelet reference range (RR), the prevalence of platelet DG deficiency in patients with suspected inherited platelet disorders (IPD) is mostly unknown in our practice. This study aimed to establish a local pediatric/adolescent RR for mean DG/platelet in a cohort of pediatric patients with clinical suspicion of IPD, which was used to determine the prevalence and clinical and laboratory features of platelet DG deficiency.</p><p><strong>Methods: </strong>WM-PTEM was performed on healthy donors. The mean DG/platelet RR was calculated by averaging the DG of 100 platelets per donor. Patients who underwent laboratory evaluation of suspected IPD were evaluated. PTEM results, clinical histories, other laboratory testing results, and pediatric ISTH BAT scores (normal < 3; abnormal ≥3) were collected and analyzed.</p><p><strong>Results: </strong>Healthy donors (<i>n</i> = 77, 41.6% female), ages 3-18 years, had a mean of 2.7 DG/platelet (±0.5), ranging from 1.9 to 3.8 per platelet. The mean DG/platelet did not correlate with age or gender. The tentative RR was calculated to be 1.9 to 3.8 DG/platelet. Of the 72 patients with suspected IPD (age 3-18 years, 69.4% female), 31 patients had BAT scores < 3 and 41 patients had BAT scores ≥3 (range 0-11). Eighteen patients (25%) were diagnosed with DG deficiency. The mean DG/platelet in patients with bleeding scores ≥3 vs. those with bleeding scores < 3 was similar. There was no difference in the number of patients with normal or abnormal bleeding scores in groups with normal vs decreased mean DG/platelet (<i>p</i> = .42) based on the pediatric DG/platelet RR. Platelet DG deficiency was also not correlated with abnormal platelet function testing results.</p><p><strong>Conclusions: </strong>Approximately 25% of pediatric patients with suspected IPD were found to have platelet DG deficiency. However, the mean DG/platelet did not correlate with the ISTH BAT scores or platelet function testing results.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"36 1","pages":"2590752"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145637915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of human platelet lysate on self-renewal and homing potential of peripheral blood -derived hematopoietic stem cells.","authors":"Zahra Najafi, Farnaz Pirsavabi, Saeed Mohammadi, Mohsen Nikbakht, Naser Ahmadbeigi, Azadeh Omidkhoda","doi":"10.1080/09537104.2025.2577969","DOIUrl":"https://doi.org/10.1080/09537104.2025.2577969","url":null,"abstract":"<p><p>Hematopoietic stem and progenitor cells (HSPCs) hold significant promise for various diseases and gene therapy, highlighting the need for improved in vitro expansion while maintaining their properties. Efficient HSPC expansion requires an environment that preserves self-renewal and homing capabilities. Human Platelet Lysates (HPL) contain bioactive molecules and growth factors that may enhance HSPC functionality. This study investigates the effects of HPL on peripheral blood HSPC proliferation, self-renewal capacity, and homing. We observed that HPL significantly promoted HSPC proliferation, resulting in a 1.7-fold increase in final cell count and reduced doubling time, without affecting colony-forming capacity. Flow cytometry analysis revealed no significant changes in the percentages of CD34⁺, CD34^-CD38⁺, CD34⁺CD38⁺, and CD34⁺CD38^- cells, though CXCR4 marker expression was notably higher in the HPL-treated group. Furthermore, real-time analysis of self-renewal genes (GFI1, HOXB4, and TAL1) indicated a significant increase in GFI1 expression, while HOXB4 and TAL1 remained unchanged. Among homing-related genes (CXCR4, VLA-4, and LFA-1), CXCR4 expression increased significantly, while VLA-4 and LFA-1 levels showed no significant alterations. These findings suggest that HPL enhances HSPC proliferation while preserving their self-renewal and homing abilities, providing a promising approach for optimizing HSPC culture conditions for both research and clinical use.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"36 1","pages":"2577969"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145459519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Talin autoinhibition is required for normal hemostasis.","authors":"Bhavya Venkatesh, Kalyan Golla, Felix Hong, Amanda Haage, Hugh Kim, Guy Tanentzapf","doi":"10.1080/09537104.2025.2555197","DOIUrl":"https://doi.org/10.1080/09537104.2025.2555197","url":null,"abstract":"<p><p>The integrin family of extracellular matrix (ECM) adhesion receptors plays a central role in platelet function, including adhesion and aggregation. In resting platelets, integrins exist in a low-affinity state for their ligands, and are activated upon ligand binding to the extracellular domain or binding of cytoplasmic proteins such as talin to the intracellular β-tail. Talin function is regulated through autoinhibition, which reduces its integrin-activating function. A point mutation that blocks talin autoinhibition, Tln1^E1770A, therefore increases integrin activation and disrupts cell migration in fibroblasts. Here, we show that talin autoinhibition also plays an important role during hemostasis. Tln1^E1770A mutant mice display defective hemostasis when examined using a tail bleeding assay. Furthermore, platelets isolated from Tln1^E1770A mice exhibit disrupted aggregation and delayed clot retraction, indicating a defect in integrin signaling. However, integrin activation was not increased in platelets with defective talin autoinhibition, suggesting a different role for talin in platelets, distinct from inside-out integrin signaling. Taken together, our data shows that talin autoinhibition is an important regulatory mechanism in platelets during hemostasis.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"36 1","pages":"2555197"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}