Platelets最新文献

{"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}

{"title":"CD39-Diannexin alleviates the platelet storage lesion by protecting platelets from activation, a new attempt from a traditional perspective.","authors":"Cheng Liu, Peng Wang, Yafei Gao, Xiaolong Ma, Yang Su, Yao Wei, Rui Qiao","doi":"10.1080/09537104.2025.2517108","DOIUrl":"https://doi.org/10.1080/09537104.2025.2517108","url":null,"abstract":"<p><p>Due to platelet storage lesions (PSL), transfused platelets are unable to function properly in the prevention and treatment of bleeding in critically ill patients. It is a traditional assumption that PSL is closely related to platelet activation during storage because of the exposure of CD62P, phosphatidylserine (PS), etc. In this standpoint, activated platelets in <i>vitro</i> cannot be reactivated in <i>vivo</i> to exert their hemostatic function and exposed PS accelerates platelet clearance. Therefore, reducing platelet activation is helpful to alleviate PSL. Diannexin is the dimer of annexin that has a higher affinity for PS. CD39 is an ADP hydrolase produced by the vascular endothelium. As a result, we construct CD39-Diannexin (CD39-DA) fusion protein and hypothesize that CD39-DA can reduce platelet activation during storage to alleviate PSL. CD39-DA can bind to the exposed PS on the surface of stored platelets by immunofluorescence. Compared to the control groups, CD39-DA reserves part of stored platelets' aggregation function confirmed by platelet aggregation assay, induced by AA, ADP and collagen. Additionally, CD39-DA reduces lactic dehydrogenase (LDH) levels and CD62P-positive events after three-day storage. Interestingly, we preliminarily discover that CD39-DA may reduce stored platelets' apoptosis and increase aggregatory platelets after activation by thrombin, collagen and calcium, which is marked by GSAO. In conclusion, we confirm that CD39-DA can alleviate PSL by reducing platelet activation.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"36 1","pages":"2517108"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258820","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":"Pre-activated lyophilized platelets show non-inferior hemostatic effect compared with fresh platelets in rabbits with traumatic bleeding and shock.","authors":"Chenglin Dai, Wenqiong Du, Na Kang, Haoyang Yang, Ting Tang, Yijun Jia, Can Chen, Zhaowen Zong","doi":"10.1080/09537104.2025.2542767","DOIUrl":"10.1080/09537104.2025.2542767","url":null,"abstract":"<p><strong>Background: </strong>A high activation level is a normal characteristic of lyophilized platelets (LPs); however, the effects of this activation level on the efficacy and safety of LPs after transfusion are debated.</p><p><strong>Objectives: </strong>We aimed to test the efficacy and safety of pre-activated LPs (PLPs) in rabbits with traumatic bleeding and shock.</p><p><strong>Methods: </strong>In vitro characteristics of PLPs, including activation level, aggregation, migration, and thromboelastography parameters, were evaluated. Limb soft tissue injury accompanied by seawater immersion and controlled hemorrhagic shock was induced in 50 rabbits, which were then divided into five groups: A (no resuscitation), B (resuscitation with Lactated Ringer's solution, LR), C (resuscitation with LR and fresh platelets), D (resuscitation with LR and LPs), and E (resuscitation with LR and PLPs pre-activated by thrombin). Blood loss, platelet count, blood urea nitrogen and lactic acid concentrations, and in vivo thromboelastography <i>R</i> value and maximum amplitude were recorded. Biotin-X-N-hydroxysuccinimide labeling and flow cytometry were used to measure the number of infused platelets left in circulation. Histology was used to assess whether aberrant thrombi were formed in the kidney, lung, or liver.</p><p><strong>Results: </strong>PLPs exhibited an increased P-selectin level, enhanced aggregation, and shortened <i>R</i> values, with no obvious changes in migration ability or maximum amplitude. PLPs transfusion had a non-inferior effect on all in vivo parameters compared with fresh platelet transfusion, and the circulation time of PLPs was much shorter than that of fresh platelets. No obvious thrombi were found.</p><p><strong>Conclusions: </strong>PLPs transfusion demonstrated non-inferior efficacy and safety compared with fresh platelet transfusion.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"36 1","pages":"2542767"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795151","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":"Use of a conditional Glanzmann thrombasthenia mouse model reveals a supportive and possibly non-adhesive role for TLT-1 in the platelet-fibrinogen interaction.","authors":"Siobhan Branfield, Nicholas Koshy, Yashieta Somani, Barbara Manfredi, Caitlin Schneider, Hanan Tlais, Vandre Figueiredo, Randal Westrick, A Valance Washington","doi":"10.1080/09537104.2025.2574379","DOIUrl":"10.1080/09537104.2025.2574379","url":null,"abstract":"<p><p>The platelet integrin receptor, αIIbβ3, binds fibrinogen to mediate platelet-platelet contacts, regulate hemostasis, and modulate inflammation. The Triggering Receptor Expressed in Myeloid (TREM) - Like (TLT)-1 is an enigmatic 34kD receptor found on platelets that affects their hemostatic and inflammatory functions. Similar to αIIbβ3, TLT-1's ligand is also fibrinogen; however, TLT-1's direct role in platelet function remains unknown. We created a tamoxifen-inducible conditional αIIb deficient (<i>^cItga2b^-/-</i>) mouse to better understand TLT-1's role in platelet function, specifically TLT-1's binding to fibrinogen and its role in hemostasis and inflammation. We first characterized our <i>^cItga2b^-/-</i> null mouse and subsequently crossed this mouse with a Treml1^-/- mouse, creating a conditional double knockout (^cDKO). While the floxed <i>^cItga2b /Treml1^-/-</i> mouse shows significant differences compared to control mice, deleting Treml1 from the <i>^cItga2b^-/-</i> mouse results in only minor differences from the <i>^cItga2b^-/-</i> strain in bleeding, aggregation, fibrinogen deposition and platelet spreading assays. Our data suggest that while TLT-1 plays a visible role in hemostasis, it primarily supports aggregation but may not function as an adhesive component.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"36 1","pages":"2574379"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12805433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145459547","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":"Challenges in diagnosing sticky platelet syndrome using light transmission aggregometry: a scoping review.","authors":"Yupeng Wu, Floris van Dellen, Hugo Ten Cate, Yvonne Henskens, Kristien Winckers","doi":"10.1080/09537104.2025.2560380","DOIUrl":"10.1080/09537104.2025.2560380","url":null,"abstract":"<p><p>Sticky Platelet Syndrome (SPS) is an inherited platelet hyperreactivity disorder associated with recurrent arterial and venous thrombosis. However, its diagnosis remains controversial due to substantial variability in light transmission aggregometry (LTA), the reference method. To map current diagnostic practices, we conducted a scoping review following PRISMA-ScR and JBI methodology, systematically searching Scopus, MEDLINE, Embase, and Google Scholar. We included 27 studies that collectively demonstrate considerable heterogeneity in patient preparation, sample handling, agonist usage, and data interpretation. These differences span pre-analytical and analytical variables such as washout periods, citrate concentration, centrifugation conditions, and threshold derivation methods. While detailed synthesis is ongoing, our preliminary observations highlight critical inconsistencies that may limit comparability across laboratories. This review underscores the need for standardized diagnostic approaches. Establishing harmonized protocols and validating them across centers could improve diagnostic accuracy and support better platelet function testing in SPS and related disorders.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"36 1","pages":"2560380"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145378577","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":"Extracellular thiol isomerase ERp5 regulates integrin αIIbβ3 activation by inhibition of fibrinogen binding.","authors":"Kaifei Sun, Yaqiong Zhang, Aizhen Yang, Yuxin Zhang, Zhenzhen Zhao, Xiaofeng Yan, Yi Lu, Yue Han, Depei Wu, Freda Passam, Jingyu Zhang, Yi Wu","doi":"10.1080/09537104.2025.2455743","DOIUrl":"10.1080/09537104.2025.2455743","url":null,"abstract":"<p><p>Recent studies have shown that anti-ERp5 antibodies inhibit platelet activation and thrombus formation; Moreover, ERp5-deficient platelets exhibit enhanced platelet reactivity via regulation of endoplasmic reticulum (ER) stress. In this study, we used a new ERp5-knockout mouse model as well as recombinant ERp5 (rERp5) protein, to examine the role of ERp5 in platelet function and thrombosis. Although platelet-specific ERp5-deficient mice had decreased platelet count, the mice had shortened tail-bleeding times and enhanced platelet accumulation in FeCl₃-induced mesenteric artery injury, compared with wild-type mice. Using platelet-specific ERp5-deficient mice, we found that ERp5 deficiency increased platelet aggregation, granule secretion, and integrin αIIbβ3 activation. Wild-type recombinant ERp5 protein (rERp5-wt) and inactive mutant ERp5 protein (rERp5-mut) both inhibited human platelet aggregation and the binding of fibrinogen to human platelets, indicating that ERp5 protein interferes with the interaction between integrin αIIbβ3 and its ligand fibrinogen, and its enzymatic activity is not required for this process. Consistently, wild-type mice injected with rERp5-wt or rERp5-mut protein had prolonged tail-bleeding times. Our results provide important evidence that platelet ERp5 negatively regulates platelet activation and thrombus formation, via steric hindrance interfering with integrin αIIbβ3 ligation.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"36 1","pages":"2455743"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067537","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":"Transcriptomic and functional characterization of megakaryocytic-derived platelet-like particles: impaired aggregation and prominent anti-tumor effects.","authors":"Kaitlin Garofano, Vera Mariani, Kameron Rashid, Sumanun Suwunnakorn, Alfateh Sidahmed, Anelia Horvath, Sanjay B Maggirwar, Travis J O'Brien, Minoli A Perera, Michael Whalen, Norman H Lee","doi":"10.1080/09537104.2024.2449344","DOIUrl":"10.1080/09537104.2024.2449344","url":null,"abstract":"<p><p>Platelet-like particles (PLPs), derived from megakaryocytic cell lines MEG-01 and K-562, are widely used as a surrogate to study platelet formation and function. We demonstrate by RNA-Seq that PLPs are transcriptionally distinct from platelets. Expression of key genes in signaling pathways promoting platelet activation/aggregation, such as the PI3K/AKT, protein kinase A, phospholipase C, and α-adrenergic and GP6 receptor pathways, was missing or under-expressed in PLPs. Functionally, PLPs do not aggregate following epinephrine, collagen, or ADP stimulation. While PLPs aggregated in response to thrombin, they did not display enhanced expression of surface markers P-selectin and activated α_2bβ₃, in contrast to platelets. We have previously demonstrated that platelets physically couple to MDA-PCa-2b and RC77T/E prostate cancer (PCa) cells via specific ligand-receptor interactions, leading to platelet-stimulated cell invasiveness and apoptotic resistance, and reciprocal cell-induced platelet aggregation. In contrast, PLP interactions with PCa cells inhibited both cell invasion and apoptotic resistance while failing to promote PLP aggregation. Moreover, PLPs reduced platelet-PCa cell interactions and antagonized platelet-stimulated oncogenic effects in PCa cells. RNA-Seq analysis identified candidate ligand-transmembrane protein combinations involved in anti-tumorigenic signaling of PLPs to PCa cells. Antibody neutralization of the TIMP3-MMP15 and VEGFB-FGFR1 signaling axes reversed PLP-mediated anti-invasion and apoptotic sensitization, respectively. In summary, PLPs lack many transcriptomic, molecular and functional features of platelets and possess novel anti-tumorigenic properties. These findings indicate that PLPs may have a potential therapeutic role in targeting and disrupting the oncogenic signaling between platelets and cancer cells, offering a new avenue for anti-cancer strategies.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"36 1","pages":"2449344"},"PeriodicalIF":3.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984432","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":"Platelet parameters for distinguishing between inherited macrothrombocytopenia and acquired thrombocytopenia: a retrospective case-control study.","authors":"Wenlan Chen, Yajie Ding, Li Cai, Mei Xue, Abdul Rehman Arif, Heng Mei, Yadan Wang","doi":"10.1080/09537104.2025.2489025","DOIUrl":"https://doi.org/10.1080/09537104.2025.2489025","url":null,"abstract":"<p><p>Inherited macrothrombocytopenia (IMT) is characterized by increased platelet volume. Using platelet parameters, including platelet count, mean platelet volume (MPV), platelet-large cell ratio (P-LCR), and platelet distribution width, to differentiate IMT from acquired thrombocytopenia (AT) in the Chinese population is unclear. This study aimed to evaluate these parameters and determine optimal thresholds for early IMT identification. This single-center, retrospective case-control study included IMT patients from 1 January 2022 to 31 January 2024. Age- and sex-matched AT patients and healthy individuals were selected (1:3 ratio). Platelet parameters were compared using a one-way analysis of variance and the Kruskal-Wallis test. The ability of platelet parameters to identify IMT was assessed using the receiver operating characteristic curve, with the optimal threshold determined using the Youden index. This study included 13 IMT patients, 39 AT patients, and 39 controls. The MPV and P-LCR were significantly higher in IMT than in AT patients (<i>P</i> < 0.05) and strongly differentiated between groups. The area under the curve (95% confidence interval) for MPV and P-LCR were 0.865 (0.724-1.000) and 0.860 (0.719-1.000), respectively. The optimal MPV and P-LCR thresholds for IMT were 14.55 fL and 58%, respectively. The MPV was most important for distinguishing IMT from patients with thrombocytopenia.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"36 1","pages":"2489025"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041596","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":"Megakaryocyte phenotyping in response to SARS-CoV-2 variants.","authors":"Marcin A Sowa, Michael Tuen, Florencia Schlamp, Yuhe Xia, Marie I Samanovic, Mark J Mulligan, Tessa J Barrett","doi":"10.1080/09537104.2025.2532459","DOIUrl":"10.1080/09537104.2025.2532459","url":null,"abstract":"<p><p>SARS-CoV-2 infection is associated with platelet hyperreactivity and increased rates of arterial and venous thrombosis. SARS-CoV-2 mutations have resulted in several variants with differences in transmissibility, infectivity, and patient outcomes. This study investigates the effects of the ancestral strain of SARS-CoV-2 (WA1) and two variants of concern, Delta and Omicron, on the human megakaryocyte (MK) phenotype and transcriptome. Human CD34⁺-derived MKs were incubated with WA1, Delta or Omicron SARS-CoV-2 variants for 24 hours. MK activation markers were measured under resting and thrombin-stimulated conditions. RNA-seq and cytokine release in response to the viruses were assessed. Plasma cytokines were measured in hospitalized COVID-19 patients. Treatment of MKs with WA1, Delta or Omicron variants of SARS-CoV-2 resulted in similar increases in classical activation markers. However, SARS-CoV-2 variants mediated distinct transcriptomic changes. Across variants, 60 genes overlapped, including <i>CXCL8</i>. Consistent with transcriptomic changes, SARS-CoV-2-incubated MKs secreted significantly elevated levels of IL-8. Among hospitalized COVID-19 patients, plasma IL-8 levels were highest in COVID-19 patients who subsequently experienced thrombotic events or died. In conclusion, WA1, Delta, and Omicron similarly induce classical MK activation responses while mediating distinct transcriptomic changes. Increased IL-8 levels may serve as a biomarker to inform platelet hyperreactivity and thrombotic events associated with COVID-19.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"36 1","pages":"2532459"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12347718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699344","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":"Regulation of lipid metabolism: a new strategy for platelet storage.","authors":"Jieyun Shi, Wenting Wang, Jinmei Xu, Wen Yin","doi":"10.1080/09537104.2025.2465321","DOIUrl":"10.1080/09537104.2025.2465321","url":null,"abstract":"<p><p>Transfusions of platelets are often used as prophylaxis in patients with hematologic malignancies and as treatment for active bleeding. However, platelets are in short supply due to the fact that they could only be kept for 5-7 days in vitro and they lose some of their functionality as a result of platelet storage lesions. To address this issue, refrigeration, cryopreservation and platelet additive solutions have been researched to determine their abilities to extend platelet storage duration. However, refrigerated platelets are quickly cleared after transfusion, while platelets in platelet additive solutions still present issues such as platelets quality and the risk of allergic reactions. Recent studies showed that changes in lipid metabolites during platelet storage and inadequate of fatty acid metabolism may also limit platelet shelf life and function. In this review, we address the principles of lipid metabolism during platelet storage and discuss the strategies for effective platelet storage systems. The findings of this review highlight the role of lipid metabolism during platelet storage, providing insights into future research focused on extending the preservation period and function of platelet.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"36 1","pages":"2465321"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414952","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}