Platelets最新文献_第2页

Immune thrombocytopenia triggered by dostarlimab in a patient with endometrial carcinoma: first reported case. 多司他单抗引起的子宫内膜癌患者的免疫性血小板减少：首例报道。

IF 2.6 3区医学

Platelets Pub Date : 2026-12-01 Epub Date: 2025-12-23 DOI: 10.1080/09537104.2025.2601056

Adolfo Fernández-Sánchez, Pablo García-Jaén, Carlos Puerta-Vázquez, M Belén Pazmiño-Zambrano, Pablo Reguera-Puertas, José Ramón González-Porras, José María Bastida

{"title":"Immune thrombocytopenia triggered by dostarlimab in a patient with endometrial carcinoma: first reported case.","authors":"Adolfo Fernández-Sánchez, Pablo García-Jaén, Carlos Puerta-Vázquez, M Belén Pazmiño-Zambrano, Pablo Reguera-Puertas, José Ramón González-Porras, José María Bastida","doi":"10.1080/09537104.2025.2601056","DOIUrl":"10.1080/09537104.2025.2601056","url":null,"abstract":"Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for various malignancies, but they are associated with a range of immunerelated adverse events, including rare hematological complications. Immune thrombocytopenia (ITP) has been reported with other antiPD1 agents such as nivolumab and pembrolizumab, but to date, no cases have been described with dostarlimab. We report the first case of ITP in a patient receiving dostarlimab for relapsed endometrial carcinoma. A 55yearold woman developed severe thrombocytopenia (3 × 109/L) accompanied by rectal bleeding, resulting in a lifethreatening condition. Secondary causes were excluded, and bone marrow findings supported a diagnosis of ITP. Initial treatment with highdose corticosteroids and intravenous immunoglobulin achieved only a partial response, while sustained platelet recovery was obtained with the addition of romiplostim. The patient remained on dostarlimab following hematological recovery without further episodes of ITP. This case highlights a potentially lifethreatening adverse effect of a widely used immunotherapy and underscores the importance of early recognition and timely escalation of treatment in ICIinduced ITP.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"37 1","pages":"2601056"},"PeriodicalIF":2.6,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145810905","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}

引用次数: 0

Single-cell transcriptome deciphers key targets of thrombopoietin receptor agonists and immune microenvironment characteristics of immune thrombocytopenia. 单细胞转录组破译血小板生成素受体激动剂的关键靶点和免疫性血小板减少症的免疫微环境特征。

IF 3.1 3区医学

Platelets Pub Date : 2026-12-01 Epub Date: 2026-04-01 DOI: 10.1080/09537104.2026.2651849

Wanru Wang, Haoxu Wang, Xiaohan Wan, Junying Cao, Ruixue Wang, Ming Hou

{"title":"Single-cell transcriptome deciphers key targets of thrombopoietin receptor agonists and immune microenvironment characteristics of immune thrombocytopenia.","authors":"Wanru Wang, Haoxu Wang, Xiaohan Wan, Junying Cao, Ruixue Wang, Ming Hou","doi":"10.1080/09537104.2026.2651849","DOIUrl":"10.1080/09537104.2026.2651849","url":null,"abstract":"Thrombopoietin receptor agonists (TPO-RAs) represent a cornerstone in immune thrombocytopenia (ITP) management, yet their molecular mechanisms remain incompletely elucidated. This study systematically deciphered the key targets and signaling networks of four TPO-RAs (romiplostim, eltrombopag, avatrombopag, hetrombopag) in ITP pathogenesis. Network pharmacology was integrated with single-cell high-dimensional weighted gene co-expression network analysis (hdWGCNA) using bone marrow scRNA-seq data from ITP patients and healthy controls. Metacell-based co-expression modules to hematopoietic bone marrow cells were identified. Drug targets were curated from multiple databases, and candidate genes were screened by intersecting differentially expressed genes (DEGs), cell specific modules, and TPO-RA targets. Molecular docking, pseudotime trajectory analysis, and in silico gene knockdown were employed for functional validation. Intersection analysis revealed five key genes (CACNA1A, CSF1R, PKN1, CD9, DSTYK). Molecular docking demonstrated strong binding affinities between TPO-RAs and key targets. The ITP bone marrow niche exhibited rewired cell-cell communication, with enhanced T cell-initiated signaling and aberrant megakaryocyte-T cell interactions. Pseudotime analysis uncovered disrupted megakaryocyte maturation dynamics. In silico knockdown revealed CACNA1A, CSF1R, and PKN1 dysregulation exacerbated neutrophil hyperactivity, while CD9 and DSTYK knockdown impaired mitotic regulation. This study delineated mechanisms of TPO-RAs, highlighting five key genes that orchestrate dysregulated thrombopoiesis and immune dysfunction in ITP. The integration of in silico strategies identified novel targets for optimizing ITP therapy.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"37 1","pages":"2651849"},"PeriodicalIF":3.1,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593941","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}

引用次数: 0

Platelet-erythrocyte complex production is exacerbated by histones and protected by small polyanion histone neutralizing compounds. 血小板-红细胞复合体的产生由组蛋白加剧，并由小聚阴离子组蛋白中和化合物保护。

IF 3.1 3区医学

Platelets Pub Date : 2026-12-01 Epub Date: 2026-09-01 DOI: 10.1080/09537104.2026.2722985

Vichari Sirimanne, Jiwon Lee, Melanie Rug, Christopher R Parish, Farzaneh Kordbacheh, Brendan J McMorran

{"title":"Platelet-erythrocyte complex production is exacerbated by histones and protected by small polyanion histone neutralizing compounds.","authors":"Vichari Sirimanne, Jiwon Lee, Melanie Rug, Christopher R Parish, Farzaneh Kordbacheh, Brendan J McMorran","doi":"10.1080/09537104.2026.2722985","DOIUrl":"https://doi.org/10.1080/09537104.2026.2722985","url":null,"abstract":"Platelet-erythrocyte (PE) complexes, composed of single erythrocytes bound to platelets, are a physiological component of the bloodstream and contribute to erythrocyte turnover. Conditions in which PE complex production is increased or their clearance from the circulation is impeded are associated with hypercoagulable states and thrombocytopenia. Sepsis is a serious acute inflammatory condition that is often complicated by major hemostatic derangements, including thrombosis, anemia and thrombocytopenia, and an important driver of sepsis pathology are extracellular histones, which are released into the circulation from activated neutrophils. Histone-neutralizing small polyanions (SPAs) have been developed to block the cytotoxic effects of histones and are beneficial in treating sepsis. This study investigated whether histones may stimulate increased PE complex production as a potential cause of the hemostatic complications in disease, and whether SPAs can prevent complex generation. Treatment with histones in co-incubated human erythrocytes and platelets, or murine blood, increased PE complex production approximately 10-fold compared with control conditions. Mice administered histones by intravenous injection displayed reduced platelet counts but sustained complex levels, suggesting complex production was enhanced within the diminished platelet pool. The platelets in the histone-stimulated complexes were also more activated than cell-free platelets, according to increased surface expression of P-selectin and the fibrin-binding form of integrin αIIbβ3, determined using flow cytometry, and their altered shape and presence of filopodia observed by scanning electron microscopy. Inclusion of SPAs in the histone-treated cells and blood prevented histone-stimulated production of complexes, indicating the importance of the histone-mediated cell injury in their generation and identifying PE complexes as a treatment target.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"37 1","pages":"2722985"},"PeriodicalIF":3.1,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866306","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}

引用次数: 0

Endogenous spermidine biosynthesis contributes to fetal liver megakaryopoiesis and platelet production in mice. 内源性亚精胺生物合成促进小鼠胎儿肝巨核生成和血小板生成。

IF 3.1 3区医学

Platelets Pub Date : 2026-12-01 Epub Date: 2026-09-02 DOI: 10.1080/09537104.2026.2714075

Xing Liu, Meijuan Xia, Jiaojiao Guo, Liang Zhao, Yezi Ma, Long Li, Pei Su, Cuicui Liu, Fei Wang, Jiaxi Zhou, Wen Zhou, Hongtao Wang

{"title":"Endogenous spermidine biosynthesis contributes to fetal liver megakaryopoiesis and platelet production in mice.","authors":"Xing Liu, Meijuan Xia, Jiaojiao Guo, Liang Zhao, Yezi Ma, Long Li, Pei Su, Cuicui Liu, Fei Wang, Jiaxi Zhou, Wen Zhou, Hongtao Wang","doi":"10.1080/09537104.2026.2714075","DOIUrl":"https://doi.org/10.1080/09537104.2026.2714075","url":null,"abstract":"Metabolic regulation is increasingly recognized as an important determinant of megakaryocyte development and platelet production, yet the metabolite-level characteristics of primary megakaryocytes from distinct developmental stages and tissue origins remain incompletely defined. Here, using microscale targeted metabolomics, we profiled primary megakaryocytes isolated from mouse liver and bone marrow. This analysis revealed distinct metabolomic profiles between the two megakaryocyte populations and identified spermidine and lysine as metabolites enriched in liver-derived megakaryocytes. Functional analyses showed that spermidine, but not lysine, promoted fetal liver-derived megakaryocyte generation and platelet-like particle formation in vitro, whereas these effects were not observed in adult bone marrow-derived cultures under the tested conditions. Maternal dietary spermidine supplementation increased fetal liver megakaryocyte generation and fetal platelet production in vivo, with limited detectable effects on megakaryopoiesis in the maternal bone marrow. Single-cell transcriptomic analysis and pharmacological perturbation further linked endogenous spermidine biosynthesis to fetal liver megakaryopoiesis. Inhibition of Odc1 or Amd1 reduced intracellular spermidine levels, impaired fetal liver-derived megakaryocyte differentiation and platelet-like particle formation, and exogenous spermidine partially rescued DFMO-induced defects. Together, these findings define distinct metabolic features of mouse liver- and bone marrow-derived megakaryocytes and support a role for endogenous spermidine biosynthesis in fetal liver megakaryopoiesis and platelet production.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"37 1","pages":"2714075"},"PeriodicalIF":3.1,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148875641","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}

引用次数: 0

Effects of serum vitamin D on platelet function and bleeding in primary immune thrombocytopenia. 血清维生素D对原发性免疫性血小板减少症患者血小板功能及出血的影响。

IF 3.1 3区医学

Platelets Pub Date : 2026-12-01 Epub Date: 2026-09-14 DOI: 10.1080/09537104.2026.2730212

Justin P Oosterlee, Dino Mehic, Tim Dreier, Alexander Tolios, Beate Eichelberger, Helmuth Haslacher, Cihan Ay, Ingrid Pabinger, Johanna Gebhart

{"title":"Effects of serum vitamin D on platelet function and bleeding in primary immune thrombocytopenia.","authors":"Justin P Oosterlee, Dino Mehic, Tim Dreier, Alexander Tolios, Beate Eichelberger, Helmuth Haslacher, Cihan Ay, Ingrid Pabinger, Johanna Gebhart","doi":"10.1080/09537104.2026.2730212","DOIUrl":"https://doi.org/10.1080/09537104.2026.2730212","url":null,"abstract":"Primary immune thrombocytopenia (ITP) is an autoimmune mediated thrombocytopenia with destruction and impaired production of platelets. Though life-threatening bleeding can occur in ITP, bleeding symptoms are often mild relative to platelet count. ITP is also associated with an increased thromboembolic risk. Variations in platelet function may contribute to the bleeding and thrombotic phenotype of ITP. Vitamin D (VD) deficiency (VDD) has been linked to enhanced platelet function in healthy individuals and patients receiving dual antiplatelet therapy. As VDD is associated with several autoimmune diseases including ITP, we aimed to investigate the influence of serum VD levels on platelet function in ITP. We assessed P-selectin and activated GPIIb/IIIa expression in naïve and stimulated platelets, soluble P-selectin levels, bleeding severity, and mean platelet volume in 79 primary ITP patients from the Vienna ITP Biobank but found no association with VD levels. Thus, low VD levels do not correlate with enhanced platelet function in ITP. Further, bleeding was not associated with VD, adjusting for platelet count. In summary, VD does not seem to be the primary driver of platelet function in ITP.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"37 1","pages":"2730212"},"PeriodicalIF":3.1,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963719","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}

引用次数: 0

Bridging specialties: repurposing platelet drugs prescribed by cardiologists to help infectious disease doctors treat Staphylococcus aureus bacteremia. 桥接专业：重新利用心脏病专家开的血小板药物来帮助传染病医生治疗金黄色葡萄球菌菌血症。

IF 2.6 3区医学

Platelets Pub Date : 2026-12-01 Epub Date: 2026-01-16 DOI: 10.1080/09537104.2025.2612045

Matthew Geriak, Dani Geriak, Victor Nizet, George Sakoulas

{"title":"Bridging specialties: repurposing platelet drugs prescribed by cardiologists to help infectious disease doctors treat Staphylococcus aureus bacteremia.","authors":"Matthew Geriak, Dani Geriak, Victor Nizet, George Sakoulas","doi":"10.1080/09537104.2025.2612045","DOIUrl":"10.1080/09537104.2025.2612045","url":null,"abstract":"The platelet is the most important cell in the bloodstream in providing endovascular immunity against Staphylococcus aureus bacteremia. Both quantitative and qualitative thrombocytopenia have been associated with increased mortality in patients with S. aureus bacteremia. Patients with end-stage renal disease are particularly vulnerable to both an increased risk of getting S. aureus bacteremia and endocarditis, but also in treatment failure resulting in prolonged infection and relapse. In this commentary, we highlight the important host-pathogen relationship between S. aureus and the human platelet. In particular, we describe virulence factor-mediated platelet clearance from the circulation and improvement in platelet counts as a marker of treatment success. P2Y12 inhibitors deployed in the treatment of cardiovascular disease have been shown to attenuate the effect of S. aureus on platelet clearance. Therefore, we believe that partnerships between investigators in cardiology, hematology, and infectious disease with particular focus on platelet pathophysiology are poised to improve outcomes in select patients with S. aureus endovascular infection.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"37 1","pages":"2612045"},"PeriodicalIF":2.6,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145990347","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}

引用次数: 0

Novel compound heterozygous ITGA2B mutations in Glanzmann thrombasthenia associated with adolescent osteoporosis. 与青少年骨质疏松症相关的Glanzmann血栓缺失的新型复合杂合ITGA2B突变

IF 2.6 3区医学

Platelets Pub Date : 2026-12-01 Epub Date: 2026-01-09 DOI: 10.1080/09537104.2025.2612049

Yang Zhang, Yujiao Luo, Guangsen Zhang

引用次数: 0

Nanobodies to GPVI as alternative reagents for platelet spreading. 纳米体可作为血小板扩散的替代试剂。

IF 3.1 3区医学

Platelets Pub Date : 2026-12-01 Epub Date: 2026-04-17 DOI: 10.1080/09537104.2026.2653068

Alexandre Slater, Hsin-Yun Pan, Tz-Han Ho, Eleyna M Martin, Stephen P Watson, Jeremy A Pike, Natalie S Poulter, Steven G Thomas

{"title":"Nanobodies to GPVI as alternative reagents for platelet spreading.","authors":"Alexandre Slater, Hsin-Yun Pan, Tz-Han Ho, Eleyna M Martin, Stephen P Watson, Jeremy A Pike, Natalie S Poulter, Steven G Thomas","doi":"10.1080/09537104.2026.2653068","DOIUrl":"10.1080/09537104.2026.2653068","url":null,"abstract":"Platelet spreading assays are widely used to assess platelet adhesion, cytoskeletal remodeling and receptor‑specific signaling, but current GPVI ligands such as Collagen Related Peptide (CRP‑XL) suffer from non‑defined structure, batch variability, and high cost. Nanobodies targeting GPVI offer an attractive alternative due to their defined stoichiometry and recombinant production. Here, we evaluated whether GPVI‑binding nanobodies can support GPVI‑dependent platelet spreading. Using automated image analysis, we compared spreading on monovalent Nb2, trivalent Nb2‑3 and CRP‑XL. Monovalent Nb2 supported full spreading in only a subset of platelets, with reduced adhesion compared to CRP‑XL. In contrast, trivalent Nb2‑3 induced platelet adhesion and spreading indistinguishable from CRP‑XL, with comparable morphology, actin organization and spread area at concentrations ≥0.1 µg mL-1. Spreading on Nb2‑3 was inhibited by soluble Nb2 and by Src kinase blockade, confirming GPVI‑dependent signaling, while the non‑blocking nanobody Nb28 had no inhibitory effect. Notably, Nb28 alone supported spreading, demonstrating that ligand‑induced GPVI clustering, rather than binding site location, drives activation. These findings show that Nb2‑3 is a potent and reproducible alternative to CRP‑XL, offering a well‑defined and standardizable reagent for GPVI‑dependent static platelet spreading assays.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"37 1","pages":"2653068"},"PeriodicalIF":3.1,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147699373","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}

引用次数: 0

Abnormal expansion of peripheral helper T cells in primary immune thrombocytopenia. 原发性免疫性血小板减少症患者外周血辅助性T细胞的异常扩增。

IF 3.1 3区医学

Platelets Pub Date : 2026-12-01 Epub Date: 2026-03-31 DOI: 10.1080/09537104.2026.2653082

Qian Liu, Tianshu Yu, Yimin Zhou, Xiran Hou, Le Jiang, Jiaqi Liu, Jiayi Zhu, Yajing Zhao, Zhenyu Yan, Xinguang Liu

{"title":"Abnormal expansion of peripheral helper T cells in primary immune thrombocytopenia.","authors":"Qian Liu, Tianshu Yu, Yimin Zhou, Xiran Hou, Le Jiang, Jiaqi Liu, Jiayi Zhu, Yajing Zhao, Zhenyu Yan, Xinguang Liu","doi":"10.1080/09537104.2026.2653082","DOIUrl":"10.1080/09537104.2026.2653082","url":null,"abstract":"Peripheral helper T (Tph) cells, a distinct T-cell subset defined as CD4+PD-1hiCXCR5- phenotypically, are increasingly recognized as key drivers of antibody-mediated autoimmunity; however, their role in primary immune thrombocytopenia (ITP) remains poorly defined. In this study, we evaluated circulating Tph cells in newly diagnosed ITP and characterized their dynamic changes following dexamethasone therapy. Circulating Tph cells were significantly expanded in patients with ITP and were positively correlated with bleeding severity, suggesting involvement of Tph cells in ITP pathophysiology. High-dose dexamethasone markedly reduced circulating Tph frequencies both in vitro and in vivo. Notably, persistently elevated Tph levels were observed in patients who were non-responsive to dexamethasone. Furthermore, plasma interleukin-21 levels declined in parallel with Tph reduction following dexamethasone treatment, and were positively correlated with Tph frequencies in untreated, newly diagnosed ITP patients, consistent with Tph-associated B-cell helper activity. Collectively, these findings identify Tph cells as a potential indicator of extrafollicular B-cell activation in ITP and highlight their relevance to dexamethasone therapeutic responsiveness.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"37 1","pages":"2653082"},"PeriodicalIF":3.1,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581913","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}

引用次数: 0

Hexokinase controls platelet activation and hemostasis. 己糖激酶控制血小板活化和止血。

IF 3.1 3区医学

Platelets Pub Date : 2026-12-01 Epub Date: 2026-06-24 DOI: 10.1080/09537104.2026.2692723

Lih T Cheah, Jawad S Khalil, Beth A Webb, Daisie M Yates, Reem Alotaibi, Mary McKay, Mohammad Ali, Thomas Palmer-Dench, Emily Horner, Mugthalana Allet, Fraser Macrae, Cedric Duval, Amanda J Unsworth, Mark T Kearney, Khalid M Naseem

{"title":"Hexokinase controls platelet activation and hemostasis.","authors":"Lih T Cheah, Jawad S Khalil, Beth A Webb, Daisie M Yates, Reem Alotaibi, Mary McKay, Mohammad Ali, Thomas Palmer-Dench, Emily Horner, Mugthalana Allet, Fraser Macrae, Cedric Duval, Amanda J Unsworth, Mark T Kearney, Khalid M Naseem","doi":"10.1080/09537104.2026.2692723","DOIUrl":"10.1080/09537104.2026.2692723","url":null,"abstract":"Platelet activation is energy-dependent and associated with a hyperglycolytic phenotype, yet the role of key glycolytic enzymes remains unclear. We investigated the role of platelet hexokinases (HK1 and HK2) in regulating thrombin- and convulxin-stimulated bioenergetics, functions, and hemostasis using pharmacological inhibitors 2-deoxyglucose (2DG; pan-HK) and 3-bromopyruvate (3BP; HK2-preferential). Platelet activation increased HK activity, with convulxin producing a stronger response than thrombin. Using 2DG and 3BP, we found that activation-induced glucose uptake, glycolytic ATP production, and glycolysis were dependent on both HK isoforms. Platelet aggregation was reduced but not abolished by HK inhibition, indicating that platelet function is underpinned by metabolic flexibility. Integrin activation and pro-coagulant platelet formation were suppressed by both inhibitors. In contrast, α-granule secretion markers (CD62P, CD40L), platelet spreading, and convulxin-induced reactive oxygen species (ROS) generation were more sensitive to 3BP, suggesting a prominent role for HK2 in secretion, outside-in signaling, and ROS regulation. In vitro thrombus formation over collagen was significantly reduced by both inhibitors. In addition, HKs play a pivotal role in the regulation of in vivo hemostasis with increased bleeding time in mice treated with HK inhibitor. These findings identify HK as a central regulator of platelet metabolism and function, with distinct contributions of HK isoforms to specific platelet responses.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":" ","pages":"2692723"},"PeriodicalIF":3.1,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148318753","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}

引用次数: 0