Journal of Thrombosis and Haemostasis最新文献

{"title":"A repeated time-to-event model for personalised treatment of patients with haemophilia A based on individual bleeding risk.","authors":"Alexander Janssen, Frank C Bennis, Marjon H Cnossen, Ron A A Mathôt","doi":"10.1016/j.jtha.2025.05.023","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.05.023","url":null,"abstract":"<p><strong>Background: </strong>Pharmacokinetic (PK)-guided dosing of factor VIII (FVIII) concentrates is widely recommended to personalise the treatment of haemophilia A patients. However, it is well known that commonly applied target FVIII plasma levels do not necessarily improve bleeding outcomes in all individuals. It is therefore desirable to adapt treatment based on individual bleeding risk rather than only factor levels. Unfortunately, there is currently no reliable clinical marker that reliably discerns between patients with low or high bleeding risk.</p><p><strong>Objectives: </strong>We explore the possibility of using repeated time-to-event (RTTE) models to quantify individual bleeding risk by combining (historical) information on annual bleeding rates and PK, without requiring the measurement of novel clinical markers.</p><p><strong>Methods: </strong>We improve upon existing RTTE models using data from 264 severe haemophilia A patients followed during three clinical trials. The model classifies patients into low, medium, or high bleeding frequency cohorts to reduce between-patient variability and predicts bleeding risk for specific categories of bleeds rather than pooled bleeding information.</p><p><strong>Results: </strong>The resulting model has high accuracy, with >70% of predictions being within one bleed of the true observed bleeding rate. We demonstrate how the proposed model can be used to compare treatment not only based on the achievement of specific factor levels and factor concentrate consumption, but also on projected bleeding outcomes. Importantly, this approach does not require the measurement of novel or unconventional biomarkers, facilitating its adoption in routine clinical practice.</p><p><strong>Conclusions: </strong>The proposed method may present an exciting new treatment paradigm for haemophilia A patients.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MAPK1 regulates platelet function and thrombus formation.","authors":"Xiaoqi Xu, Yue Dai, Hui Zhu, Jie Zhang, Yingying Li, Huimin Jiang, Xiang Chu, Yueyue Sun, Wen Ju, Mengdi Xu, Lingyu Zeng, Zhenyu Li, Kailin Xu, Jianlin Qiao","doi":"10.1016/j.jtha.2025.05.022","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.05.022","url":null,"abstract":"<p><strong>Background: </strong>Mitogen activated protein kinase 1 (MAPK1 or ERK2) is a Ser/Thr kinase and its inhibition by pharmacological inhibitors attenuated platelet function. However, conflicting results for different inhibitors were obtained due to off-target effects. Moreover, whether MAPK1 affects platelet function is unknown.</p><p><strong>Objectives: </strong>This study intends to evaluate the role of MAPK1 in platelet activity and thrombus formation.</p><p><strong>Methods: </strong>Megakaryocyte/platelet-specific MAPK1 knockout mice were generated and utilized to assess platelet aggregation, activation, procoagulant activity, spreading and clot retraction. In addition, tail bleeding time and arterial and venous thrombus formation assays were performed to evaluate the in vivo hemostatic function and thrombus formation.</p><p><strong>Results: </strong>MAPK1 deficiency impaired hemostasis, both arterial and venous thrombosis. Consistently, MAPK1-deficient platelets presented reduced platelet aggregation, granules release, αIIbβ3 activation, calcium mobilization, procoagulant activity, spreading and clot retraction. Additionally, MAPK1 deficiency inhibited phosphorylation of p38, ERK5, JNK and ASK1 as well as the release of arachidonic acid and thromboxane B2. Moreover, MAPK1 interacts with talin1 and phosphorylates it at Ser425 in activated platelets and its deletion impaired the phosphorylation of talin1 and β3. Furthermore, inhibition of platelet feedback signaling by apyrase abolished the difference of platelet aggregation compared to control platelets and inhibited the phosphorylation of ASK1 and talin1 in activated control platelets. Finally, inhibition of MAPK1 decreased human platelet function and reduced the phosphorylation of talin1 and β3.</p><p><strong>Conclusion: </strong>Our study identifies a novel mechanism for MAPK1 in the regulation of platelet function and thrombosis, implying its potential as a target to treat thrombotic disorders.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visceral adipose tissue demonstrates a stronger association with venous thromboembolism than body mass index.","authors":"Ruidong Xiang, Angela Huang, Hannah Stevens, Manika Singh, Karlheinz Peter, Fumihiko Takeuchi, James D McFadyen","doi":"10.1016/j.jtha.2025.05.020","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.05.020","url":null,"abstract":"<p><strong>Background: </strong>Increased body mass index (BMI) is associated with an increased risk of venous thrombosis. However, recent data has highlighted that visceral adipose tissue (VAT) volume may be a better marker of cardiometabolic risk.</p><p><strong>Objectives: </strong>To investigate the relationship between VAT volume and VTE risk and explore whether increased VAT volumes is associated with VTE risk.</p><p><strong>Methods: </strong>We performed a cross-sectional study utilising MRI imaging data from the UK Biobank (UKB). The association between VTE incidence and VAT measured by MRI imaging from 39,144 UKB patients was analysed by ridge regression accounting for covariates including age and sex.</p><p><strong>Results: </strong>VAT volume, as measured by MRI, was demonstrated to be associated with an increased risk of VTE [OR 4.020 (95%CI: 3.752 - 4.287) per dm³]. Moreover, we observed a significant association of VAT volume with VTE risk in both those who were overweight [VAT high; OR 1.589 (95%CI: 1.317 - 1.860), VAT medium; OR 1.303 (95%CI:1.054 -1.552)] and obese [VAT high; OR 3.222 (95%CI: 2.971 - 3.473)]. Notably, the strongest association of VAT was observed in those with obesity.</p><p><strong>Conclusion: </strong>These data demonstrate for the first time that VAT volume is associated with an increased risk of VTE and importantly has a stronger association with VTE risk as compared to BMI.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Health-related quality of life in children with von Willebrand disease: Results of the French real-life WiSH-QoL study.","authors":"Jenny Goudemand, Sophie Susen, Claire Berger, Sophie Bayart, Hervé Chambost, Fabienne Genre-Volot, Dominique Desprez, Ségolène Claeyssens, Brigitte Pan-Petesch, Annie Harroche, Laurent Ardillon, Agnès Veyradier, Malika Barthez-Toullec, Grégory Marin, Emmanuelle Lagrue, Marie Hélène André-Bonnet, Yohann Repessé, Annie Borel-Derlon, Sylvia von Mackensen","doi":"10.1016/j.jtha.2025.05.017","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.05.017","url":null,"abstract":"<p><strong>Background: </strong>Haemorrhagic episodes may have physical or psychological effects on children with von Willebrand disease (VWD) and their families. These effects can be measured by health-related quality of life (HRQoL).</p><p><strong>Objectives: </strong>The WiSH-QoL study aimed at filing this knowledge gap, using generic or disease-specific patient-reported outcome questionnaires (PROs) in France.</p><p><strong>Patients/methods: </strong>This prospective observational study included 117 children (<18 years) with all VWD types ((type 1 with basal VWF:Ag<30%). HRQoL (DISABKIDS, VWD-QoL), treatment satisfaction (VWD-SAT), and family burden (FaBeL) were assessed at baseline and 24 months via child and/or parent questionnaires.</p><p><strong>Results: </strong>The DISABKIDS questionnaire revealed age-specific patterns: preschoolers (4-7 years) showed predominant physical limitations, while older children (8-17 years) faced independence challenges. The VWD-QoL questionnaire identified early and persistent impacts on peer/family relationships. Parent-child concordance was observed in total DISABKIDS/VWD-QoL scores, though adolescents were more optimistic than parents in some domains, while 4-7-year-olds reported slightly poorer physical abilities. Gender differences emerged, with boys (8-17 years) reporting more school difficulties and younger girls (4-7 years) perceiving greater social/sports restrictions. Disease severity (VWF:RCo <15 IU/dL in types 1/2) significantly worsened overall HRQoL. Parents reported some dissatisfaction regarding treatment ease and burden. Parents also reported significant disease-related impacts on both family dynamics and personal wellbeing, particularly in type 3 VWD families.</p><p><strong>Conclusions: </strong>HRQoL was reduced in French VWD children and their families secondary to physical, mental, and social health impacts, especially (but not only) in adolescents and in children with severe VWD types.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotype versus laboratory phenotype correlation of defects in natural anticoagulants in patients with venous thromboembolism.","authors":"Christine Van Laer, Marthe Vanrenterghem, Marc Jacquemin, Andreas Verstraete, Sarissa Baert, Cyrielle Kint, Mirjam Kruijt, Renee Ruhaak, Veerle Labarque, Thomas Vanassche, Peter Verhamme, Kathelijne Peerlinck, Kathleen Freson","doi":"10.1016/j.jtha.2025.05.016","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.05.016","url":null,"abstract":"<p><strong>Introduction: </strong>Plasma-based assays or multigene panel testing can be used for the diagnosis of inherited venous thromboembolism (VTE). Our recent multigene panel data showed strictly concordant results between genetic and phenotypic laboratory testing in only half of the patients. We evaluated in detail the correlation between genotype and laboratory phenotype for defects in natural anticoagulants.</p><p><strong>Method: </strong>Gene panel test results were compared with standard thrombophilia laboratory assay data, including protein C, protein S and antithrombin plasma activity or antigen levels. We performed additional functional protein C and protein S clot-based assays and mass spectrometry (MS) for the detection of antithrombin molecular proteoforms.</p><p><strong>Results: </strong>We detected PROC, PROS1 or SERPINC1 variants in 110 of 317 VTE patients of which 61% were (likely)pathogenic variants. Oligogenic inheritance was present in 33% of all patients. Correlation studies showed that not all variants were associated with reduced plasma activity levels, while 14%, 20% and 5% of our VTE patients without a genetic variant had reduced levels for protein C, protein S and antithrombin respectively. Additional clot-based assays could diagnose additional patients but not all. MS-based antithrombin assay was able to detect SERPINC1 missense variants in plasmas that were associated with normal antithrombin activity levels.</p><p><strong>Conclusion: </strong>Thrombophilia screening using plasma-based assays can lead to potential diagnostic misclassification. In contrast, multigene panel testing is more sensitive but still associated with the detection of variants of uncertain significance. Additional studies are required to clarify the role of panel testing for inherited VTE and the impact of oligogenic inheritance.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial NADPH oxidase 5 overexpression promotes thrombosis and alters thrombus composition by sex-dependent mechanisms in mice.","authors":"Javier Marqués, Joaquín Fernández-Irigoyen, María Martínez-Azcona, Elena Ainzúa, Victor Marqués, Carmen Roncal, Josune Orbe, Enrique Santamaría, Guillermo Zalba","doi":"10.1016/j.jtha.2025.05.015","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.05.015","url":null,"abstract":"<p><strong>Background: </strong>Different members of the NADPH oxidases family (NOXs) participate in thrombosis. Nevertheless, the information about NOX5 in this process is scarce. The aim of this study was to test whether chronic expression of NOX5 may modulate thrombosis.</p><p><strong>Methods: </strong>To test this hypothesis, mice expressing human NOX5 at the endothelium and their control littermates underwent a FeCl₃-induced thrombosis model in the carotid artery. The composition of the thrombi obtained from these mice was analysed by proteomics. The derived findings were corroborated by molecular analysis in vivo, in vitro and ex vivo. Finally, the antithrombic effects of N-acetylcysteine (NAC) and the pan-NOX inhibitor ML090 were tested.</p><p><strong>Results: </strong>The results from the present assay indicate that endothelial NOX5 expression promotes thrombosis in vivo in a sex-dependent manner. In female mice, NOX5 enhances prostaglandin E₂ (PGE₂) secretion and alters the expression of endothelial adhesion molecules. In male mice, NOX5 partially promotes the activation of circulating neutrophils. Both, NAC and ML090 protect against thrombosis in vivo.</p><p><strong>Conclusions: </strong>In conclusion, our findings demonstrate that endothelial NOX5 plays a role in thrombosis, indicating that this oxidase should be considered as a therapeutic target to prevent thrombosis.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel p.C252G and p.C280X mutations in EGF-1 domain of thrombomodulin lead to a thrombosis-bleeding syndrome.","authors":"Xiaoying Wang, Aizhen Yang, Shuyi Huang, Zhenzhen Zhao, Futian Ma, Yi Lu, Yujie Guo, Yan Wang, Yi Wu, Jingyu Zhang","doi":"10.1016/j.jtha.2025.05.014","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.05.014","url":null,"abstract":"<p><strong>Background: </strong>Thrombomodulin (TM) binds thrombin forming a thrombin-TM complex, thereby regulating the balance between coagulation and fibrinolysis. We found a proband carrying compound heterozygous mutations (c.754T>G, p.C252G and c.840C>A, p.C280X) in EGF-1 of THBD gene resulting into TM deficiency.</p><p><strong>Objectives: </strong>To explore the molecular mechanism underlying the anticoagulant defect caused by C252G and C280X mutations.</p><p><strong>Results: </strong>A 5-year-old Chinese boy with lifelong large ecchymosis due to TM deficiency showed marked hypofibrinogenemia with significant increased fibrinogen/fibrin degradation products, D-dimer, thrombin-antithrombin complex, and plasmin-α2 plasmin inhibitor complex, indicating a disseminated intravascular coagulation (DIC)-like microcirculatory thrombosis-bleeding syndrome. The proband carried heterozygous mutations (C252G and C280X) in THBD gene. In HEK293T cells transfected with TM-wild-type (WT), TM-C252G and TM-C280X cDNAs, both TM-WT and TM-C252G were comparably expressed on cell surface, while TM-C280X was not expressed due to the substitution of c.840C with A leading to a stop codon formation. The recombinant TM (rTM) carrying C252G mutation in both the extracellular domain (rTM-EC/C252G) and the membrane-penetrating type exhibited attenuated inhibitory effect on thrombin generation compared to rTM-WT. Moreover, rTM-EC/C252G exhibited lower activation of thrombin catalytic protein C and thrombin activatable fibrinolysis inhibitor (TAFI) than rTM-EC/WT, which may enhance coagulation and fibrinolysis. Protein conformation heatmap analysis revealed that rTM-EC/C252G mutant induced TM structural changes with >25% relative uptake differences compared to rTM-EC/WT.</p><p><strong>Conclusion: </strong>We identified two novel TM variants (C252G and C280X) associated with DIC-like thrombosis-bleeding syndrome, providing the first genetic evidence for the critical role of Cys252-Cys265 in maintaining the structure and function of TM.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High tranexamic acid concentrations alter fibrin network structure and biophysical properties.","authors":"Samer M Issa, Yaqiu Sang, Hazar A Granko, Alisa S Wolberg","doi":"10.1016/j.jtha.2025.05.012","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.05.012","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KCNN4-mediated potassium ion efflux maintains mitochondrial functions leading to platelet biogenesis.","authors":"Qihao Chen, Sou Nakamura, Takuya Yamamoto, Naoya Takayama, Naoshi Sugimoto, Koji Eto","doi":"10.1016/j.jtha.2025.05.013","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.05.013","url":null,"abstract":"<p><strong>Background: </strong>Potassium ions (K⁺) are essential for platelet function, yet their role in thrombopoiesis-particularly through specific K⁺ channels-remains poorly understood. This gap is especially relevant in the context of in vitro platelet production from induced pluripotent stem cell (iPSC)-derived immortalized megakaryocyte progenitor cell lines (imMKCLs), which we have developed for clinical-grade platelet manufacturing.</p><p><strong>Objective: </strong>We aimed to elucidate how K⁺ channels contribute to platelet biogenesis, focusing specifically on the calcium ion (Ca²⁺)-activated K⁺ channel KCNN4 (also known as K_Ca3.1).</p><p><strong>Methods: </strong>Using imMKCLs and human cord blood-derived megakaryocytes (CB-megakaryocytes), we analyzed intracellular cation dynamics during platelet production. RNA sequencing profiling was conducted to identify K⁺ channel gene expression changes, focusing on KCNN4. Its role in proplatelet formation and platelet release was examined using pharmacological inhibitors and gene knockdown (KD). We further investigated the link between KCNN4 and microtubule organization, mitochondrial function, and reactive oxygen species (ROS) levels.</p><p><strong>Results: </strong>A progressive decline in intracellular K⁺ concentration ([K⁺]ᵢ) was observed during the six-day maturation period of imMKCLs. KCNN4 was upregulated at onset of platelet generation, and its inhibition or KD led to impaired proplatelet formation and reduced platelet yield in both imMKCLs and CB-megakaryocytes. These effects were accompanied by decreased [K⁺]ᵢ, reduced mitochondrial membrane potential, and increased ROS accumulation.</p><p><strong>Conclusions: </strong>Our findings reveal that the KCNN4-mediated reduction in [K⁺]ᵢ is a crucial mechanism linking cytoskeletal reorganization, mitochondrial function, and ROS homeostasis to effective thrombopoiesis. This study provides new insights into platelet biogenesis and offers potential avenues to optimize ex vivo platelet production.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired surface receptor expression on immature platelets in bleeding patients with abnormal light transmission aggregometry.","authors":"Dino Mehic, Anita Pirabe, Waltraud Schrottmaier, Anna Schmuckenschlager, Sabine Frühwirth, Hubert Hackl, Alexander Tolios, Cihan Ay, Ingrid Pabinger, Johanna Gebhart, Alice Assinger","doi":"10.1016/j.jtha.2025.05.011","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.05.011","url":null,"abstract":"<p><strong>Background: </strong>A platelet function defect (PFD) is diagnosed in patients with mild to moderate bleeding disorders (MBD) and abnormalities in light transmission aggregometry (LTA). The influence of platelet aging on platelet function in PFD remains unclear.</p><p><strong>Methods: </strong>Twenty-two patients with LTA alterations from the Vienna Bleeding Biobank were compared to 19 age- and sex-matched healthy controls. Blood samples were immediately analyzed using PFA-100 with epinephrine cartridges. Platelets subtypes were characterized via surface receptor profiling of CD9, CD31, CD36, CD40L, CD42b, CD62P, CD63, CD107 and toll like receptors (TLRs) 2, 4 and 9 and immature (RNA-rich) platelets were quantified.</p><p><strong>Results: </strong>Platelet counts, immature platelet fraction, and mean platelet volume, as well as other hemostatic parameters, did not differ between patients and controls, while patients demonstrated prolonged closure times (CT) on PFA-100. Principal component analysis highlighted distinct glycoprotein expression patterns between immature and mature platelets in both their resting state and after activation, in patients and healthy controls. In patients, immature platelets expressed lower levels of CD62P, CD36, CD31, TLR2, and TLR4, but increased TLR9 expression, while mature platelets showed no differences. These distinct surface receptor patterns of immature platelets were partly associated with reduced TRAP-6-induced platelet aggregation.</p><p><strong>Conclusion: </strong>This study demonstrates significant alterations in surface receptor expression on immature platelets in patients with suspected PFD, underscoring immature platelets as crucial link to platelet biology and clinical symptoms in this patient population.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}