Journal of Thrombosis and Haemostasis最新文献

{"title":"Increased Effector Memory CD4⁺ T Cells Are Associated with Chronic Childhood Immune Thrombocytopenia.","authors":"David E Schmidt, Katja M J Heitink-Pollé, Benoit P Nicolet, Leendert Porcelijn, Marrie C A Bruin, Naomi Weterings, C Ellen van der Schoot, Rick Kapur, Gestur Vidarsson, Masja de Haas","doi":"10.1016/j.jtha.2025.06.004","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.06.004","url":null,"abstract":"<p><strong>Background: </strong>Antibody- and T-cell immune responses against platelet self-antigens are key features of childhood immune thrombocytopenia (ITP). Reliable diagnostic and prognostic immune markers remain underdeveloped and are not currently used in clinical practice.</p><p><strong>Aim: </strong>To validate previously suggested biomarkers and identify novel predictors of chronic childhood ITP.</p><p><strong>Methods: </strong>We analyzed immune profiles in 158 children with newly diagnosed ITP at the time of diagnosis prior to treatment (TIKI randomized controlled trial). Spontaneous platelet recovery and response to IVIg were evaluated over one year.</p><p><strong>Results: </strong>Neither CD4⁺, CD8⁺, CD19⁺, nor NK cell populations predicted the development of chronic ITP or recovery during follow-up. However, we observed a significant age-adjusted increase in effector memory CD4⁺ T cells by 1.4% (95% CI, 0.4-2.4) in chronic ITP. A frequency of effector memory CD4⁺ T cells above the median was associated with a reduced likelihood of recovery, with an age- and treatment-adjusted hazard ratio of 0.55 (95% CI, 0.35-0.85). Stratification by effector memory CD4⁺ T cell levels demonstrated additional prognostic value over the Childhood ITP Recovery Score, a clinical prediction model. Single-cell RNA-sequencing of peripheral blood mononuclear cells of six children confirmed an expansion of effector memory CD4⁺ T cells in chronic ITP, characterized by high expression of ITGB1 (integrin β1, CD29).</p><p><strong>Conclusions: </strong>Increased integrin β1-positive effector memory CD4⁺ T cells are associated with chronic ITP and improved the prognostic value of a clinical prediction model. T cell phenotyping could be valuable for prognosis and personalized treatment in newly diagnosed childhood ITP.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285106","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":"Prothrombotic fibrin clot phenotype as a risk factor for persistent left ventricular thrombus following acute myocardial infarction.","authors":"Krystian Mróz, Elżbieta Paszek, Maciej Polak, Anetta Undas","doi":"10.1016/j.jtha.2025.06.003","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.06.003","url":null,"abstract":"<p><strong>Background: </strong>Left ventricular thrombus (LVT) occurs in up to 15% of ST-segment elevation myocardial infarction (MI) patients and may persist in 30% despite anticoagulation. We hypothesized that formation of dense and poorly lysable fibrin clots may contribute to this phenomenon.</p><p><strong>Objectives: </strong>We investigated whether unfavorable fibrin clot properties and their determinants are associated with resolution of LVT on anticoagulation.</p><p><strong>Methods: </strong>We included 149 consecutive patients with LVT during acute MI referred for diagnostic work-up. Three months after MI we determined plasma fibrin clot permeability (Ks), clot lysis time (CLT) and plasminogen activator inhibitor-1 (PAI-1), along with citrullinated histone H3 (citH3), a marker of NETosis. LVT resolution was assessed on enrollment (after 3 months of anticoagulation mostly with direct oral anticoagulants [n=121, 82%]) and 3 months thereafter.</p><p><strong>Results: </strong>Patients with LVT visible at 3 months (n=75, 50.3%) were characterized by lower Ks (-15.5%) and longer CLT (+30%), along with higher PAI-1 (+42.4%) and citH3 (+33.3%), without differences in the type of anticoagulation. At 6 months post MI on continued anticoagulation, LVT was visible in 44 (29.7%) of patients, who had an unfavorable clot phenotype compared with individuals with resolved LVT. Lower Ks and longer CLT were associated with LVT persistence at 3 and 6 months, irrespective of potential confounding factors.</p><p><strong>Conclusions: </strong>This is the first study to demonstrate that prothrombotic fibrin clot properties, which might be related to enhanced NETosis, are associated with anticoagulation failure in patients with LVT complicating acute MI.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285107","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":"Deficiencies of CPN and CPB2 have opposite effects in a virulent mouse E. coli sepsis model.","authors":"Qin Zhou, Toshihiko Nishimura, Cornelis van 't Veer, Lawrence L Leung, John Morser","doi":"10.1016/j.jtha.2025.05.036","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.05.036","url":null,"abstract":"<p><strong>Background: </strong>Two basic carboxypeptidases circulate in plasma, proCPB2 which is activated to CPB2, and CPN. These enzymes inactivate complement anaphylatoxins, C3a and C5a, with high C5a being toxic. We hypothesized that these enzymes would affect E.coli sepsis in mice differently because CPN is constitutively active while proCPB2 needs to be locally activated.</p><p><strong>Methods: </strong>Mice deficient in CPB2, CPN or both enzymes were infected with E. coli and their health and survival was compared to wild type (WT) mice. Clinical chemistry, CBC and bacterial load were assessed.</p><p><strong>Results: </strong>Lack of CPB2 prolonged survival while lack of CPN shortened survival compared to WT mice. Liver damage was higher in double deficient mice that also were thrombocytopenic and CPN deficient mice were leukopenic. Bacterial load was higher in CPB2 and double deficient mice and lower in CPN deficient mice.</p><p><strong>Conclusions: </strong>CPN provides first line protection against excessive C3a and C5a, accounting for the shortened survival in CPN-deficient mice in this sepsis model, despite reduced E. coli load. CPB2 serves a supportive role by primarily inactivating C3a locally. Apparently, CPB2 deficiency led to enhanced local levels of protective C3a and prolonged survival in the CPB2-deficienct mice in this model while lack of CPN exacerbated the infection.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285105","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":"Apolipoprotein A-IV regulates coagulation and ischemic stroke by potentiating activated protein C.","authors":"Musan Yan, Yuewei Wang, Liyuan Niu, Shaoying Wang, Haichu Yu, Qikai Yin, Dachuan Zhang, Yunduo Bai, Yuanjie Yin, Shiping Lin, Chuanfeng Liu, Mingxue Zhang, Xiaopeng Tang, Heyu Ni, Min Xue, Changjiang Li","doi":"10.1016/j.jtha.2025.05.033","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.05.033","url":null,"abstract":"<p><strong>Background: </strong>Inflammation is crucial in regulating coagulation and hemostasis. While prior research shows that Apolipoprotein A-IV (ApoA-IV) has anti-inflammatory and antiplatelet effects, its specific impact on the coagulation remains unclear.</p><p><strong>Objectives: </strong>To investigate the effects of ApoA-IV on the coagulation system, including its interactions with potential targets and the underlying mechanisms.</p><p><strong>Methods: </strong>Plasma ApoA-IV levels in deep vein thrombosis (DVT) patients were tested by enzyme-linked immunosorbent assay. The effects of ApoA-IV on coagulation were assessed through thromboelastography. Potential interactions and mechanisms were analyzed using surface plasmon resonance and AlphaFold 3. Mice bleeding and stroke models were employed to evaluate the effects on hemostasis and thrombosis.</p><p><strong>Results: </strong>ApoA-IV levels were reduced in DVT patients and correlated with increased thrombotic risk. Thromboelastography showed that ApoA-IV treatment delayed clot reaction and kinetic times while decreasing thrombus generation angle and maximum amplitude, highlighting its crucial role in inhibiting coagulation and platelet aggregation. We identified ApoA-IV as a functional activator of activated protein C (APC), with critical interactions occurring at residues 144-148 within the exosite loop of the APC protease domain. In animal models, anti-ApoA-IV antibody administration shortened bleeding time but exacerbated ischemic stroke outcomes. Notably, inhibitory peptide HE5 which inhibiting ApoA-IV-APC interaction effectively counteracted the anticoagulant activity of ApoA-IV.</p><p><strong>Conclusions: </strong>These findings establish ApoA-IV as a pivotal regulator of coagulation and hemostasis, primarily through enhancing APC activity. This research advances our understanding of the interplay between inflammation, lipid metabolism, and thrombosis, offering insights for developing novel antithrombotic therapies.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275209","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":"Clonal hematopoiesis and Thromboembolic Diseases: A review.","authors":"Jee Hyuk Byun, Jaekeun Jung, Janghee Woo","doi":"10.1016/j.jtha.2025.05.035","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.05.035","url":null,"abstract":"<p><p>Clonal hematopoiesis of indeterminate potential (CHIP) has been identified as a novel risk factor for cardiovascular diseases, primarily mediated by CHIP-induced systemic inflammation. Emerging evidence suggests that CHIP may also contribute to the risk of thromboembolic diseases. This review highlights recent findings on the impact of CHIP on various thromboembolic conditions, including deep vein thrombosis (DVT), pulmonary embolism (PE), chronic thromboembolic pulmonary hypertension (CTEPH), and ischemic stroke. Studies have demonstrated an association between CHIP and an increased risk of DVT, PE, CTEPH and ischemic stroke. CHIP-induced systemic inflammation may amplify vascular endothelial damage and complement cascade activation, which in turn promote platelet activation, fibrin deposition, and the release of neutrophil extracellular traps. These processes collectively may drive thromboembolic events. Further mechanistic studies are warranted to elucidate the biological pathways through which CHIP influences the risk of thromboembolic diseases and to identify potential therapeutic targets.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275210","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":"Structural determinants of PAR1 cleavage by activated protein C.","authors":"Bosko M Stojanovski, Enrico Di Cera","doi":"10.1016/j.jtha.2025.05.034","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.05.034","url":null,"abstract":"<p><strong>Background: </strong>Activated protein C (APC) performs cytoprotective functions mediated by cleavage of the protease activated receptor 1 (PAR1) in the presence of the endothelial protein C receptor (EPCR) and signaling through b-arrestin-2. APC cleaves PAR1 at R41 and R46, but the specificity of the reaction is low. In contrast, thrombin cleaves PAR1 at R41 only in a reaction that is independent of EPCR, produces a pro-inflammatory response mediated by signaling through G-protein intermediates and features high specificity. The molecular basis of this difference between APC and thrombin remains unknown.</p><p><strong>Objective: </strong>To identify the structural determinants of APC that influence PAR1 specificity.</p><p><strong>Methods: </strong>Using available structural information, we engineered thrombin determinants of PAR1 recognition into APC. Specifically, we replaced T99 with Leu and swapped the entire 37- and 60- loops of APC with those of thrombin.</p><p><strong>Results: </strong>The engineered APC variants feature up to 80-fold enhanced specificity toward PAR1 mediated by increased cleavage at R41 and decreased cleavage at R46. Notably, the variants APC_60/T99L and APC_37/60/T99L also show significantly reduced activity toward factor Va.</p><p><strong>Conclusion: </strong>The 37-, 60-, and 99- segments of APC determine the cytoprotective and anticoagulant properties of the enzyme.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275212","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":"Interferences Associated with the Factor XIa Inhibitors Asundexian and Milvexian in Routine and Specialised Coagulation Assays and their Removal by Activated Charcoal-Based Adsorbents.","authors":"Gavin T Buckley, Maeve P Crowley, James V Harte","doi":"10.1016/j.jtha.2025.05.030","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.05.030","url":null,"abstract":"<p><strong>Background: </strong>Direct inhibition of factor XI/XIa (FXI/FXIa) is emerging as a promising anticoagulant strategy to mitigate the risk of bleeding typically associated with antithrombotic medications, including direct oral anticoagulants (DOACs). While DOACs are known to interfere with a broad range of coagulation assays, the interferences associated with emerging FXIa inhibitors remain incompletely characterised.</p><p><strong>Objective: </strong>This study evaluated the interferences associated with the FXIa inhibitors asundexian and milvexian in a of panel routine and specialised coagulation assays. Additionally, we assessed the capacity of charcoal-based adsorbents - including raw activated charcoal and DOAC-Stop™ - to remove interferences in coagulometric assays.</p><p><strong>Methods: </strong>Human-derived plasma was anticoagulated with increasing concentrations of asundexian or milvexian (0 ng/mL - 10,000 ng/mL) and assayed for routine and specialised coagulation parameters, before and after treatment with charcoal-based adsorbents, using Sysmex CN/CS-series analysers. Plasma was anticoagulated with both asundexian and milvexian at therapeutic and supratherapeutic concentrations representative of those reported in recent pharmacokinetic trials.</p><p><strong>Results: </strong>Asundexian and milvexian produced significant, dose-dependent interferences in FXIa-dependent coagulation assays, including markedly prolonged APTT-based clotting times and markedly reduced intrinsic coagulation factor activities. Treatment with charcoal-based adsorbents effectively removed both asundexian- and milvexian-associated interferences across all affected assays.</p><p><strong>Conclusions: </strong>Emerging FXIa inhibitors interfere significantly with FXIa-dependent coagulation assays, potentially leading to misinterpretation of haemostatic function. However, charcoal-based adsorbents efficiently remove these interferences and enable routine and specialised coagulation testing in the presence of asundexian and milvexian.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275211","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":"A predominant role of platelet NLRP3 in deep vein thrombosis in mice.","authors":"Jie Zhang, Hui Zhu, Yue Dai, Huimin Jiang, Yingying Li, Shuang Chen, Yueyue Sun, Mengdi Xu, Dmitry Yu Nechipurenko, Zhenyu Li, Lingyu Zeng, Mikhail A Panteleev, Kailin Xu, Jianlin Qiao","doi":"10.1016/j.jtha.2025.05.031","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.05.031","url":null,"abstract":"<p><strong>Background: </strong>Inflammation-induced injury of venous endothelium is the first trigger of deep vein thrombosis (DVT). We previously showed NLRP3 regulates platelet function and arterial thrombosis. However, whether platelet NLRP3 involves in venous thrombosis remains unclear.</p><p><strong>Objectives: </strong>In the present study, we intend to investigate the role of NLRP3 in venous thrombosis by using NLRP3 knockout mice and platelet-specific NLRP3 knockout mice.</p><p><strong>Methods: </strong>Deep vein thrombosis (DVT) model was established through ligation of the inferior vena cava (IVC). 48 hours after ligation, IVC sample was excised to measure thrombi length and weight, the recruitment of platelets, neutrophils, monocytes, and neutrophil extracellular traps (NET) formation by immunofluorescence staining.</p><p><strong>Results: </strong>Deficiency of NLRP3 reduced the incidence and severity of venous thrombosis, inhibited the recruitment and accumulation of platelets, neutrophils and monocytes in venous thrombi, reduced NET formation as well as IL-1β and IL-18 release. Additionally, platelet NLRP3 is the major source of elevated IL-1β in the venous thrombi and adoptive transfer of platelets to NLRP3^-/- mice increased IL-1β level in thrombi, promoted venous thrombosis and NET formation. Moreover, platelet NLRP3 deficiency inhibited NET formation induced by activated platelets in vitro.</p><p><strong>Conclusions: </strong>Our study demonstrates that deficiency of NLRP3 reduces the incidence and the severity of venous thrombosis with platelet NLRP3 playing a predominant role, indicating that NLRP3 might be a therapeutic target for the treatment of venous thrombosis.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248497","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":"DOAC-Stop™ reverses the anticoagulant effect of asundexian and milvexian.","authors":"Ella K Fitzpatrick, James C Fredenburgh, Jeffrey I Weitz","doi":"10.1016/j.jtha.2025.05.032","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.05.032","url":null,"abstract":"<p><strong>Background: </strong>Asundexian and milvexian are small molecule factor (F) XIa inhibitors, whereas abelacimab is an antibody that binds FXI and blocks its activation and activity. All three FXI inhibitors are currently undergoing Phase 3 evaluation. Like heparin and dabigatran, asundexian, milvexian, and abelacimab prolong the activated partial thromboplastin time (APTT) in a concentration-dependent manner. DOAC-Stop™ (DS) is an activated charcoal-based compound that adsorbs direct oral anticoagulants such as dabigatran, but not heparin, from plasma. It is unknown whether DS also neutralizes asundexian and milvexian.</p><p><strong>Objective: </strong>To determine whether DS reverses the prolongation of the APTT caused by asundexian or milvexian. Dabigatran was used as a positive control, while abelacimab and heparin served as negative controls.</p><p><strong>Methods: </strong>The APTT in human plasma, with or without asundexian, milvexian, abelacimab, dabigatran, or heparin, was determined before and after DS treatment.</p><p><strong>Results: </strong>As expected, all drugs produced concentration-dependent prolongation of the APTT. DS returned the APTT to baseline values with asundexian, milvexian, and dabigatran, but not with abelacimab or heparin. The APTT was prolonged in a more than additive manner with the combination of 2.5 μM milvexian and 0.125 U/mL heparin. However, DS only reversed the APTT prolongation induced by milvexian, but not that by heparin.</p><p><strong>Conclusion: </strong>DS reverses the effect of asundexian and milvexian on the APTT and distinguishes between the APTT effects of milvexian and heparin.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248498","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":"Clinical Evidence for Anti-GPIIbIIIa Antibody-Induced Platelet Desialylation in Primary Immune Thrombocytopenia.","authors":"Theresa Schramm, Jan Zlamal, Jasmin Rast, Justin Oosterlee, Michael Fillitz, Dino Mehic, Daniel Kraemmer, Alexander Tolios, Helmut Haslacher, Cihan Ay, Ingrid Pabinger, Karina Althaus, Tamam Bakchoul, Johanna Gebhart","doi":"10.1016/j.jtha.2025.05.024","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.05.024","url":null,"abstract":"<p><strong>Background: </strong>Autoantibody (AAb) induced platelet desialylation resulting in increased hepatic platelet clearance has previously been reported as pathomechanism in immune thrombocytopenia (ITP).</p><p><strong>Patients and methods: </strong>The platelet desialylation capacity of serum samples of well-characterized, adult primary ITP patients from the Vienna ITP Biobank (EC 1843/2016) was investigated. The exposure of beta-Galactose and N-Acetylglucosamine on platelets was analyzed as markers of platelet desialylation.</p><p><strong>Results: </strong>Sera of 133 ITP patients (28% newly diagnosed, 72% persistent/chronic) were investigated, where sera of 38 patients (29%) induced platelet desialylation. Patients with desialylation capacity compared to those without more commonly had platelet-bound AAbs (n=19/46, 50% vs n=27/95, 28.4%, P=0.018), thrombopoietin levels >50 pg/mL (n=23/34, 67.6% vs n=37/38, 42.0%, P=0.011), and higher bleeding scores (median (IQR) 3.0 (1.0-5.0) vs 1.0 (0.0-4.0), P=0.043). While the bleeding score overall, and specifically the skin bleeding score, thrombopoietin >50 pg/mL, and the presence of AAbs showed a significant association in univariate analysis with desialylating AAbs, only positivity for antiplatelet AAbs remained significantly associated in multivariate binary logistic regression analysis. In contrast, no association of platelet desialylation capacity was seen with disease duration, ITP treatment, or previous splenectomy.</p><p><strong>Conclusion: </strong>Platelet desialylation capacity was seen in a third of primary ITP patients and was associated with platelet-bound anti-GPIIbIIIa AAbs, although more studies are required to establish the linkage with anti-GPIb-IX AAb. Desialylation capacity was associated with a more severe bleeding phenotype, while in contrast to previous data, an association with platelet counts, disease duration, ITP treatment and splenectomy refractoriness was not confirmed.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234457","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}