Search Results (87)

The formation of extracellular traps (ETs) through ETosis has emerged as a key mechanism in immunothrombosis. However, the temporal dynamics and clinical significance of ETosis in coronary thrombi of ST-elevation myocardial infarction (STEMI) patients remain incompletely understood. We investigated whether ETosis burden increases with thrombus age and is associated with DNASE1 and TREX1 genetic variants as well as impaired myocardial reperfusion. Thrombus aspirates from 81 STEMI patients undergoing primary percutaneous coronary intervention were histologically classified as fresh (n = 41) or lytic (n = 40). ETosis was quantified by citrullinated histone H3 (CitH3) immunohistochemistry and digital image analysis, complemented by multiplex staining for myeloperoxidase (MPO), CD68, caspase 3, and CD61. Plasma ET-related markers and genotyping of DNASE1 (rs1053874) and TREX1 (rs11797) were also performed. CitH3-positive cells were present in all thrombi but were more abundant in lytic (older) thrombi compared with fresh thrombi (1348 vs. 591 cells/mm², p < 0.001). Increased ETosis was associated with neutrophil and macrophage infiltration, apoptosis, prolonged ischemia time, elevated systemic inflammation (neutrophil–lymphocyte ratio and C-reactive protein), and impaired myocardial reperfusion (lower TIMI flow grades). Moreover, the DNASE1 GG genotype was associated with higher densities of MPO- and CD68-positive cells, whereas the TREX1 CC genotype was associated with increased densities of CitH3-, MPO-, and CD68-positive cells. This study demonstrates that ETosis increases with coronary thrombus maturation and is associated with local inflammation and impaired reperfusion in STEMI. Genetic variants in DNASE1 and TREX1 may modulate inflammatory cell accumulation within thrombi. These findings suggest ETosis as a potential therapeutic target, particularly in patients with delayed presentation. Full article

Vaginal dysbiosis, particularly bacterial vaginosis (BV), is associated with altered immune responses that may influence the formation of extracellular traps (ETs). This study aimed to characterize neutrophil and macrophage extracellular traps (NETs and METs) in vaginal discharge samples obtained from women with normal microbiota (NM) and BV, with particular emphasis on Gardnerella vaginalis (GV) detection. An ex vivo analysis was performed using vaginal smears from 14 patients previously classified according to the Nugent criteria. Immunofluorescence assays targeting neutrophil elastase (NE), citrullinated histone H3 (Citr-H3), CD15, and CD68 were conducted, and quantitative image analysis was performed using the TissueFAXS and StrataQuest platforms. NETs were classified into three morphotypes: spread (spr), diffuse (diff), and aggregated (agg). BV samples exhibited a substantially higher mean NET count than NM samples (842.43 vs. 91.86). The number of diffNETs was significantly higher in BV samples than in NM samples (p = 0.004), whereas GV-positive samples showed increased sprNET abundance compared with that in negative samples (248 vs. 8; p < 0.05). CD68⁺ cell counts were significantly higher in BV samples (p = 0.026), whereas no significant differences in NE or Citr-H3 fluorescence intensity were observed between groups. MET structures were also identified, suggesting macrophage involvement in the local immune response. Collectively, these findings indicate that vaginal dysbiosis and GV presence are associated with enhanced NET formation and distinct morphotype distributions, supporting a role for ETs in the immunopathology of BV. Full article

Peptidylarginine deiminases (PADs) are a family of five isozymes (PAD1–4, PAD6) in humans, with PAD2, 3 and 4 associated with the central nervous system. PAD-mediated post-translational citrullination/deimination of target proteins contributes to pathobiological processes, including in the central nervous system (CNS), where the potential of PAD inhibitor treatment has been reported. This study aimed to identify PAD-dependent pro-regenerative responses in neuronal and astrocytic cells, respectively, using human cellular in vitro models to assess the therapeutic effects of pan-PAD, PAD2- and PAD4 isozyme-specific inhibitors in an oxygen–glucose deprivation/reperfusion model of ischaemia (OGD/R) at different time windows (30 min, 1 h and 4 h) in conjunction with scratch injury and LPS stimulation. Key findings suggest that pan-PAD inhibitor Cl-amidine promotes CNS regeneration through enhancing wound-healing of both neuronal and astrocytic cells, indicating roles for several PAD isozymes in acute CNS injury. Astrocyte cells showed the most prominent PAD4 detection, with significantly lower levels of PAD1, PAD2, PAD3 and PAD6, while differentiated SH-SY5Y neuronal cells showed the highest detection of PAD3, followed by PAD2 and PAD1, as well as strong PAD6 positivity, but negligible PAD4 detection. Histone H3 citrullination was significantly reduced in response to Cl-amidine treatment in both cell types, indicating changes in histone H3-dependent events in CNS injury. Cl-amidine treatment modulated key neuronal (beta-3 tubulin) and astrocytic (GFAP) markers and also reduced inflammatory cytokine IL-6 levels in astrocytes following 4 h OGD/R in conjunction with LPS stimulation. This study indicates roles for several PAD isozymes, with differing prominence in neurons and astrocytes, and emphasises the potential for pharmacological PAD inhibitor treatment in CNS injury. Full article

Background/Objectives: Cigarette smoking is a major risk factor for periodontitis, but the salivary host-response profile associated with smoking-related periodontal inflammation remains incompletely characterized. This study compared salivary NETosis-related and oxidative-inflammatory biomarkers among current smokers, former smokers, and never-smokers with periodontitis. Methods: This cross-sectional study included 159 systemically healthy adults with periodontitis (53 per group: current smokers, former smokers, never-smokers). Individuals with systemic diseases or concomitant medications that could interfere were excluded. Unstimulated whole saliva was analyzed for NETosis-related biomarkers (MPO-DNA complexes, citrullinated histone H3, neutrophil elastase, cell-free DNA) and oxidative-inflammatory markers (MMP-8, IL-1β, IL-6, TNF-α, 8-OHdG, total antioxidant capacity). Results: Salivary MPO-DNA complexes differed significantly among groups (current smokers 33.52 ± 9.96, former smokers 26.90 ± 8.38, never-smokers 19.20 ± 7.50 ng/mL; p < 0.001, η² = 0.317). The composite NETosis score (η² = 0.702) and oxidative-inflammatory score (η² = 0.718) showed the same graded pattern. Biochemical verification confirmed clear group separation (salivary cotinine: current smokers 312.3 ± 77.0, former smokers 9.7 ± 5.1, never-smokers 3.2 ± 1.4 ng/mL). Smoking exposure was positively correlated with biomarker levels and the severity of periodontal disease. Smoking status remained independently associated with MPO-DNA complexes and the NETosis score after covariate adjustment. Conclusions: Current smoking was associated with an enhanced salivary NETosis-related and oxidative-inflammatory phenotype. Former smokers displayed an intermediate profile. Salivary MPO-DNA complexes and composite biomarker scores warrant further investigation as candidate non-invasive indicators of smoking-associated periodontal inflammatory burden, pending diagnostic performance analyses and prospective validation. Full article

Neutrophil extracellular traps (NETs) contribute to innate immunity in sepsis, but their diagnostic value in neonates is unclear. We evaluated whether circulating NET-associated biomarkers discriminate septic from non-infected neonates. In this prospective observational study 96 neonates (≥34 weeks gestational age) with clinical suspicion of infection were enrolled (36 sepsis, 60 controls). Serum cell-free DNA (cfDNA), myeloperoxidase–DNA complexes (MPO-DNA), neutrophil elastase–DNA complexes (NE-DNA), and citrullinated histone H3 (H3cit) were measured alongside CRP and IL-6 at days 1, 3, and 5. Diagnostic performance was assessed by receiver operating characteristic (ROC) analysis with bootstrap confidence intervals. CRP (AUC 0.75, 95% CI 0.66–0.85) and IL-6 (AUC 0.73, 95% CI 0.61–0.83) showed the best diagnostic performance. cfDNA demonstrated moderate discrimination (AUC 0.72, 95% CI 0.60–0.84) but was only transiently elevated at day 1. MPO-DNA (AUC 0.47), NE-DNA (AUC 0.44), and H3cit (AUC 0.47) performed no better than chance. Within the sepsis group, MPO-DNA and NE-DNA at day 3 strongly correlated with the immature-to-total neutrophil ratio (ρ = 0.76 and 0.72), suggesting these markers reflect neutrophil degranulation rather than NET formation. NET-associated biomarkers do not improve diagnostic accuracy for neonatal sepsis beyond CRP and IL-6. These findings support the concept that neonatal innate immune responses differ fundamentally from adult patterns. Full article

Excessive neutrophil extracellular trap (NET) formation (NETosis), frequently associated with reactive oxygen species (ROS), exacerbates cutaneous inflammation induced by acute ultraviolet B (UVB) exposure. Although hispidin has potent antioxidant activity, its protective effects against acute UVB-induced skin inflammation and its relationship with NET-associated responses remain unclear. We investigated the effects of topical hispidin on acute UVB-induced skin injury in mice and examined its effects on ROS-associated NET-related responses in differentiated HL-60 cells. In a mouse model, topical hispidin (0.1% and 0.5%) ameliorated UVB-induced skin damage in a dose-dependent manner, as evidenced by improved clinical and histological findings. Hispidin treatment was associated with reduced systemic oxidative stress and decreased cutaneous expression of CXCL2, C5a, IL-1β, NLRP3, Ly6G, PAD4, and citrullinated histone H3. In differentiated HL-60 cells, hispidin reduced ROS-associated signals and suppressed PMA-triggered extracellular DNA release, but did not suppress A23187-triggered extracellular DNA release under experimental conditions. Cell viability analysis showed that hispidin did not significantly affect differentiated HL-60 cell viability at tested concentrations under the present experimental conditions. Topical hispidin alleviates acute UVB-induced skin inflammation by suppressing neutrophil infiltration and NET-related inflammatory responses. Hispidin may therefore represent a promising candidate as a topical modulator of oxidative stress- and NET-associated skin inflammation. Full article

In inflammatory states, eosinophils are exposed to stimuli leading to activation, increased survival, and/or different cell death subroutines, which have differing effects on tissue inflammation. The mechanisms of signal integration are poorly understood. In this manuscript, we investigated cell death types in response to stimuli mimicking the inflammatory microenvironment. Mouse bone marrow-derived eosinophils (BMDeos) were stimulated with cytokines, cell-cell interaction mimics, pathogen-associated molecular patterns (PAMP), and broad cell activation stimuli. Both PMA and crosslinking of CD95 (cCD95) induced cell death of BMDeos. However, cCD95-induced cell death was consistent with apoptosis, while activation with PMA lead to EETosis. Both stimuli lead to caspase 3 activation and increased total level of histone H3 citrullination, indicating that these outcomes are not able to discriminate between the two cell death types. Flow cytometry for annexinV/7AAD pattern at early time points, and morphologic assessment by immunofluorescence (for DNA, eosinophil granule protein and citH3) were the most reliable outcomes for distinguishing the cell death subtypes. While LPS alone did not decrease BMDeos viability, LPS in the presence of caspase inhibition (zVAD) caused delayed cell death, which did not conform to either of the two cell death types. Finally, LPS and LPS/zVAD led to an increased level of surface expression of CD274 (type 1 activation), while both cCD95 and PMA increased the surface expression of CD101 (type 2 activation). In summary, at least three different activation-associated cell death pathways are seen in BMDeos activated with microenvironment-mimicking stimuli. Crosslinking CD95 leads to type 2 activation and apoptotic cell death. PMA also leads to type 2 activation but EETosis-associated cell death. LPS and LPS/zVAD are associated with type 1 activation, and only LPS/zVAD lead to cell death via a subtype different from both apoptosis and EETosis. Full article

Neutrophils and their extracellular traps (NETs) are pivotal elements of the immune response. This study investigates the dynamics of neutrophil-related markers during the perioperative period of branched endovascular aortic repair (BEVAR) in patients with thoracoabdominal aortic aneurysms (TAAAs) and evaluates their association with one-year clinical outcomes. A prospective, single-center study was conducted on 20 TAAA patients treated with T-branch devices. The analysis focused on surrogate markers associated with NETosis, including double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), and citrullinated histone H3 (citH3). Peripheral venous blood was collected 24 h before BEVAR, and on the third and fifth postoperative days. Patients were monitored for one year to evaluate mortality and hospitalization risks, with predictors identified using Cox regression analysis. Increased postoperative levels of inflammatory markers were significantly associated with higher risks of mortality and hospital readmission. On the third postoperative day, key parameters emerged as predictors of adverse outcomes: dsDNA (HR = 1.000; 95% CI 1.000–1.000; p = 0.027), ssDNA (HR = 1.000; 95% CI 1.000–1.000; p = 0.022), and NLR (HR = 1.226; 95% CI 1.043–1.440; p = 0.013). Markers assessed in the early postoperative period (the third postopearive day) demonstrated superior predictive utility compared to those measured on the fifth postoperative day. CitH3 levels did not show statistical significance as a prognostic factor. Early postoperative evaluation of NET-associated markers, particularly dsDNA and ssDNA, offers prognostic value for predicting mortality and hospitalization risks in TAAA patients undergoing BEVAR. These markers may provide superior predictive accuracy compared to conventional post-implantation syndrome criteria. Enhanced postoperative monitoring of these markers could help identify high-risk patients who may benefit from intensified follow-up. Full article

Macrophages are key innate immune cells in the host defense against pathogens. Ionizing radiation can impair macrophage functions such as phagocytosis and activate them, potentially exacerbating tissue injury. Macrophage extracellular traps (METs) are formed upon stimulation of macrophages with PAMPs or DAMPs. We hypothesized that macrophages exposed to ionizing radiation can release extracellular traps. Peritoneal macrophages were collected from C57BL/6 mice and subjected to 5 Gy radiation. We performed assays to detect METs, including the immunofluorescence of citrullination of histone H3 and cell-free DNA measurement in cell culture medium as well as cell death. The exposure of ionizing radiation killed a significant number of mouse peritoneal macrophages through pyroptosis, which was mediated by Gasdermin D (GSDMD). The onset of pyroptosis eventually caused METs by suicidal METosis via pyroptosis and vital METosis occurring in the cells surviving after exposure to radiation. We found that exposure of peritoneal macrophages to 5 Gy radiation significantly increased METosis, as revealed by increased levels of citrullinated histone H3 and an increased surface area of extracellular DNA surrounding the cells. We discovered that peptidyl arginine deiminase (PAD) 2 and 4 are required for peritoneal macrophages to generate extracellular traps in response to radiation exposure. Our data demonstrate that the ionizing radiation induces METs via the activation of GSDMD, and we confirmed the requirement of PADs for METosis after exposure to the ionizing radiation. Targeting METs may direct a new therapeutic strategy for mitigating radiation-induced tissue injury. Full article

Psoriasis is a common inflammatory skin disease with chronic manifestation in which the role of neutrophil extracellular traps (NETs) and alarmins are increasingly recognized as contributors to systemic and cutaneous inflammation. However, the interaction between alarmins and NET-driven immune responses remains poorly defined. The main aim of this study is to define the role of target alarmins (i.e., IL-33 and TSLP) in NETs induction and its subsequent impact on oxidative stress and inflammation in the peripheral blood. In the present study, we recruited active psoriasis patients (n = 56) and control (n = 56) subjects. The frequency of circulating neutrophils, the levels of NET-associated markers (MPO (myeloperoxidase)–DNA complex, CitH3 (citrullinated histone H3), PAD4 (peptidyl arginine deiminase4), NADPH oxidase, and NE (neutrophil elastase)), and alarmin transcripts (IL (interleukin)-33, TSLP (thymic stromal lymphopoietin), S100A7, S100B, HSP (heat shock protein) 60/70 were quantified using flow cytometry, ELISA (Enzyme-linked immunosorbent assay), and qPCR (quantitative polymerase chain reaction), respectively, in each group. The NET formation potential of isolated neutrophils was assessed in the presence or absence of rhIL-33 and rhTSLP by immunocytofluorescence. The effect of rhIL-33- and rhTSLP-primed NETs in augmenting oxidative stress and inflammation was evaluated on peripheral blood mononuclear cells (PBMCs) by ELISA. Significantly higher circulating neutrophils (p < 0.001) and levels of NET-associated markers (i.e., MPO–DNA complex, CitH3, PAD4, NADPH oxidase, and NE) were observed in active psoriasis patients compared to controls. Lesional skin exhibited strong expression of MPO (p < 0.001) compared to normal skin. The alarmins, IL-33 and TSLP, were markedly upregulated in the blood and skin (p < 0.05). The rhIL-33 and rhTSLP treated neutrophils demonstrated enhanced NETosis in patients (p < 0.001). Increased expression of inflammatory cytokines and oxidative stress markers were reported in PBMCs when incubated with rhIL-33- and rhTSLP-primed NETs. Taken together, our investigation demonstrated the novel mechanism wherein the alarmins IL-33 and TSLP exacerbate NET formation that may drive enhanced inflammation and oxidative stress in psoriasis. Full article

Neutrophil extracellular traps (NETs)—webs of DNA and granular proteins expelled by neutrophils—have been implicated in hepatocellular carcinoma (HCC) progression. NETs promote tumor angiogenesis, facilitate invasion/metastasis, and enable immune evasion. Recent data suggest that perioperative factors, including anesthetic techniques, may modulate NET formation (NETosis), thus potentially influencing oncologic outcomes. We conducted a literature review of experimental and clinical studies on NETosis pathophysiology and involvement in HCC and how anesthetic techniques may modulate NET formation and, implicitly, cancer outcomes. NET biomarkers such as citrullinated histone H3 (CitH3), cell-free DNA (cfDNA), and myeloperoxidase–DNA complexes (MPO-DNA) are elevated in HCC patients and correlate with tumor spread, showing diagnostic and prognostic potential. Perioperative anesthetic choices may influence NET activity and immune function. Regional anesthesia and local anesthetics (e.g., lidocaine infusion) attenuate the surgical stress response and preserve anti-tumor immunity. Notably, lidocaine may modulate NET formation and, in a few studies published so far, was shown to reduce postoperative NET markers and other pro-metastatic factors (MMP-9, VEGF) in cancer surgery. In conclusion, NETosis is a process that is strongly implicated in HCC biology. Data published so far suggest that the clinical significance of NETosis may lie in its potential as a marker for disease evaluation and progression, including during the perioperative period. Preliminary results suggest that lidocaine may have a role in decreasing NETosis. Future large randomized trials are needed to exactly quantify these effects. Targeting NETs may be another way to influence HCC outcomes. Full article

NETosis is assumed to be involved in the pathogenesis of common rheumatic diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). However, the levels of circulating NETosis biomarkers and the extent of changes in these markers in specific rheumatic diseases are not fully understood. In this study, cell-free DNA (cfDNA) concentration as a non-specific marker, as well as myeloperoxidase (MPO) and citrullinated histone H3 (H3cit) as specific markers of NETosis, were investigated in SLE, RA, PsA, and AS. Analysis of covariance, accounting for sex, age and disease duration, showed that total cfDNA was elevated in SLE and AS compared with healthy subjects. Nuclear and mitochondrial cfDNA were elevated in four diseases. However, nuclear cfDNA was increased to a greater extent in SLE but mitochondrial cfDNA was higher in RA. MPO and H3cit were significantly elevated in SLE compared with other diseases, although MPO was also higher in RA. Elevated concentrations of MPO and H3cit in SLE were associated with the presence of concomitant cardiovascular diseases. The effect of biological therapy on mitochondrial cfDNA, MPO, and H3cit was also shown. The proinflammatory cytokine IL-18, implicated in the induction of NETosis, was similarly elevated in the four rheumatic diseases. Thus, the most striking signs of NETosis are found in SLE, although they are also present in RA. PsA and AS were mainly characterized by an increase in cfDNA. These data highlight characteristic changes in NETosis markers in four rheumatic diseases. Full article

The peptidylarginine deiminase (PAD) family includes five isozymes (PAD1–4 and PAD6) with unique tissue distributions and substrate specificities. These enzymes facilitate citrullination, a post-translational modification where positively charged arginine residues are converted into neutral citrulline residues in the presence of calcium ions. This process significantly changes protein properties, affecting molecular interactions, structural stability, and biological functions. Over the past six years (2019–2025), there has been significant progress in understanding PAD activity mechanisms and their therapeutic potential. Recent discoveries include the regulated nuclear translocation of PAD2, PAD4’s specific role in forming cancer extracellular chromatin networks (CECNs), and the development of next-generation inhibitors with greatly improved pharmacological profiles. PAD4 is crucial in forming neutrophil extracellular traps (NETs). Citrullination of histones H3 and H4 by PAD4 destabilizes chromatin, helping release DNA-protein networks as an antibacterial defense. However, excessive NET formation can contribute to autoimmune diseases and thrombosis. Similarly, the bacterial peptidylarginine deiminase from Porphyromonas gingivalis (PPAD)—the only known prokaryotic citrullinating enzyme—plays a key role. Working with R-gingipains, PPAD triggers pathological citrullination of host proteins, leading to immune tolerance breakdown and linking periodontal disease with systemic autoimmune disorders such as rheumatoid arthritis, atherosclerosis, and Alzheimer’s disease. Once thought to be a rare post-translational modification, citrullination is now understood as a vital regulatory mechanism in both normal physiology and disease, involving both internal processes of homeostasis and external mechanisms of bacterial pathogenesis. Full article

Chronic low-grade systemic inflammation is increasingly recognized as a key mediator linking stress, pain sensitivity, and cognitive decline. Central to this process are the acute-phase reactants interleukin-6 (IL-6) and C-reactive protein (CRP), which serve as biomarkers of systemic inflammation while promoting neuroimmune dysregulation. Emerging evidence implicates the IL-6–CRP axis in the amplification of pain perception, central sensitization, and stress hypersensitivity, ultimately promoting neurodegenerative processes such as those observed in Alzheimer’s disease (AD) and vascular dementia. Monomeric CRP (mCRP), a proinflammatory isoform generated under mechanical or oxidative stress, can trigger histone modifications (e.g., H3 citrullination), activate endothelial and immune cells, and exacerbate inflammatory pain pathways. These mechanisms are further modulated by genetic and epigenetic factors, including IL-6/CRP/NR3C1 gene variant expression; promoter methylation; and stress-responsive microRNAs, which intersect with dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, impairing immune resolution and neurocognitive resilience. Psychosocial stressors, such as the burden of caregiving or perfectionistic cognitive patterns, amplify IL-6 and CRP levels, particularly when pain is present, suggesting a synergistic interaction between emotional distress and somatic inflammation. Specifically, elevated CRP is associated with increased pain sensitivity, lower pain thresholds, and cognitive decline even in subclinical populations, providing a feedforward model in which chronic stress and pain potentiate systemic inflammation, disrupt neuroendocrine feedback, and accelerate neurodegenerative pathology. However, in this model, the potentially critical mechanistic and pathological role of mCRP remains to be discovered. This review addresses the missing elements of these overlapping pathways and discusses the therapeutic potential of targeting IL-6–CRP signaling, stress regulation, and epigenetic modifiers as strategies to ameliorate inflammation-driven cognitive decline and enhance stress resistance in chronic disease contexts. We propose that plasma mCRP or more likely the isoform-aware metric, the mCRP/CRP ratio, will provide a biologically anchored, potentially more discriminative approach to vascular-neuroimmune risk and capture the propensity for local effector signaling, likely outperforming hs-CRP or IL-6 alone for risk stratification across neurovascular and stress-sensitized pain phenotypes. Full article

Background: Multiple mechanisms might lead to cancer-related hypercoagulability. In brain tumors, podoplanin, via its ability to activate platelets, seems to play a crucial role in developing venous thromboembolism (VTE). Different stimuli (including activated platelets) can trigger the release of prothrombotic neutrophil extracellular traps (NETs) by neutrophils. It remains to be elucidated whether podoplanin-induced platelet aggregates might also impact NET formation and subsequent hypercoagulability and thrombosis. Methods: Patients with glioma were enrolled in this prospective observational cohort study. The primary endpoint was VTE. Immunohistochemical staining of NETs (via citrullinated histone H3 [H3Cit]) and neutrophils (via myeloperoxidase [MPO]) was conducted in glioma specimens and correlated with intravascular platelet clusters (via CD61) and podoplanin. Results: In total, 154 patients were included. H3Cit+ tumor vessels were found in 45/154 cases. H3Cit were significantly associated with increased intravascular platelet clusters (CD61− vs. CD61+ vs. CD61++ vs. CD61+++: 3.7% (1/27) vs. 18.6% (11/59) vs. 39.4% (13/33) vs. 57.1% (20/35), p < 0.001) and podoplanin expression (PDPN− vs. PDPN+: 14.3% (7/49) vs. 36.2% (38/105), p = 0.007) in the tumor tissue. Furthermore, H3Cit+ tumor vessels were significantly associated with tumor-infiltrating MPO+ neutrophils (H3Cit− vs. H3Cit+, median [Q1-Q3]: 6.0 [3.3–12.3] vs. 12.5 [5.9–22.0] cells/mm², p < 0.001) and with D-dimer levels (H3Cit− vs. H3Cit+: 0.53 [0.32–1.10] vs. 0.84 [0.46–2.75] µg/mL, p = 0.034). The VTE risk was not linked to H3Cit+ tumor vessels (p = 0.613, log-rank). Conclusions: H3Cit in tumor vessels was not associated with VTE. However, H3Cit was linked to a local procoagulant phenotype in glioma, thereby potentially contributing to a systemic hypercoagulable state and thrombus formation. Full article