Search Results (516)

This study evaluated the effects of dietary supplementation with a commercial lactoferrin–osteopontin complexes preparation (LF-OPN; LF:OPN mass ratio 8:1; 240 mg/kg body weight) on growth, immune indices, antioxidant status, intestinal barrier-related markers, fecal microbiota, short-chain fatty acids (SCFAs), peripheral lymphocyte subsets, and the whole-blood transcriptome of growing British Shorthair kittens. Sixteen kittens were randomly assigned to either a basal diet group (CON) or a group supplemented with LF-OPN complexes (LFT) for 28 days. LF-OPN supplementation did not significantly affect body weight or average daily gain. On D28, the LFT group had a higher serum immunoglobulin M concentration and a lower tumor necrosis factor-α concentration (p < 0.05). Serum superoxide dismutase and glutathione peroxidase activities and total antioxidant capacity were higher, whereas malondialdehyde was lower (p < 0.05) in the LFT group (p < 0.01). Fecal 16S rRNA gene sequencing revealed no significant difference in alpha diversity; howerer, LEfSe identified selective taxonomic difference, including higher relative abundances of Holdemanella and Erysipelotrichaceae and lower relative abundances of Enterobacteriaceae and Escherichia-Shigella in the LFT group. Fecal short-chain fatty acid concentrations were unchanged. Flow cytometry revealed a higher proportions of peripheral CD4+ lymphocytes and a higher CD4+/CD8+ ratio in the LFT group (p < 0.01), whereas the CD8+ proportion was unchanged. Whole-blood RNA sequencing identified 283 differentially expressed genes (199 upregulated and 84 downregulated), with enrichment of immune-related pathways including hematopoietic cell lineage, antigen processing and presentation, cytokine–cytokine receptor interaction, NF-κB signaling, and IL-17 signaling, but these findings were not independently validated. The tested LF-OPN preparation was well tolerated and was associated with elevated antioxidant status, altered immune indices, and selective modulation of the fecal microbiota in growing kittens. The study does not establish synergy or identify the individual contributions of either protein. Full article

Background/Objectives: BK polyomavirus (BKPyV) establishes lifelong, asymptomatic persistence but frequently reactivates in renal transplant recipients, contributing to significant post-transplant morbidity. Although humoral responses are routinely monitored, the role of cellular immunity in viral control remains incompletely characterized. This study aimed to characterize BKPyV-specific T-cell responses and IgG-binding levels in healthy adults and renal transplant recipients and to explore their association with active BKPyV viruria. Methods: BKPyV DNA was screened and quantified in urine samples from eighty-two healthy adults and thirty-three renal transplant recipients, who were categorized into active, no, historical, and pre-transplant infection groups. BKPyV-specific cellular immunity was assessed in peripheral blood mononuclear cells using IFN-γ ELISPOT and T-cell proliferation assays, and IgG binding levels were measured in plasma using semi-quantitative ELISA. Results: Healthy BKPyV-positive individuals had significantly higher IFN-γ-secreting T-cell frequencies than BKPyV-negative individuals, with no significant difference in IgG levels. Transplant recipients with detectable viruria had markedly diminished IFN-γ responses compared with all other groups, whereas IgG levels remained comparable except in the pre-transplant group (n = 2). A strong negative correlation was observed between IgG levels and urine viral load in actively infected patients. Proliferation assays showed no detectable antigen-specific proliferation despite measurable cytokine secretion. Conclusions: Cellular immunity, rather than total binding IgG levels, may be more closely associated with BKPyV activity, particularly in transplant recipients. Given the exploratory cross-sectional design, prospective validation is needed. These findings support integrating cell-mediated immune assays into BKPyV monitoring to improve post-transplant risk assessment. Full article

Background/Objectives: Blood group antigen frequencies vary across ethnic populations and are critical for safe transfusion practice, inventory management, and alloimmunization prevention. This study aimed to determine ABO blood group, extended Rh phenotype (D, C, c, E, e), and K antigen frequencies among blood donors at the Riyadh Regional Blood Bank, and to examine their associations with donor ethnicity. Methods: This retrospective cross-sectional study analyzed 10,463 blood donors (January–December 2021) using the Immucor NEO Iris fully automated immunohematology analyzer. Donors were classified into five ethnic groups. Chi-square tests assessed associations (p < 0.05), the primary scientific contribution is the descriptive frequency data, with hypothesis testing presented as secondary and exploratory. Results: Most donors were male (95.2%). Blood group O+ was most prevalent (31.6%); AB− was rarest (0.9%). Rh D-positivity was 84.7%, lowest among Saudis (81.1%). The most frequent Rh phenotypes were CcDee (24.2%), ccDee (19.9%), and CCDee (17.7%). K antigen positivity was 13.7%. Significant associations were found between D antigen and ethnicity (p < 0.001), Rh phenotype and ethnicity (p = 0.003), and ABO and ethnicity (p < 0.001). A hypothesis-generating association between Rh phenotype and K antigen (p = 0.019) did not meet the Bonferroni-corrected threshold and is considered exploratory. Conclusions: This study provides, to our knowledge, one of the largest ethnically stratified blood group datasets from Riyadh to date. The high D-negativity among Saudi donors (18.9%) has direct implications for extended phenotyping protocols and rare donor registry development. The association between Rh phenotype and K antigen requires molecular confirmation before any biological or clinical conclusions can be drawn. Full article

Glioblastoma remains the most lethal primary malignancy of the central nervous system, and the modest gains achieved with maximal surgery, radiotherapy and temozolomide have not been matched by the immune checkpoint inhibitors and antigen-specific vaccines that reshaped the treatment of many extracranial cancers. The recurrent disappointment of these approaches has been attributed less to a single molecular lesion than to a confluence of obstacles: profound intratumoural heterogeneity, a densely immunosuppressive and myeloid-rich microenvironment, sequestration and exhaustion of conventional T cells, and the practical difficulty of delivering effectors across the blood–brain barrier. Against this background, γδ T cells have attracted interest as an unconventional effector population that recognises transformed cells through stress-associated and metabolic cues rather than peptide–major histocompatibility complex (MHC) complexes, that kills in an MHC-unrestricted manner, and that can be expanded from healthy donors for allogeneic, off-the-shelf use with little expectation of graft-versus-host disease. This narrative review examines, with a deliberately critical lens, the biological rationale and the experimental evidence for γδ T cell-based immunotherapy of glioblastoma. We summarise the developmental biology and functional subsets of human γδ T cells, the natural killer group 2 member D (NKG2D)-, DNAX accessory molecule 1 (DNAM-1)- and T-cell-receptor-dependent mechanisms through which they engage glioblastoma cells and glioma stem-like cells, and the in vitro and animal-model studies that underpin the field, taking care not to overstate efficacy that has so far been demonstrated only in preclinical or early-phase settings. We then weigh the principal opportunities—locoregional and repeated dosing, combination with chemoradiotherapy, checkpoint blockade and antibody-based redirection—against barriers that include limited persistence, uncertain intratumoural trafficking, donor and manufacturing variability, and the unsettled requirements of potency testing and trial design. We give particular weight to what becomes of γδ T cells inside a hostile tumour—the exhaustion-like dysfunction that follows chronic stimulation, the oxygen and glucose dependence of their effector programme, the interleukin-17-polarising signals generated by activated microglia and by genotoxic therapy, and the confounding effect of corticosteroids—together with the engineering and pharmacological strategies proposed to counter them. The first peer-reviewed phase 1 report of intracranially delivered, drug-resistant γδ T cells has now appeared and documents tolerability in a small, single-arm cohort without establishing survival benefit. Throughout, γδ T cells are presented as a biologically plausible but still investigational strategy whose clinical value will be determined by adequately powered trials rather than by mechanistic appeal alone. Full article

The designation of O RhD-negative blood as a “universal donor” misrepresents the complexity of red blood cell (RBC) compatibility. With 47 recognized blood group systems encompassing 366 antigens, non-ABO antigen exposure drives alloimmunization in 20–50% of chronically transfused patients. A narrative review of PubMed, Scopus, and EMBASE was conducted for studies published between 2016 and 2025, with selective inclusion of foundational pre-2016 works. Enzymatic approaches using Flavonifractor plautii CAZymes and Akkermansia muciniphila exoglycosidase cocktails enable near-complete ABO antigen removal, though group A conversion remains incomplete. CRISPR-Cas9 multiplex editing of immortalized erythroblasts has achieved simultaneous deletion of ABO, Rh, Kell, Duffy, and MNS antigens. Induced pluripotent stem cell platforms enable scalable manufacture; however, enucleation efficiency (40–70%), yield (4.6 × 10³ RBCs/iPSC), and fetal hemoglobin prevalence remain translational barriers. Convergence of enzymatic and gene-editing technologies on GMP-compatible iPSC platforms represents the most credible pathway to truly universal RBCs, although current evidence remains largely confined to immortalized cell lines and early-stage iPSC proof-of-concept studies rather than clinically validated products. Regulatory frameworks, scalability, and rigorous off-target profiling define the key challenges ahead. Full article

Background/Objectives: T-cell receptor gamma (TCRγ) clonality testing by multiplex polymerase chain reaction (PCR) is an important ancillary method in the diagnostic evaluation of T-cell lymphoproliferative disorders. Interpretation is particularly challenging in HTLV-1 infection, in which persistent antigenic stimulation may produce clonal or oligoclonal T-cell expansions overlapping with non-neoplastic patterns. This study aimed to assess the diagnostic performance and interpretative contribution of two EuroClonality/BIOMED-2 assays (TCRγ-A and TCRγ-B), considered complementary components of the same analytical panel, and a single-tube multiplex PCR assay (TCRγ-O), and to develop an integrated workflow for TCRγ clonality interpretation. Methods: A total of 107 peripheral blood samples were analyzed, including 19 healthy donors, 75 HTLV-1 carriers, and 13 patients with adult T-cell leukemia/lymphoma (ATLL). TCRγ clonality was evaluated using three multiplex PCR assays followed by capillary electrophoresis. Profiles were classified as polyclonal, oligoclonal, or monoclonal. Diagnostic performance analysis was performed using healthy donors as the reference negative group and ATLL patients as the reference positive group. Results: The combined EuroClonality approach (TCRγ-A+B) showed the highest sensitivity (100%), whereas TCRγ-O showed the highest specificity (94.7%). TCRγ-A and TCRγ-B each showed a sensitivity of 76.9%, with specificities of 84.2% and 78.9%, respectively. Classification was highly concordant in healthy donors and ATLL patients employing both assays. However, among HTLV-1 carriers, classification varied across the assays. The integrated workflow was associated with a significant change in the distribution of molecular classification patterns in the HTLV-1 group compared with EuroClonality-based interpretation alone. (Stuart–Maxwell, p < 0.001). Conclusions: The EuroClonality/BIOMED-2 strategy provided greater sensitivity, whereas TCRγ-O showed greater specificity. Their integration supported a complementary and hierarchical approach to TCRγ clonality assessment, particularly in HTLV-1 infection. These findings support an exploratory integrated framework for TCRγ clonality interpretation in HTLV-1 infection and ATLL, requiring validation in larger independent cohorts. Full article

Porcine circovirus type 2 (PCV2) and Mycoplasma hyopneumoniae (Mhp) are major contributors to the porcine respiratory disease complex. Although PCV2-Mhp bivalent inactivated vaccines are useful for simultaneous disease control, their immunogenicity may be improved by adjuvant optimization. This study evaluated a composite adjuvant consisting of porcine interleukin-2 (IL-2), IL-4, IL-6 and MnJ(beta), a colloidal manganese adjuvant, in an initial murine immunogenicity model. Thirty female Kunming mice were assigned to three groups (n = 10/group): bivalent antigen plus IL-2/IL-4/IL-6/MnJ(beta), bivalent antigen plus MnJ(beta), or phosphate-buffered saline. Body weight, complete blood count, peripheral blood T- and B-cell subsets, PCV2-specific IgG and Mhp-specific indirect hemagglutination titers were monitored after primary and booster immunization. The composite formulation did not suppress body-weight gain or induce sustained abnormalities in erythrocyte- or platelet-related indices. WBC, neutrophil, lymphocyte and monocyte counts were elevated in group A at days 7 and 28 post-primary immunization, indicating transient immune activation. Day-56 flow cytometry indicated increased CD19+IgM-IgD- B-cell and effector/memory T-cell-associated responses. PCV2-specific IgG increased from day 14 onward. At day 56, the OD450 value in group A reached 1.532 ± 0.006, compared with 1.095 ± 0.004 in group C1 and 0.102 ± 0.002 in group C2, corresponding to approximately 1.40-fold and 15.09-fold higher levels than the MnJ(beta)-adjuvanted and PBS control groups, respectively. Mhp-specific IHA titers were also maintained at high levels after booster immunization; at day 56, group A showed a log2 endpoint titer of 13.00 ± 0.00, corresponding to a GMT of 1:8192, whereas group C1 showed a log2 endpoint titer of 12.00 ± 0.00, corresponding to a GMT of 1:4096, and group C2 remained negative. These results indicate that the IL-2/IL-4/IL-6/MnJ(beta) composite adjuvant demonstrates potential for improving antibody and peripheral lymphocyte responses to PCV2-Mhp bivalent antigen, but protective efficacy must be confirmed in target-species challenge studies. Full article

Multiple outbreaks with high mortality rates and a pattern of disease occurrence similar to peste des petits ruminants (PPR) were observed in sheep and goats across many states of Sudan between 2015 and 2018. Therefore, this study aimed to investigate and identify the cause of these disease outbreaks. A total of 276 blood and lung tissue samples were collected from infected sheep (n = 223) and goats (n = 53). Sample analysis in an IC-ELISA revealed the presence of the PPRV antigen in 56.9% of sheep and 62.3% of goat samples. Twenty-seven [sheep (18) and goats (9)] PPRV-positive samples from IC-ELISA were subsequently confirmed positive using the PPRV N-gene-based RT-PCR. Two PPR viruses were isolated from infected small ruminant lung tissues in Vero cells. The partial N-gene sequences for five PPRV strains originating from sheep and goats were determined. Phylogenetic tree grouped PPRV strains identified in this study in lineage IV in sub-lineage NEA (North–East Africa), with the highest sequence identity observed with strains circulating in North African countries. This study and earlier published phylogenetic analysis and patterns of animal movements suggest that the transboundary transmission of PPRV lineage IV strains between East and North African countries has been happening since 2008 and established a new North–East Africa episystem that needs to be disrupted for the successful global eradication of PPR. Full article

Orphan enzymes are recognized and classified enzymatic activities that lack associated amino acid sequences. Since the term was coined in the mid-2000s, the proportion of orphan enzymes has substantially decreased; however, it is estimated that at least ≈900 enzymatic activities remain devoid of molecular identity to date. The putative mammalian metabolic pathway for L-fucose degradation represents a system that long consisted exclusively of orphan enzymes, with only a few recently “deorphaned” and biochemically characterized. L-Fucose is a unique monosaccharide frequently found in various glycolipids and glycoproteins synthesized by mammalian cells, such as the ABO blood group antigens in humans. While the importance of the biosynthetic pathways for its active form (GDP-L-fucose) is well established in diverse biological processes, the enzymology and physiological role of L-fucose catabolism remain largely enigmatic. In this review, we summarize the current knowledge regarding the enzymological and physiological aspects of L-fucose catabolism in mammals. Full article

Background/Objectives: Polyethylene glycol (PEG) is widely used to enhance the stability and pharmacokinetics of nanomedicines, including lipid nanoparticle (LNP)-based mRNA vaccines. However, both pre-existing and vaccine-induced anti-PEG antibodies may compromise the efficacy and safety of PEGylated therapeutics. Methods: In this study, we analyzed the specificity and avidity of anti-PEG antibodies in human blood donor samples from Unvaccinated individuals and recipients of PEGylated mRNA-LNP vaccines (Comirnaty and Spikevax), polysorbate-containing vaccines, or vaccines lacking both PEG and polysorbates. Quantitative ELISA was used to characterize anti-PEG and anti-polysorbate IgM and IgG responses in 325 plasma samples, while an equilibrium titration method was applied to assess IgG binding to PEG molecules, micelles, and PEGylated liposomes with defined structural features in 36 plasma samples. Results: Vaccination with PEGylated mRNA-LNPs was associated with increased anti-PEG antibody levels and qualitative changes in antibody binding behavior. Anti-PEG IgG antibodies displayed progressively higher avidity toward larger and structurally more complex PEG-containing antigens, with the strongest binding observed for PEGylated liposomes. Notably, vaccinated individuals, particularly those who received Spikevax, showed increased end-group and backbone-specific avidity, as well as an enhanced ability of antibody paratopes to engage shorter PEG chains. In contrast, polysorbate-containing or PEG-free vaccines did not elicit comparable effects. Conclusions: These findings suggest that vaccination with PEGylated mRNA-LNPs is associated with the emergence of altered antibody populations with increased end-group reactivity and higher avidity toward PEG-directed immune responses, despite PEG being a synthetic, nonprotein polymer. Antibody binding to LNPs, accompanied by the emergence of high-avidity anti-PEG IgG seems to be consistent with an increased risk of adverse events, particularly following repeated vaccinations, including complement activation-related pseudoallergy (CARPA) and anaphylaxis. It may also contribute to altered immune protection against the vaccine target, underscoring the need for avidity-aware risk-benefit assessment of PEGylated therapeutics. Full article

Background: BCMA-targeted Chimeric Antigen Receptor (CAR) T-cell therapy has revolutionized the treatment of Relapsed/Refractory Multiple Myeloma (RRMM). However, the disease is not curable and progression after CAR T-cell treatment remains a challenge. Clonal hematopoiesis, specifically mutations in the DNA damage response gene PPM1D, has been linked to therapy resistance and inferior survival in lymphoma patients undergoing cellular therapy. The impact of PPM1D mutations on MM patient outcome after CAR T-cell therapy remains undefined. Methods: We conducted a retrospective single-center study of 83 patients with RRMM patients treated with idecabtagene vicleucel or ciltacabtagene autoleucel between 2022 and 2025. Next-generation sequencing was performed on peripheral blood mononuclear cells collected prior to CAR T-cell infusion to identify PPM1D exon 6 mutations (variant allele frequency > 0.01). We analyzed associations between mutational status, clinical characteristics, toxicity, and survival. Results: PPM1D mutations were detected in 14.5% (12/83) of patients. PPM1D-mutated patients had fewer prior autologous stem cell transplantation compared to wild-type patients (50% vs. 82%, p = 0.02) and presented more advanced disease burden and adverse prognostic features (R-ISS stage III 58% vs. 20%, p = 0.05). Notably, PPM1D status did not impact initial efficacy; complete remission rates were comparable between groups (67% vs. 69%). However, PPM1D mutations were significantly associated with inferior progression-free survival (PFS) (median PFS: 6 months vs. 16 months, p = 0.04). Regarding toxicity, the mutated subgroup exhibited significantly higher rates of grade ≥2 cytokine release syndrome and a trend toward increased neurotoxicity (25% vs. 7%). Conclusions: PPM1D clonal hematopoiesis is frequent in RRMM and despite deep initial responses, patients harboring PPM1D mutations face a significantly higher risk of early relapse. PPM1D mutations may serve as a biomarker for poor durability of response and should be further evaluated in larger, prospective trials. Full article

Background: The aim of the study was to investigate whether red blood cell antigens (A, B, D, C^w, C, c, E, e, K, k, Jk^a, Jk^b, Fy^a, Fy^b, Le^a, Le^b, M, N, S, s, and P1) from clinically relevant blood group systems were associated with susceptibility to COVID-19. Methods: This exploratory case-control study was carried out on a group of 263 donors from the Regional Center for Transfusion Medicine, Bialystok, Poland (including 121 convalescents and 142 healthy subjects). The microplate method was applied to examine the expression of 21 antigens from eight clinically relevant systems in the donors’ red blood cells. Results: No significant correlation was found between any single blood group and susceptibility to COVID-19. For a more detailed analysis, we adopted an approach involving 3-, 4- and 5-element mutual combinations of antigens. In this exploratory analysis of multi-antigen combinations, nominal statistical significance was found for a number of associations, but none remained statistically significant after adjustment for multiple testing. In the case of three-antigen associations, the strongest association was observed for cc combined with Ee and kk, with the effect size showing approximately 4× higher odds of COVID-19 (OR = 4.49, p = 0.020); in the case of four-antigen combinations, the strongest association was found for RhD(+) combined with kk, Fy^b and P1(−), as well as RhD(+) combined with cc, Ee and kk, also indicating 4× higher odds of COVID-19 (OR = 4.49 p = 0.016). For five-antigen combinations, the strongest association was observed for blood type O combined with kk, Le^b, P1(+) and MM, with the association strength reaching an OR = 4.44, p = 0.025. Conclusions: The findings suggest that analyses based solely on single blood group antigens may have limited value for assessing the susceptibility to COVID-19. In contrast, combinations of red blood cell antigens may provide more reliable correlations with the susceptibility to COVID-19. However, these findings should be interpreted with caution and require confirmation on larger and more representative populations. Full article

Background and Objectives: Blood group antigens are well known for their importance in transfusion medicine and transplant compatibility; however, their biological role extends beyond these functions and includes associations with the risk of several diseases. In this study, we investigated the relationship between ABO blood groups and the circulating levels of 73 different molecules. Patients and Methods: Fifty-six healthy donors were enrolled, including 24 individuals with blood group O, 19 with blood group A, and 13 with blood group B. Blood samples were collected and analyzed in a single laboratory using Luminex fluorescent bead-based assay panels to determine the concentrations of 73 circulating molecules. Depending on data distribution, ANOVA or Kruskal–Wallis tests and Student’s t-test or Kolmogorov–Smirnov tests were applied to identify significant differences among groups. Associations were further assessed by binary logistic regression analysis. Results: Subjects with blood group A showed significantly higher circulating levels of IL-1R1, IL-13, IL-23, PDGF-BB, VEGF-A, VEGF-D, soluble VEGF-R2 (KDR), soluble VEGF-R3 (FLT-4), VLA-4, CD141, MMP-1, syndecan-1 (SDC-1), and mannose-binding lectin (MBL) compared with the other blood groups. In contrast, individuals with blood group B exhibited significantly higher levels of IL-22, IL-23, PDGF-BB, CD62P (P-selectin), and amyloid β1–42. Several significant associations were identified by logistic regression analysis. Conclusions: Our findings indicate that ABO blood groups are associated with distinct circulating molecular profiles, supporting the existence of biological differences that may contribute to variations in disease susceptibility among individuals with different blood types. Nevertheless, given the exploratory’s nature and limited sample size of this study, further investigations are required to validate these findings, confirm the observed associations, and clarify their potential clinical implications. Full article

Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disorder characterized by immune-mediated platelet destruction and impaired platelet production. Increasing evidence suggests that systemic inflammation plays a significant role in disease pathogenesis and clinical outcomes. This study aimed to evaluate the prognostic significance of inflammatory indices and their association with complications, mortality, treatment response, and relapse in patients with ITP. In this single-center retrospective study, 166 adult patients diagnosed with primary ITP between January 2015 and December 2024 were analyzed. Demographic, clinical, and laboratory data at diagnosis were collected. Inflammatory indices derived from complete blood count parameters, including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), were evaluated. Their associations with clinical outcomes were assessed using appropriate statistical methods. During the observation period based on retrospective medical records, complications occurred in 12% of patients, and mortality was observed in 6.6%. Patients with complications had significantly higher D-dimer levels and reduced bone marrow megakaryocyte production. In group comparisons, mortality was significantly associated with advanced age, male sex, and comorbidities. Laboratory findings revealed that lower hemoglobin, lymphocyte count, mean platelet volume, and albumin levels, along with higher PLR, erythrocyte sedimentation rate, bilirubin, and D-dimer levels, were significantly associated with mortality. Inflammatory indices such as NLR and PLR were not associated with complication development, but PLR was significantly associated with mortality. Response to intravenous immunoglobulin (IVIG) therapy was significantly associated with higher total protein, albumin, and fibrinogen levels, and lower erythrocyte sedimentation rate. Relapse was significantly associated in group comparisons with increased inflammatory activity, higher reticulocyte count, and positivity for antinuclear antibodies and Helicobacter pylori antigen. Systemic inflammation and impaired megakaryopoiesis play critical roles in the prognosis of ITP. While conventional inflammatory indices showed limited predictive value for complications, markers such as PLR, D-dimer, and albumin were associated with mortality and clinical outcomes. These findings suggest that readily available laboratory parameters may provide valuable insights for risk stratification and personalized management in patients with ITP. Full article

Objective: This study aims to explore new hematological indicators with differential diagnostic significance for clinically significant prostate cancer (csPCa) by conducting comprehensive hematological tests, and to construct a novel discrimination index (DI) (csPCa-DI) to improve the diagnostic accuracy of csPCa. Methods: A total of 542 patients suspected of prostate cancer who were admitted to Beijing Tsinghua Changgung Hospital from November 2014 to May 2025 were enrolled in this study. All patients underwent complete blood count, coagulation testing, full biochemical analysis, and prostate biopsy. According to the biopsy results, patients were divided into the csPCa group and the non-csPCa group. The differences in hematological indicators between the two groups were compared, and multivariate logistic regression analysis was used to screen independent risk factors for csPCa. Two scoring systems (Fib-PLT Score and Fib-PLT-DD Score) were constructed based on coagulation-related parameters, and a csPCa discrimination index (csPCa-DI) was further established by integrating independent risk factors. The diagnostic efficacy of these scores, csPCa-DI, and traditional PSA-related indicators was evaluated by receiver operating characteristic (ROC) curves. Stratified validation was performed in the PSA gray zone (4–10 ng/mL) population. Results: Multivariate logistic regression identified prostate-specific antigen density (PSAD) (OR = 18.063, 95% CI: 7.125–45.792, p < 0.001), age (OR = 1.062, 95% CI: 1.024–1.102, p = 0.001), and Fib-PLT-DD Score (OR = 0.388, 95% CI: 0.251–0.599, p < 0.001) as independent predictors of csPCa. Based on the regression coefficient (β) weights of the independent predictors, the csPCa-DI was formulated as: csPCa-DI = 2.894 × PSAD + 0.060 × Age − 0.946 × Fib-PLT-DD Score (Fib-PLT-DD Score = 0.672 × Fib + 0.008 × PLT − 0.028 × DD). In the overall cohort, the area under the ROC curve (AUC) of csPCa-DI for diagnosing csPCa was 0.821 (95% CI: 0.773–0.868, p < 0.001), higher than that of total PSA (0.701) and f/t PSA ratio (0.727), and slightly higher than PSAD (0.797). The optimal cut-off value of csPCa-DI in the overall cohort was 1.46 points, with a sensitivity of 87.4% and specificity of 61.8%. In the PSA gray zone population, csPCa-DI exhibited superior diagnostic efficacy with an AUC of 0.736 (95% CI: 0.634–0.838, p < 0.001), significantly higher than total PSA (0.465) and f/t PSA ratio (0.638), and slightly higher than PSAD (0.720). A csPCa-DI cut-off value of 0.92 points in the PSA gray zone achieved a high sensitivity of 96.0% (specificity = 48.0%), effectively reducing missed diagnosis, while the cut-off of 1.46 points balanced sensitivity (68.0%) and specificity (70.7%). Conclusions: The novel csPCa-DI constructed by integrating PSAD, age, and coagulation-derived Fib-PLT-DD Score based on β weights has higher diagnostic efficacy for csPCa than traditional single PSA-related parameters, especially in the PSA gray zone, which can provide a new clinical tool for the screening and differential diagnosis of csPCa. This study also clarifies the correlation between local coagulation abnormalities and csPCa, providing a new perspective for understanding the pathological mechanism of csPCa. Full article