Search Results (164)

Background/Objectives: Postbiotics are increasingly recognized as biologically active products of microorganisms with emerging potential as microbiome-inspired therapeutic interventions. While most microbiome-based strategies focus on modifying microbial composition, restoration of microbial signaling has received comparatively less attention. This review examines postbiotics through the lens of microbial signaling restoration and proposes a unified Metabolite–Immune–Redox (MIR) axis linking microbial-derived signals with immune regulation, redox homeostasis, endothelial integrity, and host resilience. Methods: This narrative review synthesizes current evidence on postbiotics, microbial metabolites, structural microbial components, and extracellular vesicles, with emphasis on their roles in immunometabolic regulation, redox biology, endothelial function, and host-directed interventions. Results: Current evidence suggests that short-chain fatty acids, indole derivatives, bile acid metabolites, and microbial extracellular vesicles are important mediators of host–microbe communication. These signals influence interconnected pathways involving mitochondrial function, inflammasome activity, immune calibration, endothelial and glycocalyx homeostasis, and disease tolerance. The review highlights the endothelium as an underrecognized therapeutic target and discusses biomarkers, including soluble thrombomodulin, von Willebrand factor, and D-dimer, as potential tools for identifying patients most likely to benefit from host-directed interventions. Major translational challenges include product heterogeneity, incomplete mechanistic characterization, uncertain exposure–response relationships, and unresolved regulatory considerations. Conclusions: The proposed MIR axis provides a hypothesis-generating framework for understanding how restoration of microbial signaling may contribute to precision host-directed therapeutic strategies. Further mechanistic and clinical studies are needed to validate this concept and define its translational potential in inflammatory, infectious, and critical illness settings. Full article

Von Willebrand disease (VWD) is the most common inherited bleeding disorder, yet the contribution of specific VWF domains to its pathogenesis remains incompletely understood. In particular, the role of the D4 domain in VWF secretion, intracellular maturation, and multimer formation has not been fully elucidated. Here, we investigated the functional impact of a heterozygous p.Cys2163Tyr variant located in the D4 domain, identified in a patient with a severe bleeding phenotype, using clinical evaluation, genetic analysis, family studies, and in vitro expression assays. Laboratory testing revealed markedly reduced VWF:Ag (6.8 IU/dL), VWF:GPIbR (0.1 IU/dL), and FVIII:C levels, indicating a severe VWD phenotype in the proband. Plasma VWF multimer analysis showed a markedly reduced overall VWF signal with an almost complete absence of high-molecular-weight multimers, supporting classification of the phenotype as severe type 2A VWD. The heterozygous c.6488G>A (p.Cys2163Tyr) variant was also present in asymptomatic family members, indicating incomplete segregation with the severe phenotype and suggesting that this variant alone is insufficient to explain the proband’s disease severity. Notably, the proband’s mother exhibited mildly reduced VWF levels in the absence of this variant, suggesting the possible contribution of an additional unidentified defect or modifier affecting the maternal allele. In vitro expression demonstrated preserved intracellular VWF antigen, markedly reduced secretion of mutant VWF, and loss of high-molecular-weight VWF multimers. Together, these findings indicate that VWF p.Cys2163Tyr is a functionally deleterious variant that markedly impairs VWF secretion and high-molecular-weight multimer formation in vitro. However, the incomplete segregation observed in the family suggests that this heterozygous variant alone may not fully account for the proband’s severe type 2A VWD phenotype. Full article

Background: Head and neck squamous cell carcinoma (HNSCC) remains a major global health challenge due to the lack of effective and non-invasive diagnostic tools, often resulting in late-stage detection of cancer. Small extracellular vesicles (sEVs) have emerged as promising biomarkers for early cancer detection and disease monitoring due to their omnipresence and stability in bodily fluids, such as blood plasma. In addition, cancer-derived sEVs specifically carry cargo reflective of oncogene-derived molecular alterations. In summary, these characteristics position sEVs as a potential platform for non-invasive testing of HNSCC. Methods: Plasma-derived sEVs from HNSCC patients (n = 71) and benign subjects (n = 25) were isolated using size exclusion chromatography. Proteomic profiling via liquid chromatography-tandem mass spectrometry identified potential candidate biomarkers, followed by ELISA validation. Results: Proteomic analyses revealed a significant enrichment of multiple proteins in HNSCC-derived sEVs compared to sEVs derived from non-cancer individuals. The von Willebrand factor (vWF) was significantly higher in HNSCC patient-derived sEVs compared to those derived from benign individuals. A validation cohort confirmed that sEV-associated vWF (sEV-vWF) effectively distinguished HNSCC patients from benign subjects, demonstrating strong diagnostic performance, specifically in laryngeal HNSCC (AUC = 0.82) and oropharyngeal HNSCC (AUC = 0.96) patient cohorts. Moreover, postoperative reductions and recurrence-associated increases in sEV-vWF levels corresponded with clinical outcomes, indicating its potential as a dynamic disease indicator. Conclusions: These findings highlight sEV-vWF as a novel and non-invasive biomarker with potential applications in early detection and real-time monitoring of HNSCC, supporting advancement toward precision liquid biopsy strategies in head and neck oncology. Full article

Background: ADAMTS13 is a protein that cleaves large multimers of von Willebrand factor, thereby limiting platelet aggregation and adhesion and regulating thrombogenesis. Research findings suggest a possible association between low ADAMTS13 levels and an increased risk of cardiovascular events, and its activity may be influenced by polymorphic variants of the ADAMTS13 gene. Methods: The study group included 259 patients diagnosed with coronary artery disease (CAD) and 238 control blood donors. Genotyping of ADAMTS13 polymorphisms (rs2301612, rs2073932, and rs2285489) was performed using TaqMan PCR. Results: ADAMTS13 gene polymorphisms showed no association with CAD risk or patient survival at 5- or 10-year follow-up. However, higher HDL cholesterol levels were observed in carriers of the G alleles (rs2301612 and rs2073932) and the T allele (rs2285489). Additionally, the rs2285489 and rs2301612 polymorphisms were associated with certain proatherogenic lipid indices. In silico analysis indicated that all studied polymorphisms influenced gene expression in certain vascular tissues or blood. Conclusions: ADAMTS13 gene polymorphisms may affect gene expression in specific tissues; however, this effect does not appear sufficient to meaningfully influence CAD onset or patient survival. A significant association between the analyzed polymorphisms and HDL levels or some proatherogenic lipid indices was observed; however, the underlying mechanism requires further investigation. Full article

Diabetes mellitus (DM) is a complex metabolic disorder associated with a heightened risk of cardiovascular events, largely driven by a hypercoagulable and hypofibrinolytic state. The pathophysiological interplay between chronic hyperglycemia, oxidative stress, insulin resistance, and systemic inflammation fosters profound alterations in the coagulation cascade, endothelial function, and platelet activity. This narrative review synthesizes evidence from studies published between 2008 and 2026, focusing on coagulation and platelet-related biomarkers selected based on their biological relevance to thrombosis, endothelial dysfunction, and inflammation, as well as the availability of clinical and interventional data across different forms of DM. Although there are numerous biomarkers involved in the pathogenesis of various forms of diabetes, this narrative review critically examines key coagulation biomarkers—including D-dimer, fibrinogen, prothrombin, tissue thromboplastin or tissue factor, P-selectin, soluble urokinase plasminogen activator receptor, thrombomodulin, plasminogen activator inhibitor-1, von Willebrand factor, and β-thromboglobulin—across distinct diabetes subtypes, including type 1, type 2, gestational, and secondary forms linked to endocrinopathies and pancreatic diseases. The literature reveals substantial subtype-specific heterogeneity in hemostatic alterations. For instance, Type 1 DM is characterized by early endothelial dysfunction and platelet activation, while Type 2 DM presents with elevated coagulation factors, impaired fibrinolysis, and a proinflammatory milieu. Gestational DM exhibits pregnancy-specific changes in coagulation, yet distinguishing them from obesity-related effects remains challenging. Secondary diabetes forms, such as those associated with Cushing’s syndrome or pancreatitis, further underscore the diversity in thrombotic risk profiles. Among the coagulation and platelet activation biomarkers reviewed, fibrinogen, P-selectin, and plasminogen activator inhibitor-1 demonstrate the most consistent associations with glycemic control, vascular dysfunction, and therapeutic modulation, particularly in type 2 diabetes, suggesting greater potential for clinical translation. In contrast, evidence for markers such as D-dimer, tissue factor or tissue thromboplastin, and soluble urokinase plasminogen activator receptor remains heterogeneous and insufficient for routine clinical application. By synthesizing mechanistic insights and clinical data, this review highlights the urgent need for subtype-tailored coagulation assessment in diabetes management. A better understanding of the dynamic alterations in coagulation pathways may facilitate earlier detection of vascular complications and inform personalized antithrombotic strategies. Full article

Background: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition resulting from a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13) deficiency, leading to the accumulation of ultra-large von Willebrand factor (vWF) multimers and widespread microvascular thrombosis. While therapeutic plasma exchange and immunosuppression have significantly improved response, refractory and relapsed disease are significant challenges. N-acetylcysteine (NAC) has emerged as a biologically plausible adjunctive therapy due to its potential to reduce disulfide bonds in vWF multimers. However, its clinical role is unclear. This systematic review aimed to evaluate the clinical evidence regarding the efficacy and safety of N-acetylcysteine in patients with immune-mediated TTP. Methods: We performed a systematic review in accordance with the PRISMA guidelines. PubMed/MEDLINE, Google Scholar, and ClinicalTrials.gov were searched until January 2026. Studies involving patients with immune-mediated TTP treated with NAC were included. Case reports, case series, and observational studies involving patients with immune-mediated TTP treated with NAC were included. Risk of bias was evaluated using adapted quality assessment tools. Results: Sixteen studies encompassing 69 patients met the inclusion criteria. Most reports were case reports or small case series; two were larger observational cohorts. NAC was predominantly used as adjunctive therapy in relapsed or refractory TTP. Dose regimens varied. Platelet recovery following NAC was reported within 1–15 days in responding cases. Predominantly positive haematological responses were observed in small series. Significant heterogeneity in patient populations, timing of initiation, concomitant therapies, and outcome reporting limited causal inference. Conclusions: The current evidence suggests that NAC has a biologically rational and potentially adjunctive value in TTP, particularly in refractory disease or resource-constrained settings. However, current data are largely heterogeneous and derived from low-level evidence. Well-designed prospective studies and randomized controlled trials are needed to determine whether NAC provides significant clinical benefit beyond standard therapy. Full article

Atrial fibrillation (AF) frequently coexists with chronic kidney disease (CKD), and their combination confers a disproportionate risk of both thromboembolic and bleeding events. Conventional anticoagulation strategies rely primarily on creatinine clearance-based dosing, which reflects pharmacokinetic safety but does not fully capture the biological processes underlying thrombohemorrhagic instability. This narrative review synthesizes recent mechanistic and translational evidence regarding the bidirectional cardio–renal axis in AF and CKD, focusing on systemic inflammation, endothelial dysfunction, platelet dysregulation, and altered coagulation. A structured literature search of PubMed/MEDLINE, Scopus, and Web of Science (2018–2026) was performed, complemented by manual review of key references and guidelines. The evidence indicates that inflammatory cytokine activation, oxidative stress, glycocalyx degradation, von Willebrand factor dysregulation, uremic platelet dysfunction, and enhanced thrombin generation converge to create a disrupted vascular interface in which stroke and bleeding arise from shared pathophysiological mechanisms. Renal trajectory and selected circulating biomarkers further highlight the dynamic and heterogeneous nature of risk in advanced CKD. These findings support reframing anticoagulation decision-making in AF with CKD from a static filtration-based model toward a biology-informed approach that integrates renal dynamics, endothelial and platelet phenotype, and clinical context to better align thromboembolic protection with hemorrhagic safety. Full article

Background/Objectives: Hidradenitis suppurativa (HS) is a chronic, immune-mediated inflammatory skin disease characterized by painful nodules, abscesses, sinus tracts, and progressive fibrosis. Vascular activation is becoming increasingly acknowledged as an important factor in HS pathogenesis; however, the effects of tumor necrosis factor alpha (TNF-α) blockade on vascular remodeling in HS remain poorly characterized. This study investigated the impact of TNF-α inhibition by adalimumab (ADA) on endothelial and fibroblast-associated markers in HS lesions. Methods: Formalin-fixed paraffin-embedded skin samples from 71 HS patients were analyzed, including treatment-naive (n = 38) and adalimumab-treated (n = 33) cases. Histopathology and immunofluorescence were performed using antibodies against CD31, von Willebrand factor (vWF), α-smooth muscle actin (αSMA), vimentin, Ki-67 (proliferation), and cleaved Caspase-3 (apoptosis). ImageJ software was used to determine the immunoexpression of selected markers and vascular density. Vascular density, assessed as vessel count per mm², was designated as the primary endpoint. Sex-related differences were analyzed as exploratory endpoints. Results: Adalimumab-treated tissue exhibited significantly reduced vascular density (p < 0.01) compared to the treatment-naive group. Conversely, vimentin immunoexpression was significantly higher (p < 0.01) in the adalimumab-treated group. No significant differences were found in endothelial Ki-67 or cleaved Caspase-3 expression between treatment groups, indicating that the observed reduction in vascular density is not associated with direct effects on endothelial cell proliferation or apoptosis, but rather may occur indirectly through attenuation of the pro-angiogenic inflammatory milieu. Exploratory sex-stratified analysis revealed that treatment-naive males had significantly higher endothelial proliferation (Ki-67; p = 0.031) and vimentin expression (p = 0.017) compared to treatment-naive females. In the ADA-treated group, males exhibited significantly lower vascular density (p = 0.036) and higher endothelial apoptosis (p = 0.039) compared to females, whereas females showed a significant increase in vimentin expression following treatment (p = 0.008), suggesting possible sex-dependent differences in vascular remodeling. Conclusions: TNF-α blockade is associated with reduced vascular density, consistent with indirect anti-angiogenic effects, suggesting that adalimumab exerts disease-modifying effects on the microenvironment beyond inflammatory cytokine suppression. Sex-dependent differences in vascular regression underscore the importance of considering sex as a biological variable in HS pathogenesis and treatment response. These results highlight the significance of vascular interactions in HS and support adalimumab as a disease-modifying treatment. These exploratory findings require confirmation in longitudinal studies with paired biopsies. Full article

Endothelial cells are key regulators of vascular homeostasis, and their dysfunction plays a central role in the development of atherosclerosis and other cardiovascular diseases. Multinucleated variant endothelial cells (MVECs) have been described in pathological vascular regions; however, their functional properties remain poorly characterized. The aim of the present study was to compare lipid handling, inflammatory activation, barrier-associated features, and secretory profiles of typical endothelial cells (TECs, EA.hy926 line) and MVECs under low-density lipoprotein (LDL) exposure. MVECs were generated by polyethylene glycol-induced fusion of EA.hy926 cells and incubated with LDL under standardized conditions. Intracellular cholesterol accumulation was assessed biochemically, cytokine secretion was quantified by ELISA, gene expression of inflammatory, endothelial, junctional, and vasoactive markers was analyzed by quantitative real-time PCR, and the endothelial secretome was characterized using data-independent acquisition liquid chromatography–tandem mass spectrometry (DIA-LC-MS). MVECs demonstrated enhanced cholesterol accumulation compared with TECs following LDL exposure. At the transcriptional level, MVECs were characterized by elevated basal expression of proinflammatory markers, including IL1B, IL6, and NFKB1, and showed a markedly amplified IL6 and IL8 response to LDL. In parallel, MVECs exhibited reduced expression of genes associated with antioxidant defense (SOD1), barrier integrity (TJP1), and hemostatic function (VWF). Consistent with transcriptional data, mass spectrometry-based secretome analysis revealed decreased secretion of von Willebrand factor (vWF), vascular endothelial growth factor C (VEGFC), and endothelin-1 (EDN1) by MVECs, accompanied by increased secretion of tissue-type plasminogen activator (t-PA). Functional enrichment analysis of secretome-associated proteins highlighted pathways related to extracellular matrix–receptor interaction, focal adhesion, cell adhesion molecules, complement and coagulation cascades, and leukocyte transendothelial migration. In contrast, TECs demonstrated a more pronounced transcriptional response in EDN1, consistent with their role in vascular tone regulation. Immunocytochemical analysis further revealed altered subcellular distribution of the tight junction protein ZO-1 in MVECs, indicating junctional destabilization. Taken together, these results indicate that MVECs represent a distinct endothelial phenotype characterized by enhanced lipid accumulation, sustained proinflammatory activation, altered secretory signaling, and reduced barrier and hemostatic potential. Such features suggest that MVECs may contribute to the maintenance of chronic endothelial dysfunction and vascular inflammation under conditions of lipid overload. Full article

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare but life-threatening thrombotic microangiopathy (TMA) caused by severe deficiency of the von Willebrand factor–cleaving protease ADAMTS13. Pregnancy is a recognized trigger for both immune-mediated and congenital TTP and is associated with increased maternal and fetal morbidity. Clinical overlap with other pregnancy-associated TMAs, including preeclampsia and Hemolysis, Elevated Liver enzymes, and Low Platelet count (HELLP) syndrome, often delays diagnosis. This review synthesizes current evidence on pathophysiology, diagnostic uncertainty, and gestation-specific management of pregnancy-associated TTP, highlighting differences between immune-mediated and congenital disease. Methods: This is a narrative review. We performed a targeted literature search of PubMed/MEDLINE (from inception to December 2025) to identify English-language publications. The study types included were case reports/series, observational studies, large database studies, randomized trials, reviews, and relevant guidelines addressing TMA in pregnancy, with emphasis on immune-mediated and congenital TTP. Search terms included “pregnancy”, “thrombotic thrombocytopenic purpura”, “hereditary TTP”, “acquired TTP”, “ADAMTS13,” “thrombotic microangiopathy,” “HELLP,” “postpartum”, and “complement-mediated TMA” alone or in combination. The search was supplemented by manual screening of reference lists and key guidelines. Articles were selected based on relevance to diagnosis and management of pregnancy-associated TTP. Conference abstracts and non-peer-reviewed sources were not routinely included and were considered only when peer-reviewed evidence was limited. Results: Pregnancy-associated TTP remains a major diagnostic challenge due to overlapping clinical and laboratory features with other obstetric thrombotic microangiopathies. Distinguishing immune-mediated from congenital TTP is essential, as management and prognosis differ substantially. Prompt recognition and early initiation of therapeutic plasma exchange, immunosuppression, or prophylactic plasma therapy markedly improve maternal outcomes. Rapid ADAMTS13 testing, structured risk stratification, and multidisciplinary care are central to optimal management. Fetal outcomes are closely linked to gestational age at onset and timeliness of therapy. Conclusions: Early differentiation of TTP from other pregnancy-associated TMAs is critical for maternal and fetal survival. Advances in rapid ADAMTS13 diagnostics and emerging targeted therapies, including caplacizumab and recombinant ADAMTS13, offer opportunities to improve precision management and outcomes in future pregnancies. Full article

Background. Non-O ABO blood groups are known to confer an increased risk of venous thromboembolism, primarily through higher circulating levels of von Willebrand factor and factor VIII. However, it remains unclear whether ABO type affects biochemical profiles at the time of presentation or alters the prognostic value of commonly used biomarkers in acute pulmonary embolism (PE). This study examined the relationship between ABO blood group, baseline biomarkers, and short-term clinical outcomes in patients with confirmed acute PE. Methods. We performed a retrospective cohort study of adults admitted with computed tomography pulmonary angiography-verified PE at a single tertiary center. Associations between biomarkers and clinical outcomes were assessed using logistic regression adjusted for age, sex, active cancer, chronic kidney disease, obesity, and ABO group. Interaction terms tested whether ABO type modified biomarker–outcome relationships. Results. Among 317 included patients (median age 69 years), in-hospital mortality was 11.0%; 29.6% experienced severe PE, 48.3% developed infection, and 11.7% developed sepsis. Baseline biomarker distributions were similar across ABO groups, and multivariable models showed no independent association between non-O type and biomarker levels. NT-proBNP, CRP, and procalcitonin predicted in-hospital mortality, while NT-proBNP, procalcitonin, and CK-MB predicted severe PE. CRP, procalcitonin, D-dimer, creatinine, and leukocyte count were associated with infectious and septic complications. ABO type did not meaningfully modify biomarker–outcome relationships, aside from one exploratory interaction for infection. Sensitivity analyses confirmed the robustness of these findings. Conclusions. ABO blood group did not influence baseline biomarker profiles or the prognostic performance of key biomarkers in acute PE. Early outcomes were instead driven by indicators of right ventricular strain, inflammation, and renal dysfunction. Full article

Background: Porphyromonas gingivalis outer membrane vesicles (OMVs) are key mediators of host–pathogen interactions and have been implicated in both periodontal disease and systemic conditions, including pregnancy complications. Although OMV production and cargo are known to be influenced by environmental stress, how oxidative stress reshapes P. gingivalis OMVs and their functional impact on trophoblast cells remains poorly understood. Here, we investigated how exposure to hydrogen peroxide (H₂O₂) affects OMV biogenesis, composition, and their ability to modulate bacterial invasion in trophoblast cells. Methods: P. gingivalis was cultured anaerobically and exposed to 30 mM H₂O₂ during the final 24 h of growth. OMVs were isolated by differential ultracentrifugation and characterized by nanoparticle tracking analysis and transmission electron microscopy and OMV protein cargo was analyzed by proteomics. Functional effects were assessed using invasion and persistence assays in HTR-8/SVneo trophoblast cells pretreated with OMVs. Results: Oxidative stress did not significantly alter total OMV yield but resulted in smaller vesicles (control OMV 168.2 ± 8.7 nm vs. OMV from H₂O₂-treated cultures 130.0 ± 13.8 nm) with reduced negative surface charge and increased membrane-associated FM4-64 fluorescence. Proteomic analysis revealed a remodeling of the OMV protein cargo under oxidative stress, including the selective enrichment of a von Willebrand factor type A domain-containing protein. Functionally, OMVs from control cultures led to a 2.5-fold increase in P. gingivalis invasion and a 4-fold increase in intracellular persistence in trophoblast cells, whereas OMVs produced under oxidative stress failed to promote these processes. Conclusions: Together, these findings highlight oxidative stress as a key determinant of OMV-mediated host–pathogen interactions at the maternal–fetal interface. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in dysregulated inflammatory and coagulation pathways that drive immunothrombosis and contribute to adverse clinical outcomes. While individual cytokines and endothelial biomarkers have been associated with disease severity and mortality, the prognostic relevance of combined inflammatory and endothelial signatures remains incompletely characterised. To identify inflammatory cytokines and markers of endothelial activation associated with mortality in patients with severe COVID-19 requiring supplemental oxygen. This retrospective observational study included 73 consecutive adults admitted to a dedicated supplemental oxygen unit with severe COVID-19. Plasma concentrations of IL-1α, IL-1β, IL-6, IL-8, IL-10, TNF-α, von Willebrand factor (VWF) antigen and propeptide, ADAMTS13 antigen and activity, and ADAMTS13 autoantibodies were measured on admission using ELISA-based assays. Associations with mortality were assessed using non-parametric analyses, age-adjusted logistic regression, multivariable logistic regression, and receiver operating characteristic (ROC) curve analysis. Increasing age was independently associated with mortality. After adjustment for age, higher IL-1α concentrations were associated with increased odds of death, whereas a higher IL-6/IL-10 ratio was independently protective. In multivariable models, including non-ratio variables, ADAMTS13 autoantibody levels remained independently associated with mortality. In ratio-based multivariable analysis, both the ADAMTS13 activity/autoantibody ratio and the IL-6/IL-10 ratio were independently protective, while age was no longer significant. IL-10 and ADAMTS13 autoantibodies demonstrated moderate discriminative performance for mortality prediction (AUC ~0.70). A combined biomarker model incorporating IL-1α, IL-8, IL-10, and ADAMTS13 autoantibodies yielded very high predicted mortality probabilities. Our findings highlight IL-1α and ADAMTS13 autoantibodies as independent predictors of mortality in severe COVID-19, reflecting the interplay between inflammatory and endothelial pathways. Biomarker ratios capturing immune and endothelial balance—particularly the ADAMTS13 activity/autoantibody ratio—may enhance risk stratification and support integrated prognostic models. Full article

Background: Postpartum haemorrhage (PPH) remains the leading cause of maternal mortality globally. Women with inherited or unexplained bleeding disorders such as von Willebrand disease (VWD), factor XI deficiency (FXI), platelet function disorders, or bleeding disorder of unknown cause (BDUC) face a higher risk. While tranexamic acid (TXA) is routinely used in obstetric care, its specific efficacy and safety in these populations remain unclear. Methods: A systematic review and meta-analysis followed PRISMA 2020 guidelines (PROSPERO: CRD420251082349). Databases searched included PubMed, Scopus, Web of Science, and Dimensions. Studies evaluating TXA for PPH prevention or treatment in women with bleeding disorders were included. Six cohort studies (2016–2024) involving 213 deliveries met the criteria. Three contributed to a meta-analysis on primary PPH; the other three were synthesised narratively. Results: TXA use was associated with a 56% reduction in primary PPH risk (risk ratio 0.44; 95% CI: 0.27–0.70; p = 0.0007), with no observed heterogeneity (I² = 0%). Because contributing cohorts were phenotypically heterogeneous (BDUC, FXI, mixed), the pooled effect reflects an average across disorders rather than disorder-specific efficacy. TXA also appeared to reduce secondary and severe PPH in some cohorts. However, bleeding occurred in 26–36% of high-risk deliveries despite prophylaxis. No maternal deaths or thromboembolic events were reported in 136 TXA-exposed cases. Attribution was complicated by concurrent use of desmopressin and platelet transfusions. Most studies had moderate to severe bias. Conclusions: TXA significantly lowers the risk of primary PPH in women with bleeding disorders and appears safe. Despite this, residual bleeding underscores the need for trials to optimise TXA use alongside disease-specific strategies. However, this conclusion is derived from only six observational studies with heterogeneous patient populations and co-interventions. The evidence remains preliminary and should be interpreted cautiously. TXA should be considered as part of a multimodal postpartum haemorrhage management algorithm rather than a stand-alone therapy. Full article

Cardiovascular diseases represent one of the leading causes of morbidity and mortality worldwide despite tremendous advancements in therapeutic interventions. Prevention remains one of the most effective strategies to reduce individual risk. Apolipoprotein E (ApoE), through its genetic variants (ε2, ε3, ε4), is a well-known modulator of cardiovascular risk, traditionally studied for its role in lipid metabolism. However, recent evidence suggests that ApoE also influences endothelial function and thrombotic processes, opening new perspectives for an integrated approach to risk assessment. This narrative review explores the potential of using the APOE genotype as a key genetic biomarker, integrated with emerging endothelial markers (e.g., plasma levels of endothelin-1, nitric oxide, von Willebrand factor, endothelial adhesion molecules) to achieve a more accurate and personalized stratification of cardiovascular and thrombotic risk. The combined approach may overcome the limitations of traditional thrombophilia screening, which is often poorly informative when performed without clear clinical criteria, and may guide more targeted therapeutic decisions, particularly in borderline-risk individuals or those with unexplained thrombotic events. Finally, the review discusses the clinical implications, current challenges, and future perspectives for integrating this model into clinical practice within the framework of precision medicine. The early identification of genetically predisposed patients, together with functional endothelial assessment, could represent a breakthrough in modern cardiovascular prevention. Full article