Search Results (120)

(TB) induces a pronounced thromboinflammatory state during active disease, characterized by elevated fibrinogen, D-dimer, and thrombin-related activity, reduced levels of endogenous anticoagulants, impaired fibrinolysis, platelet activation, and endothelial dysfunction. Although many of these abnormalities improve after treatment initiation, accumulating evidence suggests that microbiological cure may not fully restore vascular, immune, and hemostatic homeostasis. This raises the possibility that TB leaves a persistent thromboinflammatory imprint after cure. This narrative synthesizes current evidence on tuberculosis-associated hypercoagulability during active disease and after treatment, and proposes a conceptual framework for post-tuberculosis thromboinflammatory memory grounded in cellular persistence, tissue remodeling, and extracellular vesicle-mediated signaling. Candidate storage compartments include hematopoietic stem and progenitor cells, monocyte/macrophage lineages, alveolar macrophages, remodeled pulmonary endothelium, and fibrotic post-TB lung tissue. EVs may function as mobile vectors that transfer procoagulant phospholipids, tissue factor, inflammatory proteins, and regulatory microRNAs between these compartments, thereby linking local post-TB remodeling to systemic vascular and coagulation pathways. A mechanistic evidence ladder is proposed, encompassing phenotypic persistence, EV cell-of-origin attribution, molecular persistence, paired longitudinal validation, functional transfer, and clinical outcome linkage. Current data support the biological plausibility of this framework but remain insufficient to establish post-TB thromboinflammatory memory as a defined clinical entity. Direct evidence in long-term TB survivors is still lacking, particularly with respect to persistent EV signatures, cell-specific reservoirs, and the functional transfer of procoagulant phenotypes. Longitudinal, cell-resolved, multi-omic, and functionally validated studies are required to determine whether TB leaves a durable thromboinflammatory memory, where it is stored, and whether it contributes to long-term thrombotic and cardiovascular risk. This article should be interpreted as a narrative review with a conceptual framework rather than as evidence that post-tuberculosis thromboinflammatory memory is already a formally established clinical entity. Full article

Background: Patients with COVID-19 often develop COVID-19-Associated Coagulopathy (CAC)—an imbalance between procoagulant and anticoagulant pathways resulting from the uncontrolled inflammatory response triggered by SARS-CoV-2 infection. This study aims to investigate the impact of a hematological and inflammatory parameter—the platelet-to-lymphocyte ratio (PLR)—on the severity and mortality of COVID-19. Methods: We conducted a comprehensive search of the PubMed database and yielded 75 articles published in the period of 2020–2025, of which 20 studies that evaluated the prognostic value of PLR on hospital admission in COVID-19 patients were included. The review particularly focuses on ROC analyses and reported AUC values. Results: A total of 20 studies were analyzed, including 13 studies assessing disease severity and 14 studies evaluating mortality. Higher PLR values have been observed in patients with a more severe course of COVID-19 compared to those with milder disease, and in non-survivors compared to survivors. However, the literature shows inconsistency regarding the diagnostic utility of PLR based on ROC curve analysis. The reported AUC values ranged from 0.559 to 0.811 for disease severity differentiation and from 0.474 to 0.758 for mortality, which may be related to the heterogeneity of the study populations included in the analysis. Conclusions: PLR may not serve as a direct bridge between inflammation and coagulation in COVID-19-Associated Coagulopathy, but it is indirectly linked to disease severity and mortality, as it reflects changes in both platelet and lymphocyte counts. It is a complementary marker that may assist clinicians in assessing COVID-19 patients but still requires further investigation. Full article

Mesenchymal stromal cells are increasingly used for their immunomodulatory and regenerative properties, yet their interaction with the hemostatic system remains incompletely understood. This review examines the mechanisms through which these cells influence coagulation within the broader framework of immunothrombosis. Evidence from in vitro studies, animal models, and early clinical observations indicates that mesenchymal stromal cells can promote thrombin generation through tissue factor expression and phosphatidylserine exposure, while also engaging complement pathways, platelets, and innate immune responses. Counter-regulatory mechanisms, including adenosine-mediated platelet inhibition and immune reprogramming after cellular clearance, contribute to a context-dependent biological effect. Functional assays, rather than tissue factor expression alone, appear necessary to estimate the effective procoagulant potential of these products. Clinical data suggest that major thrombotic events remain uncommon, although subclinical activation of coagulation pathways may occur. The hemostatic impact of mesenchymal stromal cells depends on multiple variables, including cell source, dose, route of administration, and host inflammatory status. The available evidence supports a working model in which early coagulation and complement activation may be followed by immune modulation, supporting integrated strategies to optimise both safety and therapeutic efficacy. A central conclusion is that tissue factor, although mechanistically necessary for MSC-associated procoagulant activity, is not by itself an independent predictor of clinical thrombotic risk; the effective coagulation response also depends on phosphatidylserine exposure, membrane context, and host inflammatory conditions. Full article

Background: Pediatric liver disease is frequently associated with abnormal conventional coagulation tests; however, prothrombin time expressed as international normalized ratio (PT-INR) incompletely reflect global hemostatic balance. Thrombin generation assay (TGA) provide an integrated assessment of coagulation and may offer complementary information in children with acute liver failure (ALF) and chronic liver disease (CLD). Methods: We enrolled 61 pediatric patients with liver disease (50 CLD, 8 ALF, 3 extrahepatic portal vein obstruction EHPVO) and 51 healthy controls. Platelet-poor plasma was prepared according to international recommendations. Thrombin generation was measured using ST Genesia (STG) with normalization to reference plasma. Group comparisons were performed using non-parametric tests; correlations between PT-INR and thrombin generation parameters were assessed, and principal component analysis (PCA) was used to explore the variance structure of thrombin generation indices and conventional coagulation variables. Results: PT-INR was significantly higher in patients than controls, particularly in ALF. Bleeding events were uncommon. Compared with controls, patients showed reduced levels of fibrinogen and multiple procoagulant/anticoagulant factors (including antithrombin and protein C), with increased factor VIII. Among thrombin generation parameters, the endogenous thrombin potential (ETP) ratio differed significantly across groups (p = 0.001), while correlations between PT-INR and thrombin generation parameters were weak or absent, no significant associations were observed even at higher Pediatric/Model for End-Stage Liver Disease scores. PCA separated thrombin generation indices from PT-INR and conventional coagulation factors, suggesting complementary information. Conclusions: In pediatric liver disease, PT-INR does not reliably reflect global coagulation capacity. Thrombin generation testing provides additional, integrative information on hemostasis and may improve laboratory assessment beyond conventional tests. Full article

Background: Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, is increasingly recognized as a thromboinflammatory disorder involving coagulation, innate immunity, endothelial dysfunction, and vascular homeostasis. Emerging evidence suggests that gut microbiome-related inflammatory and metabolic signals may influence pathways potentially relevant to VTE through intestinal barrier dysfunction, microbial translocation, and microbiome-derived metabolites. This review critically examines the direct and indirect evidence relating gut dysbiosis to mechanisms potentially relevant to venous thrombogenesis. Methods: A structured literature search of PubMed, Scopus, and Web of Science was conducted from database inception to February 2026. Observational, translational, experimental, preclinical, and selected genetic studies were narratively synthesized across heterogeneous evidence types. Results: Available evidence suggests that intestinal barrier dysfunction and microbial translocation may increase systemic exposure to lipopolysaccharide and other microbial products, potentially contributing to inflammatory signaling and procoagulant responses. Proposed downstream effects include tissue factor (TF) activation, platelet reactivity, neutrophil extracellular traps (NETs) formation, complement signaling, endothelial perturbation, and impaired balance of anticoagulant and fibrinolytic pathways. Microbiome-derived metabolites, including trimethylamine N-oxide (TMAO), phenylacetylglutamine (PAGln), bile acids, and short-chain fatty acids (SCFAs), have been linked, mainly in experimental or non-VTE settings, to thrombosis-related biology. However, most evidence remains indirect, associative, or experimental, whereas direct human VTE-specific evidence is limited and heterogeneous. Conclusions: The gut microbiome–VTE axis is biologically plausible and supported mainly by mechanistic and indirect evidence, but current data are insufficient to support strong causal conclusions. Further longitudinal, well-phenotyped, mechanistically informed studies are needed to determine whether microbiome-related pathways have measurable clinical relevance in human VTE. Full article

Background and Objectives: Intrauterine growth restriction (IUGR) affects 5–10% of pregnancies and is associated with increased perinatal morbidity and long-term complications for the neonate. Extracellular vesicles (EVs), and in particular, microparticles (MPs), have emerged as potential biomarkers of pregnancy complications; however, the literature on their role in neonates remains limited. To investigate the functional characteristics, concertation in maternal blood and potential role of MPs in IUGR. Materials and Methods: PubMed, Scopus and preprint servers were systematically searched for studies on MPs in correlation with IUGR from 1 August until 18 September 2025. Data on MP characteristics and concentration in maternal blood samples in the context of IUGR were collected. The systematic review is registered in PROSPERO (CRD420251156939). Results: A total of 12 studies fulfilled the inclusion criteria and were included in the review. In IUGR-complicated pregnancies, circulating MPs exhibited preserved procoagulant activity despite minimal quantitative differences compared to controls. Platelet-, endothelial-, and placenta-derived MPs were most frequently studied. Clinically, elevated AV+ placenta-derived MPs were associated with increased risk of IUGR, whereas MPs from isolated IUGR pregnancies showed limited predictive value. Conclusions: MPs play a crucial role in the pathophysiology of IUGR through their interplay in coagulation, inflammation, and vascular dysfunction. They show potential as predictive biomarkers, particularly in cases of preeclampsia-associated IUGR, reflecting systemic maternal endothelial and inflammatory changes. However, their utility in isolated IUGR appears limited, likely due to the predominantly local placental origin of the pathology. Full article

Neutrophil extracellular traps (NETs) critically influence thrombosis by promoting platelet aggregation, fibrin formation, and thrombus stabilisation. However, primary human neutrophils present experimental limitations, including short lifespan ex vivo and ethical concerns. In this article, we discuss the available data on PLB-985 cells, a neutrophil-like model with potential to replace human neutrophils in research. Additionally, we present novel structural comparisons showing that both PLB-985- and human neutrophil-derived NETs significantly increased fibrin fibre thickness compared to thrombin-only controls, with similar fibre morphology across conditions. Notably, we also see spherical particles resembling microvesicles within PLB-985-derived NETs, suggesting potential additional procoagulant effects via microvesicle-associated tissue factor level in these cells. New and existing data presented in this article suggest that differentiated PLB-985 cells are able to effectively replicate key structural and functional aspects of human neutrophil NETs. These observations support the use of PLB-985 cells as an ethical, reproducible, and practical alternative for in vitro studies of NETs. Further characterisation is required to determine differences between human neutrophils and neutrophil-like models in macrovesicle formation and implication in NET-related thrombosis research. Full article

Background: Thrombocytopenia is traditionally perceived as a bleeding-predominant condition; however, growing evidence indicates that many thrombocytopenic states are paradoxically associated with an increased risk of venous and arterial thrombosis. This dual hemostatic derangement poses major therapeutic challenges when anticoagulant or antiplatelet therapy is indicated, particularly in complex settings such as cancer-associated thrombosis, immune thrombocytopenia, and advanced liver disease. Methods: We conducted a narrative review of the literature published between January 2021 and May 2025 using PubMed and guideline repositories. Search terms included thrombocytopenia, anticoagulation, antiplatelet therapy, cancer-associated thrombosis, immune thrombocytopenia, and cirrhosis. International guidelines from ASH, ISTH, ASCO, EHA, ESC, and AHA were prioritized. Evidence was synthesized to define platelet-based safety thresholds and disease-specific management strategies. Results/Discussion: Thrombocytopenia does not uniformly confer protection against thrombosis. Platelet activation, endothelial dysfunction, inflammatory signaling, impaired fibrinolysis, and procoagulant microparticles contribute to a prothrombotic milieu despite reduced platelet counts. Most guidelines support full-dose anticoagulation at platelet counts ≥ 50 × 10⁹/L, with dose modification between 25 and 50 × 10⁹/L and treatment interruption below 25 × 10⁹/L, depending on thrombotic risk. Antiplatelet therapy requires stricter individualization, particularly regarding dual antiplatelet therapy. Conclusions: Management of antithrombotic therapy in thrombocytopenic patients requires a dynamic, individualized approach balancing ischemic and bleeding risks. Pragmatic algorithms may guide clinical decision-making while prospective data remain limited. Full article

Pancreatic cancer (PC) is a highly lethal malignancy linked to the highest rate of thromboembolic complications (TEC) among all solid tumors. TECs occur in approximately 5–40% of PC patients. The most common type of TEC in PC is venous thromboembolism (VTE). The mechanisms leading to frequent TEC in PC are complex and involve interactions between tumor-derived procoagulant factors and the prothrombotic tumor microenvironment (TME). Secretion of tissue factor and proinflammatory cytokines by tumor cells and the TME, overexpression of heparanase and podoplanin, impaired fibrynolysis and increased neutrophil extracellular trap formation lead to platelet hyperactivation resulting in hypercoagulability in PC. Understanding these mechanisms is crucial for identifying risk factors of TEC. Current thromboembolism risk models have limited predictive accuracy, which reduces their clinical usefulness. Identifying patients with thromboembolism is challenging because these events are often asymptomatic and their clinical presentation varies depending on the location of the thrombus. Treatment of VTE in PC depends on the phase of the VTE; in the acute phase, treatment primarily involves LMWH. For long-term management, LMWH may be replaced by direct oral anticoagulants such as apixaban, edoxaban, or rivaroxaban. In cases of VTE recurrence, increasing the LMWH dose, switching to an oral anticoagulant, or placing an inferior vena cava filter should be considered. LWMH and unfractionated heparin (UFH) are preferred options for VTE prophylaxis. Novel therapies, including factor XI inhibitors, show efficacy comparable to LMWH while offering a better safety profile. Full article

The field of extracellular vesicle (EV) research offers a compelling example of a biological concept refined through continuous methodological innovation. This review traces the historical trajectory of the discipline chronologically, beginning with early observations in haemostasis, from Malpighi’s descriptions of blood clots and Chargaff and West’s identification of a procoagulant sedimentable plasma fraction, to Wolf’s “platelet dust,” Crawford’s microparticles characterised by electron microscopy, and the seminal work by Stahl and Johnstone demonstrating regulated vesicle biogenesis during reticulocyte maturation via multivesicular bodies. We highlight a pivotal conceptual shift, from viewing EVs as cellular debris to recognising them as regulated “communicasomes,” catalysed by Raposo’s discovery of antigen-presenting exosomes and subsequent evidence for EV-mediated transfer of functional receptors and nucleic acids, including the influential and sometimes debated model proposed by Ratajczak. By integrating findings from matrix vesicles, plant-derived vesicles, and diverse tissue contexts, we frame EV release as an evolutionarily conserved process with profound implications for immunity, regeneration, oncology, and cardiovascular pathology. A second central aim of this review is practical and methodological. We map how the expansion of biological claims has driven urgent standardisation efforts, notably through the establishment of the International Society for Extracellular Vesicles (ISEV) and the successive MISEV guidelines (2014, 2018, 2023). These are complemented by community resources such as EV-TRACK, MIFlowCyt-EV, and the databases ExoCarta and Vesiclepedia. We summarise core experimental choices across isolation and characterisation techniques, including ultracentrifugation, size exclusion chromatography, density gradients, flow cytometry, nanoparticle tracking analysis, and electron microscopy, while outlining persistent bottlenecks in purity, standardised nomenclature, and experimental reproducibility. Finally, we provide concise biographical sketches of key contributors and an overview of major EV-focused journals and ISEV meetings that anchor consensus-building and the translation of fundamental knowledge into clinical and industrial applications. Full article

Background/Objectives: In clinical practice today, platelet concentrates are often used for topical surgical applications. They are biomaterials that can accelerate healing processes associated with oral and maxillofacial surgery as well as in several other clinical applications through the action of growth factors released by platelets at the surgical site. However, in most cases, the exact quantification of the released growth factors is challenging in both the short and long term. The aim of this study was to determine if early platelet activation and degranulation occur during the collection and utilization of platelet-rich plasma (PRP) in the surgical room, where, before its application, PRP undergoes a procedure of gelification via reactions with procoagulant agents. Methods: PRP was prepared from the blood samples of 39 patients following the modified Whitman protocol. The samples were then analyzed at four different time points (1, 6, and 24 h during preparation and clinical application in the surgery room) using flow cytometry and enzyme-linked immunosorbent assays (ELISAs) to investigate the platelet activation/degranulation and TGFβ release in the supernatant (SN) during storage and clinical application. The mean platelet count in the whole blood was 267.5 ± 48.58 × 10³/mL (range: 189–334 × 10³/mL), and the mean concentration was 2925.5 ± 833.37 × 10³/mL (range: 748–3453 × 10³/mL). Results: The activation and degranulation of platelet cells (measured via monoclonal antibodies: CD62p and CD63, respectively) demonstrated a progressive increase at 1 h, 6 h, 24 h, and after gelification. The TGFβ dosage in the supernatant (SN) at different times exhibited a similar trend, with a mean release of 18.36 ng/mL at 1 h, 21.96 ng/mL at 6 h, and 29.45 ng/mL at 24 h. After the gelification of the PRP, a significant reduction was observed, with a value of 15.52 ng/mL. Conclusions: The results reveal that the protocol used for the preparation, storage, and application of the PRP ensures a good-quality hemoderivative and that the platelet concentrate must be applied with the correct timing to support tissue healing processes. Full article

Isothiazolinones are commonly used biocides that are extensively used in industrial areas and household products. The extensive usage of isothiazolinones raises concerns regarding their adverse human health effects. Isothiazolinones are readily absorbed and enter circulation. However, the potential systemic effects of isothiazolinones on the circulatory system remain unclear. Here, we examined whether the isothiazolinones, benzisothiazolinone (BIT) and octylisothiazolinone (OIT) affected platelets. In isolated platelets, BIT and OIT depleted intracellular glutathione, which led to mitochondrial reactive oxygen species (ROS) accumulation. Excessive mitochondrial ROS led to mitochondrial dysfunction, altering intracellular calcium and adenosine triphosphate homeostasis. These intracellular events activated phospholipid scramblase, externalizing phosphatidylserine, thereby enhancing procoagulant activity, as evidenced by thrombin generation. Overall, OIT showed a more potent effect than BIT. Notably, supplementation with N-acetyl-L-cysteine mitigated BIT- and OIT-induced effects, suggesting a thiol-dependent mechanism. Taken together, BIT and OIT stimulated the platelet-mediated coagulation pathway, which may increase prothrombotic risk and contribute to cardiovascular disease. These results could improve our understanding of the systemic adverse effects after isothiazolinone exposure. Full article

Fiber-forming polymers are increasingly used to control blood coagulation, either by accelerating the onset of hemostasis or by limiting thrombogenic events in contact with blood. Despite rapid progress in materials engineering, a unified view linking the molecular mechanisms of the coagulation cascade with specific design strategies of procoagulant and anticoagulant polymeric fibers is still missing. In this review, we summarize current knowledge on how natural and synthetic polymers interact with plasma proteins, platelets, and coagulation factors, emphasizing the role of fiber morphology, surface chemistry, charge distribution, and functionalization. Particular attention was paid to systems based on natural polysaccharides (e.g., chitosan, alginate, and cellulose derivatives), as well as synthetic polymers (e.g., PLA, PCL, polyurethanes, and zwitterionic materials). Two possible courses of action were described: their bioactivity may activate the contact pathway and/or support platelet adhesion or their ability to minimize protein adsorption and inhibit thrombin generation. We discuss how metal–polymer coordination, surface immobilization of heparin or nitric oxide donors, and nanoscale texturing modulate coagulation kinetics in opposite directions. Finally, we highlight emerging fiber-based strategies for achieving either rapid hemostasis or long-term hemocompatibility and propose design principles enabling precise tuning of coagulation responses for wound dressings, vascular grafts, and blood-contacting devices. This general compendium of knowledge on blood–material interactions provides a foundation for further design of biomaterials based on fiber-forming polymers and the development of manufacturing processes. Full article

Platelets are often described in simple terms as small anucleate cells that mediate hemostasis, but studies over more than half a century have shown that circulating platelets are heterogeneous in size, density, age, and functional responses. These subtypes not only contribute to normal hemostasis but also play pivotal roles in the pathogenesis of diverse diseases, including cardiovascular, inflammatory, and malignant disorders. Accumulating evidence indicates that alterations in specific platelet subtypes are closely linked to disease onset, progression, and severity, underscoring their importance as both biomarkers and potential therapeutic targets. Current clinical assessments of platelet status rely primarily on platelet count and mean platelet volume (MPV) as part of routine complete blood count analysis. However, these global measures often fail to capture differences in platelet subtypes, which may remain undetected despite their significant contribution to disease pathology. This gap highlights the necessity of moving beyond conventional metrics toward a more nuanced understanding of platelet heterogeneity and its clinical implications. In this review, we discuss the diversity of platelet subpopulations and their roles in health and disease, emphasizing how specific subsets contribute to divergent pathological mechanisms. We also highlight emerging strategies that target defined platelet subpopulations, illustrating how this knowledge could pave the way for more precise diagnostic and therapeutic approaches. Full article

Snake venoms are rich sources of bioactive molecules that modulate hemostasis and, among these, anticoagulant snake venom phospholipases A₂ (sPLA₂) are found in a range of snake venoms. Crotoxin (CTX), from the Crotalus durissus rattlesnake, is a heterodimeric PLA₂ complex, and literature has reported its mechanisms in anticoagulant activity. The present review revisits the biological roles of anticoagulant sPLA₂ and critically examines evidence on CTX in hemostatic regulation, aiming to clarify its mechanisms and therapeutic promise. CTX exerts anticoagulant activity via enzymatic hydrolysis of procoagulant phospholipids and direct interaction with coagulation factors, disrupting key complex assembly. It also counteracts inflammation-induced coagulation by modulating leukocyte- and endothelial-derived mediators, restoring balance among anticoagulant, procoagulant, and fibrinolytic pathways. Effects on platelet function appear comparatively modest, ranging from less potent pro-aggregatory activity to negligible aggregation. The dual anticoagulant and anti-inflammatory properties of CTX highlight its potential as a model for novel antithrombotic agents in hypercoagulable and inflammation-driven disorders, despite toxicological concerns that necessitate cautious pharmacological exploration. Full article