Search Results (184)

Carotid artery intima–media thickness (cIMT), a pre-clinical vascular change that accompanies atherosclerosis is considered as a cardiovascular risk factor. Coagulation factor XIII (FXIII) stabilizes the fibrin clot and increases its resistance to fibrinolysis. Regarding FXIII Val34Leu polymorphism, the protective effect of the Leu34 allele in the presence of elevated fibrinogen levels against myocardial infarction was demonstrated. Our aim was to investigate the effect of FXIII polymorphisms on cIMT. Patients with obesity (n = 69), type 2 diabetes mellitus (T2DM) (n = 104), and age- and sex-matched healthy controls (n = 82) were enrolled. FXIII polymorphisms (Val34Leu, His95Arg, Intron-K C>G) were determined by RT-PCR with FRET detection and melting curve analysis. cIMT was determined by B-mode ultrasound. Differences in cIMT between control (median: 0.5965, IQR: 0.5115–0.6580 mm) and T2DM (median: 0.7105, IQR: 0.5948–0.7568 mm), as well as between obese (median: 0.6105, IQR: 0.5455–0.6780 mm) and diabetic groups, were found (p < 0.0001 and p = 0.003, respectively). Genotype and allele frequencies of the studied polymorphisms did not differ between subgroups. In the study group (n = 255) after adjustment for age and sex, the presence of Intron-K G allele showed a significant and independent protective effect against cIMT progression in a separate model (p = 0.005) and after adjusting for other parameters associated with cIMT (p = 0.015). FXIII Intron-K G allele provides a protective effect against subclinical vascular disease in the studied population, and this effect is independent of the presence of obesity, as well as T2DM, Leu34 allele, and fibrinogen levels. Full article

Autoimmune diseases arise from complex interactions of genetic, environmental, and hormonal factors, yet their precise causes remain elusive. Beyond its canonical role in fibrin degradation, the fibrinolytic system is increasingly recognized as both a pathogenic driver and a regulatory modulator in autoimmunity. Key factors—plasminogen (Plg), plasmin, α2-antiplasmin (α2AP), tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), its receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1)—not only reflect secondary responses to vascular and immune dysregulation but also actively shape innate and adaptive immunity. They influence macrophage activation, dendritic cell maturation, T cell responses, and cytokine production, thereby bridging coagulation, inflammation, and tissue repair. This review integrates current evidence on the dual pathogenic and regulatory roles of fibrinolytic factors, organizing autoimmune diseases into systemic, organ-specific, and secondary syndromes. We further discuss how the imbalance of fibrinolysis can either promote inflammatory persistence or, conversely, facilitate resolution through fibrin clearance and immune homeostasis. By highlighting this bidirectional influence, the review aims to refine our understanding of fibrinolytic components as both contributors to and regulators of autoimmune disease pathogenesis. Full article

Extended platelet-rich fibrin (e-PRF) combines the prolonged resorption properties of heat-coagulated platelet-poor plasma (PPP), becoming an albumin gel (Alb-gel) that is mixed back with the respective native cell-rich buffy coat layer (BC), i.e., concentrated PRF (C-PRF). E-PRF or Alb-PRF is utilized as a barrier membrane in various clinical applications, such as guided tissue regeneration. The heating of PPP might lower its biological activity, but testing this hypothesis is necessary. To this end, we exposed gingival fibroblasts to the lysates of regular PPP, heated PPP (hPPP), and BC, followed by bulk RNA sequencing. Gingival fibroblasts responded to PPP lysates with a total of 153 up- and 71 down-regulated genes when considering a minimum 3.0-fold log2 expression change and a significance level 2.0 log-10. In sharp contrast, the response to hPPP was characterized by only five up-regulated and five down-regulated genes, clearly indicating that heating almost completely abolished the biological activity of PPP. As expected, BC was more potent than PPP and broadened the spectrum of regulated genes. RT-PCR and immunoassays confirmed the heat sensitivity of PPP as exemplified by IL11 and other genes. Moreover, PPP, but not hPPP, drives the phosphorylation of p65, representing NF-κB signaling. Taken together, these findings extend previous observations that PPP causes a robust response in gingival fibroblasts and also strengthen the hypothesis that this response is heat-sensitive. These operations support the clinical concept of e-PRF by mixing back the heated inactive PPP with the bioactive buffy coat C-PRF layer. Full article

Dugongs (Dugong dugon), classified as vulnerable marine mammals, are increasingly impacted by infectious diseases, yet the role of septicemia and disseminated intravascular coagulation (DIC) in their mortality remains uncharacterized. This study aimed to investigate the pathological and microbiological features associated with an acute mortality event in a juvenile dugong during rehabilitation in southern Thailand. Comprehensive histopathological and microbiological analyses were conducted on tissue samples collected postmortem. Bacterial isolation and identification were performed using standard culture techniques and the VITEK-2 system. Histological examination revealed multisystemic lesions, including fibrin thrombi, hemorrhage, hepatocellular degeneration, pancreatic necrosis, lymphoid depletion, and neuronal damage. Oxidative stress and DNA damage were confirmed in brain tissues through immunofluorescence detection of 4-hydroxynonenal (4-HNE) and 8-hydroxy-2′-deoxyguanosine (8-oxodG). Achromobacter xylosoxidans, an opportunistic pathogen, was isolated from multiple organs, consistent with acute systemic infection. These findings represent the first evidence of septicemia-associated DIC in dugongs caused by A. xylosoxidans, highlighting a previously undocumented cause of mortality in dugongs. The results emphasize the role of opportunistic bacteria in triggering oxidative damage and coagulopathy and underscore the importance of early detection and targeted therapeutic strategies to improve survival in stranded or rehabilitated dugongs. Full article

Plant latex is a rich source of proteolytic enzymes with potential biomedical applications, particularly in hemostasis. Among them, thrombin-like enzymes (TLEs) have garnered interest in their ability to mimic thrombin by catalyzing the conversion of fibrinogen to fibrin, facilitating clot formation. While TLEs from snake venoms have been well-characterized and applied clinically, their plant-derived counterparts remain underexplored. This review critically examines the structural and functional characteristics of TLEs from plant latex, comparing them to animal-derived TLEs and evaluating their role in both procoagulant and fibrinolytic processes. Emphasis is placed on dual fibrinogenolytic and fibrinolytic activities exhibited by latex proteases, which often vary with concentration, incubation time, and protease type. In vitro coagulation assays and electrophoretic analyses are discussed as critical tools for characterizing their multifunctionality. By addressing the knowledge gaps and proposing future directions, this paper positions plant latex proteases as promising candidates for development in localized hemostatic and thrombolytic therapies. Full article

Background/Objectives: We define severe postpartum hemorrhage (PPH) with macroscopic hematuria as clinical disseminated intravascular coagulation (DIC), a life-threatening condition. We also report a methodology using machine learning, a subtype of artificial intelligence, for developing the boundary criterion for predicting hematuria on the fibrinogen–fibrin/fibrinogen degradation product (FDP) plane. A positive FDP–fibrinogen/3–60 (mg/dL) value indicates hematuria; otherwise, non-hematuria is observed. We aimed to validate this criterion using severe placental abruption (PA), and to examine the activation of the coagulation–fibrinolytic system in clinical DIC. Methods: Of 17,285 deliveries across nine perinatal centers in Japan between 2020 and 2024, 13 had severe PA without hematuria, 18 had severe PPH without hematuria, and 3 had severe PPH with hematuria, i.e., clinical DIC. We calculated the values of the criterion formula for 13 cases of severe PA to validate the boundary criterion and compared the laboratory tests for coagulation–fibrinolytic activation among the three groups. Results: The calculated values using the criterion for the 13 PA without hematuria ranged from −108.91 to −5.87 and all were negative. In cases of clinical DIC, fibrinogen levels (median, 62 mg/dL) were lower (p < 0.05), while levels of FDP (96 mg/dL), the thrombin–antithrombin complex (120 ng/mL), and the plasmin-α₂–plasmin inhibitor complex (28.4 μg/mL) were significantly higher than in the other two groups. Conclusions: This study demonstrated the validity of the boundary criterion for predicting hematuria using severe PA. The coagulation–fibrinolytic test results suggested that PPH cases with hematuria were assumed to have clinical DIC, indicating that this criterion may be considered for diagnosing DIC during delivery. However, further additional patient data are needed to confirm the usefulness of this criterion because of the very low number of hematuria cases. Full article

Reactive nitrogen species (RNS), particularly peroxynitrite (ONOO⁻), play a central role in post-translational modifications (PTMs) of proteins, including fibrinogen, a key component of the coagulation cascade. This review explores the structural and functional consequences of fibrinogen nitration, with a focus on its impact on clot formation, morphology, mechanical stability, and fibrinolysis. Nitration, primarily targeting tyrosine residues within functional domains of the Aα, Bβ, and γ chains, induces conformational changes, dityrosine crosslinking, and aggregation into high molecular weight species. These modifications result in altered fibrin polymerization, the formation of porous and disorganized clot networks, reduced mechanical resilience, and variable susceptibility to fibrinolysis. Moreover, nitrated fibrinogen may affect interactions with platelets and endothelial cells, although current evidence remains limited. Emerging clinical studies support its role as both a prothrombotic mediator and a potential biomarker of oxidative stress in cardiovascular and inflammatory diseases. Finally, we explore both pharmacological interventions, such as NOX inhibitors, and natural antioxidant strategies at counteracting fibrinogen nitration. Overall, fibrinogen nitration emerges as a critical molecular event linking oxidative stress to thrombotic risk. Full article

Protein C (PC) is the main anticoagulant protein of the hemostasis system. It can inhibit the blood clotting cascade before the formation of a thrombus, while its concentration can decrease significantly during strong activation of blood clotting. The PC concentration was found to decrease during systemic lupus erythematosus (SLE) (with a median of 75%) and depended heavily on the inflammation index. It was also associated with the accumulation of soluble fibrin monomeric (SFMCs) (with a median of 7 µg/mL). A low PC level was detected during severe ischemic heart disease (IHD) (with medians of 60 and 63%, respectively). These pathologies also were associated with clotting activation. During abdominal aortic aneurysm (AAA), the PC level in blood plasma before surgery was found to range from 40% to 119%. A decrease in the PC level in the blood plasma of patients with AAA before surgery, lower than 78%, was associated with high blood loss (more than 1.5 L). A decrease in the PC level can lead to an imbalance between coagulation and anticoagulation. Thus, during the treatment of complex pathologies associated with the activation of coagulation, specific attention should be paid not only to classic markers of thrombus formation but also to the state of the anticoagulant link. Full article

Coagulation factor XII (FXII), the initiator of the intrinsic coagulation pathway, is not involved in hemostasis but is associated with pathological thrombosis. Bacterial infections activate coagulation cascades, although the underlying mechanisms remain not fully understood. Here, we revealed that FXII exhibits antibacterial activity through its heavy chain (hFXII) against Pseudomonas aeruginosa (P. aeruginosa), a Gram-negative bacterium. We constructed an FXII-deficient (FXII^−/−) mouse model and demonstrated that FXII plays a critical role in antibacterial functions. FXII and hFXII significantly reduced bacterial loads via intravenous injection, confirming their antibacterial activity in FXII^−/−. To further investigate the pathophysiological implications of FXII in the P. aeruginosa-induced disseminated intravascular coagulation (DIC) mouse model, FXII and hFXII effectively reduced DIC-related bacterial infections, alleviated organ damage, and decreased fibrin deposition, consequently improving survival rates. This study indicates that FXII exhibits both in vitro and in vivo antibacterial activity, primarily mediated through its heavy chain. In thrombotic diseases triggered by Gram-negative bacterial infections, the antibacterial functions of FXII may influence the progression of the disease. These results not only redefine the critical role of the intrinsic coagulation pathway in innate immune defense but also provide novel insights into the prevention and treatment of severe infection-related diseases. Full article

This study investigated the impact of increased extraplatelet content on the tissue regenerative capacity of platelet-rich plasma (PRP)-derived fibrin scaffolds. Comparative analyses were performed between a “balanced protein-concentrate plasma” (BPCP) and a standard PRP (sPRP), focusing on platelet and fibrinogen content, scaffold microstructure, and functional performance. Growth factor (GF) release kinetics from the scaffolds were quantified via ELISA over 10 days, while scaffold biomechanics were evaluated through rheological testing, indentation, energy dissipation, adhesion, and assessments of coagulation dynamics, biodegradation, swelling, and retraction. Microstructural analysis was conducted using scanning electron microscopy (SEM), with fiber diameter and porosity measurements. The results demonstrated that BPCP scaffolds released significantly higher amounts of GFs and total protein, especially beyond 24 h (* p < 0.05). Despite a delayed coagulation process (** p < 0.01), BPCP scaffolds exhibited superior structural integrity and cushioning behavior (* p < 0.05). SEM revealed thicker fibers in BPCP scaffolds (**** p < 0.0001), while adhesion and biodegradation remained unaffected. Notably, BPCP scaffolds showed reduced retraction after 24 h and maintained their shape stability over two weeks without significant swelling. These findings indicate that enhancing the extraplatelet content in PRP formulations can optimize fibrin scaffold performance. Further preclinical and clinical studies are warranted to evaluate the therapeutic efficacy of BPCP-derived scaffolds in regenerative medicine. Full article

Naturally occurring plant-based compounds are increasingly being explored for their therapeutic potential in treating a wide range of conditions, particularly those related to vascular health. The compound 3-deoxysappanchalcone (3-DSC), derived from Caesalpinia sappan L., has been proven to exhibit anti-inflammatory, anti-influenza, and anti-allergic properties, though its role in thrombosis and haemostasis remains unexplored. This study aimed to evaluate the anti-thrombotic potential of 3-DSC in both in vitro and in vivo models. The anticoagulant activities of 3-DSC were assessed using activated partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin (FIIa) and activated factor X (FXa) activity assays, as well as fibrin polymerization and platelet aggregation tests. Its effects on plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) expression were evaluated in TNF-α-stimulated human umbilical vein endothelial cells (HUVECs). The results demonstrated that 3-DSC extended aPTT and PT, suppressed thrombin and FXa activities, reduced their production in HUVECs, inhibited thrombin-induced fibrin polymerization and platelet aggregation, and exerted anticoagulant effects in mice. Furthermore, 3-DSC significantly decreased the PAI-1 to t-PA ratio. These findings suggest that 3-DSC possesses potent anti-thrombotic properties by modulating coagulation pathways and fibrinolysis. Its therapeutic potential warrants further investigation for the development of novel anticoagulant agents. Full article

Homocysteinylation, a post-translational modification involving the covalent attachment of homocysteine to proteins, has emerged as a critical mechanism linking hyperhomocysteinemia to thrombotic disease. This review focuses on the homocysteinylation of fibrinogen, a key coagulation factor, and its impact on clot structure and function. Evidence indicates that elevated homocysteine levels can induce significant changes in fibrin architecture, promoting the formation of dense, rigid clots with reduced permeability and impaired fibrinolytic susceptibility, thus fostering a prothrombotic environment. However, inconsistencies in reported effects on fiber diameter and polymerization kinetics highlight the need for standardized experimental protocols. Advances in proteomics and high-resolution imaging are expected to clarify the molecular underpinnings of these modifications. Moreover, homocysteinylation intersects with oxidative stress and may serve as a mechanistic bridge between metabolic and vascular dysfunction. Understanding its role not only enhances insight into thrombosis but also opens avenues for biomarker discovery and targeted therapies in cardiovascular and potentially neurological disorders. Full article

This study aimed to characterize and evaluate the fibrinolytic, thrombolytic, hematological, and toxicological aspects of a serine protease (AsKSP) from Aspergillus tamarii Kita UCP 1279. The enzyme was purified using a two-phase aqueous system and assessed for optimal pH (7.0) and temperature (50 °C), stability, and effects of metal ions, inhibitors, and surfactants. AsKSP exhibited stability for up to 120 min at 50 °C and 36 h at pH 7.0. Enzymatic activity was enhanced by Na⁺ and Zn²⁺ and non-ionic surfactants (Tween-80) but inhibited by Cu²⁺, Fe³⁺, Triton X-100, and SDS, reducing activity by up to 62.35%. The highest amidolytic activity was observed for the substrate N-succinyl-Gly–Gly–Phe-p-nitroanilide. SDS-PAGE analysis indicated an approximate molecular mass of 90 kDa. The enzyme showed fibrinolytic activity, degrading 38.81% of fibrin clots in vitro after 90 min, without affecting fibrinogen. Cytotoxicity assays indicated no toxicity (cell viability > 80%). Coagulation assays showed slight prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT), with no effect on thrombin time. No red blood cell lysis was observed, and albumin increased enzymatic activity by 31.70%. These findings demonstrate that Aspergillus tamarii Kita UCP 1279 produces a fibrinolytic protease with potential for thrombus treatment, providing a promising foundation for drug development. Full article

Objectives: This study aimed to differentiate patients with placenta accreta spectrum (PAS) from those with placenta previa (PP) and to assess the association between preoperative inflammatory and coagulation parameters and intraoperative blood loss. Methods: In this retrospective case-control study, 545 pregnant women were enrolled and divided into five groups: control (n = 251), PP (n = 246), PP with accreta (PPA, n = 18), PP with increta (PPI, n = 27), and PP with percreta (PPP, n = 33). Preoperative serum levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), delta neutrophil index (DNI), prothrombin time, fibrin degradation products (FDPs), D-dimer, and activated partial thromboplastin time (APTT) were analyzed. Results: The PPP group demonstrated significantly higher values of FDP, D-dimer, NLR, PLR, SII, SIRI, and DNI, and lower APTT values compared to the other groups (p < 0.001). For predicting PAS, SIRI and DNI showed the highest diagnostic performance, each achieving 100% sensitivity and specificity, with optimal cut-off values of 2.01 and 2.45, respectively. For predicting intraoperative blood loss ≥1000 mL, PLR and SIRI exhibited the highest diagnostic accuracy, with optimal cut-off values of 122.5 (sensitivity 76.6%; specificity 72.6%) and 2.25 (sensitivity 73.4%; specificity 74.1%), respectively. Conclusions: FDP, D-dimer, NLR, PLR, SII, SIRI, and DNI may serve as valuable biomarkers for differentiating PP from PAS, thereby enhancing preoperative risk assessment and guiding surgical planning to improve maternal outcomes. Additionally, PT, D-dimer, FDP, NLR, and DNI were identified as significant independent predictors of intraoperative blood loss. Full article

Background: Infective endocarditis continues to represent a challenge for healthcare systems, requiring careful management and resources. Recent studies have indicated a shift in the predominant pathogens of concern, with Streptococcus sp. a being superseded by Staphylococcus sp. and Enterococcus sp. as the leading causes of concern. This shift is of concern as it is associated with Staphylococcus Aureus which has a high virulence rate and a tendency to form a biofilm, meaning that non-surgical therapy may not be effective. It is imperative to deliberate on the likelihood of platelet blood clot formation, which may be accompanied by bacterial infestation and the development of a biofilm. Methods: MEDLINE, Embase, and Pubmed were searched using terms relating to ‘endocarditis’ and ‘Staphilococcus aureus’, along with ‘epidemiology’, ‘pathogenesis’, ‘coagulation’, ‘platelet’, ‘aggregation’, and ‘immunity’. The search focused on publications from the past 15 years, but excluded older, highly regarded articles. We also searched the reference lists of relevant articles. Recommended review articles are cited for more details. Results: An endocarditis lesion is believed to be a blood clot infected with bacteria that adheres to the heart valves. Infective endocarditis is a good example of immunothrombosis, where the coagulation system, innate immunity and the function of coagulation in isolating and eliminating pathogens interact. However, in the context of infective endocarditis, immunothrombosis unintentionally establishes an environment conducive to bacterial proliferation. The process of immunothrombosis impedes the immune system, enabling bacterial proliferation. The coagulation system plays a pivotal role in the progression of this condition. Conclusion: The coagulation system is key to how bacteria attach to the heart valves, how vegetations develop, and how complications like embolisation and valve dysfunction occur. Staphylococcus aureus, the main cause of infective endocarditis, can change blood clotting, growing well in the fibrin-rich environment of vegetation. The coagulation system is a good target for treating infective endocarditis because of its central role in the disease. But we must be careful, as using blood-thinning medicines in patients with endocarditis can often lead to an increased risk of bleeding. Full article