Search Results (97)

Background and Objectives: Acute or severe limb ischemic events are limb- and life-threatening complications of peripheral artery disease (PAD). Although cirrhosis is increasingly recognized as a systemic disorder associated with endothelial dysfunction, inflammation, and altered hemostatic balance, its relationship with coding-defined limb ischemic events among individuals with PAD remains poorly defined. We investigated whether cirrhosis is independently associated with coding-defined acute or severe limb ischemic events among hospitalized adults with PAD. Materials and Methods: We performed a retrospective discharge-level analysis of the National Inpatient Sample from 2016 to 2018. Adult hospitalizations with PAD were identified using ICD-10-CM diagnosis codes and stratified according to the presence or absence of cirrhosis. The primary outcome was coding-defined acute or severe limb ischemic events. Multivariable logistic regression was used to evaluate the association between cirrhosis and acute or severe limb ischemic events after adjustment for demographic and cardiovascular comorbidities. Propensity-score matching was additionally performed to balance baseline characteristics between hospitalizations with and without cirrhosis. Results: Among 276,702 hospitalizations with PAD, 5942 had cirrhosis. Before matching, cirrhosis was independently associated with higher odds of acute or severe limb ischemic events after multivariable adjustment (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.35–1.60; p < 0.001). After 1:1 propensity-score matching, 5883 matched pairs were analyzed. The association between cirrhosis and acute or severe limb ischemic events persisted in the matched cohort, with cirrhosis remaining significantly associated with increased odds of these events (OR 1.41, 95% CI 1.24–1.60; p < 0.001). Conclusions: In this large discharge-level analysis of hospitalizations with PAD, cirrhosis was independently associated with higher odds of coding-defined acute or severe limb ischemic events. These findings suggest that cirrhosis may represent an underrecognized vascular risk amplifier in PAD. Further prospective studies are needed to validate this association, clarify underlying mechanisms, and determine whether cirrhosis may improve PAD risk stratification. Full article

Chronic subdural hematoma (CSDH) is traditionally described as a post-traumatic blood collection within the subdural space; however, both its anatomical localization and pathophysiology have been increasingly questioned. Ultrastructural and histopathological evidence demonstrates that no true subdural space exists under physiological conditions and that CSDH originates instead within the dural border cell (DBC) layer, a mechanically fragile and biologically active meningeal interface. Accordingly, chronic “subdural” hematoma may be more accurately interpreted as an intradural border cell lesion. Beyond anatomy, CSDH is a dynamic, self-sustaining disease driven by chronic inflammation, pathological angiogenesis, vascular immaturity, and localized hemostatic dysregulation. Hypoxia-induced HIF-1α/VEGF activation promotes fragile, hyperpermeable neovessels, while local hyperfibrinolysis and kallikrein–kinin activation prevent stable clot formation, driving recurrent microbleeding and plasma exudation. Consequently, hematoma persistence and recurrence represent a biological failure rather than a purely technical surgical shortcoming. This conceptual shift provides a coherent rationale for dural-targeted therapies, including middle meningeal artery embolization and pharmacological modulation of angiogenesis and fibrinolysis. Reframing CSDH as a chronic intradural and biologically active disorder has important implications for terminology, classification, and the development of mechanism-oriented, multidisciplinary management strategies. Full article

Snake venoms are rich sources of molecules with pharmacological potential, with approximately 90% of their composition consisting of proteins and peptides responsible for their biological activities. These proteins are classified as enzymatic or non-enzymatic. Enzymatic proteins function as catalysts in regulatory chemical reactions, whereas non-enzymatic proteins, despite lacking catalytic activity, play essential roles in physiological processes. Lectins are non-enzymatic proteins of non-immune origin characterized by carbohydrate- and glycoprotein-binding domains, enabling their ability to agglutinate erythrocytes. C-type lectins and C-type lectin-like proteins are commonly found in snake venoms and are associated with hemostatic disturbances, particularly bleeding and coagulation disorders. This review provides a comprehensive analysis of studies published over the past decade on lectins isolated from snake venom, addressing their definitions, classifications, structural characteristics, and mechanisms of action, as well as their relevance in biotechnological applications. Although progress has been made in elucidating their pharmacological properties, most studies have focused on plant lectins. In contrast, research on snake venom lectins remains limited, particularly regarding their heterologous activities. This gap, especially compared to other venom-derived molecules, highlights the need to further expand research on this class of proteins. Full article

Uncontrolled bleeding, coagulation disorders, and infection-related complications still present substantial challenges in emergency medicine and trauma care. Developing multifunctional hemostatic materials represent an effective strategy for addressing clinical hemostasis problems. In this study, Galla chinensis polyphenols, the effective extract of Galla chinensis, were loaded onto calcium alginate-mesoporous silica granules (CMS-GC). The CMS granules were prepared by in situ liquid-phase technology and GC was loaded by impregnation methods. In vitro and in vivo studies showed that CMS-GC not only activate the endogenous coagulation pathway via GC, but also the multi-level interconnected pores of CMS granules can promote the cross-linking of GC with plasma proteins and formation of a three-dimensional network structure, which further enhances the coagulation effect and shortens the blood clotting time to less than 80 s. In rat liver and femoral artery hemorrhage models, CMS-GC significantly shortened hemostasis time and reduced blood loss, demonstrating superior hemostatic performance. Moreover, within the moist environment sustained by alginate, GC mitigates inflammatory responses via its antibacterial and free-radical clearance properties, and synergistically facilitates wound healing. This CMS-GC multifunctional granule provides an efficient new strategy for traumatic bleeding and subsequent repair. Full article

Background: Substance use disorder (SUD) is associated with systemic inflammatory activation and may influence hematological and coagulation-related pathways. Chronic exposure to psychoactive substances may promote immune activation, endothelial dysfunction, and increased platelet reactivity, thereby contributing to inflammation–coagulation crosstalk. Routine laboratory markers derived from complete blood count and coagulation tests have recently gained attention as potential indicators of these biological alterations. Objective: This study aimed to evaluate hematological inflammatory indices, platelet-related parameters, and coagulation markers in individuals with SUD compared with healthy controls. Methods: This cross-sectional study included individuals diagnosed with SUD (n = 55) and age- and sex-matched healthy controls (n = 40). Hematological parameters, including neutrophil, lymphocyte, monocyte, platelet indices, and derived inflammatory ratios, were analyzed. Coagulation parameters, including prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR), fibrinogen, and D-dimer levels, were also evaluated. Statistical analyses were performed to compare laboratory findings between groups. Results: Significant alterations were observed in several hematological and fibrinolytic parameters in individuals with SUD. Specifically, the neutrophil-to-lymphocyte ratio (NLR), platelet count (PLT), and D-dimer levels were significantly higher in the study group compared with the controls, suggesting increased inflammatory activity, platelet activation, and fibrinolysis. In contrast, the fibrinogen levels did not show clinically meaningful differences between the groups. Conclusions: Individuals with SUD exhibit alterations in hematological inflammatory indices, platelet-related parameters, and fibrinolytic markers. Routine hematological and coagulation parameters may provide accessible indicators of systemic inflammatory and hemostatic disturbances associated with SUD and may support future research aimed at identifying potential biological markers of addiction. Full article

Clonal hematopoiesis refers to the clonal expansion of hematopoietic stem and progenitor cells, driven by somatic mutations. Major mutated genes in clonal hematopoiesis include genes involved in epigenetic regulation including DNA methylation and/or chromatin modification (e.g., DNMT3A, TET2, and ASXL1), tumor suppressors (e.g., TP53), signal transduction (e.g., JAK2), and RNA splicing (e.g., SF3B1 and SRSF2). Clonal hematopoiesis includes clonal hematopoiesis of indeterminate potential (CHIP), clonal cytopenia of unknown significance (CCUS), and myelodysplastic syndromes/neoplasms (MDS). CHIP occurs when the frequency of the variant allele equals or exceeds 2% (4% for X-linked genes in males) in the absence of cytopenias. CHIP is common among older persons and is associated with an increased risk of hematologic cancer. CHIP is also associated with an increased risk of atherosclerotic disease including acute myocardial infarction, stroke, cardiac failure, and abdominal aneurysm. Increasing evidence suggests that CHIP is associated with venous thromboembolic disease. Somatic mutations lead to proliferation of hematopoietic progenitor cells and their progeny, resulting in excessive activation of granulocytes and monocytes. It could be postulated that chronic inflammation caused by clonal expansion of myeloid cells carrying mutations in DNMT3A, TET2, and ASXL1 (“DTA”) genes may constitute an independent risk factor in clot formation and endothelial-cell damage. DTA mutations correlate with elevated proinflammatory cytokines such as IL-1β and IL-6 and enhanced activation of inflammasomes. Moreover, JAK2 mutations may have a direct role in the activation of platelets and coagulation. In vivo murine studies have demonstrated that activation of the JAK-STAT signaling pathway promotes neutrophil extracellular trap (NET) formation, contributing to a prothrombotic state. Insights from related clonal disorders such as paroxysmal nocturnal hemoglobinuria and the VEXAS syndrome support the concept that mutation-driven innate immune activation can directly perturb hemostatic balance. This review aims to summarize the association between clonal expansion of hematopoietic cells and thrombotic disease, and highlight how somatic mutations in hematopoietic cells may contribute to vascular disease and thrombogenesis. Full article

Background: Traumatic brain injury (TBI) has been associated with coagulation disorders, and coagulation and fibrinolytic parameters are frequently monitored in the acute stage of TBI. Methods: Using a rat closed head injury model, mild and severe TBIs were induced. Blood samples were obtained at five post-injury time points, including 1 day and 1, 2, 3, and 4 weeks, to assess coagulation and fibrinolytic parameters, specifically prothrombin time (PT), partial thromboplastin time (PTT), D-dimer, and fibrinogen. Results: In mild TBI, all hemostatic parameters remained largely within physiological ranges, despite minor statistical fluctuations in PT and PTT. Conversely, severe TBI resulted in significant elevations of PT (p = 0.00015) and PTT (p = 0.01) during the first week. Additionally, D-dimer levels increased significantly at week 2 (p = 0.024) and week 4 (p = 0.014) post-injury, surpassing the upper limit of normal. Although fibrinogen levels showed a significant increase at week 2 compared to the control group (p = 0.011), they remained within the normal reference range. Conclusions: While mild TBI is characterized by stable hemostatic markers, severe TBI demonstrates a clear and significant progression from acute coagulation activation to secondary fibrinolysis. These findings suggest that severe TBI-induced coagulopathy is a progressive event requiring extended longitudinal monitoring beyond the initial acute phase. 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

Endovascular aneurysm repair (EVAR) is a widely used minimally invasive treatment for abdominal aortic aneurysms. However, postoperative type II endoleak (T2EL) remains a relevant complication associated with a risk of aneurysm rupture and the need for repeated imaging follow-up, resulting in exposure to ionizing radiation. Identification of biological factors predisposing to T2EL may improve risk stratification. This pilot study aimed to investigate whether disturbances in hemostasis are associated with early T2EL development after EVAR. A total of 103 patients treated with EVAR for symptomatic or asymptomatic abdominal aortic aneurysms in a tertiary vascular center were prospectively enrolled. Blood samples were collected preoperatively and one month postoperatively to assess fibrinogen, prothrombin fragment F1+2 (F1+2), thrombin–antithrombin complex (TAT), tissue plasminogen activator antigen (tPA), plasminogen activator inhibitor-1 (PAI-1) activity, and platelet activity. Computed tomography angiography (CTA) during follow-up was used to detect endoleaks and calculate their volume. Patients with T2EL had significantly lower levels of prothrombin fragment F1+2 and higher PAI-1 activity compared with patients without endoleak. No significant association was observed between the analyzed biomarkers and endoleak volume. These findings suggest that reduced thrombin generation and impaired fibrinolysis may contribute to endoleak formation after EVAR and warrant further investigation in larger, confirmatory studies. Full article

The concept of ‘developmental hemostasis’ from birth to infancy and onwards to childhood and adulthood was introduced in the 1980s and is used to indicate the fundamental discrepancies of hemostatic mechanism between children and adults. The underlying differentiations are more pronounced in term and even more in preterm neonates. Hemostatic alterations tend to improve throughout childhood and adolescence but still imply a great example of the basic concept that children do not simply represent small adults. Many neonatal coagulation disorders lead to severe morbidities, such as intraventricular hemorrhage and intracerebral infarct, with critical consequences on long-term neurodevelopmental outcome. As the limits of viability have decreased and many preterm and severely affected neonates survive and grow up, a broad understanding of hemorrhagic and thrombotic complications in neonates is very important, in order to provide prompt identification and treatment. Coagulation abnormalities are usually induced by specific pathophysiologic disorders, and neonatal sepsis is a significant trigger of hemostatic derangement. Despite the initial protective role of coagulation activation during the early stages of sepsis, ultimately hemostatic abnormalities exert a substantial impact on clinical outcome and prognosis. This review explores developmental aspects of coagulation, particularly in relation to neonatal sepsis. Full article

Blood platelets are derived from megakaryocytes with functions extending beyond hemostasis to inflammation, immunity, and cancer. Myeloproliferative neoplasms (MPNs) are clonal stem cell disorders driven by somatic mutations affecting JAK-STAT signaling, leading to excessive myeloid proliferation. Thrombosis affects approximately one-fifth of patients at diagnosis and remains elevated throughout the disease course, while the paradoxical coexistence of bleeding further complicates clinical management. In addition, MPNs may progress to advanced disease stages, including bone marrow fibrosis and transformation to acute myeloid leukemia, leading to ineffective hematopoiesis, worsening symptom burden, and poor clinical outcomes. This review outlines how peripherally circulating platelets provide a unique window into MPN pathophysiology, with emphasis on their functional and molecular abnormalities. We summarize current understanding of platelet-mediated hemostatic imbalance across MPN subtypes. We discuss the potential of platelet transcriptomics and proteomics to reveal disease-specific signatures. We further highlight emerging platelet-associated candidates with potential utility as dynamic biomarkers for both the pathological marrow niche and thrombotic and bleeding risk. Together, these insights underscore the potential of platelet-based approaches to complement existing diagnostic and prognostic strategies in MPNs. Full article

The interaction between Angiostrongylus vasorum and the vascular endothelium of the host plays a key role in the pathogenesis of canine angiostrongylosis. The adult stage of A. vasorum resides in right ventricles and pulmonary arteries of dogs and foxes and maintains close contact with the endothelium, whose activation may contribute to the hemostatic and hemorrhagic disorders observed in infected animals. However, the molecular mechanisms underlying this endothelial dysfunction remain poorly understood. To investigate this interaction, an in vitro model of vascular endothelial cells was stimulated with the adult A. vasorum homogenate. Quantitative proteomic analysis, combined with bioinformatic tools, identified 691 and 6011 protein groups in the cell supernatants and the cell lysates, respectively. Of these, 213 proteins in the cell supernatants (193 up-regulated and 20 down-regulated) and 564 in the cell lysates (358 up-regulated and 206 down-regulated) showed differential expression compared to control cells. Up-regulated proteins included TFPI, CD59, VWF, ANGPT2, MMRN1, and FLT1, which are involved in endothelial activation, angio-genesis, and coagulation regulation. Conversely, C3, SERPINE1, SERPINB2, PLAU, PLAUR, and ICAM1 were down-regulated, suggesting modulation of fibrinolysis, inflammation, and cell adhesion pathways. These findings indicate that adult A. vasorum homogenate induces a multifactorial endothelial activation characterized by dysregulation of coagulation, complement, and vascular remodelling pathways. Future studies focusing on the temporal and molecular characterization of endothelial responses to excretory/secretory antigens in both definitive and accidental hosts will further clarify the mechanisms of vascular pathology and parasite tolerance. Full article

WIB-801CE, a standardized Cordyceps militaris extract containing 7.0% cordycepin, suppresses platelet activation induced by thrombin, collagen, and adenosine diphosphate (ADP). As these agonists generate thromboxane A₂ (TXA₂), which amplifies platelet activation via a self-propagating feedback loop, blockade of TXA₂-mediated signaling offers strong antithrombotic potential. TXA₂-antagonistic effects were evaluated using U46619, a stable TXA₂ analog. Platelet activation was assessed by fibrinogen binding to integrin αIIbβ₃, aggregation, and phosphorylation of platelet-activating proteins—PI3K (Tyr458), Akt (Ser473), p38 MAPK (Thr180/Tyr182), ERK1 (Thr202/Tyr204), JNK1 (Thr183/Tyr185)—and inhibitory proteins—VASP (Ser157) and IP₃RI (Ser1756)—via immunoblotting. Thrombin-induced fibrin clot retraction, cytotoxicity, coagulation parameters, and antioxidant capacity were also examined. WIB-801CE significantly inhibited U46619-induced fibrinogen binding to integrin αIIbβ₃ and platelet aggregation, without inducing cytotoxicity or impairing hemostatic function. It also significantly downregulated the phosphorylation of platelet-activating proteins and upregulated the phosphorylation of platelet-inhibiting proteins. Additionally, WIB-801CE abolished thrombin-induced fibrin clot retraction and demonstrated antioxidant capacity. WIB-801CE disrupts TXA₂-driven platelet activation and thrombus stabilization by selectively modulating phosphorylation of key signaling proteins at defined regulatory sites. These properties highlight its promise as a therapeutic candidate for thrombotic disorders with platelet hyperreactivity. Full article

Legg–Calvé–Perthes disease (LCPD) is a rare disease caused by avascular necrosis of the femoral head. Although its etiology is still not fully understood, evidence suggests that heritable prothrombotic and inflammatory factors, as well as environmental factors, may be implicated in its onset and progress. The objective of this study is to describe the genetic, biochemical, and environmental factors that may be associated with the etiology of LCPD. This study was conducted in three families and included seven related patients with an LCPD diagnosis. We evaluated the following gene alterations using real-time PCR: MTHFR, CBS, COL1A1, COL2A1, PT, FVL, FVIII, FIX, PAI-1, eNOS, IL-23R, TNF-α, RANNK, RANNK-L, OPG and IL-6. Additionally, we assessed fourteen thrombophilia-associated biochemical markers, as well as environmental factors that may be associated with the etiology of LCPD in family cases. The results show different hemostatic alterations in every individual analyzed, presenting out-of-range values in one or more parameters. Concentrations of hemoglobin and fibrinogen and the FIX activity percentage showed statistically significant differences (p < 0.001) when compared with healthy controls. All patients presented at least one mutated allele for the MTFHR (rs1801133), IL-23R (rs1569922) and OPG (rs2073618) polymorphisms, as well as isolated cases with other genetic variants. Our results show environmental elements from every family, and hemostatic and inflammatory disorders, may be involved in the development of LCPD. Furthermore, genetic variants could contribute to the onset of the disease. This study highlights the multifactorial nature of this pathology, involving various environmental, genetic, inflammatory, and prothrombotic factors in three families that included seven patients diagnosed with LCPD. 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