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14 pages, 7744 KB  
Article
Effect of Perfluorooctanesulfonic Acid on Fibrin Clot Properties and Thrombin Generation: Linking Environmental Pollution with Cardiovascular Diseases
by Jakub Kuciński, Krzysztof Krawczyk, Konrad Kieca, Aleksander Siniarski, Michał Ząbczyk and Ewa Konduracka
J. Cardiovasc. Dev. Dis. 2026, 13(5), 209; https://doi.org/10.3390/jcdd13050209 - 13 May 2026
Viewed by 199
Abstract
Perfluorooctanesulfonic acid (PFOS) is a persistent organic pollutant linked in epidemiological studies to increased coronary artery disease (CAD) risk, higher LDL-cholesterol, hypertension, and other adverse outcomes. However, the mechanisms by which PFOS affects cardiovascular physiology, particularly coagulation, remain insufficiently understood. We evaluated the [...] Read more.
Perfluorooctanesulfonic acid (PFOS) is a persistent organic pollutant linked in epidemiological studies to increased coronary artery disease (CAD) risk, higher LDL-cholesterol, hypertension, and other adverse outcomes. However, the mechanisms by which PFOS affects cardiovascular physiology, particularly coagulation, remain insufficiently understood. We evaluated the ex vivo effects of PFOS on fibrin clot structure and thrombin generation in platelet-poor plasma (PPP) and citrated whole blood from ten healthy volunteers (five women, aged 27–32 years; mean serum PFOS: 2.63 ± 0.85 μg/L). PPP samples were incubated with PFOS at 50, 200, and 400 μg/L. Assays included calibrated automated thrombogram, clot permeability (Ks), clot lysis time (CLT), thromboelastography (400 μg/L), and scanning electron microscopy (SEM). PFOS did not significantly modify endogenous thrombin potential or peak thrombin. In contrast, it reduced Ks and prolonged CLT at 200 and 400 μg/L, indicating impaired fibrinolysis. SEM images confirmed the formation of thinner, tightly packed fibrin fibers with reduced pore size at higher PFOS concentrations. These findings were consistent across dilution models, with only minimal changes observed in low-dilution protocols. Overall, PFOS appears to disrupt fibrin polymerization, generating denser and more fibrinolysis-resistant clots without major effects on thrombin generation. Such alterations may promote a prothrombotic state and predispose exposed individuals to clinically relevant thrombotic events, including myocardial infarction and stroke. Further studies are required to define the clinical consequences of PFOS-related coagulation abnormalities in exposed populations. Full article
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16 pages, 2583 KB  
Article
Functional Aspects of Fibrin Structure Alterations by Tranexamic Acid in the Inhibition of Fibrinolysis
by Kata Balog Virag, Barbara Baráth, Kristóf Molnár, Petra Csikós, Alexandra Raska, László Szabó, Natalia Nikolova, Kiril Tenekedjiev, Krasimir Kolev and Nikolett Wohner
Biomolecules 2026, 16(5), 696; https://doi.org/10.3390/biom16050696 - 8 May 2026
Viewed by 524
Abstract
Background: Tranexamic acid (TXA) is a synthetic lysine analog widely used as an antifibrinolytic agent. Large randomized trials have demonstrated life-saving benefits when TXA is administered early in acute hemorrhage, but results regarding prophylactic administration have been conflicting, and several trials have not [...] Read more.
Background: Tranexamic acid (TXA) is a synthetic lysine analog widely used as an antifibrinolytic agent. Large randomized trials have demonstrated life-saving benefits when TXA is administered early in acute hemorrhage, but results regarding prophylactic administration have been conflicting, and several trials have not shown improved clinical outcomes. The mechanisms underlying this discrepancy remain incompletely understood. Objectives: To investigate the molecular and structural mechanisms that determine TXA efficacy in purified fibrin clots under conditions mimicking therapeutic versus prophylactic administration. Methods: We examined fibrinolysis induced by tissue plasminogen activator (tPA) in vitro using confocal microscopy, viscoelastic testing (ClotPro), turbidimetry, and plasmin generation assays at physiologically and therapeutically relevant concentrations of plasminogen and TXA. Scanning electron microscopy (SEM) was employed to assess fibrin structure. Results: When TXA was incorporated into fibrin clots before the addition of tPA, physiological plasminogen concentrations (2.5 µM) reversed the antifibrinolytic effect, resulting in paradoxical acceleration of lysis. By contrast, when clotting and fibrinolysis occurred simultaneously in the presence of TXA and tPA, TXA consistently prolonged lysis time irrespective of plasminogen concentration. SEM demonstrated that TXA, even at concentrations as low as 16 µM, doubled the top-quartile values of the fibrin fiber diameter, altering susceptibility to plasmin-mediated degradation without accelerating plasminogen activation. Conclusions: TXA efficacy is determined not only by dose but also by timing and the plasminogen availability in the clot microenvironment. These findings provide mechanistic insight into the failure of prophylactic TXA administration and highlight the importance of context in optimizing its clinical use. Full article
(This article belongs to the Special Issue Fibrinogen and Fibrin in Human Diseases)
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15 pages, 3223 KB  
Article
First Clinical Description of Coagulation of Whole Blood with Resonant Acoustic Rheometry
by Connor M. Bunch, Weiping Li, Kiera Downey, Timothy L. Hall, Allen Chehimi, Samuel J. Thomas, Afsheen Mansoori, Miguel Velasco, Marie N. Karam, Jenny Chen, Jacob Tuttle, Matthew R. Walsh, Scott G. Thomas, Mark M. Walsh, Joseph B. Miller, Jan P. Stegemann and Cheri X. Deng
Diagnostics 2026, 16(1), 47; https://doi.org/10.3390/diagnostics16010047 - 23 Dec 2025
Viewed by 1255
Abstract
Background/Objectives: The timely evaluation of blood clot formation and breakdown is essential in the care of patients with severe bleeding or critical illness. Resonant acoustic rheometry is a novel, non-contact ultrasound method that measures changes in the viscoelastic properties of blood in [...] Read more.
Background/Objectives: The timely evaluation of blood clot formation and breakdown is essential in the care of patients with severe bleeding or critical illness. Resonant acoustic rheometry is a novel, non-contact ultrasound method that measures changes in the viscoelastic properties of blood in a standard microplate format. Here, we present the first clinical description of whole blood coagulation and fibrinolysis assessed with resonant acoustic rheometry, with paired thromboelastography measurements for comparison. Methods: In this retrospective analysis, whole blood samples from three critically ill patients were divided and tested under four different conditions that included a control mixture, kaolin activation, tissue factor activation, and a tissue factor mixture supplemented with tissue plasminogen activator. The resonant acoustic rheometry system obtained real time measurements of resonant surface waves and displacements from the samples. Heat maps and spectrograms of the resonant surface waves were analyzed to determine the onset of clotting, the rate of viscoelastic stiffening, the time to maximum rigidity, and the onset as well as magnitude of fibrinolysis. These measurements were compared with thromboelastography reaction time, clot strength, fibrinogen contribution, and lysis values. Results: Resonant acoustic rheometry detected reproducible transitions from liquid to clot and from clot to lysis in all samples. Activator-dependent changes in clot initiation and propagation matched the expected hierarchy observed in thromboelastography. Significantly, samples exposed to tissue plasminogen activator demonstrated a clear fall in resonant frequency and a corresponding rise in surface displacement that reflected fibrinolysis. The technique also reproduced clinically meaningful patterns of hemostasis that aligned with each patient’s underlying disease. Conclusions: Whole blood clotting can be measured with resonant acoustic rheometry in a manner that aligns with established clinical assays. These results suggest strong potential for future use of resonant acoustic rheometry as a cost-effective, complementary platform for rapid, scalable, and clinically informative hemostatic assessment. Full article
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21 pages, 412 KB  
Article
Unveiling the Hemostatic Signature of Prematurity: A Prospective Rotational Thromboelastometry-Based Analysis
by Martha Theodoraki, Alexia Eleftheria Palioura, Aikaterini-Pothiti Palioura, Abraham Pouliakis, Zoi Iliodromiti, Theodora Boutsikou, Nicoletta Iacovidou and Rozeta Sokou
Medicina 2025, 61(9), 1718; https://doi.org/10.3390/medicina61091718 - 21 Sep 2025
Cited by 2 | Viewed by 1478
Abstract
Background and Objectives: The evaluation of the haemostatic mechanism in premature neonates remains particularly challenging, due to their immature haemostatic system, the influence of inflammation and the variety of clinical factors. This prospective study aimed at (a) assessing the haemostatic profile of [...] Read more.
Background and Objectives: The evaluation of the haemostatic mechanism in premature neonates remains particularly challenging, due to their immature haemostatic system, the influence of inflammation and the variety of clinical factors. This prospective study aimed at (a) assessing the haemostatic profile of clinically stable preterm neonates by Rotational Thromboelastometry [ROTEM; (EXTEM, INTEM, FIBTEM assays)], (b) establishing reference ranges, and (c) investigating potential differences in comparison to healthy term neonates. We also evaluated the impact of clinical and perinatal factors on the haemostatic status of this vulnerable population. Materials and Methods: 69 premature neonates with no underlying morbidity and 226 healthy term neonates were the study subjects. In term neonates, blood was collected on the 2nd-3rd day of life, if sampling was required for any other reason (hyperbilirubinemia, ABO blood group incompatibility screening, maternal thyroid antibodies, or insufficient prenatal care), whereas in premature neonates, blood was collected between the 4nd-10th day after stabilisation. The parameters measured for each ROTEM assay included Clotting Time (CT), Clot Formation Time (CFT), Alpha angle (α, degrees), Clot Amplitude at 5 and 10 min (A5, A10), Maximal Clot Firmness (MCF), and Lysis Index at 30, 45 and 60 min (Li30, Li45, and Li60 respectively). Results: The data analysis demonstrated a prothrombotic profile in preterm neonates, characterized by increased values of A5, A10, (MCF), and α-angle, and shortened CT and CFT across all assays (EXTEM, INTEM, FIBTEM), when compared to term neonates. A statistically significant inverse correlation was observed between gestational age and clot lysis parameters (INTEM Li45, Li60). Additionally, hematocrit levels were negatively correlated with clot amplitude and kinetics of clot development, while platelet count was positively associated with clot firmness parameters (A5, A10, MCF) and α-angle. Mode of delivery and the presence of gestational diabetes did not significantly affect ROTEM assay values. Preterm neonates with a history of respiratory distress syndrome (RDS) exhibited a more pronounced hypercoagulable profile compared to those without RDS, as reflected by the enhanced clot strength and reduced CT, findings that may be attributed to postnatal pulmonary inflammation and its systemic effects on coagulation. Conclusions: This study introduces for the first time reference values for the parameters of ROTEM assays (EXTEM, INTEM, FIBTEM) in clinically stable preterm neonates—a highly vulnerable patient group with a distinct need for accurate and individualized monitoring of their haemostatic status. The combined assessment of these assays enhances diagnostic precision, and offers a more comprehensive evaluation of neonatal haemostasis. By defining reference ranges in whole blood, this work provides novel data that support the integration of ROTEM into clinical transfusion algorithms. Full article
(This article belongs to the Special Issue From Conception to Birth: Embryonic Development and Disease)
28 pages, 3553 KB  
Article
Investigation of Analgesic, Anti-Inflammatory, and Thrombolytic Effects of Methanolic Extract and Its Fractions of Dischidia bengalensis: In Vitro and In Vivo Studies with In Silico Interventions
by Ainun Nahar, Md. Jahin Khandakar, Md. Jahirul Islam Mamun, Md. Hossain Rasel, Abu Bin Ihsan, Asef Raj, Saika Ahmed, Mohammed Kamrul Hossain, Md Riasat Hasan and Takashi Saito
Molecules 2025, 30(18), 3724; https://doi.org/10.3390/molecules30183724 - 12 Sep 2025
Cited by 16 | Viewed by 4085
Abstract
In a continued search for novel plant-based therapeutics with multi-target pharmacological potential, the medicinal plant Dischidia bengalensis (Apocynaceae) was investigated for the first time for its anti-inflammatory, analgesic, and thrombolytic properties, addressing critical therapeutic areas such as rheumatoid arthritis, acute pain, and thrombosis. [...] Read more.
In a continued search for novel plant-based therapeutics with multi-target pharmacological potential, the medicinal plant Dischidia bengalensis (Apocynaceae) was investigated for the first time for its anti-inflammatory, analgesic, and thrombolytic properties, addressing critical therapeutic areas such as rheumatoid arthritis, acute pain, and thrombosis. The methanolic extract and solvent fractions (dichloromethane, n-hexane, and ethyl acetate) were evaluated through integrated in vivo, in vitro, and in silico approaches. Phytochemical screening and GC–MS profiling revealed a diverse array of bioactive constituents, including fatty acids, terpenoids, and phenolic derivatives, many of which are reported to exhibit pharmacological activities. In vivo assays demonstrated that the methanolic extract (400 mg/kg) markedly suppressed carrageenan-induced paw edema (92.31% inhibition) from the 2nd to 4th hour (p  <  0.05, p  <  0.01), while the n-hexane fraction produced the most pronounced analgesic response in both writhing and tail-immersion models (p  <  0.001). Furthermore, the methanolic extract displayed significant thrombolytic activity (33.38  ±  4.27% at 20 mg/mL, p < 0.001) in human blood clot lysis, suggesting potential application in cardiovascular disorders. The scientific novelty of this study was further underscored by in silico molecular docking, ADME/T, and PASS prediction studies. Key bioactive compounds, identified by GC-MS, showed strong binding affinities and promising drug-like properties against pivotal human targets such as TNF-α (PDB: 2AZ5), COX-2 (PDB: 6COX), and tissue plasminogen activator. These findings conclusively establish D. Bengalensis as a promising and novel source of lead compounds for the development of novel therapeutics against inflammatory, pain-related, and cardiovascular disorders. Full article
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26 pages, 643 KB  
Review
The Fibrinolytic System in Bacterial Sepsis: A Comprehensive Review of Current Assessment Methods
by Florin Scarlatescu, Ecaterina Scarlatescu, Jecko Thachil, Dana R. Tomescu and Daniela Bartos
J. Clin. Med. 2025, 14(17), 6055; https://doi.org/10.3390/jcm14176055 - 27 Aug 2025
Cited by 3 | Viewed by 2364
Abstract
Background: Fibrinolytic impairment is one of the key factors involved in the pathogenesis of hemostasis disturbances in sepsis, significantly contributing to microthrombosis, organ dysfunction, and mortality rates. While hemostatic assessment in sepsis typically focuses on coagulation activation, evaluating fibrinolytic activity remains challenging due [...] Read more.
Background: Fibrinolytic impairment is one of the key factors involved in the pathogenesis of hemostasis disturbances in sepsis, significantly contributing to microthrombosis, organ dysfunction, and mortality rates. While hemostatic assessment in sepsis typically focuses on coagulation activation, evaluating fibrinolytic activity remains challenging due to methodological limitations and a lack of standardization of the currently available methods. Objectives: This comprehensive review examines current methods for assessing fibrinolytic activity in bacterial sepsis, their clinical applications, strengths and limitations, and future perspectives for improved diagnostic approaches. Methods: We conducted a systematic literature search and identified 52 studies that investigated fibrinolysis assessment in adult patients with bacterial sepsis using biomarkers or global tests. Studies included mainly observational cohorts examining various fibrinolytic assessment methods. Results: Fibrinolytic shutdown, primarily mediated by the overproduction of plasminogen activator inhibitor-1 (PAI-1), occurs early in sepsis and correlates with disease severity and mortality. Current assessment methods include plasma biomarker measurements (PAI-1, plasmin-antiplasmin complexes, D-dimer), global plasma-based tests (clot lysis time, plasmin generation assays), and whole-blood viscoelastic testing (rotational thromboelastometry, ROTEM; thromboelastography, TEG). Modified viscoelastic tests incorporating tissue plasminogen activators demonstrate enhanced sensitivity for detecting fibrinolytic resistance. Despite efforts, standardization is still limited, and routine clinical implementation has not been achieved yet. Conclusions: Fibrinolytic assessment provides important prognostic information in sepsis, despite methodological challenges. The integration of point-of-care viscoelastic testing with modified protocols shows promise for real-time evaluation. Future research should focus on developing standardized, automated assays suitable for routine clinical practice, enabling personalized therapeutic interventions that target fibrinolytic dysfunction in sepsis. Full article
(This article belongs to the Special Issue Sepsis: Current Updates and Perspectives)
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27 pages, 1379 KB  
Article
A Multifaceted Exploration of Shirakiopsis indica (Willd) Fruit: Insights into the Neuropharmacological, Antipyretic, Thrombolytic, and Anthelmintic Attributes of a Mangrove Species
by Mahathir Mohammad, Md. Jahirul Islam Mamun, Mst. Maya Khatun, Md. Hossain Rasel, M Abdullah Al Masum, Khurshida Jahan Suma, Mohammad Rashedul Haque, Sayed Al Hossain Rabbi, Md. Hemayet Hossain, Hasin Hasnat, Nafisah Mahjabin and Safaet Alam
Drugs Drug Candidates 2025, 4(3), 31; https://doi.org/10.3390/ddc4030031 - 1 Jul 2025
Cited by 18 | Viewed by 2284
Abstract
Background: Shirakiopsis indica (Willd.) (Family: Euphorbiaceae), a mangrove species found in the Asian region, is a popular folkloric plant. Locally, the plant is traditionally used to treat various types of ailments, especially for pain relief. Therefore, the current study investigates the neuropharmacological, [...] Read more.
Background: Shirakiopsis indica (Willd.) (Family: Euphorbiaceae), a mangrove species found in the Asian region, is a popular folkloric plant. Locally, the plant is traditionally used to treat various types of ailments, especially for pain relief. Therefore, the current study investigates the neuropharmacological, antipyretic, thrombolytic, and anthelmintic properties of the S. indica fruit methanolic extract (SIF-ME). Methods: The neuropharmacological activity was evaluated using several bioactive assays, and the antipyretic effect was investigated using the yeast-induced pyrexia method, both in Swiss albino mice models. Human blood clot lysis was employed to assess thrombolytic activity, while in vitro anthelmintic characteristics were tested on Tubifex tubifex. Insights into phytochemicals from SIF-ME have also been reported from a literature review, which were further subjected to molecular docking, pass prediction, and ADME/T analysis and validated the wet-lab outcomes. Results: In the elevated plus maze test, SIF-ME at 400 mg/kg demonstrated significant anxiolytic effects (200.16 ± 1.76 s in the open arms, p < 0.001). SIF-ME-treated mice exhibited increased head dipping behavior and spent a longer time in the light box, confirming strong anxiolytic activity in the hole board and light–dark box tests, respectively. It (400 mg/kg) also significantly reduced depressive behavior during forced swimming and tail suspension tests (98.2 ± 3.83 s and 126.33 ± 1.20 s, respectively). The extract induced strong locomotor activity, causing mice’s mobility to gradually decrease over time in the open field and hole cross tests. The antipyretic effect of SIF-ME (400 mg/kg) was minimal using the yeast-induced pyrexia method, while it (100 μg/mL) killed T. tubifex in 69.33 ± 2.51 min, indicating a substantial anthelmintic action. SIF-ME significantly reduced blood clots by 67.74% (p < 0.001), compared to the control group’s 5.56%. The above findings have also been predicted by in silico molecular docking studies. According to the molecular docking studies, the extract’s constituents have binding affinities ranging from 0 to −10.2 kcal/mol for a variety of human target receptors, indicating possible pharmacological activity. Conclusions: These findings indicate that SIF-ME could serve as a promising natural source of compounds with neuropharmacological, anthelmintic, thrombolytic, and antipyretic properties. Full article
(This article belongs to the Section Drug Candidates from Natural Sources)
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12 pages, 432 KB  
Article
Comparison of Fibrinolysis in Peripartum and Non-Pregnant Mares Using Modified Thromboelastography
by Kira L. Epstein, Kelsey A. Hart, Ella J. Chakravarty and Steeve Giguère
Animals 2025, 15(13), 1822; https://doi.org/10.3390/ani15131822 - 20 Jun 2025
Cited by 1 | Viewed by 686
Abstract
During pregnancy and the peripartum period in women, hypofibrinolysis and hypercoagulation minimize excessive hemorrhage risk during parturition. While hypercoagulation is documented in peripartum mares, hypofibrinolysis is not. This study aimed to characterize and compare the fibrinolytic potential of healthy, non-pregnant mares and peripartum [...] Read more.
During pregnancy and the peripartum period in women, hypofibrinolysis and hypercoagulation minimize excessive hemorrhage risk during parturition. While hypercoagulation is documented in peripartum mares, hypofibrinolysis is not. This study aimed to characterize and compare the fibrinolytic potential of healthy, non-pregnant mares and peripartum mares using tissue-factor (TF)-activated, tissue-plasminogen-activator (tPA)-modified thromboelastography (TEG). TF-activated TEG modified with tPA (500 and 650 U/mL) was performed on plasma samples from 9 pregnant mares at 3, 2, and 1 month pre-partum and 1, 7, and 30 days post-partum, as well as on time-matched samples from 6 non-pregnant mares. At both tPA concentrations, there were relative increases in clot strength [MA] and changes in lysis parameters consistent with hypofibrinolysis (increased CL30 and decreased Ly30) in the pregnant mares compared to the non-pregnant mares. The differences were most frequently detected 1 month pre-partum and at 1 and 7 days post-partum, providing preliminary evidence suggesting pregnant mares are hypofibrinolytic during late gestation and the early post-partum period. However, our small sample size, the unexpected changes in fibrinolysis in the non-pregnant mares over time, and the inconsistent performance of the assay indicate a need for a larger study after further assay optimization to confirm the results. Further investigations of the tPA-modified TEG assay and fibrinolysis in clinical cases are warranted. Full article
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23 pages, 1513 KB  
Article
A New Serine Protease (AsKSP) with Fibrinolytic Potential Obtained from Aspergillus tamarii Kita UCP 1279: Biochemical, Cytotoxic and Hematological Evaluation
by José P. Martins Barbosa-Filho, Renata V. Silva Sobral, Viviane N. S. Alencar, Marllyn Marques Silva, Juanize M. Silva Batista, Galba Maria Campos-Takaki, Wendell W. C. Albuquerque, Romero M. P. Brandão-Costa, Ana Lúcia Figueiredo Porto, Ana C. L. Leite and Thiago Pajéu Nascimento
Catalysts 2025, 15(6), 561; https://doi.org/10.3390/catal15060561 - 5 Jun 2025
Viewed by 1788
Abstract
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), [...] Read more.
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
(This article belongs to the Section Catalysis for Pharmaceuticals)
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13 pages, 269 KB  
Article
Markers of Inflammation and Hypofibrinolysis Are Associated with Cognitive Dysfunction and Motor Performances in Atrial Fibrillation Patients on Oral Anticoagulant Therapy: Insights from the Strat-AF Study
by Francesco Alfano, Francesca Cesari, Anna Maria Gori, Martina Berteotti, Emilia Salvadori, Betti Giusti, Alessia Bertelli, Filippo Fratini, Angela Rogolino, Benedetta Formelli, Francesca Pescini, Enrico Fainardi, Eleonora Barucci, Giulia Salti, Arianna Cavaliere, Andrea Ginestroni, Rossella Marcucci and Anna Poggesi
Biomedicines 2025, 13(4), 941; https://doi.org/10.3390/biomedicines13040941 - 11 Apr 2025
Cited by 2 | Viewed by 1069
Abstract
Background: Atrial fibrillation (AF) is the most common supraventricular arrythmia and one of the most commonly encountered heart conditions in clinical practice. Emerging evidence suggests a significant role of inflammation in the pathogenesis of AF. Population studies have also suggested an association between [...] Read more.
Background: Atrial fibrillation (AF) is the most common supraventricular arrythmia and one of the most commonly encountered heart conditions in clinical practice. Emerging evidence suggests a significant role of inflammation in the pathogenesis of AF. Population studies have also suggested an association between AF and cognitive impairment and dementia. The aim of this study is therefore to assess, in a population of AF patients on oral anticoagulant therapy, the association between circulating biomarkers involved in the pathogenesis of AF and the cognitive and motor performances of the enrolled patients. Methods: The Strat-AF study is an observational, prospective, single-center, hospital-based study enrolling elderly patients with AF. Results refer to 180 subjects who underwent a complete clinical, biohumoral, cognitive, and functional evaluation. Results: At multivariate logistic regression, Clot Lysis Time (CLT) and circulating levels of von Willebrand Factor (vWF) remained significantly associated with pathological performances at the Stroop test (expressed as execution time) [OR 95% CI 1.54 (1.02–2.35), p = 0.042 and 1.75 (1.08–2.82), p = 0.023, respectively]. With regard to the Short Physical Performance Battery (SPPB), the circulating levels of IL-8 remained significantly associated with the clinical endpoint [OR 95% CI 2.19 (1.13–4.25), p = 0.020]. Conclusions: Our results suggest a potential innovative tool able to identify AF patients at risk of worse prognosis in terms of cognitive and motor performances. The clinical relevance of these results is due to the fact that we have no efficient methods to predict a deterioration in the cognitive performance and, consequently, the possible onset of dementia in AF patients undergoing oral anticoagulant therapy. Full article
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14 pages, 444 KB  
Article
Hemostatic Status of Neonates with Perinatal Hypoxia, Studied via NATEM in Cord Blood Samples
by Marina Tsaousi, Rozeta Sokou, Abraham Pouliakis, Marianna Politou, Nicoletta Iacovidou, Theodora Boutsikou, Alma Sulaj, Eleni Karapati, Andreas G. Tsantes, Argirios E. Tsantes, Serena Valsami and Zoi Iliodromiti
Children 2024, 11(7), 799; https://doi.org/10.3390/children11070799 - 29 Jun 2024
Cited by 2 | Viewed by 2476
Abstract
Background: Perinatal hypoxia may result in coagulation dysfunction. Diminished blood flow or oxygen to the fetus/neonate during the perinatal period can cause bone marrow and liver function impairment, leading to thrombocytopenia, impaired synthesis of clotting and fibrinolytic factors, and increased destruction of platelets [...] Read more.
Background: Perinatal hypoxia may result in coagulation dysfunction. Diminished blood flow or oxygen to the fetus/neonate during the perinatal period can cause bone marrow and liver function impairment, leading to thrombocytopenia, impaired synthesis of clotting and fibrinolytic factors, and increased destruction of platelets in the small blood vessels. The goal of the present study was to evaluate the hemostatic status of newborns with perinatal hypoxia via the non-activated thromboelastometry (NATEM) assay in cord blood samples. Methods: 134 hypoxic neonates born in our maternity unit over a 1.5-year period were enrolled in this observational cohort study, and 189 healthy neonates served as the control group. Participation in the study was voluntary and parents signed informed consent prior to recruitment. Demographic and clinical data were recorded on admission, and the NATEM method was performed on cord blood samples. The following NATEM values were evaluated: clotting time (CT), alpha angle (α-angle), clot formation time (CFT), clot amplitude at 5 and 10 min. (A5, A10), maximum clot firmness (MCF), clot lysis index at 60 min. after CT (LI60), and maximum clot elasticity (MCE). Statistical analysis was conducted utilizing the SAS for Windows 9.4 software platform. Results: Neonates with perinatal hypoxia exhibited decreased fibrinolytic potential in comparison to healthy neonates, as indicated by increased LI60, and this difference was statistically significant (LΙ60: 94 (92–96) Vs 93 (91–95), p value = 0.0001). There were no statistically significant differences noted among the remaining NATEM variables. Conclusion: Our findings indicate decreased fibrinolytic potential in hypoxic neonates in comparison to healthy neonates, suggesting that NATEM could serve as an effective tool for promptly identifying hemostasis dysfunction in this group of neonates. Full article
(This article belongs to the Section Pediatric Neonatology)
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24 pages, 2021 KB  
Article
Association of Metallic and Nonmetallic Elements with Fibrin Clot Properties and Ischemic Stroke
by Hieronim Jakubowski, Marta Sikora, Ewa Bretes, Joanna Perła-Kaján, Olga Utyro, Izabela Wojtasz, Radosław Kaźmierski, Marcin Frankowski and Anetta Zioła-Frankowska
Life 2024, 14(5), 634; https://doi.org/10.3390/life14050634 - 16 May 2024
Cited by 2 | Viewed by 2138
Abstract
Objectives—Metallic elements and fibrin clot properties have been linked to stroke. We examined metallic and nonmetallic elements, fibrin clot lysis time (CLT), and maximum absorbance (Absmax) in relation to ischemic stroke. Design—A case–control study of ischemic stroke patients vs. healthy individuals. [...] Read more.
Objectives—Metallic elements and fibrin clot properties have been linked to stroke. We examined metallic and nonmetallic elements, fibrin clot lysis time (CLT), and maximum absorbance (Absmax) in relation to ischemic stroke. Design—A case–control study of ischemic stroke patients vs. healthy individuals. Subjects and Methods—Plasma and serum were collected from 260 ischemic stroke patients (45.0% women; age, 68 ± 12 years) and 291 healthy controls (59.7% women; age, 50 ± 17 years). Fibrin CLT and Absmax were measured using a validated turbidimetric assay. Serum elements were quantified by inductively coupled plasma mass spectrometry (ICP-MS) and optical emission spectrometry (ICP-OES). Data were analyzed by bivariate correlations and multiple or logistic regression. Results—In female stroke patients, copper, lithium, and aluminum were significantly lower compared with controls; in male stroke patients, potassium was lower, and beryllium was elevated. In female and male stroke patients, iron, zinc, nickel, calcium, magnesium, sodium, and silicon were significantly lower, while strontium was elevated. Positive correlations between fibrin clot properties and metals, observed in healthy controls, were lost in ischemic stroke patients. In multivariate regression analysis, fibrin CLT and/or Absmax was associated with zinc, calcium, potassium, beryllium, and silicon in stroke patients and with sodium, potassium, beryllium, and aluminum in controls. In logistic regression analysis, stroke was independently associated with lithium, nickel, beryllium, strontium, boron, and silicon and with sodium, potassium, calcium, and aluminum but not with fibrin CLT/Absmax. Conclusions—Various elements were associated with fibrin clot properties and the risk of ischemic stroke. Lithium, sodium, calcium, and aluminum abrogated the association of fibrin clot properties with ischemic stroke. Full article
(This article belongs to the Section Medical Research)
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19 pages, 3418 KB  
Article
Transcriptomic Analysis of Extracellular Vesicles in the Search for Novel Plasma and Thrombus Biomarkers of Ischemic Stroke Etiologies
by Florencio J. D. M. Machado, Juan Marta-Enguita, Susan U. Gómez, Jose A. Rodriguez, José Antonio Páramo-Fernández, María Herrera, Beatriz Zandio, Nuria Aymerich, Roberto Muñoz, Rebeca Bermejo, Javier Marta-Moreno, Begoña López, Arantxa González, Carmen Roncal and Josune Orbe
Int. J. Mol. Sci. 2024, 25(8), 4379; https://doi.org/10.3390/ijms25084379 - 16 Apr 2024
Cited by 5 | Viewed by 2947
Abstract
Accurate etiologic diagnosis provides an appropriate secondary prevention and better prognosis in ischemic stroke (IS) patients; still, 45% of IS are cryptogenic, urging us to enhance diagnostic precision. We have studied the transcriptomic content of plasma extracellular vesicles (EVs) (n = 21) [...] Read more.
Accurate etiologic diagnosis provides an appropriate secondary prevention and better prognosis in ischemic stroke (IS) patients; still, 45% of IS are cryptogenic, urging us to enhance diagnostic precision. We have studied the transcriptomic content of plasma extracellular vesicles (EVs) (n = 21) to identify potential biomarkers of IS etiologies. The proteins encoded by the selected genes were measured in the sera of IS patients (n = 114) and in hypertensive patients with (n = 78) and without atrial fibrillation (AF) (n = 20). IGFBP-2, the most promising candidate, was studied using immunohistochemistry in the IS thrombi (n = 23) and atrium of AF patients (n = 13). In vitro, the IGFBP-2 blockade was analyzed using thromboelastometry and endothelial cell cultures. We identified 745 differentially expressed genes among EVs of cardioembolic, atherothrombotic, and ESUS groups. From these, IGFBP-2 (cutoff > 247.6 ng/mL) emerged as a potential circulating biomarker of embolic IS [OR = 8.70 (1.84–41.13) p = 0.003], which was increased in patients with AF vs. controls (p < 0.001) and was augmented in cardioembolic vs. atherothrombotic thrombi (p < 0.01). Ex vivo, the blockage of IGFBP-2 reduced clot firmness (p < 0.01) and lysis time (p < 0.001) and in vitro, diminished endothelial permeability (p < 0.05) and transmigration (p = 0.06). IGFBP-2 could be a biomarker of embolic IS and a new therapeutic target involved in clot formation and endothelial dysfunction. Full article
(This article belongs to the Special Issue Roles and Function of Extracellular Vesicles in Diseases 2.0)
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17 pages, 4321 KB  
Article
Effect of Centhaquine on the Coagulation Cascade in Normal State and Uncontrolled Hemorrhage: A Multiphase Study Combining Ex Vivo and In Vivo Experiments in Different Species
by Athanasios Chalkias, Gwendolyn Pais and Anil Gulati
Int. J. Mol. Sci. 2024, 25(6), 3494; https://doi.org/10.3390/ijms25063494 - 20 Mar 2024
Cited by 5 | Viewed by 2558
Abstract
Centhaquine is a novel vasopressor acting on α2A- and α2B-adrenoreceptors, increasing venous return and improving tissue perfusion. We investigated the effects of centhaquine on blood coagulation in normal state and uncontrolled hemorrhage using ex vivo and in vivo experiments in different species. Thromboelastography [...] Read more.
Centhaquine is a novel vasopressor acting on α2A- and α2B-adrenoreceptors, increasing venous return and improving tissue perfusion. We investigated the effects of centhaquine on blood coagulation in normal state and uncontrolled hemorrhage using ex vivo and in vivo experiments in different species. Thromboelastography (TEG) parameters included clotting time (R), clot kinetics [K and angle (α)], clot strength (MA), and percent lysis 30 min post-MA (LY30). In normal rat blood, centhaquine did not alter R, K, α, MA, or LY30 values of the normal vehicle group or the antithrombotic effects of aspirin and heparin. Subsequently, New Zealand white rabbits with uncontrolled hemorrhage were assigned to three resuscitation groups: Sal-MAP 45 group (normal saline to maintain a mean arterial pressure, MAP, of 45 mmHg), Centh-MAP 45 group (0.05 mg kg−1 centhaquine plus normal saline to maintain a MAP of 45 mmHg), and Sal-MAP 60 group (normal saline to maintain a MAP of 60 mmHg). The Sal-MAP 45 group was characterized by no change in R, reduced K and MA, and increased α. In the Centh-MAP 45 group, TEG showed no change in R, K, and α compared to saline; however, MA increased significantly (p = 0.018). In the Sal-MAP 60 group, TEG showed no change in R, an increase in α (p < 0.001), a decrease in K (p < 0.01), and a decrease in MA (p = 0.029) compared to the Centh-MAP 45 group. In conclusion, centhaquine does not impair coagulation and facilitates hemostatic resuscitation. Full article
(This article belongs to the Section Molecular Biology)
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15 pages, 663 KB  
Article
Hemostatic Profile of Intrauterine Growth-Restricted Neonates: Assessment with the Use of NATEM Assay in Cord Blood Samples
by Eleni Karapati, Serena Valsami, Rozeta Sokou, Abraham Pouliakis, Marina Tsaousi, Alma Sulaj, Zoi Iliodromiti, Nicoletta Iacovidou and Theodora Boutsikou
Diagnostics 2024, 14(2), 178; https://doi.org/10.3390/diagnostics14020178 - 13 Jan 2024
Cited by 7 | Viewed by 2217
Abstract
Background: Intrauterine growth restriction (IUGR) is associated with hemorrhagic and thrombotic complications during the perinatal period. Thrombocytopenia, platelet dysfunction, and prolonged standard coagulation tests are observed in this population. The aim of this study is to examine the hemostatic profile of IUGR neonates [...] Read more.
Background: Intrauterine growth restriction (IUGR) is associated with hemorrhagic and thrombotic complications during the perinatal period. Thrombocytopenia, platelet dysfunction, and prolonged standard coagulation tests are observed in this population. The aim of this study is to examine the hemostatic profile of IUGR neonates with the use of a non-activated assay (NATEM) in cord blood samples. Methods: During an 18 month period, a NATEM ROTEM assay was performed on cord blood samples of 101 IUGR neonates. A total of 189 appropriate for gestational age (AGA) neonates were used as a control group. The NATEM variables recorded include the following: clotting time (CT); clot formation time (CFT); clot amplitude at 5, 10, and 20 min (A5, A10, A20); α-angle (a°); maximum clot firmness (MCF); lysis index at 30 and 60 min (LI30, LI60); and maximum clot elasticity (MCE). Results: IUGR neonates demonstrate a hypocoagulable state, with lower A5, A10, A2, MCF, and MCE values when compared to AGA. Using multiple linear regression, we determined IUGR as an independent factor influencing all NATEM parameters (except CT and LI30) exhibiting a hypocoagulable and hypofibrinolytic profile. Platelet count was positively correlated with A5, A10, A20, MCF, alpha angle, and MCE, and negatively correlated with CFT. Conclusion: IUGR neonates appear with lower clot strength and elasticity and prolonged clot kinetics, as illustrated by ROTEM variables. Full article
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