Search Results (126)

The hemostatic system in the newborn is a complex entity, characterized by dynamism in its development; therefore, the correct measurement of its potential is challenging. In this narrative review, we analyzed the current knowledge of the “developmental hemostasis” of the newborn; we also studied the performance of routine coagulation tests in its evaluation, with considerations about the establishment of neonatal age-specific normal ranges and about the role of preanalytical variables, in particular, hematocrit (which could represent an important cause of error); we also focused on the increasing importance of viscoelastic coagulation tests, which are becoming increasingly widespread (especially in some settings such as intensive care unit) and are able to quickly provide information about the hemostatic function of the newborn, even if they lack adequate standardization in the neonatal period. Full article

Platelets are attributed an increasing role in the post-traumatic immune response. The exact mechanisms, particularly the link between immune response and hemostasis, have not been conclusively established. This study aimed to investigate the activity marker CD63 on platelets after polytrauma and its significance for hemostasis. A non-interventional, prospective clinical study was conducted, in which the blood of 20 polytraumatized patients was analyzed at nine time points within 10 days following trauma. Peripheral blood platelets were analyzed using flow cytometry to determine CD63 expression and rotational thromboelastometry (ROTEM^®) for hemostatic platelet function. Additionally, the clinical parameters of age, gender, and injury severity were correlated to the experimental outcomes. During the observation period, an increase in platelet count and CD63 expression was observed. Simultaneously, a hemostasiological dysfunction with reduced platelet maximum clot firmness (MCF) was observed. The factors of age, gender, and injury severity showed no significant influence on immunological activation or coagulation function. These results suggest that polytrauma induces a platelet response and CD63 activation while simultaneously impairing hemostasis. This reveals a novel perspective on post-traumatic coagulation disorders, indicating that immunologically active platelets may lose their ability to contribute effectively to blood clotting. Consequently, these findings emphasize the critical role of platelet immunology in hemostatic regulation. Full article

Background and Clinical Significance: Hereditary Fibrinogen Disorders (HFDs) are a group of rare, inherited coagulation disorders with a wide spectrum of clinical presentations, ranging from asymptomatic cases to severe bleeding or thrombotic events. Among these, hereditary hypofibrinogenemia (HH) poses particular challenges in obstetric care due to its unpredictable course and limited evidence-based guidelines. Case Presentation: This case report describes the novel obstetrical management of a 37 years old multiparous woman with severe HH (SHH) guided not only by fibrinogen levels but also by rotational thromboelastometry (ROTEM^®), a global test of hemostasis using specific parameters such as FIBTEM^® and NATEM^® assays. Despite persistent low fibrinogen levels during labor and peripartum (<100 mg/dL), favorable maternal and neonatal outcomes were achieved by relying on ROTEM^®-based parameters to guide clinical decisions. Conclusions: Current recommendations for managing pregnancies in women with HFDs are largely based on expert consensus and exclusively use fibrinogen levels. This case supports the use of specific assays (FIBTEM^® and NATEM^®) of the ROTEM^® global test of hemostasis as valuable tools in the obstetric management of women with HH. The use of FIBTEM^® and NATEM^® assays could provide individualized perinatal care, avoiding unnecessary therapeutic interventions and aiming for optimal perinatal outcomes. Full article

The genus Clinopodium L. (Lamiaceae) comprises perennial herbaceous plants known for their diverse pharmacological properties. Clinically, these plants are mainly used for the treatment of various hemorrhagic disorders. This review systematically summarizes the research progress on the chemical composition, pharmacological activity, quality control, toxicity, and pharmacokinetics of the genus Clinopodium by searching Google Scholar, Scopus-Elsevier, Wiley, Springer, Taylor & Francis, Medline, Web of Science, CNKI, Weipu, Wanfang, and other academic databases over the last decade (March 2015–February 2025). To date, more than one hundred and thirty structurally diverse secondary metabolites have been isolated and identified from this genus, including flavonoids, triterpenoid saponins, diterpenoid glycosides, lignans, and phenylpropanoids. In addition, numerous volatile oil constituents have been identified in over forty species of the genus Clinopodium. Crude extracts and purified compounds exhibit a variety of pharmacological activities, including hemostatic, anti-myocardial cell injury, cardiovascular protective, anti-inflammatory, antimicrobial, antitumor, hypoglycemic, and insecticidal properties. However, current quality assessment protocols in the genus Clinopodium are limited to flavonoid- and saponin-based evaluations in C. chinense (Benth.) O. Kuntze and C. gracile (Benth.) O. Matsum. Further research is needed to elucidate the pharmacological mechanisms, toxicity, and possible interactions with other drugs. Therefore, the genus Clinopodium has a wide range of biologically active compounds with potential applications in drug development for hemostasis and cardiovascular protection. Nevertheless, there is also an urgent need to establish standardized methodologies to address uncertainties concerning the safety and efficacy of injectable extracts or compounds. Full article

Platelet activation processes begin when injury to blood vessels exposes the subendothelial matrix, leading platelets to attach to it, where they become activated and exert their hemostatic function. Excessive platelet aggregation is associated with thrombotic disorders such as arterial thrombosis. To manage such diseases, medications that inhibit thrombosis are continuously sought, despite potential drawbacks that include hemorrhage. This study described the development of a novel peptide-based vaccine that targets the purinergic ADP P2Y₁ receptor (abbreviated EL2Vac) and its pharmacological characterization. Thus, we designed and developed an EL2Vac that targets the ligand-binding domain of the P2Y₁ receptor protein, which is located in its second extracellular loop (EL2). We then evaluated the vaccine’s ability to trigger an immune response (antibody production) in immunized mice, modulate platelet function, its antithrombotic activity, and any effects on hemostasis, by employing a thrombosis model and the tail bleeding time assay. Results showed significant levels of antibody production in mice treated with EL2Vac, in comparison with the random peptide vaccine control (EL2rVac), which persisted at least up to six months post vaccination. Moreover, we observed significant inhibition of the ADP-induced aggregation response in platelets from EL2Vac-treated mice, relative to those from EL2rVac controls. This inhibition was selective for ADP, as other agonists, such as the thromboxane A₂ receptor (TPR) agonist U46619 or high-dose collagen, had no detectable effect on aggregation. As for its capacity to protect against thrombosis, our data showed a significant delay in the occlusion time of the EL2Vac mice when compared with the random peptide control vaccine, which was also observed (at least) six months post vaccination. Interestingly, EL2Vac did not appear to prolong the tail bleeding time, supporting the notion that it is devoid of a bleeding diathesis. As a conclusion, this study documents the design and evaluation of a novel peptide-based vaccine, EL2Vac, which appears to selectively target the P2Y₁ receptor and protect against thrombus formation without impairing hemostasis. Thus, EL2Vac may provide a promising clinical option to treat thromboembolic disorders. Full article

Background: Hemophilia A is an X-linked recessive bleeding disorder associated with high risk for intracranial hemorrhage, requiring complicated neurosurgical interventions. Perioperative management is based on quick factor replacement therapy, control of hemostasis, and deciding whether surgery will be beneficial. Methods: We report the case of a 49-year-old male with severe hemophilia A who had purulent secernation via a skin fistula as a late complication of decompressive craniectomy for epidural hematoma at younger age. Results: Revision surgery was successfully managed with perioperative administration of clotting factor VIII, and the patient showed indications of titanium cranioplasty. Conclusions: A direct preoperative preparation prior to surgery in a postoperative period with controlled hemostasis has been shown to reduce hemorrhagic complications in hemophilic patients, increasing the quality of life and significant neurological complications. Full article

Background: Traumatic hemorrhage management is challenging due to the need to control severe bleeding and support tissue repair. An ideal material would possess both hemostatic and wound-healing properties. Methods: Silkworm cocoon-derived carbon dots (SC-CDs) were synthesized via a hydrothermal method. After physical and chemical characterization using techniques such as HR-TEM and XPS, their hemostatic efficacy was assessed in rat liver injury, tail transection, and mouse coagulation disorder models. Moreover, the effects of the SC-CDs on platelet aggregation and activation were evaluated. The potential of the SC-CDs to promote wound healing was investigated through cell scratch assays and a mouse full-thickness skin defect model. Results: The SC-CDs showed a high quantum yield (12.9% ± 0.42%), with low hemolytic activity and cytotoxicity. In the hemostasis models, the SC-CDs significantly reduced the bleeding time and volume. In the rat liver injury model, the bleeding time was shortened from 152.67 ± 4.16 s (Control) to 55.33 ± 9.50 s (p < 0.05). In the rat tail transection model, the bleeding volume was reduced from 1.71 ± 0.16 g (Control) to 0.4 ± 0.11 g (p < 0.05). In the mouse coagulation disorder model, an 8 mg/kg dose reduced the bleeding volume to 11.80% ± 0.39% of that of the Control (p < 0.05). Mechanistic studies suggested enhanced platelet activation and aggregation. In the wound healing experiments, the SC-CDs reduced the wound area (88.53 ± 11.78 mm² (Control) vs. 70.07 ± 6.71 mm² (SC-CDs), p < 0.05) and promoted fibroblast migration (24 h scratch width: 372.34 ± 9.06 μm (Control) vs. 259.49 ± 36.75 μm (SC-CDs), p < 0.05). Conclusions: SC-CDs show promise for hemorrhage management and tissue regeneration, with potential applications in cases of internal bleeding or coagulation disorders. Full article

Fibrinogen, a pivotal plasma glycoprotein, plays an essential role in hemostasis by serving as the precursor to fibrin, which forms the structural framework of blood clots. Beyond coagulation, fibrinogen influences immune responses, inflammation, and tissue repair. Oxidative stress, characterized by an imbalance between reactive oxygen species (ROS) and antioxidants, induces fibrinogen oxidation, significantly altering its structure and function. This narrative review synthesizes findings from in vitro, ex vivo, and clinical studies, emphasizing the impact of fibrinogen oxidation on clot formation, architecture, and degradation. Oxidative modifications result in denser fibrin clots with thinner fibers, reduced permeability, and heightened resistance to fibrinolysis. These structural changes exacerbate prothrombotic conditions in cardiovascular diseases, diabetes, chronic inflammatory disorders and cancer. In contrast, “low-dose” oxidative stress may elicit protective adaptations in fibrinogen, preserving its function. The review also highlights discrepancies in experimental findings due to variability in oxidation protocols and patient conditions. Understanding the interplay between oxidation and fibrinogen function could unveil therapeutic strategies targeting oxidative stress. Antioxidant therapies or selective inhibitors of detrimental oxidation hold potential for mitigating thrombotic risks. However, further research is essential to pinpoint specific fibrinogen oxidation sites, clarify their roles in clot dynamics, and bridge the gap between basic research and clinical practice. Full article

Platelet dysfunction plays a critical role in the pathogenesis of various disorders affecting the hemostatic-coagulant system. This review aims to explore the mechanisms by which platelet dysfunctions contribute to the disruption of hemostasis, leading to an increased risk of both thrombosis and bleeding. Platelets, traditionally known for their role in clot formation, can exhibit altered functionality under pathological conditions such as cardiovascular diseases, metabolic disorders, and autoimmune diseases, impacting their interaction with coagulation factors and vascular endothelium. The review discusses the molecular and cellular mechanisms underlying platelet dysfunction, including aberrations in platelet activation, aggregation, and secretion. It also highlights the interplay between platelets and other components of the coagulation cascade, such as fibrinogen and clotting factors, in maintaining vascular integrity. Moreover, the review examines clinical implications, including how platelet dysfunction can be a contributing factor in conditions like deep vein thrombosis, stroke, and disseminated intravascular coagulation (DIC). Finally, current therapeutic approaches targeting platelet dysfunctions, including antiplatelet agents and emerging therapies, are reviewed to provide insights into potential strategies for managing fluid-coagulation system imbalances. This review underscores the importance of a comprehensive understanding of platelet dysfunction to improve diagnosis and treatment of hemostatic disorders. Full article

Echis ocellatus envenomings are a public health problem in West Africa, leading to bleeding and hypocoagulability. The aim of this study was to assess the hemostasis disorders associated with E. ocellatus envenoming. Envenomed patients with an abnormal whole blood clotting test (WBCT) were prospectively included at Tanguiéta, Benin. A WBCT with a sequential reading (i.e., at 20, 30, and 60 min), viscoelastic analysis (VA) using the Quantra analyzer, and blood count were performed on admission. VA and the WBCT were also assessed at 4, 8, 12, 24, 48, and 72 h after antivenom administration. Nineteen patients were included. On admission, the main results were an absence of a clot on VA and a slight decrease in platelets. Clot time gradually decreased over time while clot stiffness, fibrinogen, and platelet contributions to stiffness increased. Sequential reading improved the sensitivity of the WBCT. At H48, all patients with recurrence bleeding after antivenom administration had an abnormal WBCT while patients with a normal WBCT never had bleeding during their follow-up. VA allows the identification of various hemostasis disorders. Hypofibrinogenemia was the main disorder that persisted for several days after treatment. A WBCT with a sequential reading is an effective alternative for monitoring hypocoagulability in the absence of a laboratory. Full article

The literature analysis conducted in this review discusses the latest achievements in the identification of cardiovascular damage induced by oxidative stress with secondary platelet mitochondrial dysfunction. Damage to the platelets of mitochondria as a result of their interactions with reactive oxygen species (ROS) and reactive nitrogen species (RNS) can lead to their numerous ischemic events associated with hypoxia or hyperoxia processes in the cell. Disturbances in redox reactions in the platelet mitochondrial membrane lead to the direct oxidation of cellular macromolecules, including nucleic acids (DNA base oxidation), membrane lipids (lipid peroxidation process) and cellular proteins (formation of reducing groups in repair proteins and amino acid peroxides). Oxidative changes in biomolecules inducing tissue damage leads to inflammation, initiating pathogenic processes associated with faster cell aging or their apoptosis. The consequence of damage to platelet mitochondria and their excessive activation is the induction of cardiovascular and neurodegenerative diseases (Parkinson’s and Alzheimer’s), as well as carbohydrate metabolism disorders (diabetes). The oxidation of mitochondrial DNA can lead to modifications in its bases, inducing the formation of exocyclic adducts of the ethano and propano type. As a consequence, it disrupts DNA repair processes and conduces to premature neoplastic transformation in critical genes such as the p53 suppressor gene, which leads to the development of various types of tumors. The topic of new innovative methods and techniques for the analysis of oxidative stress in platelet mitochondria based on methods such as a nicking assay, oxygen consumption assay, Total Thrombus formation Analysis System (T-Tas), and continuous-flow left ventricular assist devices (CF-LVADs) was also discussed. They were put together into one scientific and research platform. This will enable the facilitation of faster diagnostics and the identification of platelet mitochondrial damage by clinicians and scientists in order to implement adequate therapeutic procedures and minimize the risk of the induction of cardiovascular diseases, including ischemic events correlated with them. A quantitative analysis of the processes of thrombus formation in cardiovascular diseases will provide an opportunity to select specific anticoagulant and thrombolytic drugs under conditions of preserved hemostasis. Full article

Background and Clinical Significance: Veno-venous extracorporeal membrane oxygenation (VV ECMO) has become a widely accepted supportive treatment for severe acute respiratory distress syndrome (ARDS) in intensive care units (ICUs). Although it has gained popularity, some of its aspects, including optimal anticoagulation management and the best means of monitoring hemostasis, remain unresolved. Thrombosis and bleeding are still important complications of ECMO. Case Presentation: A 44-year-old male patient, with no underlying conditions, was diagnosed with severe acute respiratory distress syndrome (ARDS) due to AH1N1 influenza. He presented severe hypoxemia despite the use of mechanical ventilation, neuromuscular blocking agent infusion and prone position. VV ECMO was used, and coagulation was stopped on ECLS day 6 due to severe pulmonary hemorrhage. The systemic hemostatic disorders found in this patient were difficult to differentiate from disseminated intravascular coagulation (DIC) or sepsis-induced coagulopathy (SIC), improved transiently after circuit exchange, and resolved only after discontinuation of ECMO. The patient was discharged fully conscious and cooperative, with no apparent neurological deficit. Conclusions: Systemic hemostatic abnormalities may precede oxygenator failure and mimic DIC or SIC. Timely oxygenator exchange may therefore be considered. However, it is a high-risk procedure, especially in fully ECLS-dependent patients. Full article

Backgrounds/Objectives: Abnormal platelet functions are associated with human morbidity and mortality. Platelets have emerged as critical regulators of numerous physiological and pathological processes beyond their established roles in hemostasis and thrombosis. Maintaining physiological platelet function is essential to hemostasis and preventing platelet-associated diseases such as cardiovascular disease, cancer metastasis, immune disorders, hypertension, diabetes, sickle cell disease, inflammatory bowel disease, sepsis, rheumatoid arthritis, myeloproliferative disease, and Alzheimer’s disease. Platelets become hyperactive in obesity, diabetes, a sedentary lifestyle, hypertension, pollution, and smokers. Platelets, upon activation, can trawl leukocytes and progenitor cells to the vascular sites. Platelets release various proinflammatory, anti-inflammatory, and angiogenic factors and shed microparticles in the circulation, thus promoting pathological reactions. These platelet-released factors also maintain sustained activation, further impacting these disease processes. Although the mechanisms are unknown, multiple stimuli induce platelet hyperreactivity but involve the early pathways of platelet activation. The exact mechanisms of how hyperactive platelets contribute to these diseases are still unclear, and antiplatelet strategies are inevitable for preventing these diseases. Reducing platelet function during the early stages could significantly impact these diseases. However, while this is potentially a worthwhile intervention, using antiplatelet drugs to limit platelet function in apparently healthy individuals without cardiovascular disease is not recommended due to the increased risk of internal bleeding, resistance, and other side effects. The challenge for therapeutic intervention in these diseases is identifying factors that preferentially block specific targets involved in platelets’ complex contribution to these diseases while leaving their hemostatic function at least partially intact. Since antiplatelet drugs such as aspirin are not recommended as primary preventives, it is essential to use alternative safe platelet inhibitors without side effects. Methods: A systematic search of the PUBMED database from 2000 to 2023 was conducted using the selected keywords: “functional foods”, “polyphenols”, “fatty acids”, “herbs”, fruits and vegetables”, “cardioprotective agents”, “plant”, “platelet aggregation”, “platelet activation”, “clinical and non-clinical trial”, “randomized”, and “controlled”. Results: Potent natural antiplatelet factors have been described, including omega-3 fatty acids, polyphenols, and other phytochemicals. Antiplatelet bioactive compounds in food that can prevent platelet hyperactivity and thus may prevent several platelet-mediated diseases, including cardiovascular disease. Conclusions: This narrative review describes the work during 2000–2023 in developing functional foods from natural sources with antiplatelet effects. Full article

Liver transplantation is a complex surgical procedure in which various forms of coagulation dysfunction can occur, including perioperative hypercoagulability. The hemostasis balance in liver graft recipients with end-stage liver disease can shift to thrombosis or haemorrhage, depending on the associated risk factors and clinical conditions. Hypercoagulability can result in serious complications such as thromboembolism, which can affect the vessels of the newly transplanted liver graft. Standard coagulation tests (SCTs), such as prothrombin time and activated partial thromboplastin time (aPTT), have a poor ability to diagnose and monitor an early stage of hypercoagulability. Recent studies demonstrated that viscoelastic hemostatic elastic tests (VETs), such as rotational thromboelastometry (ROTEM) and thromboelastography (TEG), are promising alternative tools for diagnosing hypercoagulability disorders. VETs measure clotting and clot formation time, clot strength (maximum clot firmness), fibrin and platelet contribution to clot firmness, and fibrinolysis, which makes them more sensitive in identifying liver graft recipients at risk for thrombosis as compared with SCTs. However, developing evidence-based guidelines for the prophylaxis and treatment of hypercoagulability based on VET results is still needed. Full article

Platelets are essential blood components that maintain hemostasis, prevent excessive bleeding, and facilitate wound healing. Reduced platelet counts are implicated in various diseases, including leukemia, hepatitis, cancer, and Alzheimer’s disease. Enhancing megakaryocytic differentiation is a promising strategy to increase platelet production. Compound K (CK), a major bioactive metabolite of ginsenosides from Panax ginseng, has demonstrated anti-cancer and neuroprotective properties. In this study, we investigated the effects of CK on megakaryocytic differentiation and apoptosis in chronic myeloid leukemia (CML) cell lines K562 and Meg-01. CK treatment significantly upregulated the mRNA expression of key megakaryocytic differentiation markers, including CD61, CD41, and CD42a, and promoted the formation of large, multinucleated cells in K562 cells. Additionally, flow cytometry analysis revealed that CK at 5 µM induced apoptosis, a critical process in thrombocytopoiesis, in both K562 and Meg-01 cells. RT² Profiler PCR array analysis further identified a marked increase in the expression of genes associated with the activation of the NLRP3 inflammasome in CK-treated K562 and Meg-01 cells. This study is the first to demonstrate that CK promotes megakaryocytic differentiation and apoptosis through the activation of the ERK/EGR1 and NLRP3 inflammasome pathways. These findings suggest that CK may enhance platelet production, indicating its potential as a therapeutic candidate for platelet-related disorders and other associated diseases. Full article