Search Results (445)

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

Patient blood management (PBM) is a multidisciplinary approach aimed at improving patient outcomes through targeted anemia treatment that minimizes allogeneic blood transfusions, employs blood conservation techniques, and avoids inappropriate use of blood product transfusions. Viscoelastic testing (VET) techniques, such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM), have led to significant advancements in PBM. These techniques offer real-time whole-blood assessment of hemostatic function. This provides the clinician with a more complete hemostasis perspective compared to that provided by conventional coagulation tests (CCTs), such as the prothrombin time (PT) and the activated partial thromboplastin time (aPTT), which only assess plasma-based coagulation. VET does this by mapping the complex processes of clot formation, stability, and breakdown (i.e., fibrinolysis). As a result of real-time whole-blood coagulation assessment during hemorrhage, hemostasis can be achieved through targeted transfusion therapy. This approach helps fulfill an objective of PBM by helping to reduce unnecessary transfusions. However, challenges remain that limit broader adoption of VET, particularly in hospital settings. Of these, standardization and the high cost of the devices are those that are faced the most. This discussion highlights the potential of VET application in PBM to guide blood-clotting therapies and improve outcomes in patients with coagulopathies from various causes that result in hemorrhage. Another aim of this discussion is to highlight the limitations of implementing these technologies so that appropriate measures can be taken toward their wider integration into clinical use. Full article

Platelets have long been known to be critically involved in hemostasis and thrombosis. However, platelets are also recognized as metabolically active cells that require well-regulated mitochondrial function to support their multiple functions in hemostasis, thrombosis, and inflammation. Mitochondrial activity has also recently been shown to play a crucial role in determining platelet activation, survival, and pro-inflammatory potential. A key nexus in these processes is the mitochondrial permeability transition pore (mPTP), a high-conductance channel in the inner mitochondrial membrane. Sustained mPTP opening triggers mitochondrial depolarization, the cessation of ATP synthesis, osmotic swelling, and, finally, platelet dysfunction or clearance. However, its transient opening might play physiological signaling roles. This review summarizes the current understanding of the molecular components and regulatory factors governing the platelet mPTP, explores its physiological and pathological relevance, and evaluates its potential as a therapeutic target in cardiovascular disease, inflammation, cancer, and potentially neurodegenerative diseases. We also highlight the ongoing challenges and crucial future directions in deciphering the complexities of platelet mitochondrial dynamics and mPTP functions. Full article

Although platelets have been traditionally thought of to be essential hemostasis mediators, new research shows how important they are for controlling cellular oxidative stress, inflammatory processes, and immunological responses—particularly during major surgery on the abdomen. Perioperative problems are largely caused by the continually changing interaction of inflammatory cytokines, the formation of reactive oxygen species (ROS), and platelet activation. The purpose of this review is to summarize the most recent data regarding the complex function of platelets in abdominal surgery, with an emphasis on how they interact with inflammation and oxidative stress, and to investigate the impact on postoperative therapy and subsequent studies. Recent study data on platelet biology, redox signals, surgical stress, and antiplatelet tactics was reviewed in a systematic manner. Novel tailored therapies, perioperative antiplatelet medication, oxidative biomarkers of interest, and platelet-derived microscopic particles are important themes. In surgical procedures, oxidative stress dramatically increases the reactive capacity of platelets, spurring thromboinflammatory processes that affect cardiac attacks, infection risk, and recovery. A number of biomarkers, including soluble CD40L, thromboxane B2, and sNOX2-derived peptide, showed potential in forecasting results and tailored treatment. Antiplatelet medications are still essential for controlling risk factors for cardiovascular disease, yet using them during surgery necessitates carefully weighing the risks of thrombosis and bleeding. Biomarker-guided therapies, antioxidant adjuncts, and specific platelet inhibitors are examples of evolving tactics. In abdominal procedures, platelets strategically operate at the nexus of oxidative stress, inflammatory processes, and clotting. Improved patient classification, fewer problems, and the creation of individualized surgical care strategies could result from an increased incorporation of platelet-focused tests and therapies into perioperative processes. To improve clinical recommendations, subsequent studies may want to focus on randomized studies, biomarker verification, and using translational approaches. Full article

Endophytic microorganisms inhabiting plant tissues constitute a unique and largely untapped reservoir of bioactive metabolites, including phenolics, terpenoids, alkaloids, polysaccharides, and anthraquinones, among others. This review focuses on the potential of these compounds to modulate the complex processes of wound repair, such as hemostasis, inflammation, proliferation, and remodeling. Uniquely, this review delineates the specific mechanisms supported not only by indirect evidence but by primary research directly linking endophytic metabolites to wound repair. We synthesized and evaluated evidence from 18 studies, of which over 75% directly assessed wound healing effects through in vitro and in vivo models. Metabolites from endophytic microorganisms promoted wound contraction, suppressed biofilm formation by key pathogens (e.g., MRSA, P. aeruginosa), and accelerated tissue re-epithelialization in animal models. Other compounds demonstrated >99% wound closure in rats, while several extracts showed anti-inflammatory and cytocompatible profiles. Nevertheless, the majority of studies applied unstandardized methods and used crude extracts, hindering precise structure–activity assessment. The originality of this review lies in drawing attention to direct evidence for wound healing from diverse endophytic sources and systematically identifying gaps between preclinical promise and clinical translation, positioning endophytes as a sustainable platform for next-generation wound therapeutics. Full article

Background: The enzyme A Disintegrin and metalloprotease with thrombospondin type 1 motif, member 13 (ADAMTS13) regulates hemostasis by cleaving von Willebrand factor (VWF) multimers. ADAMTS13–VWF axis dysregulation leads to different thrombotic conditions. This study investigated changes in ADAMTS13 activity during major cardiac procedures and their relationship to VWF changes and clinical complications. Methods: A total of 628 ADAMTS13 activity and inhibitor measurements were carried out in 168 patients who underwent cardiac surgery. ADAMTS13 activity was measured after the initiation of anesthesia and daily for up to 6 days postoperatively via Technozym chromogenic ELISA. The von Willebrand factor antigen (VWF:Ag) and collagen binding (VWF:CB) were also measured. Clinical complications and correlations with liver function biomarkers were also assessed. Results: ADAMTS13 activity significantly decreased during surgery, with mean values markedly decreasing from preoperative to postoperative measurements (p = 0.01). A clear inverse relationship between ADAMTS13 activity and the VWF:CB/VWF:AG ratio was observed, indicating that increased high-molecular-weight VWF multimers are associated with decreased ADAMTS13 activity. Correlation analyses (CHE, Spearman’s rho = 0.39) indicated that the reduction in ADAMTS13 activity was not attributable to impaired liver synthesis but likely resulted from peripheral consumption, potentially influenced by surgical stress. Conclusions: Perioperative reductions in ADAMTS13 activity are associated with an accumulation of high-molecular-weight VWF multimers and a higher incidence of postoperative complications. These results demonstrate that ADAMTS13 could be a useful perioperative risk biomarker for cardiac surgery patients. Full article

Assessment for the presence or absence of lupus anticoagulant (LA) represents a common investigation in hemostasis laboratories. In particular, LA represents one of the laboratory criteria for the diagnosis of definite antiphospholipid syndrome (APS). The other laboratory criteria are the solid phase assays (anticardiolipin (aCL) and anti-β2Glycoprotein I (aβ2GPI) antibodies of IgG and IgM isotypes). Current International Society on Thrombosis and Haemostasis (ISTH) guidance recommends testing LA by at least two tests based on different principles, with the activated partial thromboplastin time (aPTT) and dilute Russell viper venom time (dRVVT) being preferred. Additional assays may be used in addition, or instead of these assays in particular situations. For example, aPTT and dRVVT assays are very sensitive to the presence of various anticoagulants, and this may lead to false-positive identification of LA. This is particularly problematic in the age of the DOACs (direct oral anticoagulants), which are now the leading anticoagulants in use worldwide. We review recent literature on LA testing as well as our local practice to provide an update on this common test procedure. Our experience should be useful for laboratories struggling with LA interpretation for diagnosis or exclusion of APS. Full article

Radiation therapy, a highly effective cancer treatment that targets cancer cells, may produce challenging side effects, including radiation-induced skin tissue injuries. The wound healing process involves complex cellular responses, with key phases including hemostasis, inflammation, proliferation, and remodeling. However, radiation-induced injuries disrupt this process, resulting in delayed healing, excessive scarring, and compromised tissue integrity. This review explores innovative approaches related to wound healing in post-radiotherapy defects, focusing on the integration of adipose-derived stem cells (ADSCs) in protein/polysaccharide bioengineered scaffolds. Such scaffolds, like hydrogels, sponges, or 3D-printed/bioprinted materials, provide a biocompatible and biomimetic environment that supports cell-to-cell and cell-to-matrix interactions. Various proteins and polysaccharides are discussed for beneficial properties and limitations, and their compatibility with ADSCs in wound healing applications. The potential of ADSCs-polymeric scaffold combinations in radiation-induced wound healing is investigated, alongside the mechanisms of cell proliferation, inflammation reduction, angiogenesis promotion, collagen formation, integrin binding, growth factor signaling, and activation of signaling pathways. New strategies to improve the therapeutic efficacy of ADSCs by integration in adaptive polymeric materials and designed scaffolds are highlighted, providing solutions for radiation-induced wounded skin, personalized care, faster tissue regeneration, and, ultimately, enhanced quality of the patients’ lives. 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

A series of new isatin hydrazones bearing phosphorus-containing moiety was synthesized through a simple, high-yield and easy work-up reaction of phosphine oxide (Phosenazide) or phosphinate (2-chloroethyl (4-(dimethylamino)phenyl)(2-hydrazinyl-2-oxoethyl)phosphinate, CAPAH) hydrazides with aryl-substituted isatins. The ³¹P NMR technique showed that, in most cases, out of 12 examples in solution, the ratio of the two spatial isomers varied from 1:1 to 1:3. Quantum chemical calculations confirmed the predominance of Z,syn form both in the gas phase and in solution. According to X-ray analysis data in crystals, they exist only in Z,syn form too. Most of the phosphine oxide derivatives and 5-methoxy- and 5-bromoaryl phosphinate analogs exhibit anti-aggregant activity at the level of acetylsalicylic acid but inhibit platelet activation processes more effectively. The 5-chloro type phosphinate derivative exhibits anti-aggregant properties more effectively than acetylsalicylic acid under the conditions of the tissue factor (TF)-activated thromboelastography (TEG) model, the ex vivo thrombosis model. Thus, all the obtained results can become the basis for future pharmaceutical developments to create effective anti-aggregation drugs with broad antithrombotic potential. Full article

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

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

This review provides an in-depth analysis of argatroban as an alternative anticoagulant in cardiac surgery, with a focus on its use in patients with heparin-induced thrombocytopenia (HIT). We examine argatroban’s pharmacokinetics and dosing regimens and the challenges associated with cosnventional monitoring methods—such as activated clotting time (ACT) and activated partial thromboplastin time (aPTT)—to evaluate its safety and effectiveness in high-risk surgical settings. Drawing on data from multiple case reports and series, our review highlights both the potential benefits and limitations of argatroban, including complications such as clot formation in extracorporeal circulation systems and prolonged postoperative coagulopathy. In addition to the literature review, we present a detailed clinical case of urgent HeartMate 3 left ventricular assist device implantation in a patient with advanced heart failure and active HIT. In this case, despite targeting an ACT above 400 s, intraoperative complications such as clot formation in the heart–lung machine and difficulty achieving hemostasis highlight the need for improved monitoring and dosing protocols. Our findings call for refined anticoagulation strategies and advanced monitoring techniques to optimize argatroban use in cardiac surgery, offering valuable insights for clinicians managing complex scenarios where conventional heparin therapy is contraindicated. Full article

Cyanoacrylate-based adhesives have gained increasing attention in dentistry for their rapid polymerization, biocompatibility, and antimicrobial activity. This review analyzes the clinical use of cyanoacrylate adhesives—particularly the Glubran II formulation—in dental procedures, including wound closure, tissue management, and bleeding control. A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science databases for studies published between 2000 and 2024, using specific inclusion criteria (clinical and in vitro studies focusing on dental applications of cyanoacrylates) and exclusion criteria (non-dental uses, insufficient data). The findings indicate that compared to traditional sutures, cyanoacrylates, especially n-butyl and octyl derivatives, significantly reduce operative time, postoperative pain, and infection rates. However, differences among formulations—such as degradation rate and cytotoxicity—require further exploration. Glubran II, in particular, shows promising results in hemostasis and wound stability. This review highlights the potential of cyanoacrylate adhesives as effective, minimally invasive alternatives in dental surgery and underlines the need for standardized protocols and long-term comparative studies. Full article

Infective endocarditis (IE) arises from complex interactions between microbial pathogens and host hemostasis systems, where dysregulated coagulation mediates microbial persistence and systemic thromboembolic complications. Alterations in primary, secondary, and tertiary hemostasis in the acute IE phase have direct clinical implications for vegetation formation and detachment. Staphylococcus aureus is one of the most common pathogens that causes IE, and it is capable of profoundly altering the coagulation cascade through several mechanisms, such as platelet activation, prothrombin activation through staphylocoagulase release, and plasminogen stimulation via staphylokinase production. Understanding these complex and yet unmasked mechanisms is of pivotal importance to promoting targeted therapeutic intervention aimed at reducing IE morbidity and mortality. Moreover, the management of antiplatelet and anticoagulant treatment during IE onset is a controversial issue and needs to be tailored to patient comorbidities and IE-related complications, such as cerebral embolism. This review provides a roadmap to promote clinicians’ understanding of the complex interactions between hemostasis and IE clinical manifestations and complications, discussing pathogen-specific coagulation profiles while addressing critical knowledge gaps for IE management. Full article