Search Results (73)

Fibrinolysis assessment is critical for diagnosing and managing clinical blood disorders. Currently available viscoelastic testing platforms provide an overview of global coagulation and fibrinolysis profiles but lack fibrinolysis specific assessment of a preformed clot substrate. The lack of a sensitive, standardized testing platform for fibrinolysis assessment can limit risk stratification and the management of blood disorders. We describe herein the plasma annular clot lysis assay. The assay adapts the previously standardized FITC-tagged fibrin annular clot assay to plasma obtained from healthy human donors. Plasmin at concentrations ranging from 200–800 nM was used as a direct thrombolytic to assess fibrinolysis in plasma-derived annular clots. The Maximum Fibrinolysis Rate (V_MFR), FLU200, T90, and MaxFLU were calculated via tracking of the clot digestion curve over time. V_MFR was correlated with plasma thromboelastography (TEG) parameters to compare with the global viscoelastic testing system. Additionally, plasma annular clot digestion was monitored in the presence of pentamidine to assess drug-specific effects on fibrinolysis tracking. Plasma annular clots linearly tracked fibrinolysis with increasing plasmin concentration. V_MFR across multiple tested plasmin concentrations showed a moderate to strong negative correlation (0.58–0.74) with the observed maximum amplitude from plasma TEG. In the presence of pentamidine (75 µM), the assay was sensitive to identifying differences in the V_MFR across treatment groups. Plasma annular clots provide a platform for fibrinolysis evaluation using a patient’s own plasma to assess therapeutic dosing clinically in addition to testing novel therapeutics preclinically to further understand mechanistic aspects of fibrinolysis. Full article

Background and Objectives: Percutaneous coronary intervention (PCI) has markedly improved outcomes in coronary artery disease through the implantation of bare-metal stents (BMS) or drug-eluting stents (DES). However, in-stent restenosis (ISR) remains a significant complication, often necessitating repeat interventions. This study aimed to identify risk factors associated with ISR in patients with ST-elevation myocardial infarction (STEMI) who underwent PCI. Materials and Methods: We conducted a retrospective, non-randomized observational study of 107 STEMI patients treated with PCI between January 2016 and December 2019 who subsequently underwent clinically indicated (predominantly symptom-driven) follow-up coronary angiography within 12 months. ISR was defined as ≥50% luminal narrowing at follow-up angiography. Time-to-event analysis was performed using Cox regression models, incorporating clinical, biochemical, and angiographic variables. Results: In this selected cohort of patients undergoing follow-up angiography, ISR of any degree was identified in 87% of patients, and 52% had restenosis >70%. Advanced age, prior cardiovascular events, diabetes mellitus, chronic kidney disease, and history of stroke significantly increased the hazard of ISR. Smoking, dyslipidemia, and hypertension were prevalent in patients with severe ISR. Women presented with more severe clinical profiles (higher Killip class and troponin levels). DES showed slightly better TIMI flow than BMS, but stent type, dimensions, and number did not significantly impact restenosis risk. Thrombolytic therapy was associated with a significantly reduced ISR hazard. Mortality was 6% in patients with severe ISR. The highest restenosis incidence occurred in the LAD and RCA territories. Conclusions: ISR is a multifactorial process influenced by demographic, clinical, and procedural factors. Despite technological advances, ISR remains a prevalent issue, particularly in high-risk groups undergoing clinically indicated follow-up angiography. Secondary prevention strategies, optimized stent deployment, and targeted therapies addressing inflammation and vascular remodeling are essential to improving long-term PCI outcomes. Full article

Intravenous thrombolysis with recombinant tissue-type plasminogen activator (tPA) remains a keystone of acute ischemic stroke treatment but in a subset of patients is complicated by angioedema, a potentially life-threatening adverse event largely mediated by bradykinin signaling. The unpredictable and idiosyncratic nature of this reaction has long suggested an underlying genetic contribution, yet its molecular architecture has remained poorly characterized. We hypothesized that alteplase-associated angioedema represents a multigenic susceptibility phenotype, arising from the convergence of rare genetic variants across multiple interacting physiological systems rather than from a single causal variant. To explore this hypothesis, we performed clinical exome sequencing in a cohort of 11 patients who developed angioedema following alteplase administration. Rather than identifying a shared pathogenic variant, we observed distinct yet convergent patterns of genetic vulnerability, allowing patients to be grouped according to dominant, but overlapping, biological axes. These included alterations affecting bradykinin regulation (e.g., ACE, SERPING1, XPNPEP2), endothelial structure and hemostasis (e.g., VWF, COL4A1), neurovascular and calcium signaling (e.g., SCN10A, RYR1), and vascular repair or remodeling pathways (e.g., PSEN2, BRCA2). Notably, many of the identified variants were classified as Variant of Uncertain Significance (VUS) or likely benign significance in isolation. However, when considered within an integrated, pathway-based framework, these variants can be interpreted as capable of contributing cumulatively to system level fragility, a phenomenon best described as “contextual pathogenicity”. Under the acute biochemical and proteolytic stress imposed by thrombolysis, this reduced physiological reserve may allow otherwise compensated vulnerabilities to become clinically manifest. Together, these findings support a model in which severe alteplase-associated angioedema appears as an emergent property of interacting genetic networks, rather than a monogenic disorder. This systems level perspective underscores the limitations of gene centric interpretation for adverse drug reactions and highlights the potential value of pathway informed, multi-genic approaches to risk stratification. Such frameworks may ultimately contribute to safer, more personalized thrombolytic decision, while providing a conceptual foundation for future functional and translational studies. Full article

Feline cardiogenic arterial thromboembolism (ATE) is a severe complication of cardiac disease in cats, often causing severe clinical signs and poor prognosis. Despite its importance, standardized guidelines for prevention and treatment are lacking. This systematic review evaluated available evidence on preventive, acute, and chronic management strategies for feline cardiogenic ATE. A comprehensive search using PubMed, Scopus and Web of Science was performed, following PRISMA 2020 guidelines. Peer-reviewed studies investigating therapeutic interventions for ATE were included. Risk of bias was assessed using the SYRCLE tool. Nineteen studies involving 909 cats were included. Preventive therapy with clopidogrel and rivaroxaban improved survival. Acute multimodal treatment combining anticoagulant and antiplatelet drugs improved survival compared to monotherapy. Thrombolytic therapy showed some efficacy but had frequent severe complications. Long-term management with clopidogrel and rivaroxaban achieved the longest survival and lowest recurrence, while acetylsalicylic acid provided inconsistent benefits and more adverse effects. Eleven of the nineteen (58%) studies had high risk of bias due to small sample size and heterogeneous protocols. Current evidence supports dual therapy, particularly clopidogrel with rivaroxaban or enoxaparin, as the most effective and well-tolerated approach for prevention and treatment. Larger, standardized prospective trials are urgently needed to strengthen the evidence. Full article

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

Coronary artery disease (CAD) constitutes a major contributor to morbidity, mortality and healthcare burden worldwide. Recent innovations in imaging modalities, pharmaceuticals and interventional techniques have revolutionized diagnostic and treatment options, necessitating the reevaluation of established drug protocols or the consideration of newer alternatives. The utilization of beta blockers (BBs) in the setting of acute myocardial infarction (AMI), shifting from the pre-reperfusion to the thrombolytic and finally the primary percutaneous coronary intervention (pPCI) era, has become increasingly more selective and contentious. Nonetheless, the extent of myocardial necrosis remains a key predictor of outcomes in this patient population, with large trials establishing the beneficial use of beta blockers. Computed tomography coronary angiography (CTCA) has emerged as a highly effective diagnostic tool for delineating the coronary anatomy and atheromatous plaque characteristics, with the added capability of MESH-3D model generation. Induction and preservation of a low heart rate (HR), regardless of the underlying sequence, is of critical importance for high-quality results. Landiolol is an intravenous beta blocker with an ultra-short duration of action (t1/2 = 4 min) and remarkable β1-receptor specificity (β1/β2 = 255) and pharmacokinetics that support its potential for systematic integration into clinical practice. It has been increasingly recognized for its importance in both acute (primarily studied in STEMI and, to a lesser extent, NSTEMI pPCI) and chronic (mainly studied in elective PCI) CAD settings. Given the limited literature focusing specifically on landiolol, the aim of this narrative review is to examine its pharmacological properties and evaluate its current and future role in enhancing both diagnostic imaging quality and therapeutic outcomes in patients with CAD. Full article

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

Most cardiological drugs need intravenous administration to have a fast effect in an emergency. Intravenous administration is linked to complications, such as tissue infiltration and thrombophlebitis. Aiming to supply an effective tool for the development of appropriate policies, this systematic review provides practical recommendations about the diluent, pH, osmolarity, dosage, vesicant properties, and phlebitis rate of the most commonly used cardiological drugs evaluated in randomized controlled trials (RCTs) till 31 August 2024. The authors searched for available IV cardiological drugs in RCTs in PUBMED EMBASE^®, EBSCO-CINAHL^®, and Cochrane Controlled Clinical trials. Drugs’ chemical features were obtained online, in drug data sheets, and in scientific papers, establishing that the drugs with a pH of <5 or >9, an osmolarity > 600 mOsm/L, and a high incidence of phlebitis reported in the literature, as well as vesicant drugs, require utmost caution during administration. A total of 857 papers were evaluated and 316 studies were included. A total of 84 cardiological drugs were identified, of which only 31 (37%) can be safely infused via a peripheral route. Thrombolytics and anticoagulants are considered the safest classes of drugs, with only one drug flagged as a “red flag” medication. However, a higher percentage of drugs in other categories meet the “red flag” criteria, including antiarrhythmics (52%), antiplatelet agents (67%), diuretics (67%), antihypertensives (70%), other drugs (77%), and vasoconstrictors and inotropics (89%). Understanding the physicochemical properties of cardiological drugs is essential for significantly improving patient safety and preventing administration errors and local side effects. Full article

The Lamiaceae family of medicinal plants holds immense promise in the development of functional foods aimed at preventing and treating cardiovascular diseases (CVDs). These plants are rich in bioactive compounds, such as phenolic acids, flavonoids, and terpenoids, which act as potent enzyme inhibitors and exhibit strong antioxidant, anti-inflammatory, and antihyperlipidemic properties. Key phenolic compounds, such as rosmarinic acid and caffeic acid, along with flavonoids like luteolin, apigenin, and quercetin, contribute to these health benefits. Essential oils derived from Lamiaceae species have demonstrated diverse biological activities, including vasorelaxant, thrombolytic, and cytotoxic effects, making them valuable in nutraceutical formulations. This study analyzes and investigates global patent trends related to Lamiaceae plants targeting cardiovascular health, focusing on applications in nutraceuticals and functional foods. Using patent databases, we examine the technological landscape, identify leading applicants, and evaluate the geographical distribution of innovations. Our analysis reveals a notable increase in patent filings since the late 1970s, peaking in 2007, indicating a growing interest in leveraging Lamiaceae plants for cardiovascular health. Tianjin Tasly Pharmaceuticals Co., Ltd. emerges as a leading applicant, reflecting active engagement by pharmaceutical companies alongside independent researchers and organizations. Geographically, China leads patent activity, followed by the United States and Europe, underscoring global interest and market potential. Key International Patent Classification (IPC) codes identified include A61K36/53 (Lamiaceae extracts), A61P9/00 (cardiovascular drugs), and A61P9/10 (treatments of ischemic or atherosclerotic diseases). These findings highlight the therapeutic and commercial relevance of Lamiaceae bioactives, offering insights into their potential in advancing cardiovascular health and shaping the future of the functional food and nutraceutical industries. Full article

Thrombosis is the occlusion of a blood vessel and is responsible for the highest number of deaths worldwide. Its treatment comprises the use of anticoagulants, antiplatelets, and thrombolytics. Although many antithrombotic drugs are currently available, none is completely effective and safe. Plants are a valuable source of compounds with antithrombotic properties. Some orchid species have been used in traditional medicine for their antithrombotic properties. This review informs about the contribution of orchids in this field and the studies that have validated their properties. 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

As an essential thrombolytic agent, the tissue plasminogen activator receives increasing attention due to its longer half-life, lower immunogenicity, and easier administration, which are superior to other thrombolytic agents. In this study, the isolated and purified plasminogen activator from the sandworm (Perinereis aibuhitensis) was expressed in E. coli (Escherichia coli) to investigate its potential for simplifying the development process. The sandworm plasminogen activator was previously successfully cloned and expressed in E. coli with low yield and activity in the culture supernatant. This low yield and activity prompted us to optimize its DNA sequence. Furthermore, to raise the efficiency in the separation of the target protein, the protein’s solubility was enhanced by fusing it with maltose-binding protein (MBP) tags. Eventually, the fibrinolytic activity was successfully restored after digestion with tobacco etch virus (TEV) protease. This study provides an innovative method of efficiently expressing and purifying plasminogen activators from sandworm in E. coli and broadens its applications in therapeutic treatment of cardiovascular diseases, including thrombosis, stroke, and coronary atherosclerotic heart disease. Full article

Venous thromboembolism (VTE) is a serious health condition and represents an important cause of morbidity and, in some cases, mortality due to the lack of effective treatment options. According to the Centers for Disease Control and Prevention, 3 out of 10 people with VTE will have recurrence of a clotting event within ten years, presenting a significant unmet medical need. For some VTE patients, symptoms can last longer and have a higher than average risk of serious complications; in contrast, others may experience complications arising from insufficient therapies. People with VTE are initially treated with anticoagulants to prevent conditions such as stroke and to reduce the recurrence of VTE. However, thrombolytic therapy is used for people with pulmonary embolism (PE) experiencing low blood pressure or in severe cases of DVT. New drugs are under development, with the aim to ensure they are safe and effective, and may provide an additional option for the treatment of VTE. In this review, we summarize all ongoing trials evaluating anticoagulant interventions in VTE listed in clinicaltrials.gov, clarifying their underlying mechanisms and evaluating whether they prevent the progression of DVT to PE and recurrence of thrombosis. Moreover, this review summarizes the available evidence that supports the use of antiplatelet therapy for VTE. Since thrombolytic agents would cause off-target effects, targeted drug delivery platforms are used to develop various therapeutics for thrombotic diseases. We discuss the recent advances achieved with thrombus-targeting nanocarriers as well as the major challenges associated with the use of nanoparticle-based therapeutics. Full article

Background: Intravenous thrombolysis is one of the most effective therapies for the treatment of acute ischemic stroke (AIS), with urokinase offering a cost-effective alternative to newer agents like alteplase and tenecteplase, especially in resource-limited settings. Methods: This review provides a comprehensive overview of the application of intravenous thrombolysis with urokinase for AIS in the clinical practice of stroke management, including the efficacy, safety, and cost-effectiveness of urokinase compared to other thrombolytic agents. Results: Urokinase, a first-generation thrombolytic drug, is a non-specific plasminogen activator that offers a cost-effective alternative. It has been used in clinical practice for over two decades to improve neurological outcomes in patients with AIS if administered within 6 h of ictus. Numerous studies have indicated that urokinase remains a viable option for patients who cannot access alteplase or tenecteplase because of economic constraints, time window limitations, availability, or other reasons. Conclusions: In low- and middle-income countries, urokinase is a cost-effective alternative thrombolytic drug. High-level evidence-based medical research is therefore urgently needed to confirm that urokinase is not inferior to new-generation thrombolytic drugs, and to assess whether it may even be superior in some patient populations. Full article

The fibrinolytic kinase identified in the nereid worm (Perinereis aibuhitensis Grub) displays exceptional kinase activity, stability, and specificity, suggesting its potential as a promising candidate for the advancement of new thrombolytic drugs. In this study, a process was optimized for the production of fibrinolytic kinase using Escherichia coli, and the effects of factors such as inoculum, pH, OD, temperature, inducer concentration, and time on the protein yield were investigated. The optimum points of key parameters were determined by single-factor experiments, and the initial pH, OD, and time were determined to be significant by PB (Plackett–Burman design) with six factors at two levels of experiments. The response surface experiments highlighted the key roles of initial pH and induced OD values, and the convergence of the model and experimental data confirmed the optimal conditions and reasonable fluctuation intervals, which proved the reliability of the model. Full article