Target-specific anticoagulant

Anticoagulant therapy is a mainstay in the management of patients with cardiovascular disease and related conditions characterized by a heightened risk for thrombosis. Acute coronary syndrome, chronic coronary syndrome, ischemic stroke, and atrial fibrillation are the most common. In addition to their proclivity for thrombosis, each of these four conditions is also characterized by local and systemic inflammation, endothelial/endocardial injury and dysfunction, oxidative stress, impaired tissue-level reparative capabilities, and immune dysregulation that plays a critical role in linking molecular events, environmental triggers, and phenotypic expressions...

During inflammation and situations of cellular stress Protein Disulfide Isomerase (PDI) is released in the blood plasma from the platelet and endothelial cells to influence thrombosis. The addition of exogenous PDI makes the environment pro-thrombotic by inducing disulfide bond formation in specific plasma protein targets like vitronectin, factor V, and factor XI. However, the mechanistic details of PDI interaction with its target remain largely unknown. A decrease in the coagulation time was detected in activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) in addition to the purified recombinant PDI (175nM)...

Thrombosis remains one of the leading causes of death in the world. The history of anticoagulation has evolved considerably from non-specific drugs (i.e., heparins and vitamin K antagonists, VKA) to agents that directly target specific coagulation factors (i.e., argatroban, fondaparinux and direct oral anticoagulants, DOAC). Since the last decade, DOAC are widely used in clinical practice because of their ease to use, their favorable pharmacological profile and the fact that they do not require monitoring. However, despite having a better safety profile than vitamin K antagonist, their bleeding risk is not negligible...

Arterial and venous thromboembolism is a major medical concern that requires therapeutic anticoagulation in various medical fields to prevent its drastic consequences. Despite significant advances in anticoagulant therapy, thrombosis remains a leading cause of morbidity and mortality worldwide. Traditional anticoagulants like heparin and vitamin K antagonists (VKAs) have shown efficacy in preventing and treating thrombosis but come with an inherent risk of bleeding due to their non-specific inhibition of multiple coagulation factors...

The process of blood coagulation, wherein circulating blood transforms into a clot in response to an internal or external injury, is a critical physiological mechanism. Monitoring this coagulation process is vital to ensure that blood clotting neither occurs too rapidly nor too slowly. Anticoagulants, a category of medications designed to prevent and treat blood clots, require meticulous monitoring to optimise dosage, enhance clinical outcomes, and minimise adverse effects. This review article delves into the various stages of blood coagulation, explores commonly used anticoagulants and their targets within the coagulation enzyme system, and emphasises the electrochemical methods employed in anticoagulant testing...

OBJECTIVE: This study aims to investigate the risk factors associated with the development of venous thromboembolism (VTE) in patients diagnosed with gynecologic malignant tumors. METHODS: A comprehensive meta-analysis was conducted by searching databases such as The Cochrane Library, PubMed, EMbase, Web of Science, CNKI, etc., covering the period from January 2010 to January 2020. Inclusion and exclusion criteria were applied to identify relevant literature. Two researchers independently conducted literature screening, data extraction, and quality assessment of the included studies...

UNLABELLED: Many mechanisms responsible for COVID-19 pathogenesis are well-established, but COVID-19 includes features with unclear pathogenesis, such as autonomic dysregulation, coagulopathies, and high levels of inflammation. The receptor for the SARS-CoV-2 spike protein receptor-binding domain (RBD) is angiotensin-converting enzyme 2 (ACE2). We hypothesized that some COVID-19 patients may develop antibodies that have a negative molecular image of RBD sufficiently similar to ACE2 to yield ACE2-like catalytic activity-ACE2-like abzymes...

Heparin, an anticoagulant with a century-long history of use, has been investigated over the past decade as a potential drug delivery vehicle. Despite its safety and efficacy, its interactions with many proteins through specific sulfate patterns can complicate drug delivery by mediating diverse biological functions. Here, we present the synthesis of a three-component drug delivery system comprising de-sulfated heparin as the carrier, galactose as the targeting moiety, and paclitaxel as the therapeutic drug...

Factor XIIa (FXIIa) functions as a plasma serine protease within the contact activation pathway. Various animal models have indicated a substantial role for FXIIa in thromboembolic diseases. Interestingly, individuals and animals with FXII deficiency seem to maintain normal hemostasis. Consequently, inhibiting FXIIa could potentially offer a viable therapeutic approach for achieving effective and safer anticoagulation without the bleeding risks associated with the existing anticoagulants. Despite the potential, only a limited number of small molecule inhibitors targeting human FXIIa have been documented...

BACKGROUND: Spontaneous acute intracerebral hemorrhage (ICH) is associated with greater stroke-related disability and mortality. Hematoma expansion (HME), an important treatment target in acute ICH, is time-dependent, with a greater probability of hematoma growth occurring <3 hours from ICH onset. SUMMARY: Promising treatment options to reduce HME include early intensive blood pressure (BP) reduction and the administration of hemostatic or anticoagulant reversal agents, yet large phase III clinical trials have so far failed to show overwhelming benefit for these interventions in acute ICH...

Inflammation and coagulation are critical self-defense mechanisms for mitigating infection that can nonetheless induce tissue injury and organ dysfunction. In severe cases, like sepsis, a dysregulated thromboinflammatory response may result in multiorgan dysfunction. Sepsis-associated acute kidney injury (AKI) is a significant contributor to patient morbidity and mortality. The connection between AKI and thromboinflammation is largely due to unique aspects of the renal vasculature. Specifically, the interaction between blood cells with the endothelial, glomerular, and peritubular capillary systems during thromboinflammation reduces oxygen supply to tubular epithelial cells...

BACKGROUND: The influence of child characteristics on warfarin dosing has been reported; however, there is no consensus on the nature and extent of this effect. OBJECTIVES: To investigate the impacts of the demographic and clinical characteristics of children on the warfarin dose required to achieve a therapeutic international normalization ratio (INR). METHODS: This retrospective cohort study included children aged 3 months to 14 years old who were prescribed warfarin for 3 months or longer with a "stable INR...

BACKGROUND: Extracellular vesicles (EVs), including microvesicles, hold promise for the management of bladder urothelial carcinoma (BLCA), particularly because of their utility in identifying therapeutic targets and their diagnostic potential using easily accessible urine samples. Among the transmembrane glycoproteins highly enriched in cancer-derived EVs, tissue factor (TF) and CD147 have been implicated in promoting tumor progression. In this in vitro study, we explored a novel approach to impede cancer cell migration and metastasis by simultaneously targeting these molecules on urothelial cancer-derived EVs...

BACKGROUND: Underlying mechanisms for bleeding and impaired thrombin generation (TG) and plasma clot formation (PCF) in patients with mild to moderate bleeding disorders (MBDs) are still to be elucidated, especially in bleeding disorder of unknown cause (BDUC). The role of the natural anticoagulants activated protein C (APC) and free protein S (PS) has not yet been investigated in this patient population. AIMS: To analyze antigen levels of APC and PS in patients with MBDs and BDUC and investigate associations to clinical bleeding phenotype and severity as well as and hemostatic capacity...

The study deals with the environmental residues of anticoagulant rodenticides (ARs) in Slovenia to evaluate the toxicological risk of secondary poisoning of red foxes (Vulpes vulpes) as representatives of non-target wildlife, and in relation to the investigated use patterns of ARs and specific local parameters in Slovenia. From 2019 to 2022, 148 liver tissue samples of adult red foxes were collected from almost all state geographical regions. The samples were extracted with methanol/water (2:1, v/v), cleaned-up using a solid supported liquid-liquid extraction, and measured by liquid chromatography-electrospray tandem mass spectrometry (LC-ESI-MS/MS) with reporting limits of 0...

Apixaban and dabigatran are the two major direct oral anticoagulant drugs to treat thromboembolic disordered patients. Increasing the clinical application for the thromboembolic disorder and monitoring the concentrations of apixaban, dabigatran, and their metabolites are essential in most clinical circumstances. In this work, we developed a rapid analytical methodology comprising of vortex-assisted salt-enhanced liquid-liquid microextraction technique coupled with UHPLC-MS/MS for the extraction and simultaneous determination of two major direct oral anticoagulant drugs (apixaban, dabigatran), and their two major metabolites from plasma, serum, and urine samples of patients...

Patients with hematologic malignancies are often complicated not only by severe bleeding due to thrombocytopenia and disseminated intravascular coagulation but also by thromboembolic events, just like in patients with solid cancers, and these events can negatively impact patient outcomes. Nevertheless, the prevention and treatment of cancer-associated thrombosis (CAT) in hematologic malignancies has not been adequately investigated due to the limited size, heterogeneity, and unique pathophysiology of the patient population...

It is well known that rodenticides are widely used, and there are multiple routes by which they can reach non-target wildlife species. Specifically, in the Canary Islands, a high and concerning incidence of these compounds has been reported. However, in this scenario, reptiles remain one of the least studied taxa, despite their potential suitability as indicators of the food chain and environmental pollution has been noted on several occasions. In this context, the California Kingsnake ( Lampropeltis Californiae ), widely distributed on the island of Gran Canaria, occupies a medium trophic level and exhibits feeding habits that expose it to these pollutants, could be studied as a potential sentinel of exposure to these compounds...

Tumor-associated thrombus (TAT) accounts for a high proportion of venous thromboembolism. Traditional thrombolysis and anticoagulation methods are not effective due to various complications and contraindications, which can easily lead to patients dying from TAT rather than the tumor itself. These clinical issues demonstrate the need to research diverse pathways for adjuvant thrombolysis in antitumor therapy. Previously, the phenotypic and functional transformation of monocytes/macrophages is widely reported to be involved in intratribal collagen regulation...

OBJECTIVES: To evaluate the efficacy of integrating antithrombotic-focused pharmaceutical algorithms (PAs) into a pharmaceutical decision support system (PDSS) for detecting drug-related problems (DRPs) and facilitating pharmaceutical interventions. METHODS: A set of 26 PAs (12.4%) out of a total of 210 were created to model patient situations involving antithrombotics, and their contributions were compared with the entire PDSS system.The observational prospective study was conducted between November 2019 and June 2023 in two health facilities with 1700 beds...