Target-specific anticoagulant

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...

Metastasis is the leading cause of cancer-related deaths. Despite this relevance, there is no specific therapy targeting metastasis. The interaction of the tumor cell with platelets, forming microemboli is crucial for successful hematogenous dissemination. Heparin disrupts it by a P-selectin-mediated event. However, its clinical use for this purpose is hindered by the requirement of high doses, leading to anticoagulant-related side effects. In this study, we obtained a low-anticoagulant heparin through the fractionation of a pharmaceutical bovine heparin...

BACKGROUND: Unfractionated heparin (UFH) is commonly used during cardiac surgery with a cardiopulmonary bypass to prevent blood clotting. However, empirical administration of UFH leads to variable responses. Pharmacokinetic and pharmacodynamic modeling can be used to optimize UFH dosing and perform real-time individualization. In previous studies, many factors that could influence UFH pharmacokinetics/pharmacodynamics had not been taken into account such as hemodilution or the type of UFH...

Antiphospholipid antibodies (aPL) in primary or secondary antiphospholipid syndrome (APS) are a major cause for acquired thrombophilia, but specific interventions preventing autoimmune aPL development are an unmet clinical need. While autoimmune aPL cross-react with various coagulation regulatory proteins, lipid-reactive and COVID-19 patient-derived aPL recognize the endo-lysosomal phospholipid lysobisphosphatidic acid (LBPA) presented by the cell surface expressed endothelial protein C receptor (EPCR). This specific recognition leads to complement-mediated activation of tissue factor (TF) dependent proinflammatory signaling and thrombosis...

Objective: To evaluate the clinical application performance of a domestic D-dimer assay reagent (ADX D-dimer). Methods: A total of 546 residual sodium citrate anticoagulated plasma samples (530 of which were used for comparability validation and 16 for sample preparation of other validation components) were selected after the completion of clinical testing at Peking Union Medical College Hospital from Jun 2022 to May 2023. According to the American Clinical Laboratory Standards Institute (CLSI) guidelines, national health industry standards and relevant references, the performance of ADX D-dimer used in Sysmex CS 5100 fully automated coagulation analyzer which included accuracy, precision, linear range, carryover rate, interference resistance capability and reference interval were validated and the agreement compared with two mainstream imported detection reagents (reagent A: Vidas D-dimer reagent; reagent B: Innovance D-dimer detection reagent) was evaluated...

Metabolomics has been used to characterise many biological matrices and obtain detailed pictures of biological systems based on many metabolites. Plasma and serum are two blood-derived biofluids commonly used to assess and monitor the organismal metabolism and obtain information on the physiological and health conditions of an animal. Plasma is the supernatant that is separated from the cellular components after centrifugation of the blood that is first added with an anticoagulant. Serum is obtained after centrifugation of the blood that has been coagulated...

In observational studies weighting techniques are often used to overcome bias due to confounding. Modeling approaches, such as inverse propensity score weighting, are popular, but often rely on the correct specification of a parametric model wherein neither balance nor stability are targeted. More recently, balancing approach methods that directly target covariate imbalances have been proposed, and these allow the researcher to explicitly set the desired balance constraints. In this study, we evaluate the finite sample properties of different modeling and balancing approach methods, when estimating the marginal hazard ratio, through Monte Carlo simulations...

KEY CLINICAL MESSAGE: Middle-aged male athletes, with or without underlying coronary artery disease, exhibiting exercise induced blood pressure (BP) variability and diabetes can have an increased risk of developing atrial fibrillation (AF). Assessment in athletes should include long-term arrhythmia monitoring. In addition, it is important to exert patients beyond their calculated target heart rate (HR) during an exercise stress test to detect exercise-induced AF. We suggest this strategy be specifically used for athletes with complaints of intermittent palpitation and chest pain...

Ingestion of an additional blood meal(s) by a hematophagic insect can accelerate development of several vector-borne parasites and pathogens. Most studies, however, offer blood from the same vertebrate host species as the original challenge (for e.g., human for primary and additional blood meals). Here, we show a second blood meal from bovine and canine hosts can also enhance sporozoite migration in Anopheles stephensi mosquitoes infected with the human- and rodent-restricted Plasmodium falciparum and P. berghei, respectively...

Aging is a growing problem worldwide, and the prevalence and mortality of arterial and venous thromboembolism (VTE) are higher in the elderly than in the young population. To address this issue, various anticoagulants have been used. However, no evidence can confirm that antithrombotic agents are suitable for the elderly. Therefore, this study aims to investigate the platelet proteome of aged mice and identify antithrombotic drug targets specific to the elderly. Based on the proteome analysis of platelets from aged mice, 308 increased or decreased proteins were identified...

Lower extremity deep venous thrombosis (LEDVT) affects patient's quality of life for a long time, and even causes pulmonary embolism, which threatens human health. Current anticoagulant drugs in clinical treatment are hampered by the risk of bleeding due to poor targeting and low drug penetration. Here, we used platelet (PLT)-like biological targeting to enhance the delivery and accumulation of nanomedicines in thrombus and reduce the risk of bleeding. Meanwhile, the parallel strategy of "thrombus thermal ablation and anticoagulation" was applied to increase the permeability of drugs in thrombus and achieve the optimal antithrombotic effect...

PURPOSE OF THE REVIEW: Short-term and durable mechanical circulatory support (MCS) devices represent life-saving interventions for patients with cardiogenic shock and end-stage heart failure. This review will cover the epidemiology, risk factors, and treatment of stroke in this patient population. RECENT FINDINGS: Short-term devices such as intra-aortic balloon pump, Impella, TandemHeart, and Venoatrial Extracorporal Membrane Oxygenation, as well as durable continuous-flow left ventricular assist devices (LVADs), improve cardiac output and blood flow to the vital organs...

To investigate the expression alterations of specific genes that occur after venous stroke, we identified differentially expressed genes (DEGs) between sham and damaged cortical tissues at 2 and 7 days after induction of cerebral venous sinus thrombosis (CVST) model. The profiles of DEGs were analyzed using GO, KEGG, GSEA, and PPI, and the crucial gene was further verified by western blot and immunofluorescence. We found 969 and 883 DEGs at 2 and 7 days after CVST, respectively. A marked increase in biological-process categories, such as immune system process and inflammatory response, and a decrease in neuropeptide signaling pathway were observed both at 2 and 7 days post-CVST...

Zika virus (ZIKV) infection during pregnancy can result in severe birth defects, such as microcephaly, as well as a range of other related health complications. Heparin, a clinical-grade anticoagulant, is shown to protect neural progenitor cells from death following ZIKV infection. Although heparin can be safely used during pregnancy, it retains off-target anticoagulant effects if directly employed against ZIKV infection. In this study, we investigated the effects of chemically modified heparin derivatives with reduced anticoagulant activities...

AIM: Errors with prescribing high-risk medicines (HRMs) have a greater propensity to cause harm than with non-HRMs. Prescribing errors arise due to multiple factors and it can be particularly challenging for junior doctors to prescribe safely during the on-call period. Knowledge regarding the challenges of prescribing HRM during the on-call period would be useful to target preventative interventions. The aim of this study was to explore the challenges encountered by foundation doctors (doctors who have graduated medical school within the last two years) when prescribing specific HRMs (anticoagulants, insulin, and opioids) safely during the on-call period...