Anticoagulant Agents Research Articles

Diastolic Dysfunction and the Risk of Stroke and Major Bleeding.

Left ventricular diastolic dysfunction (DD) is associated with adverse cardiovascular outcomes including atrial fibrillation. Whether DD is independently associated with incident stroke and transient ischemic attack (TIA) and with bleeding events is not known. We performed this observational cohort analysis to examine the impact of DD on the risk of stroke/TIA and major bleeding. Patients who underwent at least 1 cardiac echocardiogram and were followed for at least 3 months were included in this study. Patients with a prior history of stroke, TIA, or major bleeding, as determined by International Classifications of Diseases codes, were excluded. Smart key-phrase search was applied to echocardiographic reports to classify patients into 4 groups based on the most severe DD assessment. Patients in whom the presence of DD could not be determined were excluded. The final study cohort was followed to the end point of hospital admission for stroke/TIA and major bleeding, and independent predictors of these events were evaluated using the multivariable Cox proportional hazards method. The final study cohort (age, 56±18 years; 56% women) had 96 702 patients with no DD and 18 164, 5881, and 1340 patients with DD grades I, II, and III, respectively. Over a median follow-up of 3.4 years, 2938 (2.4%) patients were hospitalized for stroke/TIA and 5567 (4.6%) for major bleeding. After adjusting for age, the CHA2DS2-VASc score, chronic kidney disease, use of antiplatelet agents, use of anticoagulation agents, the year of echocardiographic testing, household income, and history of atrial fibrillation, DD remained a strong predictor of incident stroke/TIA (hazard ratio, 1.22 per grade increase in DD [95% CI, 1.16-1.29]; P<0.001) and major bleeding (hazard ratio, 1.20 per grade increase in DD [95% CI, 1.16-1.25]; P<0.001). DD is independently associated with a higher risk of cerebrovascular accidents and major bleeding. DD should be considered when counseling patients regarding their risk profile and management options.

Aeruginosin 525 (AER525) from Cyanobacterium Aphanizomenon Sp. (KUCC C2): A New Serine Proteases Inhibitor

Aeruginosins (AERs) are one of the most common classes of cyanobacterial peptides synthesised through a hybrid non-ribosomal peptide synthase/polyketide synthase pathway. They have been found in Microcystis, Nodularia spumigena, Oscillatoria/Plantothrix, and Nostoc. The presence of AER in Aphanizomenon isolated from the Curonian Lagoon was reported for the first time in our previous work. Here, the structure of aeruginosin 525 (AER525), isolated from Aphanizomenon sp. KUCC C2, was characterised based on high-resolution mass spectrometry. This new AER variant shows potent activity against thrombin. It also inhibits trypsin and carboxypeptidase A but has no effect on elastase and chymotrypsin. In terms of the N-terminal residue and biological activity, AER525 displaces some similarity to dysinosins, which belongs to the most potent inhibitors of thrombin among AERs. The findings underline the potential of AER525 as a new anticoagulant agent.

Protective effects of long term antiplatelet and anticoagulant therapy in hospitalized patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD), with its rising prevalence rates is associated with an increased risk of cardiovascular and thromboembolic events. Antiplatelets and/or anticoagulants agents are often prescribed but the literature on the impact of long-term anticoagulation and/or antiplatelet use among patients hospitalized with IBD is scarce. The aim of this study is to assess the outcomes of patients hospitalized with IBD on antiplatelet and/or anticoagulant agents. To investigate the effects of long-term use of antiplatelets/anticoagulants on clinical outcomes in patients hospitalized with IBD. We conducted a retrospective cohort study using the Nationwide Inpatient Sample database, including all adult IBD patients hospitalized in the United States from 2016 to 2019. Patient cohorts were stratified based on antiplatelet/anticoagulant therapy status. Multivariate regression analysis was done to assess outcomes, adjusting for potential confounders. The primary outcome was mortality, whereas length of stay (LOS), total parenteral nutrition, acute kidney injury, sepsis, shock, gastrointestinal bleeding, need for colonoscopy/sigmoidoscopy, abdominal surgery and total hospitalization charges were secondary outcomes. Among 374744 hospitalized IBD patients, antiplatelet or anticoagulant therapy alone was associated with significantly lower in-hospital mortality and reduced healthcare utilization, including shorter LOS and decreased hospitalization costs. Combined therapy was associated with a protective effect on mortality, but did not reach statistical significance. Notably, therapy did not exacerbate disease severity or complications, although higher odds of gastrointestinal bleeding were observed. Our study highlights the potential benefits of long-term anticoagulation/antiplatelet therapy in hospitalized IBD patients, with improved mortality outcomes and healthcare utilization. While concerns regarding gastrointestinal bleeding exist, the overall safety profile suggests a role for these agents in mitigating thromboembolic risks without exacerbating disease severity. Further research is needed to look at optimal treatment strategies and addressing limitations to guide clinical decision-making in this population.

Non-surgical spinal cord infarction: case series & long-term follow-up of functional outcome

IntroductionSpinal cord infarction is a rare but often devastating disorder. The pathogenesis of most non-surgical cases involves atherothrombosis and treatment with anticoagulation and antiplatelet agents may be indicated. Functional recovery in most cases is poor. We describe five cases of spinal cord infarction and provide details on their functional outcomes after long-term (>10 years) follow-up.Case presentationA 28-year-old female presented at 16 weeks gestation with chest and back pain and paraesthesia in her fingers. Magnetic resonance imaging on admission revealed a spinal cord lesion extending from C5-T8. She was treated with anticoagulation and rehabilitation. Six years following presentation she was able to return to work. A 42-year-old male experiencing central chest pain and leg weakness was initially diagnosed as having acute coronary syndrome. Following discharge, he was re-admitted with urinary retention and leg weakness. Magnetic resonance imaging revealed a spinal cord lesion extending from T4 to T7. He was treated with anticoagulation, and eight months following presentation he regained full muscle strength but required intermittent self-catherisation. Three further cases are described.DiscussionThe aetiology of non-surgical spinal cord infarction is not always evident, but is commonly associated with atherothrombosis. There are often delays in making a diagnosis, but early recognition and prompt treatment of spinal cord infarction is essential. Long-term functional outcomes are often poor and typically reflect the severity of initial presentation. This case series is unique as it has one of the longest follow-up periods described in the literature.

Strategies for Perioperative Anticoagulant Reversal in Orthopedic Surgery: A Review.

The administration of anticoagulation therapy during major orthopedic surgeries is a clinical challenge due to the risk of thrombotic events and bleeding complications. This review aims to evaluate the current strategies and emerging developments in perioperative anticoagulation reversal. We conducted a literature review on the management of perioperative anticoagulant therapy, which included the current status of anticoagulant reversal agents, as well as personalized medicine, pharmacogenomics, artificial intelligence (AI), and novel drug delivery systems. The review indicates that reversal agents such as idarucizumab and andexanet alfa are crucial in managing bleeding associated with direct oral anticoagulants (DOACs). Personalized medicine, guided by pharmacogenomics, allows for tailored anticoagulation regimens. AI and machine learning (ML) algorithms can enhance the predictive capabilities for bleeding and thrombotic risks. Additionally, nanotechnology and biomarkers offer innovative approaches to drug delivery and personalized treatment. Integrating evidence-based guidelines with innovative reversal agents, personalized medicine, AI and nanotechnology opens a new era in perioperative anticoagulation management. These advancements can ensure patient safety, minimize bleeding risks, and improve surgical outcomes. Future research should focus on the clinical validation of these strategies to ensure their effectiveness across diverse patient populations.

Meta-Analysis Comparing Oral Anticoagulant Monotherapy Versus Dual Antithrombotic Therapy in Patients With Atrial Fibrillation and Stable Coronary Artery Disease.

Oral anticoagulants (OACs) are routinely used for the management of atrial fibrillation (AF) while antiplatelet agents are used in coronary artery disease (CAD). However, data regarding the comparative clinical outcomes of OAC monotherapy versus dual antithrombotic therapy (anticoagulant plus antiplatelet agent) in patients with AF and stable CAD are limited. A comprehensive search of major databases including PubMed/MEDLINE, Cochrane Library, and Embase was performed from inception to September 1, 2024 to identify randomized control trials (RCTs) that compared OAC monotherapy with dual antithrombotic therapy in patients with AF and stable CAD. The risk ratios (RRs) were estimated with corresponding 95% confidence intervals (CIs) for all outcomes. A total of three RCTs reported data for 3945 patients with AF and stable CAD. The mean age of patients was 73.8 (±11.85) years and the mean follow-up was 22 months. OAC monotherapy was associated with a significantly reduced relative risk of major bleeding (RR: 0.55, 95% CI: 0.32-0.95) compared to dual therapy. The risk of all-cause death (RR: 0.85, 95% CI: 0.49-1.48), cardiovascular death (RR: 0.84, 95% CI: 0.50-1.41), any stroke event (RR: 0.74, 95% CI: 0.46-1.18), and myocardial infarction (RR: 1.57, 95% CI: 0.79-3.12) remained comparable across the two groups. OAC monotherapy led to a significant relative risk reduction for major bleeding with similar rates of ischemic events and mortality compared to dual antithrombotic therapy in patients with AF and stable CAD.

Knowledge, Attitudes, and Practices of Prescribing Doctors Towards Direct Oral Anticoagulants: First Cross-sectional Study from Sudan

Background: During recent years, the prescription rates of direct oral anticoagulants (DOACs) have increased rapidly worldwide. Little is known about situation of DOACs in Sudan. Therefore, this study was conducted to assess prescribing doctors’ knowledge, attitude, and practice level regarding DOACs. Methods: A cross-sectional, hospital-based study was conducted at three large hospitals in Khartoum, Sudan. The doctors were recruited from a wide range of disciplines such as cardiology, surgery, and nephrology. A four-section questionnaire consisting of questions on demographics, knowledge, attitude, and practice was designed and administered. Results: A total of 100 doctors responded over a period of four months, 52% of them were found to correlate with a low level of knowledge. Moreover, 56% and 81% of the doctors demonstrated inappropriate attitude and practice levels, respectively. With regard to switching protocols between DOACs and warfarin, the majority of the doctors did not have sufficient information when converting from rivaroxaban to warfarin and vice versa. Conclusion: The overall knowledge, attitudes, and practices of prescribing doctors regarding the use of the DOACs were found to be inadequate and insufficient for maintaining high therapeutic outcomes in patients necessitating anticoagulants agents. A well-structured educational program about DOACs is urgently needed.

Challenges in laboratory testing of patients suspected of antiphospholipid syndrome: practical implications for clinicians.

This paper focuses on the laboratory tests necessary for the diagnosis of antiphospholipid syndrome (APS). Diagnosis starts with the selection of patients suspicious of having APS. The timing related to the clinical event is important to avoid false classification of APS patients. For the interpretation of the test results of antiphospholipid antibodies (aPL) understanding of all pitfalls and interferences is necessary. Lupus anticoagulant (LA) measurement remains a complex procedure with many pitfalls and interferences. The effect of anticoagulant therapy, the main confounder of LA measurement, can be overcome by removal agents for direct oral anticoagulants (DOAC) or by considering assays as Taipan snake venom time / Ecarin clotting time not affected by antivitamin K therapy and anti-Xa DOAC. However, both procedures have limitations. Solid-phase assays for anticardiolipin antibodies (aCL) and anti-β2-glycoprotein 1 antibodies (aβ2GPI) show inter-assay differences. Diagnosis is based on the measurement of three groups of aPL: LA, aCL and aβ2GPI, of IgG and IgM isotype. This allows to make antibody profiles that helps in identifying patients at risk. Other aPL, such as antibodies against the domain I of β2GPI and anti-phosphatidylserine-prothrombin antibodies may be useful in risk stratification of APS patients and in some specific situations of patients with incomplete antibody profile, but are not needed for diagnosis. Laboratory diagnosis of APS remains challenging. To increase the diagnostic efficacy and reliability, an integrated interpretation of all results and an interpretative comment should be provided on the laboratory report. Therefore, a close interaction between clinical pathologists and clinicians is mandatory.

Chemical Diversity, Pharmacology, Synthesis and Detection of Naturally Occurring Peroxides.

Natural occurring peroxides are interesting bioprospecting targets due to their molecular structural diversity and the wide range of pharmacological activities. In this systematic review, a total of 123 peroxide compounds were analysed from 99 published papers with the compounds distributed in 31 plants, 18 animals and 41 microorganisms living in land and water ecosystems. The peroxide moiety exists as both cyclic and acyclic entities and can include 1,2-dioxolanes, 1,2-dioxane rings and common secondary metabolites with a peroxo group. These peroxides possessed diverse bioactivities including anticancer, antimalarial, antimicrobial, anti-inflammatory, neuroprotective, adipogenic suppressor, antituberculosis, anti-melanogenic and anti-coagulant agents. Biosynthetic pathways and mechanisms of most endoperoxides have not been well established. Method development in peroxide detection has been a challenging task requiring multidisciplinary investigation and exploration on peroxy-containing secondary metabolites are necessary.

Are There any Differences in the Outcome of Non-valvular AF Patients with Moderate CKD, Taking Rivaroxaban or Warfarin?

Background: Warfarin has long been a reliable anticoagulant, prized for its affordability and extensive track record. However, with advancements in anticoagulant therapies, many uses of warfarin have been replaced by Novel Oral Anticoagulant (NOAC) agents. Atrial fibrillation (AF) is the most common heart rhythm disorder, affecting approximately 3% of the population. This arrhythmia significantly increases the risk of both morbidity and mortality, with the risk of ischemic stroke being five times higher compared to those without AF. The outcomes for patients with different comorbidities may vary when treated with either Rivaroxaban or Warfarin. Objectives: This study aims to evaluate renal function outcomes in AF patients with moderate chronic kidney disease (CKD) who are treated with either Warfarin or Rivaroxaban. Methods: This prospective cohort study involved 99 patients recently diagnosed with non-valvular AF (&lt; 1 year) and moderate CKD, who were treated with either Warfarin or Rivaroxaban. These patients were followed for one year after their initial presentation to our center. Laboratory data and other relevant documents were collected at each visit until the conclusion of the study year. Data were analyzed using SPSS version 27, with chi-square tests and t-tests applied as appropriate. Results: The study included two groups: 25 patients on Warfarin and 74 patients on Rivaroxaban. Gender and other demographic factors were evenly distributed between the two groups. The mean glomerular filtration rate (GFR) in the Rivaroxaban group improved non-significantly at 6 and 12 months, whereas a slight, non-significant decrease in GFR was observed in the Warfarin group. Acute kidney injury (AKI) occurred in 2 patients in the Rivaroxaban group. Gastrointestinal bleeding was reported in 5 patients, with incidents evenly distributed between the two groups. Conclusions: There was no significant difference in renal outcomes between patients with newly diagnosed non-valvular AF (&lt; 1 year) with moderate CKD treated with Warfarin or Rivaroxaban. However, for women with hypertension or high-risk thrombosis, Rivaroxaban may be associated with better renal outcomes.

Probiotic Lactobacillus salivarius mediated synthesis of silver nanoparticles (AgNPs-LS): A sustainable approach and multifaceted biomedical application

Biogenic synthesis of silver nanoparticles (AgNPs) has emerged as an eco-friendly and sustainable approach with diverse biological applications. This study presents synthesis of AgNPs-LS using a probiotic strain Lactobacillus salivarius (L. salivarius) and explores their multifaceted biological activities, including antibacterial, antibiofilm, anti-quorum sensing, antifungal, antioxidant, anticancer, anticoagulant and thrombolytic properties. The biosynthesis of AgNPs-LS was successfully achieved using L. salivarius cell free supernatants, resulting in well-characterized nanoparticles as confirmed by UV–Vis spectroscopy, Fourier Transform Infrared (FTIR) spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering (DLS) and zeta potential analysis. The AgNPs-LS demonstrated potent antibacterial activity against different pathogenic bacteria (C. violaceum, P. aeruginosa, S. aureus, E. coli and S. marcescens), emphasizing their potential in combating bacterial infections. Moreover, these AgNPs-LS were effective in inhibiting biofilm formation (>60 % at 1/2 MIC), a key mechanism of bacterial virulence, highlighting their utility in preventing biofilm-related infections. AgNPs-LS exhibited anti-quorum sensing activity, disrupting bacterial communication systems and potentially reducing virulence factor such as, violacein production in C. violaceum, pyocyanin production in P. aeruginosa and prodigiosin production in S. marcescens. Additionally, AgNPs-LS also exhibited notable antifungal activity towards a different pathogenic fungus (F. proliferatum, P. purpurogenum, A. niger and R. stolonifer). In terms of health applications, the AgNPs-LS displayed significant antioxidant activity, effectively scavenging DPPH• (IC50 = 42.65 μg/mL) and ABTS•+ (IC50 = 53.77 μg/mL) free radicals. Furthermore, AgNPs-LS showed cytotoxicity against breast cancer cells (MCF-7) (IC50 = 52.29 μg/mL), positioning them as promising candidates for cancer therapy. Moreover, AgNPs-LS were also shown promising anticoagulant and thrombolytic activities under practical conditions. Therefore, the biogenic synthesis of AgNPs-LS using L. salivarius offers a sustainable and cost-effective route for producing AgNPs with an array of biological activities. These AgNPs-LS have the potential to address various challenges in healthcare, ranging from antimicrobial, anticancer applications to biofilm inhibition, antioxidant therapy, anticoagulant and thrombolytic agents.

Asundexian versus Apixaban in Patients with Atrial Fibrillation.

Stroke prevention with direct-acting oral anticoagulant agents in patients with atrial fibrillation confers a risk of bleeding and limits their use. Asundexian, an activated factor XI (XIa) inhibitor, is an oral anticoagulant that may prevent strokes with less bleeding. In a phase 3, international, double-blind trial, we randomly assigned high-risk patients with atrial fibrillation in a 1:1 ratio to receive asundexian at a dose of 50 mg once daily or standard-dose apixaban. The primary efficacy objective was to determine whether asundexian is at least noninferior to apixaban for the prevention of stroke or systemic embolism. The primary safety objective was to determine whether asundexian is superior to apixaban with respect to major bleeding events. A total of 14,810 randomly assigned patients were included in the intention-to-treat population. The mean (±SD) age of the patients was 73.9±7.7 years, 35.2% were women, 18.6% had chronic kidney disease, 18.2% had a previous stroke or transient ischemic attack, 16.8% had received oral anticoagulants for no more than 6 weeks, and the mean CHA2DS2-VASc score (range, 0 to 9, with higher scores indicating a greater risk of stroke) was 4.3±1.3. The trial was stopped prematurely at the recommendation of the independent data monitoring committee. Stroke or systemic embolism occurred in 98 patients (1.3%) assigned to receive asundexian and in 26 (0.4%) assigned to receive apixaban (hazard ratio, 3.79; 95% confidence interval [CI], 2.46 to 5.83). Major bleeding occurred in 17 patients (0.2%) who received asundexian and in 53 (0.7%) who received apixaban (hazard ratio, 0.32; 95% CI, 0.18 to 0.55). The incidence of any adverse event appeared to be similar in the two groups. Among patients with atrial fibrillation at risk for stroke, treatment with asundexian at a dose of 50 mg once daily was associated with a higher incidence of stroke or systemic embolism than treatment with apixaban in the period before the trial was stopped prematurely. There were fewer major bleeding events with asundexian than with apixaban during this time. (Funded by Bayer; OCEANIC-AF ClinicalTrials.gov number, NCT05643573; EudraCT number, 2022-000758-28.).

Eco-Friendly One-Pot Synthesis of Tetrahydrobenzo[b]Pyran and Dihydropyrano[3,2-c]Chromene Derivatives Using Functionalized Fe3O4@SiO2@SO3H Under MWI

The present work describes a greener method of preparation of Fe3O4 nanoparticles, which are then functionalized to Fe3O4@SiO2@SO3H, and employed in the one-pot three-component synthesis of tetrahydrobenzo[b]pyran and dihydropyrano[3,2-c]chromene derivatives. These synthesized derivatives are an important class of heterocyclic scaffolds and exhibit significant potential as anti-coagulant, diuretic, spasmolytic, anticancer, and anti-anaphylactic agents. The prepared MNP-based catalysts were characterized using XRD, FE-SEM, VSM, TG-DTA, and Raman spectroscopy. The synthesis of derivatives involved the condensation reaction of enolizable compounds with aldehyde, dimedone, and ethyl cyanoacetate for tetrahydrobenzo[b]pyran, and the reaction of aromatic aldehyde, 4-hydroxycoumarin, and malononitrile for dihydropyrano[3,2-c]chromene synthesis. The reaction was optimized using different techniques such as stirring, ultrasonication, and microwave irradiation, with microwave irradiation method demonstrating faster product separation and high yield. The homogeneity of the isolated product was analyzed by FT-IR,1H-13C-NMR, and mass spectrometry. The advantages of this method include its simplicity, eco-friendliness, cost-effectiveness, and it also evades the use of toxic metals and solvents. The product is easily isolated through a simple workup process and recrystallization using ethanol yields pure product isolation.

Occult Amyloid-β-Related Angiitis: Neuroimaging Findings at 1.5T, 3T, and 7T MRI.

Cerebral amyloid angiopathy (CAA) is a progressive neurodegenerative small vessel disease that is associated with intracranial hemorrhage and cognitive impairment in the elderly. The clinical and radiographic presentations have many overlapping features with vascular cognitive impairment, hemorrhagic stroke, and Alzheimer disease (AD). Amyloid-β-related angiitis (ABRA) is a form of primary CNS vasculitis linked to CAA, with the development of spontaneous autoimmune inflammation against amyloid in the vessel wall with resultant vasculitis. The diagnosis of ABRA and CAA is important. ABRA is often fatal if untreated and requires prompt immunosuppression. Important medical therapies such as anticoagulation and antiamyloid agents for AD are contraindicated in CAA. Here, we present a biopsy-proved case of ABRA with underlying occult CAA. Initial 1.5T and 3T MR imaging did not suggest CAA per the Boston Criteria 2.0. ABRA was not included in the differential diagnosis due to the lack of any CAA-related findings on conventional MR imaging. However, a follow-up 7T MR imaging revealed extensive cortical/subcortical cerebral microbleeds, cortical superficial siderosis, and intragyral hemorrhage in extensive detail throughout the supratentorial brain regions, which radiologically supported the diagnosis of ABRA in the setting of CAA. This case suggests an increased utility of high-field MR imaging to detect occult hemorrhagic neuroimaging findings with the potential to both diagnose more patients with CAA and diagnose them earlier.

Eco-Friendly Synthesis, Characterization, and Biomedical Applications of Biosynthesized Bimetallic Silver-Gold Nanoparticles by Culture Supernatant of Aspergillus niger.

Green synthesis of bimetallic nanoparticles of noble metals is highly desirable in nanomedicine because of their potential use as anticoagulant, thrombolytic and anticancer agents. In this study, it was discovered that the filamentous fungus Aspergillus niger proved effective in producing bimetallic Ag-Au nanoparticles. A. niger culture supernatant was able to produce Ag-AuNPs by reducing the solution of chloroauric acid/silver nitrate (1.0:1.0 mM) within 2 min at 100 °C and pH 8. Experimental Ag-AuNP detection was performed by visually observing the color change to reddish brown. The produced nanoparticles displayed maximal absorbance at 530 nm in UV-vis spectroscopy. According to transmission electron microscopy, most of the nanoparticles were spherical, with a mean diameter of 8-10 nm. The biosynthesis of Ag-AuNPs by A. niger was confirmed by Fourier transform infrared spectroscopy, X-ray diffraction and energy dispersive X-ray analytical techniques. Its zeta potential was discovered to be -34.01 mV. The biosynthesized Ag-AuNPs exhibited effective thrombolytic and antiplatelet aggregation actions by totally preventing and dissolving the blood clot which was verified by microscopic examination, amelioration of blood coagulation assays, and carrageenan-induced tail thrombosis model. The findings verified the effectiveness of biosynthesized Ag-AuNPs as a powerful antitumor agent against HepG2 and A549 cell lines with IC50 values of 15.57 and 27.07 μg/mL, respectively. Crystal violet assay validated the cytopathic effects of Ag-AuNPs on A549 and HepG2 cell lines. Therefore, the produced Ag-AuNPs from A. niger are a promising candidate in the management of thrombosis.

Formulation Optimization and Characterization of Solid Lipid Nanoparticles of Apixaban.

Unpredictable situations such as clotting of blood, deep vein thrombosis, and pulmonary embolism arise in the body, which is the leading cause of mortality. Such conditions generally arise after surgery as well as after treatment with oral anticoagulant agents. Apixaban is a novel oral anticoagulant widely recommended for the prevention and treatment of strokes and blood clots suffering from nonvalvular atrial fibrillation by suppressing factor Xa. Apixaban has a log P of 2.71 with poor solubility and reported maximum bioavailability of approximately 50%. Hence, the current research mainly focused on the improvement of solubility, bioavailability, and therapeutic efficacy of Apixaban via solid lipid nanoparticles (SLN). The SLN was developed using the hot-homogenization method using a high-pressure homogenizer. The drug-lipid compatibility study was assessed by the FTIR, and the thermal analysis was performed using differential scanning calorimetry (DSC). During the scrutiny of lipids, the highest solubility of Apixaban was estimated in the glyceryl monostearate, hence selected for the formulation. Moreover, the colloidal solution was stabilized by the polyethylene glycol 200. The Design of Expert software (Version 13, Stat-Ease) was implemented for the optimization analysis by considering the 3-independent factors and 2-dependent parameters. The Patents on the SLN are Indian 202321053691, U.S. Patent, 10,973,798B2, U.S. Patent, U.S. Patent 2021/0069121A1, U.S. Patent 2022/0151945A1. Box-Behnken design was applied along with ANOVA, which showed a p-value less than 0.05 for the dependent parameters such as particle size and entrapment efficiency (p-value: 0.0476 and 0.0379). The optimized batch F10 showed a particle size of 167.1 nm, -19.5 mV zeta potential, and an entrapment efficiency of 87.32%. The optimized batch F10 was lyophilized and analyzed by Scanning electron microscopy (SEM), which showed a particle size of 130 nm. The solid powder was filled into the capsule for oral delivery. The marked improvement in solubility and bioavailability was achieved with F10- loaded Apixaban via Solid lipid nanoparticles. Moreover, the sustained released profile also minimizes the unseen complications that occur due to the clotting of blood.

Anticoagulant Use in COVID-19 Patients: A Longitudinal Study From Zanjan, Iran.

Background The mortality and morbidity of thrombotic events in patients with coronavirus disease 2019 (COVID-19) are increasing worldwide. The clinical impact of prophylactic anticoagulation regimens among these patients in Iran remains unclear. This study aimed to evaluate the use of prophylactic anticoagulants and outcomes among COVID-19 patients admitted to a tertiary referral hospital. Methodology Patients diagnosed with COVID-19 and hospitalized between March 20 and June 20, 2020, were included in this longitudinal study after obtaining informed consent. Demographic and clinical data were collected from the hospital information system and medical records. Outcomes during this period were also evaluated. The data were entered into the preparation checklist and analyzed using SPSS version 24 software (IBM Corp., Armonk, NY, USA), employing chi-square, Fisher's exact, and Mann-Whitney U tests. Results Of the 831 enrolled patients, 51.9% were female, and 10.6% needed to be admitted to the intensive care unit (ICU). The mean age of the patients was 57.16 ± 17.32 years, and the mortality rate was estimated to be 9.4%. Mortality rates were significantly higher at older ages, in men, patients with ICU admission, severe pulmonary involvement, malignancy, airway obstruction, ischemic heart disease, and previous cerebrovascular accidents. ICU admission and mortality were statistically significantly higher in those who received concurrent prophylactic anticoagulants and aspirin than in other individuals. Conclusions Our study demonstrated that administering prophylactic aspirin with or without anticoagulant agents in COVID-19 patients did not reduce mortality rates or ICU transfers. However, it is worth noting that anticoagulant prescription was associated with a decrease in ICU admissions, which could potentially alleviate the significantly higher mortality rates observed among ICU patients in this study. Further research is needed to explore the potential benefits of anticoagulants in COVID-19 treatment.

Effects of batroxobin on the antithrombotic system in patients with cerebral venous thrombosis: Clues to mechanisms.

More evidence supports the benefits of batroxobin combined with anticoagulation in correcting acute cerebral venous thrombosis (CVT). The dynamic fluctuations of peripheral blood platelets, fibrinolysis, and coagulation biomarkers during this therapy were analyzed. We investigated batroxobin's effects on the antithrombotic system under two regimens. The pretreatment group included patients on anticoagulants for at least 1 week before starting batroxobin. The simultaneous treatment group began both treatments upon admission. The control group received only anticoagulation. Batroxobin was given on alternate days at doses of 10BU, 5BU, and 5BU, totaling three doses. Anticoagulation was continuous. Baseline data were T0; the next day after each batroxobin dose was T1, T2, and T3. Data from these four time points was analyzed. The time-point paired sample T-test results of the pretreatment group [n = 60; mean age (SD), 43.3(16.5); 38 (63.35%) women] showed that batroxobin significantly inhibited ADP-induced platelet aggregation rate (T1-T0: p = 0.015; T2-T0: p = 0.025; T3-T0: p = 0.013), decreased fibrinogen level (T1-T0: p < 0.001; T2-T0: p < 0.001; T3-T0: p < 0.001), and increased D-dimer (T1-T0:p < 0.001; T2-T0: p < 0.001; T3-T0: p < 0.001), TT (T1-T0:p = 0.046; T2-T0: p = 0.003; T3-T0: p < 0.001), and APTT (T1-T0:p = 0.021; T2-T0: p = 0.012; T3-T0: p = 0.026). Compared to the control group, the simultaneous treatment group showed significantly higher TT (T2: p = 0.002; T3: p = 0.004) and D-dimer (T1: p < 0.001; T2: p < 0.001; T3: p < 0.001) values, while fibrinogen (T2: p < 0.001; T3: p < 0.001) levels were significantly lower. Using batroxobin can alleviate the amplitude of changes in coagulation indicators other than TT caused by anticoagulants. The above conclusions are consistent with the results of repeated measurement data analysis. Batroxobin can significantly inhibit ADP-induced platelet aggregation rate, increase D-dimer, decrease fibrinogen, and prolong TT and APTT in the presence of anticoagulant agents. Using batroxobin can reduce the amplitude of changes in coagulation indicators caused by anticoagulants. These results reveal the potential mechanism of batroxobin combined with anticoagulation in the safe and effective treatment of CVT.

Risks of bleeding and thromboembolic events in patients undergoing colonoscopy on uninterrupted and interrupted anticoagulant therapy in real-world setting

BackgroundAlthough anticoagulants may potentially increase the risk of post-colonoscopy bleeding events, temporary discontinuation of medications could elevate the risk of thromboembolism (TE). There is a paucity of data regarding the incidence of bleeding and TE events in patients undergoing colonoscopy while on uninterrupted or interrupted anticoagulant therapy. Therefore, we aimed to ascertain the risks of post-colonoscopy TE and bleeding in patients with continuous or interrupted use of anticoagulant agents. MethodsThe electronic databases of PubMed, Embase, and the Cochrane library were comprehensively searched from inception to March 15, 2024. We identified studies reporting the incidence of bleeding and TE events in patients undergoing colonoscopy with uninterrupted or interrupted anticoagulant therapy. The pooled incidence rate of bleeding and TE events was estimated using a random-effects model. ResultsThis study included a total of 15 studies involving 63, 017 patients. Overall, the incidence of post-procedural bleeding for uninterrupted and interrupted direct oral anticoagulants (DOACs) was found to be 3.60 % (95 % CI: 1.60 %–5.60 %), and 0.90 % (95 % CI: 0.10 %–10.30 %), respectively. Subgroup analysis revealed that older age patients (≥65 years) had a significantly higher rate of bleeding with uninterrupted DOACs therapy compared to younger age patients (< 65 years) (7.20 % vs. 2.00 %). The highest rate of bleeding was observed in Asia (7.20 %, 95 % CI: 2.20 %–12.10 %). Similarly, the risk of bleeding was significantly increased among patients interrupting DOACs therapy in Asia compared to North America (1.40 % vs. 0.26 %). For patients on uninterrupted and interrupted warfarin, a higher rate of bleeding events was observed in older age patients than younger age patients (4.90 % vs. 0.80 %, and 2.20 % vs. 1.70 %, respectively). Uninterrupted warfarin showed a more significant risk of bleeding in Asia (4.20 %, 95%CI: 1.90 %–6.60 %) compared to North America (1.00 %, 95%CI: 0.50 %–1.50 %). Among those who did not interrupt DOACs therapy, the incidence of TE was the lowest (0.08 %, 95%CI: 0.04 %–0.11 %). ConclusionThis study provides a comprehensive assessment of bleeding and TE risks in patients undergoing colonoscopy while receiving uninterrupted or interrupted anticoagulant therapy in the real-world setting. The overall incidence of post-colonoscopy bleeding and TE events is relatively low. However, the uninterrupted DOACs and warfarin are associated with an elevated risk of bleeding, particularly among elderly patients and the Asian population.

Potential Role of Mineralocorticoid Receptor Antagonists in Nondiabetic Chronic Kidney Disease and Glomerular Disease.

Glomerular disease is a leading cause of CKD and ESKD. Although diabetic kidney disease is the most common cause of glomerular disease, nondiabetic causes include malignancy, systemic autoimmune conditions, drug effects, or genetic conditions. Nondiabetic glomerular diseases are rare diseases, with a paucity of high-quality clinical trials in this area. Furthermore, late referral can result in poor patient outcomes. This article reviews the current management of nondiabetic glomerular disease and explores the latest developments in drug treatment in this area. Current treatment of nondiabetic glomerular disease aims to manage complications (edema, hypertension, proteinuria, hyperlipidemia, hypercoagulability, and thrombosis) as well as target the underlying cause of glomerular disease. Treatment options include renin-angiotensin-aldosterone system inhibitors, statins/nonstatin alternatives, loop diuretics, anticoagulation agents, immunosuppressives, and lifestyle and dietary modifications. Effective treatment of nondiabetic glomerular disease is limited by heterogeneity and a lack of understanding of the disease pathogenesis. Sodium-glucose cotransporter-2 inhibitors and nonsteroidal mineralocorticoid receptor antagonists (ns-MRAs, such as finerenone), with their broad anti-inflammatory and antifibrotic effects, have emerged as valuable therapeutic options for a range of cardiorenal conditions, including CKD. ns-MRAs are an evolving drug class of particular interest for the future treatment of nondiabetic glomerular disease, and there is evidence that these agents may improve kidney prognosis in various subgroups of patients with CKD. The benefits offered by ns-MRAs may present an opportunity to reduce the progression of CKD from a spectrum of glomerular disease. Several novel ns-MRA are in clinical development for both diabetic and nondiabetic CKD.