Search

There is significant practice variation in the use of antithrombotic therapy after endovascular intervention for lower limb peripheral arterial disease, with differences in medication choice and duration. Prescriber decision making is complex, and patient factors have been shown to substantially contribute to prescribing variation. To determine the influence of patient factors on antithrombotic prescribing, a discrete choice experiment was distributed to vascular surgeons and trainees across Australia and Aotearoa New Zealand. After pilot testing, the discrete choice experiment questionnaire was distributed to 300 vascular surgeons and trainee members of the Australian and New Zealand Society for Vascular Surgery. Multinomial logistic regression models were used to analyse patient factors that had the most influence on decisions to prescribe a second antithrombotic agent, and the preferred choice of antithrombotic (clopidogrel 75 mg daily or rivaroxaban 2.5 mg twice daily) in addition to aspirin 100 mg daily. The odds ratio (OR) with 95% confidence interval (CI) reported preference strength. A total of 44 questionnaires were completed between September and October 2023, reaching the 15% targeted response rate. Prescribing a second antithrombotic was more likely after femoropopliteal stenting compared with angioplasty (OR 1.89, 95% CI 1.20 – 2.13), and in chronic limb threatening ischaemia compared with intermittent claudication (OR 1.58, 95% CI 1.20 – 2.13). Most respondents preferred clopidogrel over rivaroxaban (62%), with over a third of respondents exclusively prescribing clopidogrel. Patients with stents (OR 1.77, 95% CI 1.32 – 2.37) or moderate bleeding risk (OR 1.38, 95% CI 0.97 – 1.84) were more likely to receive clopidogrel than rivaroxaban. This study demonstrates that vascular surgeons primarily prioritise antithrombotic prescribing decisions by procedure type. Clopidogrel is more likely to be prescribed than rivaroxaban as a second agent in combination with aspirin, especially after stenting. Knowing these clinician preferences can target implementation strategies towards supporting decision making in subgroups of patients according to individual risk profiles. [ABSTRACT FROM AUTHOR]

Existing antithrombotic drugs have side effects such as bleeding, and there is an urgent need to discover antithrombotic drugs with better efficacy and fewer side effects. In this study, a zebrafish thrombosis model was used to evaluate the antithrombotic activity and mechanism of Brevianamide F, a deep-sea natural product, with transcriptome sequencing analysis, RT-qPCR analysis, and molecular docking. The results revealed that Brevianamide F significantly attenuated the degree of platelet aggregation in the thrombus model zebrafish, leading to an increase in the number of circulating platelets, an augmentation in the return of blood to the heart, an elevated heart rate, and a significant restoration of caudal blood flow velocity. Transcriptome sequencing and RT-qPCR validation revealed that Brevianamide F may exert antithrombotic effects through the modulation of the MAPK signaling pathway and the coagulation cascade reaction. Molecular docking analysis further confirmed this result. This study provides a reference for the development of therapeutic drugs for thrombosis. [ABSTRACT FROM AUTHOR]

Summary In this work, the antihypertensive and antithrombotic activities of milk fermented with Lacticaseibacillus rhamnosus GG and Lactobacillus delbrueckii ssp. Bulgaricus NCFB 2772 (monoculture and co‐culture), were studied. It was observed that both species, as well as the co‐culture, showed an increase in proteolytic activity during fermentation, which is related to the increase in the biological activities studied. Both biological activities increased as a function of fermentation time, describing a curve similar to that of their proteolytic activity, which could indicate the release of bioactive peptides due to the proteolytic activity of the bacteria. The highest antihypertensive activity was obtained at 12 h of fermentation and was 74.9% for Lb. rhamnosus, 79.1% for L. delbrueckii and 77.6% for the co‐culture, with no significant difference between these values. On the other hand, the antithrombotic activity was 56.1% for Lb. rhamnosus, 49.9% for L. delbrueckii and 72.3% for the co‐culture. These findings contribute to the knowledge about the influence of fermentation conditions on biological activity of fermented milk, while emphasising the additional benefits of probiotic and industrially important lactic acid bacteria. [ABSTRACT FROM AUTHOR]

Objective: Coronavirus Disease-2019 (COVID-19), has affected the whole world and is still an important disease with its mutations. In our study, we aimed to evaluate the effects of antithrombotic agents [acetylsalicylic acid (ASA), P2Y12 inhibitors, oral anticoagulants (OACs)] and statin treatments used before hospitalization on COVID-19 mortality and clinical severity.Methods: A retrospective study was conducted on 5577 patients hospitalized with positive swab tests or findings consistent with COVID-19 on computed tomography. The 6-month mortality, in-hospital mortality, need for intensive care and intubation, and recurrent hospitalization outcomes of patients receiving chronic ASA (n=1210), P2Y12 inhibitors (n=357), OACs (n=1192), and statin (n=607) treatment were evaluated.Results: The 6-month mortality rate was 13.5% (n=754), in-hospital mortality rate was 11.2% (n=627), the rate of admission to the intensive care unit was 16.1% (n=897), the need for intubation was 8.8% (n=493), and the rate of recurrent hospitalization was 10.4% (n=579). ASA and OACs reduced all outcomes. P2Y12 inhibitors provided benefit in other endpoints except intubation. Statins used before hospitalization did not provide a statistically significant decrease in 6-month mortality (p: 0.06), but were associated with a decrease in the rates of in-hospital mortality, need for intensive care, recurrent hospitalization, and intubation. Conclusion: We found that long-term ASA, P2Y12 inhibitors, OACs and statin treatments used before hospitalization in patients hospitalized with COVID-19, reduced COVID-19 mortality and clinical severity. We think that these treatments may be beneficial in selected patient groups where post-COVID effects are observed.

Inflammation and thrombosis are implicated in several chronic disorders. Recent studies have outlined the way in which several compounds can offer protection against inflammation. Within this comprehensive review the so-far reported anti-inflammatory health-promoting effects of several metal-based complexes, both in vitro and in vivo, are thoroughly presented. These metal-based compounds usually interfere with various biochemical processes associated with the inflammatory response and thrombus formation and become capable of inhibiting these biochemical pathways with proposed health benefits. Emphasis is given to the multifaceted actions of metal-based complexes that have exhibited potent anti-inflammatory and antithrombotic activities against the inflammatory mediator, platelet-activating factor (PAF), and its thrombo-inflammatory signaling, as well as on their anti-platelet and antitumor health promoting properties. Furthermore, the enhancement of the anti-inflammatory potency of well-established bioactive compounds by their incorporation as ligands in several metal-based complexes is discussed. Metal-based complexes bearing natural anti-inflammatory bioactives are also outlined. Characteristic examples of both free and metal-based porphyrins are explored. These compounds are recognized to have anti-inflammatory and antithrombotic assets, in addition to other pleiotropic advantages including antibacterial or anticancer actions. Additionally, applications of metal complexes in various models of inflammatory and thrombotic complications are demonstrated. The combined results of this study show that further research is required towards the preparation of several metal-based complexes with improved pharmacological profiles. Finally, restrictions on the application of these metal-based compounds are also covered, along with their prospects for the future and the need for additional study in order to improve their efficacy and safety.

Background: Following transient ischemic attack (TIA) and minor stroke, the risk of recurrent stroke can be significantly reduced with short-duration dual antiplatelet therapy (DAPT). We wish to investigate whether 10 days of DAPT is as effective as 21 days' treatment. Study design: This is an open-label, randomized, parallel-group study comparing whether 10 days of DAPT treatment (ASA + clopidogrel) is non-inferior to 21 days of DAPT in patients with acute ischemic stroke (AIS) or high-risk TIA. In both groups, DAPT is started within 24 hours of symptom onset. This study is being conducted in approximately 15 study sites in the Kingdom of Saudi Arabia. The planned sample size is 1932. Outcomes: Non-inferiority of 10 days compared to 21 days of DAPT in the prevention of the composite endpoint of stroke and death at 90 days in AIS/TIA patients. The primary safety outcome is major intra-cranial and systemic hemorrhage. Study period: Enrolment started in the second quarter of 2023, and the completion of the study is expected in the fourth quarter of 2025. Discussion: The trial is expected to show that 10 days of DAPT is non-inferior for the prevention of early recurrence of vascular events in patients with high-risk TIAs and minor strokes. [ABSTRACT FROM AUTHOR]

The current investigation focused on separating Cerastes cerastes venom to produce the first Kunitz-type peptide. Based on its anti-trypsin effect, Cerastokunin, a 7.75 kDa peptide, was purified until homogenity by three steps of chromatography. Cerastokunin was found to include 67 amino acid residues that were obtained by de novo sequencing using LC-MALDI-MSMS. Upon alignment with Kunitz-type peptides, there was a high degree of similarity. Cerastokunin's 3D structure had 12% α-helices and 21% β-strands with pI 8.48. Cerastokunin showed a potent anticoagulant effect by inhibiting the protease activity of thrombin and trypsin as well as blocking the intrinsic and extrinsic coagulation pathways. In both PT and aPPT, Cerastokunin increased the blood clotting time in a dose-dependent way. Using Lys48 and Gln192 for direct binding, Cerastokunin inhibited thrombin, Factor Xa and trypsin as shown by molecular docking. Cerastokunin exhibited a dose–response blockade of PARs-dependent pathway platelet once stimulated by thrombin. An increased concentration of Cerastokunin resulted in a larger decrease of tail thrombus in the mice-carrageenan model in an in vivo investigation when compared to the effects of antithrombotic medications. At all Cerastokunin doses up to 6 mg/kg, no in vivo toxicity was seen in challenged mice over the trial's duration. [ABSTRACT FROM AUTHOR]

Clinical implications of screening for blunt cerebrovascular injury (BCVI) after low-energy mechanisms of injury (LEMI) remain unclear. We assessed BCVI incidence and outcomes in LEMI versus high-energy mechanisms of injury (HEMI) patients. In this retrospective cohort study, blunt trauma adults admitted between July 2015 and June 2021 with cervical spine fractures, excluding single spinous process, osteophyte, and chronic fractures were included. Demographics, comorbidities, injuries, screening and treatment data, iatrogenic complications, and mortality were collected. Our primary end point was to compare BCVI rates between LEMI and HEMI patients. Eight hundred sixty patients (78%) were screened for BCVI; 120 were positive for BCVI. LEMI and HEMI groups presented similar BCVI rates (12.6% versus 14.4%; P = 0.640). Compared to HEMI patients (n = 95), LEMI patients (n = 25) were significantly older (79 ± 14.9 versus 54.3 ± 17.4, P < 0.001), more likely to be on anticoagulants before admission (64% versus 23.2%, P < 0.001), and less severely injured (LEMI injury severity score 10.9 ± 6.6 versus HEMI injury severity score 18.7 ± 11.4, P = 0.001). All but one LEMI and 90.5% of the HEMI patients had vertebral artery injuries with no significant difference in BCVI grades. One HEMI patient developed acute kidney injury because of BCVI screening. Eleven HEMI patients developed BCVI-related stroke with two related mortalities. One LEMI patient died of a BCVI-related stroke. BCVI rates were similar between HEMI and LEMI groups when screening based on cervical spine fractures. The LEMI group exhibited no screening or treatment complications, suggesting that benefits may outweigh the risks of screening and potential bleeding complications from treatment. [ABSTRACT FROM AUTHOR]

Purpose: Abiraterone, apalutamide, darolutamide and enzalutamide are second-generation hormone therapies used for advanced prostate cancer; the majority of patients receiving these treatments are elderly, poly-medicated patients. Since their first market authorizations, their pharmacokinetic (PK) characteristics are increasingly well known. A potential risk of drug-drug interaction (DDI), especially with cardiovascular drugs, needs to be considered. In the case of antithrombotics, treatment imbalance can lead to severe consequences. Objectives: To describe PK profiles of hormone therapies and antithrombotics and to predict DDIs and potentially related clinical events. Methods: PK profiles (CYP450 and P-gp substrate, inducer or inhibitor) are described by cross-referencing data sources (summary of product characteristics, European public assessment reports, PubMed database, Micromedex®, etc.); a description of the potential interactions with anti-cancer drugs for each DDI and related clinical events is provided. We discuss management recommendations, including those set out in international guidelines. Results: Antithrombotics are mainly metabolized by CYP 2C9, 2C19 or 3A4. For abiraterone (CYP 2C8, 2D6 inhibitor) and darolutamide (CYP 3A4 inducer), no interaction was identified with antithrombotics. For apalutamide (CYP 2C9, 2C19, 3A4 and P-gp inducer) and enzalutamide (CYP 2C9, 2C19, 3A4 inducer and P-gp inhibitor), several PK interactions were identified with antithrombotics, which could lead to various clinical events (haemorrhage or thromboembolism). Conclusion: Numerous interactions are expected between enzalutamide or apalutamide and antithrombotics, for which management should be deployed on a case-by-case basis. PK and pharmaco-epidemiological studies could shed light on whether or not there are clinically significant events related to DDIs with antithrombotics. [ABSTRACT FROM AUTHOR]

Featured Application: Utilization of Freshwater aquatic plants' bioactives for functional foods, cosmetic and pharmaceutical applications with anti-inflammatory, antithrombotic and antioxidant health promoting properties. Despite significant progress, certain inflammation related to chronic disorders, including cardiovascular diseases (CVD) and cancer, still present high mortality rates. Thus, further study is needed to address such pathologies more appropriately. Apart from classic therapeutics, natural bioactives with less toxic side effects have gained attention, including those with potential pharmaceutical properties derived from several plants. Within this article, the potential utilization of freshwater aquatic plants as sources of bioactives with antithrombotic, anti-inflammatory and antioxidant properties is outlined. Emphasis is given to a well-established aquatic plant with known but not fully clarified and overviewed bio-functional and pharmaceutical properties, the Chinese lotus (Nelumbo nucifera), as well as to a so far neglected aquatic plant, Lemna minor, which has not yet been thoroughly reviewed for such applications. The latent usually grows naturally in large numbers at the surface of stored water basins of retrieved water from the last stages of wastewater treatment facilities. The continuous growth of this aquatic plant in such conditions further suggests that it can be a sustainable source of natural bioactives, if appropriately valorized, with an economic benefit and in a friendly environmental approach. The abundant content of both freshwater aquatic plants in bioactive components with potent antioxidant, anti-inflammatory and antithrombotic activities is thoroughly outlined, while their applications as functional ingredients in several functional products (functional foods, cosmetics and pharmaceuticals) are also discussed. The outlined outcomes urge further study of both aquatic plants and especially of Lemna spp. to fully elucidate their potential as alternative sustainable sources of bioactive ingredients for functional foods, supplements, nutraceuticals, nutricosmetics, cosmeceuticals, cosmetics and pharmaceutical products with health-promoting properties against inflammation and thrombosis related manifestations and their associated chronic disorders. [ABSTRACT FROM AUTHOR]

We aimed to determine the diagnostic yield and outcome of patients receiving antithrombotic drug therapy subjected to small bowel capsule endoscopy (SBCE) for the investigation of small bowel bleeding (SBB). A multicenter retrospective analysis of collected data from all patients undergoing SBCE for the investigation of SBB from March 2003 to June 2023 was performed. The diagnostic yield of SBCE was defined as the detection of positive findings that could explain the cause of the patient's bleeding. Rebleeding was defined as evidence of bleeding within 1 year after the index episode. During the study period, 8401 patients underwent SBCE for SBB investigation. Bleeding lesions were detected in 1103/2535 (43.5%) antithrombotic users, compared to 1113/5866 (18.9%) in nonusers (p < 0.00001). Following capsule endoscopy, a therapeutic intervention was possible in 390/2216 (17.5%) patients with a bleeding lesion. Rebleeding occurred in 927 (36.5%) of antithrombotic users (36.5%), compared to 795 (13.5%) of nonusers (13.5%, p < 0.00001). Both the diagnostic yield of SBCE and the rebleeding rates were higher in patients with SBB receiving antithrombotics. Therapeutic intervention was possible in a real-world setting only for a minority of patients with positive findings. [ABSTRACT FROM AUTHOR]

Hypolipidemia and platelet activation play key roles in atherosclerotic diseases. Pirinixic acid (WY-14643) was originally developed as a lipid-lowering drug. Here we focused on its antiplatelet and antithrombotic abilities and the underlying mechanism. The effects of WY-14643 on platelet aggregation was measured using a lumi-aggregometer. Clot retraction and spreading on fibrinogen were also assayed. PPARα−/− platelets were used to identify the target of WY-14643. The interaction between WY-14643 and glycoprotein Ibα (GPIbα) was detected using cellular thermal shift assay (CETSA), surface plasmon resonance (SPR) spectroscopy and molecular docking. GPIbα downstream signaling was examined by Western blot. The antithrombotic effect was investigated using mouse mesenteric arteriole thrombosis model. Mouse tail bleeding model was used to study its effect on bleeding side effects. WY-14643 concentration-dependently inhibits human washed platelet aggregation, clot retraction, and spreading. Significantly, WY-14643 inhibits thrombin-induced activation of human washed platelets with an IC 50 of 7.026 μM. The antiplatelet effect of WY-14643 is mainly dependent of GPIbα. CESTA, SPR and molecular docking results indicate that WY-14643 directly interacts with GPIbα and acts as a GPIbα antagonist. WY-14643 also inhibits phosphorylation of PLCγ2, Akt, p38, and Erk1/2 induced by thrombin. Noteworthily, 20 mg/kg oral administration of WY-14643 inhibits FeCl 3 -induced thrombosis of mesenteric arteries in mice similarly to clopidogrel without increasing bleeding. WY-14643 is not only a PPARα agonist with lipid-lowering effect, but also an antiplatelet agent as a GPIbα antagonist. It may have more significant therapeutic advantages than current antiplatelet agents for the treatment of atherosclerotic thrombosis, which have lipid-lowering effects without bleeding side effects. • WY-14643 has excellent antiplatelet and antithrombotic properties without increasing bleeding. • In nucleated cells, PPARα functions as a transcription factor and nuclear receptor protein, but WY-14643 acts as a PPARα agonist, whereas its antiplatelet effect is mainly dependent of GPIbα. • WY-14643 impairs GPIbα-mediated signaling in platelets. [ABSTRACT FROM AUTHOR]

Background and aims: Cerebral microbleeds are magnetic imaging resonance (MRI) markers of hemorrhage-prone cerebral small vessel disease that predict future risk of ischemic stroke and intracranial hemorrhage (ICrH). There exist concerns about the net benefit of antithrombotic therapy in patients with microbleeds. We aimed to investigate the effects of an oral factor-XIa inhibitor (asundexian), that is hypothesized to inhibit thrombosis without compromising hemostasis, on the development of new microbleeds over time and interactions between microbleeds and asundexian treatment on clinical outcomes. We additionally assessed associations between baseline microbleeds and the risks of clinical and neuroimaging outcomes in patients with non-cardioembolic ischemic stroke. Methods: This is a secondary analysis of the PACIFIC-STROKE, international, multi-center Phase 2b double-blind, randomized clinical trial. PACIFIC-STROKE enrolled patients aged ⩾ 45 years with mild-to-moderate non-cardioembolic ischemic stroke who presented within 48 h of symptom onset for whom antiplatelet therapy was intended. Microbleeds were centrally adjudicated, and participants with an interpretable T2*-weighted sequence at their baseline MRI were included in this analysis. Patients were randomized to asundexian (10/20/50 mg daily) versus placebo plus standard antiplatelet treatment. Regression models were used to estimate the effects of (1) all pooled asundexian doses and (2) asundexian 50 mg daily on new microbleed formation on 26-week MRIs. Cox proportional hazards or regression models were additionally used to estimate interactions between treatment assignment and microbleeds for ischemic stroke/transient ischemic attack (TIA) (primary outcome), and ICrH, all-cause mortality, hemorrhagic transformation (HT), and new microbleeds (secondary outcomes). Results: Of 1746 participants (mean age, 67.0 ± 10.0; 34% female) with baseline MRIs, 604 (35%) had microbleeds. During a median follow-up of 10.6 months, 7.0% (n = 122) had ischemic stroke/TIA, 0.5% (n = 8) ICrH, and 2.1% (n = 37) died. New microbleeds developed in 10.3% (n = 155) of participants with adequate follow-up MRIs and HT in 31.4% (n = 345). In the total sample of patients with adequate baseline and 26-week follow-up MRIs (n = 1507), new microbleeds occurred in 10.2% of patients assigned to any asundexian dose and 10.5% of patients assigned to placebo (OR, 0.96; 95% CI, 0.66–1.41). There were no interactions between microbleeds and treatment assignment for any of the outcomes (p for interaction > 0.05). The rates of new microbleeds, HT, and ICrH were numerically less in patients with microbleeds assigned to asundexian relative to placebo. The presence of microbleeds was associated with a higher risk of HT (aOR, 1.6; 95% CI, 1.2–2.1) and new microbleeds (aOR, 4.4; 95% CI, 3.0–6.3). Conclusion: Factor XIa inhibition with asundexian appears safe in patients with non-cardioembolic ischemic stroke and hemorrhage-prone cerebral small vessel disease marked by microbleeds on MRI. These preliminary findings will be confirmed in the ongoing OCEANIC-STROKE randomized trial. Trial Registration: ClinicalTrials.gov Identifier: NCT04304508. [ABSTRACT FROM AUTHOR]

Background and Aims: Small bowel gastrointestinal bleeding (GIB) is associated with multiple blood transfusions, prolonged and/or multiple hospital admissions, utilization of significant healthcare resources, and negative effects on patient quality of life. There is a well-recognized association between antithrombotic medications and small bowel GIB. We aimed to identify the diagnostic yield of small bowel capsule endoscopy (SBCE) in patients on antithrombotic medications and the impact of SBCE on treatment course. Methods: The electronic medical records of nineteen hundred eighty-six patients undergoing SBCE were retrospectively reviewed. Results: The diagnostic yield for detecting stigmata of recent bleeding and/or actively bleeding lesions in SBCE was higher in patients that were on antiplatelet agents (21.6%), patients on anticoagulation (22.5%), and in patients that had their SBCE performed while they were inpatient (21.8%), when compared to the patients not on antiplatelet agents (12.1%), patients not on anticoagulation (13.5%), and with patients that had their SBCE performed in the outpatient setting (12%). Of 318 patients who had stigmata of recent bleeding and/or actively bleeding lesion(s) identified on SBCE, SBCE findings prompted endoscopic evaluation (small bowel enteroscopy, esophagogastroduodenoscopy (EGD), and/or colonoscopy) in 25.2%, with endoscopic hemostasis attempted in 52.5%. Conclusions: Our study, the largest conducted to date, emphasizes the importance of performing SBCE as part of the evaluation for suspected small bowel bleeding, particularly in patients taking antithrombotic therapy, and especially during their inpatient hospital stay. [ABSTRACT FROM AUTHOR]

Inflammation and thrombosis are implicated in several chronic disorders. Recent studies have outlined the way in which several compounds can offer protection against inflammation. Within this comprehensive review the so-far reported anti-inflammatory health-promoting effects of several metal-based complexes, both in vitro and in vivo, are thoroughly presented. These metal-based compounds usually interfere with various biochemical processes associated with the inflammatory response and thrombus formation and become capable of inhibiting these biochemical pathways with proposed health benefits. Emphasis is given to the multifaceted actions of metal-based complexes that have exhibited potent anti-inflammatory and antithrombotic activities against the inflammatory mediator, platelet-activating factor (PAF), and its thrombo-inflammatory signaling, as well as on their anti-platelet and antitumor health promoting properties. Furthermore, the enhancement of the anti-inflammatory potency of well-established bioactive compounds by their incorporation as ligands in several metal-based complexes is discussed. Metal-based complexes bearing natural anti-inflammatory bioactives are also outlined. Characteristic examples of both free and metal-based porphyrins are explored. These compounds are recognized to have anti-inflammatory and antithrombotic assets, in addition to other pleiotropic advantages including antibacterial or anticancer actions. Additionally, applications of metal complexes in various models of inflammatory and thrombotic complications are demonstrated. The combined results of this study show that further research is required towards the preparation of several metal-based complexes with improved pharmacological profiles. Finally, restrictions on the application of these metal-based compounds are also covered, along with their prospects for the future and the need for additional study in order to improve their efficacy and safety. [ABSTRACT FROM AUTHOR]

Objective: Subclinical leaflet thrombosis (SLT) develops in 15% of patients undergoing trans‐catheter aortic valve replacement (TAVR). TAVR is a procedure in which a faulty aortic valve is replaced with a mechanical one. An aortic valve replacement can be done with open‐heart surgery; this is called surgical aortic valve replacement (SAVR). A significant problem is defining the best course of treatment for asymptomatic individuals with SLT post‐TAVR, including the use of oral anticoagulation (OAC) in it. Study design: Systematic review. Method: The most pertinent published research (original papers and reviews) in the scientific literature were searched for and critically assessed using the online, internationally indexed databases PubMed, Medline, and Cochrane Reviews. Keywords like "Transcatheter valve replacement" and "Subclinical leaflet thrombosis" were used to search the papers. Selected studies were critically assessed for inclusion based on predefined criteria. Results: The review examined the prevalence and characteristics of SLT after TAVR. To note, the incidence of SLT is seen to be higher in TAVR compared SAVR. Dual antiplatelet therapy, which is utilized in antithrombotic regimens post‐TAVR, can possibly hasten SLT progression which could result in the impaired mobility of leaflets and the worsening of pressure gradients. Conclusion: The use of dual antiplatelet drugs in routine antithrombotic therapy tends to accelerate initial subclinical leaflet thrombosis after TAVI, which results in a developing restriction of leaflet mobility and an increase in pressure differences. [ABSTRACT FROM AUTHOR]

Introduction: Herbal medicine has been used worldwide for thousands of years to treat human diseases and their associated secondary complications due to their medicinal efficacy, easy availability, and reduced side effects. Coreopsis tincica is a small, glabrous, aromatic annual plant with antioxidant, antihyperglycemic, and cardioprotective properties. Okanin and isookanin are an important phytochemicals of capitula of Coreopsis tinctoria. Methods: The aim of this review is to describe the medicinal efficacy, pharmacological activity, and analytical aspects of okanin and isookanin, along with their possible mechanisms of action. In the current review, we searched literature databases such as Google, Science Direct, PubMed, and Google Scholar to collect all the scientific information of okanin and isookanin. However, this review also addresses the pharmacokinetic and analytical parameters of okanin and isookanin. Scientific data on the separation, isolation, and identification of okanin and isookanin in various biological and non-biological samples are also presented here in this review. Results: The scientific evidence of this review shows the biological potential of okanin and isookanin in medicine. Okanin has potential antithrombotic, antioxidant, and antihyperuricemic effects in medicine. However, okanin has potential against neurodegenerative diseases, xanthine oxidase, inducible nitric oxide synthase, Candida albicans, aromatase, and intestinal absorption. Furthermore, this review demonstrated the angiogenic, anti-inflammatory, antiviral, antidiabetic, and antioxidant potential of isookanin. Additionally, isookanin also has effectiveness on aromatase and amylase enzymes. This review also discusses analytical aspects of okanin and isookanin in medicine. The scientific data presented in this review also supports the traditional uses of Coreopsis tinctoria. Discussion: Okanin and isookanin have great therapeutic potential in medicine and may be used for the development of new drugs in modern medicine. However, detailed pharmacological studies are very important for clinical applications and molecular mechanisms of okanin and isookanin in the scientific field.

[Display omitted] [ABSTRACT FROM AUTHOR]

INTRODUCTION: The antiplatelet effect of clopidogrel can vary between patients. A modified thromboelastography (TEG) protocol (TEG-Platelet Mapping assay® [TEG-PM]) can be used for clopidogrel monitoring but is not widely available. Thrombin generation (TG) assays could offer a novel alternative. The main objective of this pilot study was to assess TG assay variables (lag time, peak, endogenous thrombin potential [ETP]) in dogs before and after 7 days of clopidogrel administration and compare with TEG-PM variables (maximum amplitude [MA]-ADP and percentage (%) inhibition). METHODS: Six healthy mix-breed dogs were enrolled in this pilot study. Blood samples for platelet count, TG assays, and TEG-PM were obtained at two time points, corresponding to baseline, and after 7 days of clopidogrel administration (mean 2.3 +/- 0.3 mg/kg PO q24 hours). Data were then compared with a Students t-test. RESULTS: There was no significant change in TG assay variables performed on platelet poor plasma after 7 days of clopidogrel administration: lag time (Day 1: 1.8 +/- 0.2 min, Day 7: 1.8 +/- 0.2 min, p = 0.42); peak (Day 1: 76 +/- 7 nM, Day 7: 72 +/- 10 nM, p = 0.49); and ETP (Day 1: 399 +/- 27 nM*min, Day 7: 392 +/- 32 nM*min; p = 0.49). There were significant changes in TEG MA-ADP (Day 1: 19 +/- 8 mm, Day 7: 9 +/- 6 mm, p = 0.04) and % inhibition (Day 1: 58 +/- 27, Day 7: 99 +/- 0.3, p = 0.02). DISCUSSION: Clopidogrel administration did not lead to changes in TG assay variables performed on platelet poor plasma samples, despite concomitant changes in TEG-PM variables consistent with platelet inhibition. Based on this pilot study, thrombin generation performed on platelet poor plasma may not be a useful antiplatelet monitoring tool in dogs.

Background and Objectives: Cerebral microinfarcts (CMIs) are the most common type of brain ischemia; however, they are extremely rare in the general population. CMIs can be detected by magnetic resonance diffusion-weighted imaging (MRI-DWI) only for a very short period of approximately 2 weeks after their formation and are associated with an increased stroke risk and cognitive impairment. We aimed to examine CMI detection rate in patients with lung cancer (LC), which is strongly associated with ischemic stroke risk relative to other cancer types. Methods: We used the Clalit Health Services record (representing more than 5 million patients) to identify adults with LC and breast, pancreatic, or colon cancer (non-lung cancer, NLC) who underwent brain magnetic resonance diffusion (MRI) scan within 5 years following cancer diagnosis. All brain MRI scans were reviewed, and CMIs were documented, as well as cardiovascular risk factors. Results: Our cohort contained a total of 2056 MRI scans of LC patients and 1598 of NLC patients. A total of 143 CMI were found in 73/2056 (3.5%) MRI scans of LC group compared to a total of 29 CMI in 22/1598 (1.4%) MRI scans of NLC (p < 0.01). Cancer type (e.g. LC vs NLC) was the only associated factor with CMI incidence on multivariate analysis. After calculating accumulated risk, we found an incidence of 2.5 CMI per year in LC patients and 0.5 in NLC. Discussion: CMIs are common findings in cancer patients, especially in LC patients and therefore might serve as a marker for occult brain ischemia, cognitive decline, and cancer-related stroke (CRS) risk. [ABSTRACT FROM AUTHOR]

• Antithrombotic ability. • 11 South African plants. • H. natalensis - best candidate. Venous thromboembolism (VTE) is a collective term for the cardiovascular diseases namely, deep vein thrombosis and pulmonary embolism. Thrombosis causes the progression of VTE. Many of those who live in developing countries rely on herbal medicinal products as a primary source of healthcare. The study investigated the antithrombotic properties of the selected South African plant extracts. Eleven (11) plant species traditionally used for pain management and wound healing including plants reported in literature with anti-inflammatory and antioxidant activity were selected for this study. Extracts were prepared for each plant using ethanol, dichloromethane, and water. The extracts were tested for their antiproliferative effects on human liver carcinoma (HepG2) cells as well as antioxidant, activated coagulation factor X (anti-FXa) and cyclooxygenase-1 (COX-1) inhibitory activity. The results were interpreted using published information on the phytochemistry of the relevant active extracts. The most effective antioxidant activity was observed for the aqueous extract of Heteropyxis natalensis (H. natalensis) (IC 50 = 2.71 µg/mL), which also displayed potent anti-FXa activity with an IC 50 value of 2.64 µg/mL. The same extract inhibited COX-1 at an IC 50 value of 25.32 µg/mL. Due to the potent antiproliferative, antioxidant, and anti-FXa activity, as well as favourable COX-1 inhibition, the aqueous extract of H. natalensis was identified as the best candidate for future antithrombotic studies. [ABSTRACT FROM AUTHOR]

Feline arterial thromboembolism has been reported to be secondary to various feline cardiomyopathies; however, it has not been described in cats with transient myocardial thickening. A previously healthy, one-year-old, castrated male cat presented with acute paraparesis and congestive heart failure. Echocardiography revealed asymmetric left ventricular free wall thickening and left atrial enlargement. Antithrombotic treatment and cardiac medication resulted in reperfusion and mobility on day seven in one limb and on day 10 in the other. Different complications were managed successfully, including worsening acute kidney injury, inflammation, pleural effusion, and anemia. After three weeks, the cat was discharged and prescribed oral antithrombotic drugs (clopidogrel and rivaroxaban) and cardiac medication. Within five months, echocardiographic findings normalized, and medical treatment was gradually discontinued. To date, the cat remains healthy at 1735 days after the initial diagnosis and 1494 days after the last antithrombotic medication. To the best of our knowledge, this is the first case report on feline arterial thromboembolism combined with transient myocardial thickening, with favorable long-term survival. [ABSTRACT FROM AUTHOR]

The present work demonstrates the milk whey extraction, proximate analysis, and biochemical characterization of bioactive compounds in MWE. Effects of MWE on plasma coagulation and platelet aggregation. Proximate analysis of MWE was done according to AOAC. Whey protein banding was confirmed in 12%, 15%, and 18% SDS-PAGEs. A quantitative analysis of bioactive compounds was done. The anticoagulant effects of MWE were tested using plasma recalcification time in both PRP and PPP, further confirmed by PT and APTT assays and in tail bleeding assays at concentrations of 0-100 pg. The non-toxic property of MWE was screened by edema, hemorrhage, and direct hemolytic activities. MWE proximate analysis showed the presence of both micro- and macronutrients. Qualitative analysis confirmed the presence of proteins and carbohydrates. A similar protein-banding pattern was observed in 12%, 15%, and 18% SDS-PAGE's in both reduced and non-reduced conditions. MWE prolonged the clotting time of human citrated plasma, both PRP and PPP, against the control 210 sec to 770 sec, suggesting its anticoagulant property. MWE delayed the clot progress of only the APTT ratio (8.99 ± 0.09), and PT was not altered, suggesting its role in an intrinsic pathway of blood coagulation. MWE exhibited antiplatelet activity in PRP against ADP and epinephrine-induced platelet aggregation. The percentage of inhibition was 74% and 100% for ADP and epinephrine, respectively. Interestingly, MWE exhibits nontoxic properties, it does not cause hemolysis, hemorrhage, or edema. Milk whey extraction and studies confirm bioactive compounds, and these exhibit antithrombotic, antiplatelet, and non-toxic properties. Hence, MWE not only acts as a good nutritive source but also may prove tobe a therapeutic bioactive compound in the management of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Marine natural products are important sources of novel drugs. In this study, we isolated 4-hydroxyphenylacetic acid (HPA) from the marine-derived fungus Emericellopsis maritima Y39–2. The antithrombotic activity and mechanism of HPA were reported for the first time. Using a zebrafish model, we found that HPA had a strong antithrombotic activity because it can significantly increase cardiac erythrocytes, blood flow velocity, and heart rate, reduce caudal thrombus, and reverse the inflammatory response caused by Arachidonic Acid (AA). Further transcriptome analysis and qRT–PCR validation demonstrated that HPA may regulate autophagy by inhibiting the PI3K/AKT/mTOR signaling pathway to exert antithrombotic effects. [ABSTRACT FROM AUTHOR]

Background: Antithrombotic therapy, such as acetylsalicylic acid (ASA) and clopidogrel, may interfere with platelet aggregation in thrombotic strokes. Therefore, a platelet aggregation test is essential for monitoring therapy. A previous study observed a decrease in platelet aggregation using antithrombotics with a manual LTA analyzer. Further research is required to compare this with an automatic tool to determine whether both instruments have similar detection capabilities. Methods: PPP and PRP samples were collected from 30 thrombotic stroke outpatients and 30 healthy controls. Platelet aggregation tests were performed using ADP 5μM and Collagen 2μg/mL on both instruments, Chronolog® Model 490, and Sysmex® CS-2500. The tests were then analyzed using the Wilcoxon test for differences, the Spearman test for correlation, and the Bland-Altman analysis for agreement. Results: No differences were observed in MA values and numerical alignment between the two instruments for ADP and Collagen. If the MA result for the platelet aggregation test on Chrono-log® Model 490 was high, it was likewise high on Sysmex CS-2500 and vice versa. Although the values of LP and Vel differed, the numbers for ADP and Collagen in both instruments were consistent. Conclusion: The comparison between both instruments indicates good agreement. Automated LTA demonstrates the same suitability as manual LTA and can be applied in clinical routines to assess platelet aggregation function. Due to many variations in the pre-analytics stage that might affect the results, it is vital to standardize both the pre-analytics, analytics, and post-analytics stages to compare platelet aggregation tests on the two instruments. [ABSTRACT FROM AUTHOR]

With approximately 3 million people worldwide affected each year and the highly associated mortality and morbidity, intracerebral hemorrhage is the stroke subtype with the most severe clinical consequences. This is mainly due, on the one hand, to the lack of specific acute treatments, as opposed to the ischemic counterpart of stroke, on the other hand, to the occurrence of further vascular events after the index bleeding [...].

BackgroundAtrial fibrillation (AF), a potential trigger for stroke development, is considered a modifiable condition that can halt complications, decrease mortality, and prevent morbidity. The CHA₂DS₂-VASc and HAS-BLED scores are categorized as risk assessment tools used to estimate the risk of thrombosis development and assess major bleeding among atrial fibrillation patients.ObjectivesOur study aims to assess the adherence to post-discharge treatment recommendations according to CHA₂DS₂-VASc score risk group and evaluate the impact of CHA₂DS₂-VASc score and HAS-BLED score risk categories on death, length of hospital stay, complications, and hospital readmission among United Arab Emirates (UAE) patients.MethodsThis was a multicenter retrospective study conducted from November 2022 to April 2023 in the United Arab Emirates. Medical charts for AF patients were assessed for possible enrolment in the study.ResultsA total number of 400 patients were included with a mean age of 55 (±14.5) years. The majority were females (67.8%), and most had high CHA₂DS₂-VASc and HAS-BLED scores (60% and 57.3%, respectively). Our study showed that adherence to treatment recommendations upon discharge was 71.8%. The bivariate analysis showed that patients with a high CHA₂DS₂-VASc score had a significantly higher risk of death (p-value of 0.001), hospital readmission (p-value of 0.007), and complications (p-value of 0.044) vs. the low and moderate risk group with a p-value of

Thamer S Alhowaish,1,2 Moustafa S Alhamadh,2,3 Abdullah Alsulayhim,2,4 Najla Alotaibi,5 Azzam Abdulaziz Alrashid,2,3 Abdulrahman Yousef Alhabeeb,2,3 Muhannad Q Alqirnas,2,3 Eythar Alrushid,1,2 Mohammed S Alnafisah,1,2 Ajmal Ali Anversha1,2 1Division of Neurology, Department of Medicine, King Abdulaziz Medical City, Ministry of the National Guard Health Affairs (MNGHA), Riyadh, Kingdom of Saudi Arabia; 2King Abdullah International Medical Research Center, Ministry of the National Guard-Health Affairs, Riyadh, 11481, Kingdom of Saudi Arabia; 3College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of the National Guard-Health Affairs, Riyadh, 14611, Kingdom of Saudi Arabia; 4Radiology Department, King Abdul Aziz Medical City, Riyadh, Kingdom of Saudi Arabia; 5College of Public Health, Oregon State University, Corvallis, OR, USACorrespondence: Ajmal Ali Anversha, Division of Neurology, King Abdulaziz Medical City, King Abdullah International Medical Research Center, Ministry of the National Guard Health Affairs, Riyadh, Kingdom of Saudi Arabia, Tel +966-11-8011111 Ext: 13460, Email drajmalali@yahoo.comBackground: Intraluminal thrombus (ILT) of the cervical arteries is an uncommon finding that can lead to acute or recurrent ischemic stroke. Currently, antithrombotic therapy in the form of antiplatelet and/or anticoagulation is considered the mainstay of treatment, but evidence of which one has a better outcome is lacking.Methods: A retrospective cohort study included 28 patients diagnosed with acute stroke or transient ischemic attack with ILT of the extracranial arteries from 2013 to 2022. The primary efficacy outcome was assessed as recurrent stroke, and the primary safety outcome was assessed as hemorrhagic complications. Secondary outcomes were assessed as the resolution of thrombi by CT angiography (CTA) and clinical improvement by the Modified Rankin Scale (mRS) and NIH Stroke Scale (NIHSS).Results: Out of 28 patients, more than half (57.1%; n = 16) were males with a mean age of 57.8 ± 9.5 years and an average BMI of 26.9 ± 4.5 kg/m2. As initial treatment, twenty-four patients received anticoagulation and four received antiplatelet agents. Recurrent strokes were found in four patients (14.29%), and all were initially treated with anticoagulation. One patient in the anticoagulation group had a significant retroperitoneal hemorrhage. None of the patients in the antiplatelets group had a recurrent stroke or bleeding event. Initial treatment with antiplatelet agents significantly improved the NIHSS on day 7 (P = 0.017). A significant improvement in NIHSS on day 90 was observed in the anticoagulant group (P = 0.011). In the follow-up CTA performed on 24 patients, 18 (75%) showed complete resolution (3 out of 3 (100%) in the antiplatelet group and 15 out of 21 (71.43%) in the anticoagulant group).Conclusion: Initial treatment with anticoagulants improves neurologic outcomes in patients with ILT-induced acute ischemic stroke but carries the risk of recurrent stroke and bleeding. However, initial treatment with dual antiplatelet agents appears to have comparable efficacy without sequelae, particularly in atherosclerosis-induced ILT.Keywords: stroke, free-floating thrombus, intraluminal thrombus, Intraluminal clot, doughnut sign, antithrombotic, anticoagulation, antiplatelet agents, stroke in Saudi Arabia

Nattokinase has been one of the most widely discussed and researched extracellular enzymes since it was first introduced in 2005. Nattokinase belongs to the subtilisin family and is a proteolytic enzyme (serine protease) with a powerful fibrinolytic effect. Nattokinase is purified and extracted from fermented soybean seeds under the effect of the Bacillus subtilis (Natto) bacteria. Its main natural source is the fermented vegetable cheese called natto, which is a traditional Japanese food consumed in Japan for more than 2000 years (1). All over the world, natto is regarded as a fibrinolytic miracle food. The enzyme discovery became a fact thanks to the Japanese scientist Hiroyuki Sumi, a researcher at the Medical University in Chicago, who in 1980 after testing more than 173 natural foods as possible thrombolytic agents(2), discovered that natto possesses the ability to break down artificial fibrin in vitro. Later in 1987, Sumi and his team introduced the new fibrinolytic enzyme, extracted from natto, and named it nattokinase (NK), known also as subtilisin NAT. The major interest in the enzyme is namely because of its direct fibrinolytic activity, provided that it remains stable in the gastrointestinal tract after oral administration. This determines it as a highly valuable, safe and easy-to-use nutraceutical with a wide area of medical applications for the treatment of thrombotic, neurological and dyslipidemia conditions, arterial hypertension, diabetes mellitus, atherosclerosis, hemorrhoids, endometriosis, uterine fibroids, muscle spasms, infertility in reproductive medicine and obstetrics.

Existing antithrombotic drugs have side effects such as bleeding, and there is an urgent need to discover antithrombotic drugs with better efficacy and fewer side effects. In this study, a zebrafish thrombosis model was used to evaluate the antithrombotic activity and mechanism of Brevianamide F, a deep-sea natural product, with transcriptome sequencing analysis, RT-qPCR analysis, and molecular docking. The results revealed that Brevianamide F significantly attenuated the degree of platelet aggregation in the thrombus model zebrafish, leading to an increase in the number of circulating platelets, an augmentation in the return of blood to the heart, an elevated heart rate, and a significant restoration of caudal blood flow velocity. Transcriptome sequencing and RT-qPCR validation revealed that Brevianamide F may exert antithrombotic effects through the modulation of the MAPK signaling pathway and the coagulation cascade reaction. Molecular docking analysis further confirmed this result. This study provides a reference for the development of therapeutic drugs for thrombosis.

Vaccinium dunalianum leaf buds make one of the most commonly used herbal teas of the Yi people in China, which is used to treat articular rheumatism, relax tendons, and stimulates blood circulation in the body. In addition, 6′-O-caffeoylarbutin (CA) is a standardized extract of V. dunalianum, which has been found in dried leaf buds, reaching levels of up to 31.76%. Because of the uncommon phenomenon, it is suggested that CA may have a potential therapeutic role in hyperlipidemia and thrombosis. This study was designed to study the efficacy of CA on treating hyperlipidemia and thrombosis and the possible mechanisms behind these effects. Hyperlipidemia and thrombosis zebrafish models were treated with CA to observe variations of the integrated optical density within the vessels and the intensity of erythrocyte staining within the hearts. The possible mechanisms were explored using network pharmacology and molecular docking. The results demonstrate that CA exhibits an excellent hypolipidemic effect on zebrafish at concentrations ranging from 3.0 to 30.0 μg/mL and shows thrombosis inhibitory activity in zebrafish at a concentration of 30.0 μg/mL, with an inhibition rate of 44%. Moreover, network pharmacological research shows that MMP9, RELA, MMP2, PRKCA, HSP90AA1, and APP are major targets of CA for therapy of hyperlipidemia and thrombosis, and may relate to pathways in cancer, chemical carcinogenesis-receptor activation, estrogen signaling pathway, and the AGE–RAGE signaling pathway in diabetic complications. [ABSTRACT FROM AUTHOR]

Apple pomace (AP) is a bio-waste product of apples that is co-produced as a by-product during apples' processing for making apple-based products, mainly apple juice, cider and vinegar. AP is a rich source of several bioactives that can be valorized as ingredients for developing novel functional foods, supplements and nutraceuticals. Within the present study, food-grade extracts from AP with different tannin contents were found to contain bioactive polar lipids (PLs), phenolics and carotenoids with strong anti-oxidant, antithrombotic and anti-inflammatory properties. The extract from the low-in-tannins AP showed stronger anti-inflammatory potency in human platelets against the potent thrombo-inflammatory mediator platelet-activating factor (PAF), while it also exhibited considerable anti-platelet effects against the standard platelet agonist, adenosine diphosphate (ADP). The infusion of 0.5–1.0 g of this bioactive AP extract as functional ingredients for whole-grain bread-making resulted in the production of novel bio-functional bread products with stronger anti-oxidant, antithrombotic and anti-inflammatory potency against both PAF and ADP in human platelets, compared to the standard non-infused control breads. Structural analysis by LCMS showed that the PL-bioactives from all these sources (AP and the bio-functional breads) are rich in bioactive unsaturated fatty acids (UFA), especially in the omega-9 oleic acid (OA; 18:1n9), the omega-3 alpha linolenic acid (ALA; 18:n3) and the omega-6 linoleic acid (LA; 18:2n6), which further supports their strong anti-inflammatory and antithrombotic properties. All food-grade extracted AP including that infused with AP-bioactives novel functional breads showed higher hydrophilic, lipophilic and total phenolic content, as well as total carotenoid content, and subsequently stronger antioxidant capacity. These results showed the potential of appropriately valorizing AP-extracts in developing novel bio-functional bakery products, as well as in other health-promoting applications. Nevertheless, more studies are needed to fully elucidate and/or validate the anti-inflammatory, antithrombotic and antioxidant potential of novel bio-functional products across the food and cosmetic sectors when infused with these AP bioactives. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases（CVDs） are a group of diseases with high prevalence, disability and mortality rates, and are the number one killer of human health, with coronary and peripheral occlusive vascular diseases posing a great threat. To reduce the threat of CVDs to human life, small-caliber artificial blood vessel transplantation is a relatively common treatment. The materials widely used for the preparation of artificial blood vessels include polyester, expanded polytetrafluoroethylene, polyurethane and silk, etc. The former three are widely used in large vessel replacement surgery, but their use in small vessels is prone to thrombus formation, which clogs the artificial blood vessels and ultimately leads to the death of the organism. Silk has good biocompatibility, mechanical properties, degradability and promotion of cell adhesion, which has become a research hotspot for the preparation of small-caliber artificial blood vessels in recent years.To comprehensively understand the application status and performance advantages of silk small-caliber artificial blood vessels and accelerate the research and transformation of small-caliber blood vessels, this paper analyzed the advantages and problems of using silk as raw material to prepare small-caliber blood vessels from the aspects of preparation method, biocompatibility, anti-thrombotic ability and promoting vascular endothelialization, and put forward the possible development direction in the future. The results of most of the studies show that small-caliber artificial blood vessels prepared with silk as raw material exhibit good repair and long-term patency in animals. Silk can be prepared by gel spinning, weaving, knitting, electrostatic spinning, 3D printing, decellularization, freeze drying, etc. These methods have both advantages and defects. For instance, freeze drying is easy to mold but the mechanical properties of the artificial blood vessels are weak, the method of gel spinning can produce a uniform and loose network structure but is poor in mechanical properties, the artificial blood vessels prepared by knitting have uniform texture and flat surface but are easy to unravel at the anastomosis. On the whole, the artificial blood vessels produced by electrostatic spinning have high porosity to meet the requirements of cell growth, and this method is widely used. Although these methods have defects, they provide researchers with much space for improvement. Silk-based small-caliber blood vessels show effects such as promotion of cell adhesion and proliferation when co-cultured with smooth muscle cells, endothelial cells, fibroblasts, etc. When co-cultured with vascular scaffolds, the cells are able to colonize and grow on the scaffolds smoothly, and these properties indicate that biomedical materials prepared with silk as the raw material have excellent cytocompatibility, but there is an over-proliferation phenomenon when the cells are cultured with smooth muscle, which suggests that over-proliferation of cells should be avoided when silk is used as the biomaterial. The formation of thrombus after vascular transplantation is very likely to lead to death, the excellent mechanical properties and biocompatibility of silk are important factors to avoid the formation of thrombus, but the excessive proliferation of smooth muscle caused by silk-based artificial blood vessels may also lead to thrombus. In the future, artificial blood vessels can be prepared by combining with anticoagulant factors to prevent the formation of thrombus. After silk-based vascular grafting, vascular endothelial cells are able to migrate and colonize into the lumen of the graft smoothly, and the surface of the lumen is able to produce fused endothelium; although this process is relatively slow, it is sufficient to prove that silk-based artificial blood vessels are able to promote the endothelialization process after grafting.Although the advantages of silk-based small-caliber blood vessels are significant, whether the reagent residues in the preparation process have side effects needs to be further verified, and a large number of experimental improvements are needed to accelerate the clinical application, and the amount and degree of endotheliosis are strictly controlled in silk-based vascular grafts. In addition, more in-depth research on their controllable degradation needs be carried out. In conclusion, silk-based small-caliber blood vessels have unique advantages and certain defects, which bring opportunities and challenges for their clinical application, and it is necessary to increase the research investment on silk-based small-caliber blood vessels in the future to promote the development of silk in the field of biomedical materials. [ABSTRACT FROM AUTHOR]

Background: There have been significant changes in the optimal antithrombotic regimen post transcatheter aortic valve implantation (TAVI) after the results of major clinical trials in the past few years. Given the clinical importance of the optimal antithrombotic therapy post TAVI, we performed a narrative description of the major clinical trials behind the scientific evidence supporting these changes, as well the current guideline recommendations and knowledge gaps. Methods: We performed a narrative description of the major clinical trials behind the scientific evidence supporting these changes. We used PubMed as a major source to collect the major clinical trials including the following key words: "transcatheter aortic valve replacement", "transcatheter aortic valve implantation", "antithrombotic", "antiplatelet" and "anticoagulation". We selected the major clinical trials on this topic. This is not a systematic review or meta-analysis. Results: We describe the results of the major clinical trials on antithrombotic therapy post TAVI: POPULAR-TAVI A, POPULAR-TAVI B, ENVISAGE-TAVI AF, GALILEO, ATLANTIS and ADAPT-TAVR trials. Based on the results of these trials, single antiplatelet therapy is recommended post TAVI in patients without concomitant indication for oral anticoagulation or dual antiplatelet therapy, especially in elderly patients. In younger patients, it is advised to evaluate the patient's bleeding and thrombotic risk, and dual antiplatelet therapy may be reasonable in patients with a high thrombotic risk and low bleeding risk. In patients with a concurrent indication for oral anticoagulation or dual antiplatelet therapy, it is recommended to continue oral anticoagulation or dual antiplatelet therapy post TAVI. Conclusion: In most patients without concomitant indication for oral anticoagulation, single antiplatelet therapy is recommended post TAVI. [ABSTRACT FROM AUTHOR]

Objective: The objective of the present study was to describe the knowledge, perception, and practices of general dentists and dentists with various specializations regarding the management of patients on antithrombotic drug therapy. Methods: A cross-sectional survey of dentists and specialists from different educational institutions and workplaces was conducted in Turkey between May 2022 and July 2022. The sample size comprised 153 subjects, and participants completed an electronic questionnaire containing 24 questions. Descriptive statistical analyses were performed to evaluate the data. Results: Most of the surveyed dentists were aware of acetylsalicylic acid (ASA) and warfarin, while the novel antithrombotic agents apixaban and rivaroxaban were less known. Regarding the management of patients on novel oral antithrombotic medication during different dental procedures, there were no significant differences within groups according to clinical experience year (P = .409), whereas, for patients on ASA, both years of experience and area of expertise affected the participant’s approach (P = .001). Monitoring of patients before dental procedures regarding blood tests did not differ according to years of clinical experience or specialty (P = .185, P = .688). Most participants (92%) sought a physician’s opinion before invasive dental procedures, regardless of the type of oral antithrombotic medication. Conclusion: The knowledge and dental management of patients on oral antithrombotic medications varied among dentists. Evident hesitancy toward treating such patients indicates a necessity for continuing education programs among dentists to provide better care for the patients without any fear of cardiovascular consequences. [ABSTRACT FROM AUTHOR]

Dipsaci Radix may possess antithrombotic properties, and one of its primary active ingredients is Asperosaponin VI. However, the antithrombotic effects and pharmacological mechanisms of Asperosaponin VI remain unclear. An in vivo experimental study has demonstrated the antithrombotic activity of Asperosaponin VI. Asperosaponin VI also exhibits anticoagulant properties. Asperosaponin VI significantly hindered collagen adrenergic-induced acute pulmonary thrombosis in mice and enhanced their survival rate. This hinders the formation of acute pulmonary embolisms induced by adenosine diphosphate (ADP) and decreases recovery time. A comprehensive strategy that combines metabolomics, network pharmacology, molecular docking, and experimental validation has the potential to reveal the antithrombotic mechanisms of Asperosaponin VI. Metabolomic evidence suggests that Asperosaponin VI may influence platelet aggregation and the production of anti-inflammatory metabolites through the regulation of pathways such as phenylalanine and arachidonic acid metabolism, thereby inhibiting thrombosis. Network pharmacology identified the pharmacological targets of Asperosaponin VI and indicated that it treats thrombi by partially regulating the signaling pathways related to inflammation and platelet aggregation. Asperosaponin VI showed strong binding affinity for F2, PTPRC, JUN, STAT3, SRC, AKT1. The antiplatelet aggregation activity of Asperosaponin VI was validated based on the metabolomic and network pharmacology results. Asperosaponin VI inhibits platelet aggregation induced by ADP, AA, and collagen. Therefore, Asperosaponin VI exerts antithrombotic effects through antiplatelet aggregation. Therefore, Asperosaponin VI is a promising antithrombotic agent.

Background Cerebral cavernous malformations are complex vascular anomalies in the central nervous system associated with a risk of intracranial hemorrhage. Traditional guidelines have been cautious about the use of antithrombotic therapy in this patient group, citing concerns about potential bleeding risk. However, recent research posits that antithrombotic therapy may actually be beneficial. This study aims to clarify the association between antithrombotic therapy, including antiplatelet and anticoagulant medications, and the risk of intracranial hemorrhage in patients with cerebral cavernous malformations. Methods and Results A comprehensive literature search was conducted in PubMed, Web of Science, and Scopus databases, following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. Nine single‐center, nonrandomized cohort studies involving 2709 patients were included. Outcomes were analyzed using random‐effects model, and a network meta‐analysis was conducted for further insight. Of the 2709 patients studied, 388 were on antithrombotic therapy. Patients on antithrombotic therapy had a lower risk of presenting with intracranial hemorrhage (odds ratio [OR], 0.56 [95% CI, 0.45–0.7]; P

Nattokinase (NK), a serine protease, can be used as a thrombolytic agent. Compared with clinical thrombolytic drugs (urokinase and streptokinase), NK has the advantages of low price, high thrombolytic efficiency, oral administration, and no toxic side effect, making it an ideal natural thrombolytic agent. At present, commercial thrombolytic NK products have the problems of low activity and bioavailability, which enter the bloodstream to exert thrombolytic effects through the oral and gastrointestinal digestion and absorption system. The gastrointestinal tract (GIT) environment (strong acidity, pepsin and trypsin) can destroy the spatial structure of NK, leading to a decrease or loss of its thrombolytic activity. The construction of functional vectors for NK delivery using natural biomaterials such as lipids, polysaccharides, and proteins can effectively avoid these adverse factors in the digestive system, enhancing the stability of NK, and improving its biological activity and bioavailability in the body. Beginning with an overview of the structural and functional properties of NK, this paper summarizes recent progress in research on functional vectors for NK delivery in order to provide a theoretical basis and technical support for efficient and stable thrombolytic NK products.

IntroductionIn COVID-19 pneumonia, there is a massive increase in fatty acid levels and lipid mediators with a predominance of cyclooxygenase metabolites, notably TxB2 ≫ PGE2 > PGD2 in the lungs, and 11-dehydro-TxB2, a TxA2 metabolite, in the systemic circulation. While TxA2 stimulates thromboxane prostanoid (TP) receptors, 11-dehydro-TxB2 is a full agonist of DP2 (formerly known as the CRTh2) receptors for PGD2. Anecdotal experience of using ramatroban, a dual receptor antagonist of the TxA2/TP and PGD2/DP2 receptors, demonstrated rapid symptomatic relief from acute respiratory distress and hypoxemia while avoiding hospitalization.Areas coveredEvidence supporting the role of TxA2/TP receptors and PGD2/DP2 receptors in causing rapidly progressive lung injury associated with hypoxemia, a maladaptive immune response and thromboinflammation is discussed. An innovative perspective on the dual antagonism of TxA2/TP and PGD2/DP2 receptor signaling as a therapeutic approach in COVID-19 is presented. This paper examines ramatroban an anti-platelet, immunomodulator, and antifibrotic agent for acute and long-haul COVID-19.Expert opinionRamatroban, a dual blocker of TP and DP2 receptors, has demonstrated efficacy in animal models of respiratory dysfunction, atherosclerosis, thrombosis, and sepsis, as well as preliminary evidence for rapid relief from dyspnea and hypoxemia in COVID-19 pneumonia. Ramatroban merits investigation as a promising antithrombotic and immunomodulatory agent for chemoprophylaxis and treatment.

Despite significant progress, certain inflammation related to chronic disorders, including cardiovascular diseases (CVD) and cancer, still present high mortality rates. Thus, further study is needed to address such pathologies more appropriately. Apart from classic therapeutics, natural bioactives with less toxic side effects have gained attention, including those with potential pharmaceutical properties derived from several plants. Within this article, the potential utilization of freshwater aquatic plants as sources of bioactives with antithrombotic, anti-inflammatory and antioxidant properties is outlined. Emphasis is given to a well-established aquatic plant with known but not fully clarified and overviewed bio-functional and pharmaceutical properties, the Chinese lotus (Nelumbo nucifera), as well as to a so far neglected aquatic plant, Lemna minor, which has not yet been thoroughly reviewed for such applications. The latent usually grows naturally in large numbers at the surface of stored water basins of retrieved water from the last stages of wastewater treatment facilities. The continuous growth of this aquatic plant in such conditions further suggests that it can be a sustainable source of natural bioactives, if appropriately valorized, with an economic benefit and in a friendly environmental approach. The abundant content of both freshwater aquatic plants in bioactive components with potent antioxidant, anti-inflammatory and antithrombotic activities is thoroughly outlined, while their applications as functional ingredients in several functional products (functional foods, cosmetics and pharmaceuticals) are also discussed. The outlined outcomes urge further study of both aquatic plants and especially of Lemna spp. to fully elucidate their potential as alternative sustainable sources of bioactive ingredients for functional foods, supplements, nutraceuticals, nutricosmetics, cosmeceuticals, cosmetics and pharmaceutical products with health-promoting properties against inflammation and thrombosis related manifestations and their associated chronic disorders.

We aimed to determine the diagnostic yield and outcome of patients receiving antithrombotic drug therapy subjected to small bowel capsule endoscopy (SBCE) for the investigation of small bowel bleeding (SBB). A multicenter retrospective analysis of collected data from all patients undergoing SBCE for the investigation of SBB from March 2003 to June 2023 was performed. The diagnostic yield of SBCE was defined as the detection of positive findings that could explain the cause of the patient’s bleeding. Rebleeding was defined as evidence of bleeding within 1 year after the index episode. During the study period, 8401 patients underwent SBCE for SBB investigation. Bleeding lesions were detected in 1103/2535 (43.5%) antithrombotic users, compared to 1113/5866 (18.9%) in nonusers (p < 0.00001). Following capsule endoscopy, a therapeutic intervention was possible in 390/2216 (17.5%) patients with a bleeding lesion. Rebleeding occurred in 927 (36.5%) of antithrombotic users (36.5%), compared to 795 (13.5%) of nonusers (13.5%, p < 0.00001). Both the diagnostic yield of SBCE and the rebleeding rates were higher in patients with SBB receiving antithrombotics. Therapeutic intervention was possible in a real-world setting only for a minority of patients with positive findings.

Background Reasons for the relatively poor performance of bleeding prediction models are not well understood but may relate to differences in predictors for various anatomical sites of bleeding.

Thrombin is a key enzyme involved in the development and progression of many cardiovascular diseases. Direct thrombin inhibitors (DTIs), with their minimum off-target effects and immediacy of action, have greatly improved the treatment of these diseases. However, the risk of bleeding, pharmacokinetic issues, and thrombotic complications remain major concerns. In an effort to increase the effectiveness of the DTI discovery pipeline, we developed a two-stage machine learning pipeline to identify and rank peptide sequences based on their effective thrombin inhibitory potential. The positive dataset for our model consisted of thrombin inhibitor peptides and their binding affinities (KI) curated from published literature, and the negative dataset consisted of peptides with no known thrombin inhibitory or related activity. The first stage of the model identified thrombin inhibitory sequences with Matthew's Correlation Coefficient (MCC) of 83.6%. The second stage of the model, which covers an eight-order of magnitude range in KI values, predicted the binding affinity of new sequences with a log room mean square error (RMSE) of 1.114. These models also revealed physicochemical and structural characteristics that are hidden but unique to thrombin inhibitor peptides. Using the model, we classified more than 10 million peptides from diverse sources and identified unique short peptide sequences (<15 aa) of interest, based on their predicted KI. Based on the binding energies of the interaction of the peptide with thrombin, we identified a promising set of putative DTI candidates. The prediction pipeline is available on a web server. [ABSTRACT FROM AUTHOR]