Antiplatelet Effects Research Articles

Effects of thienopyridine class antiplatelets on bleeding outcomes following robot-assisted radical prostatectomy.

This study aimed to assess the effects of thienopyridine-class antiplatelet agents (including ticlopidine, clopidogrel, and prasugrel) on bleeding complications in patients who underwent robot-assisted radical prostatectomy. This cohort study used a database for robot-assisted radical prostatectomy at 23 tertiary centers nationwide between 2011 and 2022. Patients who received thienopyridines (thienopyridine group) were compared with those who received aspirin monotherapy (aspirin group). The primary outcome was the incidence of bleeding complications. High-grade complications were defined as Clavien-Dindo grade III or higher. The risks of these outcomes were evaluated using inverse probability of treatment weighted regression models. The study results demonstrated that thienopyridine therapy was associated with a higher risk of overall bleeding complications (OR: 3.62, 95%CI 1.54-8.49). The increased risks of the thienopyridine group were detected for low-grade bleeding complications (OR: 3.20, 95%CI 1.23-8.30) but not for high-grade bleeding complications (OR: 5.23, 95%CI 0.78-34.9). The increased risk of bleeding complications was not observed when thienopyridine was discontinued (OR: 2.52, 95%CI 0.83-7.70); however, it became apparent when it was continued perioperatively (OR: 4.35, 95%CI 1.14-16.61). In conclusion, thienopyridine increased the incidence of bleeding complications, particularly low-grade bleeding complications, following robot-assisted radical prostatectomy. These bleeding effects emerged when thienopyridine was continued perioperatively.

Representation of Patients With Chronic Kidney Disease in Clinical Trials of Cardiovascular Disease Medications

Patients with chronic kidney disease (CKD) are at high risk for cardiovascular disease, but their systematic underrepresentation in cardiovascular randomized clinical trials (RCTs) limits the generation of appropriate evidence to guide cardiovascular risk management (CVRM). To evaluate the underrepresentation of patients with CKD in cardiovascular RCTs, and to highlight evidence gaps in CVRM medications in this population. A systematic search was conducted in ClinicalTrials.gov from February 2000 through October 2021 for RCTs with full-text publications. If no full-text publications were found in ClinicalTrials.gov, MEDLINE, Embase, and Google Scholar were also searched. Eligible RCTs were those evaluating the effectiveness of antiplatelets, anticoagulants, blood pressure-lowering drugs, glucose-lowering drugs, or cholesterol-lowering drugs in adults with cardiovascular disease or cardiovascular risk factors. Trials with a sample size of fewer than 100 patients were excluded. In total, 1194 RCTs involving 2 207 677 participants (mean [SD] age, 63 [6] years; 1 343 970 males [64%]) were included. Since 2000, the percentage of cardiovascular RCTs excluding patients with CKD has increased from 66% to 79% (74% overall [884 RCTs]). In 864 RCTs (72%), more patients were excluded than anticipated on safety grounds (63% [306] of trials required no dose adjustment, and 79% [561] required dose adjustment). In total, 158 RCTs (13%) reported results for patients with CKD separately (eg, in subgroup analyses). Significant evidence gaps exist in most CVRM interventions for patients with CKD, particularly for those with CKD stages 4 to 5. Twenty-three RCTs (2%) reported results for patients with an estimated glomerular filtration rate less than 30 mL/min/1.73 m2, 15 RCTs (1%) reported for patients receiving dialysis, and 1 RCT (0.1%) reported for recipients of kidney transplant. Results of this systematic review suggest that representation of patients with CKD in cardiovascular RCTs has not improved in the past 2 decades and that these RCTs excluded more patients with CKD than expected on safety grounds. Lack of reporting or underreporting of results for this patient population is associated with evidence gaps in the effectiveness of most CVRM medications in patients with all stages of CKD, particularly CKD stages 4 to 5.

The Platelet Aggregation Inhibition Activity of Polyphenols can be Mediated by 67kda Laminin Receptor: A New Therapeutic Strategy For the Treatment of Venous Thromboembolism.

Thrombotic disease is still a major killer. Aspirin, Ticagrelor, Clopidogrel, etc. are the most widely used conventional antiplatelet drugs. The significant number of patients who are resistant to this drug shows a poor outcome. Developing a new antiplatelet agent with a stable antiplatelet effect and minimal bleeding risk is required for a patient who is resistant to antiplatelet drugs. Protein-ligand docking was performed using Autodock Vina 1.1.2 to study the interaction of 67LR with different Polyphenols. Among the 18 polyphenols, thearubigin has the highest binding affinity towards 67LR and gallic acid shows the lowest binding affinity. Among the 18 molecules, the top 4 molecules from the highest to lowest binding affinity range from-10.6 (thearubigin) to -6.5 (Epigallocatechin). Polyphenols may inhibit platelet aggregation through 67 LR and can be an alternative treatment for Thrombotic Disease. Moreover, it will be interesting to know whether polyphenols interfere with the same pathways as aspirin and clopidogrel. Effective polyphenols could help prototype the compound development of novel antiplatelet agents.

Cangrelor - Expanding therapeutic options in patients with acute coronary syndrome.

Cangrelor is the only intravenous P2Y12 receptor antagonist. It is an adenosine triphosphate analog that selectively, directly, and reversibly binds to the platelet P2Y12 receptors exerting its antiaggregatory effect. Cangrelor is characterized by linear, dose-dependent pharmacokinetics and rapid onset of action providing potent platelet inhibition exceeding 90%. Cangrelor is rapidly metabolized by endothelial endonucleotidase; thus, its half-life is 2.9 to 5.5 min, and its antiplatelet effect subsides within 60 to 90 min. Data originating from three pivotal cangrelor trials (CHAMPION PLATFORM, CHAMPION PCI, and CHAMPION PHOENIX) indicate that cangrelor reduces the risk of periprocedural thrombotic complications during percutaneous coronary intervention at the expense of mild bleedings. Its unique pharmacological properties allow it to overcome the limitations of oral P2Y12 receptor inhibitors, mainly related to the delayed and decreased bioavailability and antiplatelet effect of these agents, which are often observed in the setting of acute coronary syndrome. Subgroups of patients who could theoretically benefit the most from cangrelor include those in whom pharmacokinetics and pharmacodynamics of oral P2Y12 receptor antagonists are most disturbed, namely patients with ST-segment elevation myocardial infarction, those treated with opioids, with mild therapeutic hypothermia, or in cardiogenic shock. Cangrelor could also be useful if bridging is required in patients undergoing surgery. According to the current guidelines cangrelor may be considered in P2Y12 receptor inhibitor-naïve patients undergoing percutaneous coronary intervention in both acute and stable settings.

Optimizing aspirin dose for colorectal cancer patients through deep phenotyping using novel biomarkers of drug action.

Background: Low-dose aspirin's mechanism of action for preventing colorectal cancer (CRC) is still debated, and the optimal dose remains uncertain. We aimed to optimize the aspirin dose for cancer prevention in CRC patients through deep phenotyping using innovative biomarkers for aspirin's action. Methods: We conducted a Phase II, open-label clinical trial in 34 CRC patients of both sexes randomized to receive enteric-coated aspirin 100mg/d, 100mg/BID, or 300mg/d for 3 ± 1weeks. Biomarkers were evaluated in blood, urine, and colorectal biopsies at baseline and after dosing with aspirin. Novel biomarkers of aspirin action were assessed in platelets and colorectal tissues using liquid chromatography-mass spectrometry to quantify the extent of cyclooxygenase (COX)-1 and COX-2 acetylation at Serine 529 and Serine 516, respectively. Results: All aspirin doses caused comparable % acetylation of platelet COX-1 at Serine 529 associated with similar profound inhibition of platelet-dependent thromboxane (TX)A2 generation ex vivo (serum TXB2) and in vivo (urinary TXM). TXB2 was significantly reduced in CRC tissue by aspirin 300mg/d and 100mg/BID, associated with comparable % acetylation of COX-1. Differently, 100mg/day showed a lower % acetylation of COX-1 in CRC tissue and no significant reduction of TXB2. Prostaglandin (PG)E2 biosynthesis in colorectal tumors and in vivo (urinary PGEM) remained unaffected by any dose of aspirin associated with the variable and low extent of COX-2 acetylation at Serine 516 in tumor tissue. Increased expression of tumor-promoting genes like VIM (vimentin) and TWIST1 (Twist Family BHLH Transcription Factor 1) vs. baseline was detected with 100mg/d of aspirin but not with the other two higher doses. Conclusion: In CRC patients, aspirin 300mg/d or 100mg/BID had comparable antiplatelet effects to aspirin 100mg/d, indicating similar inhibition of the platelet's contribution to cancer. However, aspirin 300mg/d and 100mg/BID can have additional anticancer effects by inhibiting cancerous tissue's TXA2 biosynthesis associated with a restraining impact on tumor-promoting gene expression. EUDRACT number: 2018-002101-65. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03957902.

Cuban policosanol: a natural compound for ischemic stroke treatment

Stroke is among the leading causes of mortality and disability; therefore, it constitutes a relevant health problem. Cuban policosanol presents lipid-lowering, antiplatelet, antioxidant and vascular endothelium protective properties, all of which give it a comprehensive anti-atherosclerotic effect. This review is aimed to show, analyze and discuss the main preclinical and clinical evidence of the effects of Cuban policosanol on ischemic stroke. Preclinical studies evidenced the anti-ischemic effects of preventive and therapeutic oral treatment with Cuban policosanol in Mongolian gerbils with cerebral ischemia induced by unilateral and permanent ligation of a carotid artery, and in global cerebral ischemia induced by bilateral clamping and recirculation of both carotids; being similar or superior to other anti-ischemic agents. Also, combination therapy with aspirin produced greater anti-stroke efficacy compared with aspirin monotherapy, but being similar to policosanol plus atorvastatin combination. This anti-stroke effect was associated to a serum thromboxane A2 (TxA2) concentrations reduction and prostacyclin (PgI2) increase, leading to a favorable TxA2/PgI2 balance, and also to the malondialdehyde (MDA) and sulfhydryl groups (SHG, lipid peroxidation and protein oxidation markers, respectively) reduction. Cuban policosanol combined with aspirin (standard therapy) improved and benefited patients with prior ischemic stroke in terms of functional and neurological outcomes, in open-label studies and in randomized, double-blind, controlled studies. These beneficial effects on stroke patients were associated with antioxidant and antiplatelet effects of policosanol. Also, the combinations of Cuban policosanol plus aspirin and atorvastatin plus aspirin compared in a clinical study significantly and similarly improved the neurological recovery of patients with ischemic stroke. Cuban policosanol was safe and well tolerated, with no serious adverse events occurring during the trials. In conclusion, Cuban policosanol is a safe and effective natural drug for ischemic stroke treatment, which is supported by preclinical and clinical evidences.

Antiplatelet effects of the CEACAM1-derived peptide QDTT

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) restricts platelet activation via platelet collagen receptor GPVI/FcRγ-chain. In this study, screening against collagen-induced platelet aggregation was performed to identify functional CEACAM1 extracellular domain fragments. CEACAM1 fragments, including Ala-substituted peptides, were synthesized. Platelet assays were conducted on healthy donor samples for aggregation, cytotoxicity, adhesion, spreading, and secretion. Mice were used for tail bleeding and FeCl3-induced thrombosis experiments. Clot retraction was assessed using platelet-rich plasma. Extracellular segments of CEACAM1 and A1 domain-derived peptide QDTT were identified, while N, A2, and B domains showed no involvement. QDTT inhibited platelet aggregation. Ala substitution for essential amino acids (Asp139, Thr141, Tyr142, Trp144, and Trp145) in the QDTT sequence abrogated collagen-induced aggregation inhibition. QDTT also suppressed platelet secretion and “inside-out” GP IIb/IIIa activation by convulxin, along with inhibiting PI3K/Akt pathways. QDTT curtailed FeCl3-induced mesenteric thrombosis without significantly prolonging bleeding time, implying the potential of CEACAM1 A1 domain against platelet activation without raising bleeding risk, thus paving the way for novel antiplatelet drugs.

Enrichment of Whole-Grain Breads with Food-Grade Extracted Apple Pomace Bioactives Enhanced Their Anti-Inflammatory, Antithrombotic and Anti-Oxidant Functional Properties.

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.

Antiplatelet and Antithrombotic Activities of Lespedeza cuneata via Pharmacological Inhibition of Integrin αIIbβ3, MAPK, and PI3K/AKT Pathways and FeCl3-Induced Murine Thrombosis.

Cardiovascular diseases (CVDs) have been the major cause of mortality all around the globe. Lespedeza cuneata abbreviated as L. cuneata with the authority name of Dumont de Courset (G. Don) is a perennial flowering plant commonly grown in Asian countries such as Korea, Japan, China, and Taiwan. We aimed to investigate the L. cuneata extract's antiplatelet and antithrombotic properties as GC-MS analysis indicated that the extract contained short-chain fatty acids, which have been reported to possess beneficial cardiovascular effects. L. cuneata was extracted using water, 50% EtOH, 70% EtOH, and 100% EtOH. For in vitro antiplatelet analysis, washed platelets were prepared and incubated with L. cuneata with 200 μg/mL of 50% EtOH in the presence of 1 mM of CaCl2 for 1 minute followed by agonist (collagen 2.5 μg/mL or ADP 10 μM or thrombin 0.1 U/mL) stimulation for 5 minutes over light transmission aggregometer. Scanning electron microscopy was performed to assess platelet shape change. ATP release and intracellular calcium mobilization were quantified to assess the granular content. Fibrinogen-binding assay and clot retraction assay assessed integrin αIIbβ3-mediated inside-out and outside-in signaling. Protein phosphorylation expression was investigated by western blot analysis. Finally, the in vivo antithrombotic efficacy was investigated by oral dosage of L. cuneata 200 and 400 mg/kg and aspirin 100 mg/kg for 7 days, and tail bleeding and FeCl3-induced murine thrombus model were performed. In vitro platelet aggregation and platelet shape change were dose-dependently suppressed by L. cuneata. Calcium mobilization, dense granules secretion, integrin αIIbβ3-mediated inside-out and outside-in signaling, and protein phosphorylation of MAPK and PI3K/Akt pathways were significantly inhibited. In vivo assays revealed that L. cuneata prevents side effects of synthetic drugs via nonsignificantly increasing bleeding time and improving coronary artery blood flow and animal survival. Our results demonstrate that L. cuneata exhibited potent antiplatelet and antithrombotic effects and can be considered a potential herbal medicine with cardioprotective effects.

The protective effect and mechanism of piperazine ferulate in rats with 5/6 nephrectomy-caused chronic kidney disease.

Chronic kidney disease (CKD) is a type of chronic disease in which multiple factors are responsible for the structural and functional disorders of the kidney. Piperazine ferulate (PF) has anti-platelet and anti-fibrotic effects, and its mechanism of action remains to be elucidated. This study aimed to investigate the protective effect of PF against CKD in rats and to determine its mechanism of action. Network pharmacology was used to predict potential PF action targets in the treatment of CKD and to further validate them. A rat model of CKD was established; blood was collected, etc., for the assessment of the renal function; renal pathologic damage was examined using hematoxylin and eosin (HE) staining and Masson staining; changes in the levels of TGF-β1 and α-SMA were determined with ELISA; EPOR, FN, and COL I expression were detected utilizing immunohistochemistry; and HIF-1α, HIF-2α, and EPO protein molecules were analyzed deploying western blotting. PF reduces Scr, BUN, and 24h UP levels; decreases FN and COL I expression; and attenuates renal injury. Additionally, PF inhibited TGF-β1 and stimulated the production of HIF-1α and HIF-2α, which downregulated α-SMA and upregulated EPO. PF attenuated the progression of the CKD pathology, and the mechanism of its action is possibly associated with the promotion of HIF-1α/HIF-2α/EPO production and TGF-β1 reduction.

Ginkgetin effectively mitigates collagen and AA-induced platelet activation via PLCγ2 but not cyclic nucleotide-dependent pathway in human.

Platelets assume a pivotal role in the cardiovascular diseases (CVDs). Thus, targeting platelet activation is imperative for mitigating CVDs. Ginkgetin (GK), from Ginkgo biloba L, renowned for its anticancer and neuroprotective properties, remains unexplored concerning its impact on platelet activation, particularly in humans. In this investigation, we delved into the intricate mechanisms through which GK influences human platelets. At low concentrations (0.5-1 μM), GK exhibited robust inhibition of collagen and arachidonic acid (AA)-induced platelet aggregation. Intriguingly, thrombin and U46619 remained impervious to GK's influence. GK's modulatory effect extended to ATP release, P-selectin expression, intracellular calcium ([Ca2+ ]i) levels and thromboxane A2 formation. It significantly curtailed the activation of various signaling cascades, encompassing phospholipase Cγ2 (PLCγ2)/protein kinase C (PKC), phosphoinositide 3-kinase/Akt/glycogen synthase kinase-3β and mitogen-activated protein kinases. GK's antiplatelet effect was not reversed by SQ22536 (an adenylate cyclase inhibitor) or ODQ (a guanylate cyclase inhibitor), and GK had no effect on the phosphorylation of vasodilator-stimulated phosphoproteinSer157 or Ser239 . Moreover, neither cyclic AMP nor cyclic GMP levels were significantly increased after GK treatment. In mouse studies, GK notably extended occlusion time in mesenteric vessels, while sparing bleeding time. In conclusion, GK's profound impact on platelet activation, achieved through inhibiting PLCγ2-PKC cascade, culminates in the suppression of downstream signaling and, ultimately, the inhibition of platelet aggregation. These findings underscore the promising therapeutic potential of GK in the CVDs.

The Complement System and C4b-Binding Protein: A Focus onthe Promise of C4BPα as a Biomarker to Predict Clopidogrel Resistance.

The complement system plays a dual role in the body, either as a first-line defense barrier when balanced between activation and inhibition or as a potential driver of complement-associated injury or diseases when unbalanced or over-activated. C4b-binding protein (C4BP) was the first circulating complement regulatory protein identified and itfunctions as an important complement inhibitor. C4BP can suppress the over-activation of complement components and prevent the complement system from attacking the host cells through the binding of complement cleavage products C4b and C3b, working in concert as a cofactor for factor I in the degradation of C4b and C3b, and consequently preventing or reducing the assembly of C3 convertase and C5 convertase, respectively. C4BP, particularly C4BP α-chain (C4BPα), exerts its unique inhibitory effects on complement activation and opsonization, systemic inflammation, and platelet activation and aggregation. It has long been acknowledged that crosstalk or interplay exists between the complement system and platelets. Our unpublished preliminary data suggest that circulating C4BPα exerts its antiplatelet effects through inhibition of both complement activity levels and complement-induced platelet reactivity. Plasma C4BPα levels appear to be significantly higher in patients sensitive to, rather than resistant to, clopidogrel, and we suggest that a plasma C4BPα measurement could be used to predict clopidogrelresistance in the clinical settings.

Identification and validation of platelet-related diagnostic markers and potential drug screening in ischemic stroke by integrating comprehensive bioinformatics analysis and machine learning.

Ischemic stroke (IS), caused by blood and oxygen deprivation due to cerebral thrombosis, has links to activated and aggregated platelets. Discovering platelet-related biomarkers, developing diagnostic models, and screening antiplatelet drugs are crucial for IS diagnosis and treatment. Combining and normalizing GSE16561 and GSE22255 datasets identified 1,753 upregulated and 1,187 downregulated genes. Fifty-one genes in the platelet-related module were isolated using weighted gene co-expression network analysis (WGCNA) and other analyses, including 50 upregulated and one downregulated gene. Subsequent enrichment and network analyses resulted in 25 platelet-associated genes and six diagnostic markers for a risk assessment model. This model's area under the ROC curve outperformed single genes, and in the peripheral blood of the high-risk group, immune infiltration indicated a higher proportion of CD4, resting CD4 memory, and activated CD4 memory T cells, along with a lower proportion of CD8 T cells in comparison to the low-risk group. Utilizing the gene expression matrix and the CMap database, we identified two potential drugs for IS. Finally, a rat MACO/R model was used to validate the diagnostic markers' expression and the drugs' predicted anticoagulant effects. We identified six IS platelet-related biomarkers (APP, THBS1, F13A1, SRC, PPBP, and VCL) for a robust diagnostic model. The drugs alpha-linolenic acid and ciprofibrate have potential antiplatelet effects in IS. This study advances early IS diagnosis and treatment.

The Effect of Antiplatelet Therapy on COVID-19.

Platelets are one of the major targets of SARS-CoV-2. Activated platelets release prothrombotic substances, express adhesion molecules, and activate coagulation, thereby contributing to the thrombotic tendency in COVID-19. However, the antiplatelet therapy is not recommended in the current international guidelines. We think that the initiation timing and the target severity are the causes of the failure in clinical trials. As shown in the clinical studies that examined the effects of anticoagulants, early initiation in moderate severity is necessary for the success of antithrombotic therapy. Future trials are warranted to study the effects of antiplatelets in such conditions.

Evaluation of pharmacogenetic automated clinical decision support for clopidogrel.

Aim: Clopidogrel requires CYP2C19 activation to have antiplatelet effects. Pharmacogenetic testing to identify patients with impaired CYP2C19 function can be coupled with clinical decision support (CDS) alerts to guide antiplatelet prescribing. We evaluated the impact of alerts on clopidogrel prescribing.Materials & methods: We retrospectively analyzed data for 866 patients in which CYP2C19-clopidogrel CDS was deployed at a single healthcare system during 2015-2023.Results: Analyses included 2,288 alerts. CDS acceptance rates increased from 24% in 2015 to 63% in 2023 (p<0.05). Adjusted analyses also showed higher acceptance rates when clopidogrel had been ordered for a percutaneous intervention (OR: 28.7, p<0.001) and when cardiologists responded to alerts (OR: 2.11, p= 0.001).Conclusion: CDS for CYP2C19-clopidogrel was effective in reducing potential drug-gene interactions. Its influence varied by clinician specialty and medication indications.

"In Vitro Evaluation of the Antiplatelet Activity of Paravat Shakrita"

Platelet aggregation, a crucial process in thrombotic disorders, underscores the necessity for effective preventive and therapeutic measures. This study compares the antiplatelet effects of Aspirin, a well-established drug, with Paravat Shakrita, a lesser-known formulation from Ayurvedic texts. It underwent GCMS and microbiological analysis to determine its chemical composition and microbial load. Using an in vitro model with rat blood samples, we conducted a Platelet Aggregation Inhibition Assay. As expected, Aspirin inhibited platelet aggregation in a concentration-dependent manner, consistent with its known mechanism. Despite limited documentation, Paravat Shakrita exhibited potent antiplatelet properties, also showing dose-dependent effects. Interestingly, Paravat Shakrita demonstrated comparable or even superior effects at higher concentrations compared to Aspirin. The IC50 values revealed similar inhibitory potency between Paravat Shakrita and Aspirin. This comparison unveiled distinct mechanisms of action, providing various therapeutic options against platelet-mediated thrombosis. While promising, further investigation is crucial to understand Paravat Shakrita's mechanism, ensure its safety, and determine its clinical significance.

Omega-3 Fatty Acids Reduce Remnant-like Lipoprotein Cholesterol and Improve the Ankle-Brachial Index of Hemodialysis Patients with Dyslipidemia: A Pilot Study.

Background and Objectives: Omega-3 fatty acids have potent lipid-lowering and antiplatelet effects; however, randomized controlled trials have yet to examine the effect of high-dose omega-3 fatty acid administration on peripheral artery disease (PAD) in hemodialysis patients with dyslipidemia. Therefore, this study aimed to evaluate the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the ankle-brachial index (ABI) and remnant-like lipoprotein cholesterol (RLP-C) levels, which are indicators of PAD severity. Materials and Methods: Thirty-eight participants (mean age: 73.6 ± 12.7 years) were randomly assigned using stratified block randomization to either conventional therapy alone or conventional therapy supplemented with high-dose EPA/DHA (EPA: 1860 mg; DHA: 1500 mg) for a three-month intervention period. Patients in the conventional therapy alone group who opted to continue were provided with a low-dose EPA/DHA regimen (EPA: 930 mg; DHA: 750 mg) for an additional three months. The baseline and 3-month values for RLP-C, an atherogenic lipid parameter, and the ABI were recorded. Results: The results of the 3-month assessments revealed that the mean RLP-C changes were -3.25 ± 3.15 mg/dL and 0.44 ± 2.53 mg/dL in the EPA/DHA and control groups, respectively (p < 0.001), whereas the changes in the mean ABI values were 0.07 ± 0.11 and -0.02 ± 0.09 in the EPA/DHA and control groups, respectively (p = 0.007). In the EPA/DHA group, a significant negative correlation was found between the changes in RLP-C levels and the ABI (r = -0.475, p = 0.04). Additionally, the change in the RLP-C levels independently influenced the change in the ABI in the EPA/DHA group, even after adjusting for age, sex, and statin use (p = 0.042). Conclusions: Add-on EPA/DHA treatment improved the effectiveness of conventional therapy (such as statin treatment) for improving the ABI in hemodialysis patients with dyslipidemia by lowering RLP-C levels. Therefore, clinicians involved in dialysis should focus on RLP-C when considering residual cardiovascular disease risk in hemodialysis patients and should consider screening patients with elevated levels.

Analysis of Platelet Function Testing in Children Receiving Aspirin for Antiplatelet Effects.

Aspirin (ASA) remains the most common antiplatelet agent used in children. VerifyNow Aspirin Test® (VN) assesses platelet response to ASA, with therapeutic effect defined by the manufacturer as ≤ 549 aspirin reaction units (ARU). Single-center, observational, analysis of 195 children (< 18years-old) who underwent first VN between 2015 and 2020. Primary outcome was proportion of patients with ASA biochemical resistance (> 549 ARU). Secondary outcomes included incidence of new clinical thrombotic and bleeding events during ≤ 6months from VN in those who received ASA monotherapy (n = 113). Median age was 1.8years. Common indications for ASA included cardiac anomalies or dysfunction (74.8%) and ischemic stroke (22.6%). Median ASA dose before VN was 4.6mg/kg/day. Mean VN was 471 ARU. ASA biochemical resistance was detected in 14.4% (n = 28). Of 113 patients receiving ASA monotherapy, 14 (12.4%) had a thrombotic event and 2 (1.8%) had a bleeding event. Mean VN was significantly higher at initial testing in patients experiencing thrombotic event compared to those without thrombosis (516 vs 465 ARU, [95% CI: 9.8, 92.2], p = 0.02). Multivariable analysis identified initial VN ASA result ≥ 500 ARU at initial testing as the only significant independent risk factor for thrombosis (p < 0.01). VN testing identifies ASA biochemical resistance in 14.4% of children. VN ASA ≥ 500 ARU rather than ≥ 550 ARU at initial testing was independently associated with increased odds of thrombosis. Designated cut-off of 550 ARU for detecting platelet dysfunction by ASA may need reconsideration in children.

Oil from Mullet Roe Byproducts: Effect of Oil Extraction Method on Human Erythrocytes and Platelets.

Background: The valorization of byproducts to obtain high nutritional value foods is of utmost importance for our planet where the population is booming. Among these products are oils rich in ω-3 fatty acids produced from fishery byproducts. Recently, mullet roe oil from roe byproducts was produced that was rich in the ω-3 fatty acids eicosatetraenoic acid (EPA) and docosahexaenoic acid (DHA). Oils are customarily characterized for their composition and degree of oxidation but little is known of their biological effects, especially the effect of the extraction method. Methods: The purpose of this study was to evaluate the effects of freshly extracted mullet roe oil from mullet roe byproducts and the effect of the extraction method on human red blood cells (hRBCs) and platelets. To this end, the hemocompatibility (cytotoxicity), oxidative effects, and erythrocyte membrane changes were examined after 1 and 24 h of incubation. Antiplatelet effects were also assessed in vitro. Results: The expeller press oil extraction method and alcalase-assisted extraction produced the most biocompatible oils, as shown by hemocompatibility measurements and the absence of erythrocyte membrane alterations. Solvent extracts and protease-assisted extraction oils resulted in the rupture of red blood cells at different examined dilutions, creating hemolysis. Conclusions: It seems that the proper functioning of oil-erythrocyte interactions cannot be explained solely by ROS. Further investigations combining chemical analysis with oil-cell interactions could be used as an input to design high nutritional value oils using green extraction technologies. All samples exhibited promising antiplatelet and antiblood clotting effects in vitro.

Periprocedural antiplatelet medication assessed by VerifyNow for neuroendovascular treatment: Comparison of prasugrel with clopidogrel

Objective The maintenance dose of prasugrel (PRAS) for neuroendovascular treatment requires much research. We report the antiplatelet effect of PRAS measured by VerifyNow P2Y12 reaction units (PRUs) in patients during the perioperative period of neuroendovascular treatment. Methods Between January 2017 and January 2023, 230 patients who underwent endovascular treatment for unruptured intracranial aneurysms or carotid artery stenosis at our institution were retrospectively identified. Patients received dual antiplatelet therapy with 100 mg aspirin (ASA) and 75 mg clopidogrel (CLP)/day (CLP group, n = 186) or 100 mg ASA and 3.75 mg PRAS/day (PRAS group, n = 44) 2 weeks before the procedures. The PRU value was compared between the CLP and PRAS groups. In the study, we defined 95≦PRU &lt; 208 as the optimal range. Perioperative complications within seven days of surgery were also analyzed. Results The mean value of PRU was significantly low in the PRAS group (179.13 ± 66.03 in CLP vs. 154.75 ± 54.01 in PRAS, p = 0.024). The proportion of the patients who exhibited 95≦PRU &lt; 208 was significantly higher in the PRAS group (55.4% vs. 72.7%, p = 0.036). Ischemic and hemorrhagic complication rates were not significantly different between the CLP and PRAS groups (7.6% vs. 0%, p = 0.076; 4.7% vs. 0%, p = 0.361). The ischemic complication rate was higher in patients with a PRU &gt; 208 than in those with PRU &lt; 208 (12.5% vs. 3.8%, p = 0.044). The hemorrhagic complication rate was not significantly different between the PRU &lt; 95 and 95≦PRU groups (8.4% vs. 3.2%, p = 0.224). Conclusions Maintenance dose PRAS further decreased the PRU value and reached the optimal range in more cases than CLP during the perioperative period of neuroendovascular treatment. Ischemic complications significantly increased in the 208 &lt; PRU group.