-
Advances in Nutrition (Bethesda, Md.) Mar 2019Increased blood platelet activation, especially platelet aggregation, plays an important function in cardiovascular disease; however, various dietary components may... (Review)
Review
Increased blood platelet activation, especially platelet aggregation, plays an important function in cardiovascular disease; however, various dietary components may inhibit platelet activation. Recent clinical and epidemiologic studies indicate that both fruits and vegetables, and their products, contain various phytoprotective substances possessing biological properties such as antiplatelet and antioxidant effects that may work synergistically to ameliorate the effect of cardiovascular disease. In addition, the consumption of vegetables and their products may also play an important role in prevention. However, the mechanisms involved have not been clearly defined. Various studies clearly indicate that certain vegetables (e.g., onions, garlic, and tomatoes) have beneficial effects on blood platelet hyperactivity, an important cardiovascular risk factor, and hence may offer new prophylactic and therapeutic possibilities for the treatment of blood platelet hyperactivation and cardiovascular disease. This mini-review evaluates the current literature on the relationship between the consumption of onion (Allium cepa L.), garlic (Allium sativum L.), tomato (Solanum lycopersicum L.), and beetroot (Beta vulgaris L.), and blood platelet activation, which may have important implications for the prophylaxis and treatment of cardiovascular disease.
Topics: Beta vulgaris; Cardiovascular Diseases; Garlic; Humans; Solanum lycopersicum; Onions; Phytochemicals; Platelet Aggregation; Platelet Aggregation Inhibitors; Vegetables
PubMed: 30759176
DOI: 10.1093/advances/nmy085 -
International Journal of Molecular... Apr 2024The role of antiplatelet therapy in patients with acute coronary syndromes is a moving target with considerable novelty in the last few years. The pathophysiological... (Review)
Review
The role of antiplatelet therapy in patients with acute coronary syndromes is a moving target with considerable novelty in the last few years. The pathophysiological basis of the treatment depends on platelet biology and physiology, and the interplay between these aspects and clinical practice must guide the physician in determining the best therapeutic options for patients with acute coronary syndromes. In the present narrative review, we discuss the latest novelties in the antiplatelet therapy of patients with acute coronary syndromes. We start with a description of platelet biology and the role of the main platelet signal pathways involved in platelet aggregation during an acute coronary syndrome. Then, we present the latest evidence on the evaluation of platelet function, focusing on the strengths and weaknesses of each platelet's function test. We continue our review by describing the role of aspirin and P2Y12 inhibitors in the treatment of acute coronary syndromes, critically appraising the available evidence from clinical trials, and providing current international guidelines and recommendations. Finally, we describe alternative therapeutic regimens to standard dual antiplatelet therapy, in particular for patients at high bleeding risk. The aim of our review is to give a comprehensive representation of current data on antiplatelet therapy in patients with acute coronary syndromes that could be useful both for clinicians and basic science researchers to be up-to-date on this complex topic.
Topics: Humans; Acute Coronary Syndrome; Platelet Aggregation Inhibitors; Aspirin; Blood Platelets; Platelet Aggregation
PubMed: 38612792
DOI: 10.3390/ijms25073981 -
Current Pharmaceutical Design 2018Antiplatelet pharmacotherapy for endovascular interventions has been widely adopted, with clopidogrel being one of the most common agents prescribed. A fraction of... (Review)
Review
Antiplatelet pharmacotherapy for endovascular interventions has been widely adopted, with clopidogrel being one of the most common agents prescribed. A fraction of patients is resistant to clopidogrel resulting in decreased platelet inhibition despite adequate use. This finding is often termed high on-treatment platelet reactivity (HPR) and may lead to decreased patency in lower extremity arterial endovascular interventions. Current literature on HPR with lower extremity arterial endovascular interventions is limited to only a few studies. Resistance to clopidogrel is largely a result of CYP2C19 enzyme loss of function alleles. Several tests are available to measure clopidogrel resistance but light transmittance aggregometry remains the gold standard, yet direct genetic testing may be more reliable. One-year patency rates following lower extremity arterial endovascular interventions in patients with clopidogrel resistance (HPR) range between 35%-83% whereas those with the proper response to clopidogrel range between 73%-100%. Patients with decreased CYP2C19 activity show a significant decrease in one-year patency of endovascular femoropopliteal interventions (35% vs. 73%; p=0.006). Among patients tested for platelet function after in-stent thrombosis, up to 53% are resistant to clopidogrel. Lack of robust data limits our ability to predict patency in lower extremity arterial interventions for patients with HPR, but there is little doubt that longer patency seems to favor non-HPR patients. Large population, prospective trials are needed to guide our practice.
Topics: Clopidogrel; Drug Resistance; Endovascular Procedures; Humans; Lower Extremity; Peripheral Vascular Diseases; Platelet Aggregation; Platelet Aggregation Inhibitors
PubMed: 30621557
DOI: 10.2174/1381612825666190101111123 -
Bulletin of Experimental Biology and... May 2022We studied the effect of antiviral agent riamilovir on ADP-induced platelet aggregation in the absence and presence of LPS. Unlike acetylsalicylic acid (reference drug),...
We studied the effect of antiviral agent riamilovir on ADP-induced platelet aggregation in the absence and presence of LPS. Unlike acetylsalicylic acid (reference drug), riamilovir did not exhibit antiplatelet effect in vitro. However, it markedly suppressed platelet reactivity in LPS-treated blood samples and was 2.2-fold superior to acetylsalicylic acid in terms of IC value. In in vivo experiments, riamilovir under conditions of hypercytokinemia blocked platelet aggregation in rats by 64%.
Topics: Animals; Antiviral Agents; Aspirin; Blood Platelets; Lipopolysaccharides; Platelet Aggregation; Platelet Aggregation Inhibitors; Rats; Triazines; Triazoles
PubMed: 35616790
DOI: 10.1007/s10517-022-05489-0 -
Platelets 2019Previous genome-wide association studies (GWAS) have identified several variants associated with platelet function phenotypes; however, the proportion of variance... (Meta-Analysis)
Meta-Analysis
Previous genome-wide association studies (GWAS) have identified several variants associated with platelet function phenotypes; however, the proportion of variance explained by the identified variants is mostly small. Rare coding variants, particularly those with high potential for impact on protein structure/function, may have substantial impact on phenotype but are difficult to detect by GWAS. The main purpose of this study was to identify low frequency or rare variants associated with platelet function using genotype data from the Illumina HumanExome Bead Chip. Three family-based cohorts of European ancestry, including ~4,000 total subjects, comprised the discovery cohort and two independent cohorts, one of European and one of African American ancestry, were used for replication. Optical aggregometry in platelet-rich plasma was performed in all the discovery cohorts in response to adenosine diphosphate (ADP), epinephrine, and collagen. Meta-analyses were performed using both gene-based and single nucleotide variant association methods. The gene-based meta-analysis identified a significant association (P = 7.13 × 10) between rare genetic variants in ANKRD26 and ADP-induced platelet aggregation. One of the ANKRD26 SNVs - rs191015656, encoding a threonine to isoleucine substitution predicted to alter protein structure/function, was replicated in Europeans. Aggregation increases of ~20-50% were observed in heterozygotes in all cohorts. Novel genetic signals in ABCG1 and HCP5 were also associated with platelet aggregation to ADP in meta-analyses, although only results for HCP5 could be replicated. The SNV in HCP5 intersects epigenetic signatures in CD41+ megakaryocytes suggesting a new functional role in platelet biology for HCP5. This is the first study to use gene-based association methods from SNV array genotypes to identify rare variants related to platelet function. The molecular mechanisms and pathophysiological relevance for the identified genetic associations requires further study.
Topics: Adult; Exome; Female; Humans; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Nuclear Proteins; Platelet Aggregation
PubMed: 29185836
DOI: 10.1080/09537104.2017.1384538 -
Migfilin supports hemostasis and thrombosis through regulating platelet αIIbβ3 outside-in signaling.Haematologica Nov 2020Elucidating the regulation mechanism of integrin αIIbβ3 is key to understand platelet biology and thrombotic diseases. Previous in vitro studies have implicated a role...
Elucidating the regulation mechanism of integrin αIIbβ3 is key to understand platelet biology and thrombotic diseases. Previous in vitro studies have implicated a role of migfilin in the support of platelet αIIbβ3 activation, however, contribution of migfilin to thrombosis and hemostasis in vivo and a detailed mechanism of migfilin in platelets are not known. In this study, with migfilin deletion (migfilin-/-) mice, we report that migfilin is a pivotal positive regulator of hemostasis and thrombosis. Migfilin-/- mice showed a nearly doubled tail-bleeding time and a prolonged occlusion time in Fecl3-induced mesenteric arteriolar thrombosis. Migfilin deficiency impedes platelet thrombi formation on collagen surface and impairs platelet aggregation and dense-granule secretion. Supported by characteristic functional readings and phosphorylation status of distinctive signaling molecules in the bidirectional signaling processes of αIIbβ3, the functional defects of migfilin-/- platelets appear to be mechanistically associated with a compromised outside-in signaling, rather than inside-out signaling. A synthesized cell-permeable migfilin peptide harboring filamin A binding sequence rescued the defective function and phosphorylation of signaling molecules of migfilin-/- platelets. Finally, migfilin does not influence the binding of filamin A and β3 subunit of αIIbβ3 in resting platelets, but hampers the re-association of filamin A and β3 during the conduct of outside-in signaling, suggesting that migfilin functions through regulating the interaction dynamics of αIIbβ3 and filamin A in platelets. Our study enhances the current understanding of platelet integrin αIIbβ3-mediated outside-in signaling and proves that migfilin is an important regulator for platelet activation, hemostasis and thrombosis.
Topics: Animals; Blood Platelets; Hemostasis; Mice; Platelet Activation; Platelet Aggregation; Platelet Glycoprotein GPIIb-IIIa Complex; Thrombosis
PubMed: 33131250
DOI: 10.3324/haematol.2019.232488 -
The Journal of International Medical... Jul 2020To determine the multiple functions of policosanol in elderly dyslipidemia patients. There were 294 elderly dyslipidemia patients enrolled into this clinical study. They... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To determine the multiple functions of policosanol in elderly dyslipidemia patients. There were 294 elderly dyslipidemia patients enrolled into this clinical study. They were randomly divided into four groups, as follows: 20 mg policosanol (group A, n = 64); 10 mg policosanol (group B, n = 72); 20 mg atorvastatin (group C, n = 91); and 10 mg policosanol + 20 mg atorvastatin (group D, n = 62). Plasma platelet count, platelet aggregation rate, circulating endothelial cell (CEC) count, high sensitivity C-reactive protein (hs-CRP), and carotid intima-media thickness (IMT) were measured before the study (week 0) and at weeks 12, 24, and 52.
RESULTS
In group A, the platelet aggregation rate caused by adenosine diphosphate (ADP) after treatment was significantly decreased compared with before treatment (48.79% ± 20.29% vs. 40.37% ± 23.56%), but the arachidonic acid (AA)-induced platelet aggregation rates were similar. The platelet aggregation rates induced by AA and ADP in groups B, C, and D did not change significantly. CEC counts and hs-CRP and homocysteine levels in all groups after treatment were significantly lower compared with before treatment, but carotid IMTs were similar.
CONCLUSION
Policosanol regulates blood lipid levels and improves endothelial cell function, and it could delay the progress of atherosclerosis. ChiCTR-RRC-17013396 (retrospectively registered).
Topics: Aged; Carotid Intima-Media Thickness; Dyslipidemias; Fatty Alcohols; Humans; Platelet Aggregation
PubMed: 32703038
DOI: 10.1177/0300060520936082 -
Journal of Healthcare Engineering 2017Platelet hyperactivity plays an important role in arterial thrombosis and atherosclerosis. The present study was aimed to investigate the effects of different extracts...
Platelet hyperactivity plays an important role in arterial thrombosis and atherosclerosis. The present study was aimed to investigate the effects of different extracts of propolis and components of flavonoids on platelet aggregation. Platelet-rich plasma was prepared and incubated in vitro with different concentrations of the tested extracts and components of flavonoids. Platelets aggregation was induced by different agonists including adenosine diphosphate (ADP, 10 M), thrombin receptor activator peptide (TRAP, 50 M), and collagen (5 g/mL). At 25 mg/L to 300 mg/mL, the water extract propolis (WEP) inhibited three agonists-induced platelet aggregations in a dose-dependent manner. The flavonoids isolated from the propolis also showed markedly inhibited platelet aggregation induced by collagen, ADP, and TRAP, respectively. The components including caffeic acid phenethyl ester (CAPE), galangin, apigenin, quercetin, kaempferol, ferulic acid, rutin, chrysin, pinostrobin, and pinocembrin and their abilities of inhibiting platelet aggregation were studied. It was concluded that propolis had an antiplatelet action in which flavonoids were mainly implicated.
Topics: Coronary Artery Disease; Humans; Phytotherapy; Platelet Aggregation; Platelet Aggregation Inhibitors; Propolis; Trees
PubMed: 29129989
DOI: 10.1155/2017/3050895 -
Toxins Jul 2022Isoquinoline alkaloids have multiple biological activities, which might be associated with positive pharmacological effects as well as negative adverse reactions. As...
Isoquinoline alkaloids have multiple biological activities, which might be associated with positive pharmacological effects as well as negative adverse reactions. As bleeding was suggested to be a side effect of the isoquinoline alkaloid berberine, we decided to ascertain if different isoquinoline alkaloids could influence hemocoagulation through the inhibition of either platelet aggregation or blood coagulation. Initially, a total of 14 compounds were screened for antiplatelet activity in whole human blood by impedance aggregometry. Eight of them demonstrated an antiplatelet effect against arachidonic acid-induced aggregation. Papaverine and bulbocapnine were the most potent compounds with biologically relevant IC values of 26.9 ± 12.2 μM and 30.7 ± 5.4 μM, respectively. Further testing with the same approach confirmed their antiplatelet effects by employing the most physiologically relevant inducer of platelet aggregation, collagen, and demonstrated that bulbocapnine acted at the level of thromboxane receptors. None of the alkaloids tested had an effect on blood coagulation measured by a mechanical coagulometer. In conclusion, the observed antiplatelet effects of isoquinoline alkaloids were found mostly at quite high concentrations, which means that their clinical impact is most likely low. Bulbocapnine was an exception. It proved to be a promising antiplatelet molecule, which may have biologically relevant effects.
Topics: Alkaloids; Blood Platelets; Humans; Isoquinolines; Platelet Aggregation; Platelet Aggregation Inhibitors
PubMed: 35878229
DOI: 10.3390/toxins14070491 -
Clinical and Applied... 2019Platelet function (PF) plays a pivotal role in both hemostasis and thrombosis, and manual light transmission aggregometry (LTA) is considered the standard of care for...
Platelet function (PF) plays a pivotal role in both hemostasis and thrombosis, and manual light transmission aggregometry (LTA) is considered the standard of care for platelet function testing but is an error-prone and time-consuming procedure. We aimed to test the agreement regarding maximum aggregation (MA), velocity (VEL), and lag-phase (LagP) of platelet aggregation of the automated Sysmex CS-2100 analyzer (Siemens, Germany) against the APACT 4004 (Elitech, France) in samples derived from healthy participants and patients with hemostaseologic disorders. In total, 123 patient-derived samples were investigated, including 42 patients with acetylsalicylic acid and/or clopidogrel intake and 20 patients with other hemostaseologic disorders. Both MA and VEL showed good or excellent intermethod correlation. Agreement between the testing methods was only partially achieved, and values were indicative for a systematic bias to lower measurements below a threshold of 50% MA with the CS-2100 compared to the APACT 4004. All patients with impaired PF in the APACT 4004 were successfully identified with the CS-2100, and reference values for automated LTA are provided. Conclusively, automated LTA with the CS-2100 is a highly standardized and reliable PF testing method and represents a decisive step in the simplification of platelet function testing in clinical routine.
Topics: Blood Coagulation Tests; Female; Humans; Male; Platelet Aggregation; Platelet Function Tests
PubMed: 31773967
DOI: 10.1177/1076029619885184