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BMJ Open Apr 2022Ischaemic stroke is the leading cause of adult disability. Thus, a strategy based on an efficient antiplatelet therapy has been developed. The monitoring of antiplatelet...
INTRODUCTION
Ischaemic stroke is the leading cause of adult disability. Thus, a strategy based on an efficient antiplatelet therapy has been developed. The monitoring of antiplatelet therapy is now limited to high risk and poor prognosis patients. Indeed, the biological monitoring of the antiplatelet therapy with available platelet function assays do not provide a global integrative approach. Platelet transmission electron microscopy, recently validated for assessing distinct ultrastructural abnormalities is a reliable morphological platelet structural analysis tool which could be used to collect all the ultrastructural platelet characteristics and assess the degree of activation of platelets.
METHODS AND ANALYSIS
Our pilot prospective and descriptive study will include 50 consecutive patients hospitalized for an ischaemic stroke. We expect to identify ultrastructural characteristics that will be correlated with the degree of platelet activation to guide clinicians in decision making regarding the antiplatelet therapy strategy.
ETHICS AND DISSEMINATION
The French Ethics Committee (comité de protection des personnes d'Ile-de-France VII) approved the information notice that will be given to participants and the protocol of this trial (protocol No 21-031).The results of the trial will be disseminated through scientific publications.
TRIAL REGISTRATION NUMBER
NCT05004233.
Topics: Adult; Blood Platelets; Brain Ischemia; Humans; Microscopy, Electron, Transmission; Platelet Aggregation Inhibitors; Prospective Studies; Stroke
PubMed: 35379612
DOI: 10.1136/bmjopen-2021-050060 -
Journal of Vascular Surgery Dec 2009Atherothrombosis, characterized by atherosclerotic plaque rupture and subsequent occlusive or subocclusive thrombus formation is the primary cause of acute ischemic... (Review)
Review
Atherothrombosis, characterized by atherosclerotic plaque rupture and subsequent occlusive or subocclusive thrombus formation is the primary cause of acute ischemic syndromes involving all vascular beds and accounts for more than one-third of all deaths in the developed world. Platelet activation and aggregation constitute the most critical component in the pathophysiology of atherothrombotic disease. Aspirin is currently the most commonly used antiplatelet agent and one of the most frequently prescribed drugs, with as many as 30 million Americans on chronic aspirin regimens. Multiple well-designed prospective randomized clinical trials have demonstrated aspirin's efficacy in both primary and secondary prevention of a wide variety of entities that the atherothrombotic disease spectrum encompasses, such as cerebrovascular, coronary artery, and peripheral vascular disease. Despite its proven benefit, however, a growing body of evidence suggests that up to 70% of aspirin-takers may still be at risk for atherothrombotic complications due to resistance. Patients with laboratory-confirmed aspirin resistance seem to have an almost fourfold increase in their risk for acute thrombotic episodes, which underlines the magnitude of the problem for the vascular specialist. In this article, we review the physiology of platelet activation and the role of aspirin as an antiplatelet agent; the various laboratory assays used in assessing aspirin effectiveness; and current data on aspirin resistance and its clinical implications in patients with cardiovascular disease. We also review the studies that explore this phenomenon in patients with peripheral arterial disease and discuss the optimal management options in aspirin-resistant individuals. Suggestions are advanced for the direction of future trials evaluating aspirin resistance in patients with vascular disease.
Topics: Aspirin; Bleeding Time; Cardiovascular Diseases; Drug Resistance; Evidence-Based Medicine; Fibrinolytic Agents; History, 18th Century; History, 19th Century; History, 20th Century; History, Ancient; Humans; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Predictive Value of Tests; Vascular Surgical Procedures
PubMed: 19679423
DOI: 10.1016/j.jvs.2009.06.023 -
JACC. Cardiovascular Interventions Sep 2013
Topics: Cilostazol; Clopidogrel; Coronary Artery Disease; Drug-Eluting Stents; Female; Humans; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Tetrazoles; Ticlopidine
PubMed: 24050861
DOI: 10.1016/j.jcin.2013.06.006 -
British Journal of Pharmacology Feb 2010Platelet inhibitors are the mainstay treatment for patients with vascular diseases. The current 'gold standard' antiplatelet agent clopidogrel has several... (Review)
Review
Platelet inhibitors are the mainstay treatment for patients with vascular diseases. The current 'gold standard' antiplatelet agent clopidogrel has several pharmacological and clinical limitations that have prompted the search for more effective platelet antagonists. The candidates include various blockers of the purinergic P2Y12 receptor such as prasugrel, an oral irreversible thienopyridine; two adenosine triphosphate analogues that bind reversibly to the P2Y12 receptor: ticagrelor (oral) and cangrelor (intravenous); elinogrel, a direct-acting reversible P2Y12 receptor inhibitor (the only antiplatelet compound that can be administered both intravenously and orally); BX 667, an orally active and reversible small-molecule P2Y12 receptor antagonist; SCH 530348, SCH 205831, SCH 602539 and E5555, highly selective and orally active antagonists on the protease-activated receptor 1. A number of drugs also hit new targets: terutroban, an oral, selective and specific inhibitor of the thromboxane receptor; ARC1779, a second-generation, nuclease resistant aptamer which inhibits von Willebrand factor-dependent platelet aggregation; ALX-0081, a bivalent humanized nanobody targeting the GPIb binding site of von Willebrand factor and AJW200, an IgG4 monoclonal antibody of von Willebrand factor. The pharmacology and clinical profiles of new platelet antagonists indicate that they provide more consistent, more rapid and more potent platelet inhibition than agents currently used. Whether these potential advantages will translate into clinical advantages will require additional comparisons in properly powered, randomized, controlled trials.
Topics: Adenosine; Adenosine Monophosphate; Benzofurans; Blood Platelets; Carbamates; Clinical Trials as Topic; Clopidogrel; Humans; Lactones; Piperazines; Platelet Aggregation; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Pyridines; Receptor, PAR-1; Receptors, Proteinase-Activated; Thiophenes; Ticagrelor; Ticlopidine; von Willebrand Factor
PubMed: 20050853
DOI: 10.1111/j.1476-5381.2009.00555.x -
Nutrients Jan 2020Honey is a sweet, viscous syrup produced by the honey bee ( ). It is probably the first natural sweetener ever discovered, and is currently used as a nutritious food... (Review)
Review
Honey is a sweet, viscous syrup produced by the honey bee ( ). It is probably the first natural sweetener ever discovered, and is currently used as a nutritious food supplement and medicinal agent. The aim of the present mini-review is to summarize and update the current knowledge regarding the role of honey in CVDs based on various experimental models. It also describes the role of its phenolic compounds in treating CVDs. Many such phenolic and flavonoid compounds, including quercetin, kaempferol, apigenin, and caffeic acid, have antioxidant and anti-platelet potential, and hence may ameliorate cardiovascular diseases (CVDs) through various mechanisms, such as by decreasing oxidative stress and inhibiting blood platelet activation. However, as the phenolic content of a particular type of honey is not always known, it can be difficult to determine whether any observed effects on the human cardiovascular system may be associated with the consumption of honey or its constituents. Therefore, further experiments in this area are needed.
Topics: Antioxidants; Apitherapy; Cardiovascular Diseases; Cardiovascular System; Flavonoids; Honey; Humans; Oxidative Stress; Phenols; Platelet Aggregation Inhibitors
PubMed: 31973186
DOI: 10.3390/nu12020283 -
Haemostasis 2001Lebetins from Macrovipera lebetina snake venom constitute a new class of inhibitors of platelet aggregation. There are two groups of peptides: lebetin 1 (L1; 11- to... (Review)
Review
Lebetins from Macrovipera lebetina snake venom constitute a new class of inhibitors of platelet aggregation. There are two groups of peptides: lebetin 1 (L1; 11- to 13-mer) and lebetin 2 (L2; 37- to 38-mer). The short lebetins are identical to the N-terminal segments of the longer ones. They inhibit platelet aggregation induced by various agonists (e.g. thrombin, PAF-acether or collagen). The shortest lebetin (11-mer) shows potent inhibition of rabbit (IC(50) = 7 nM) and human (IC(50) = 5 nM) platelets. They prevent collagen-induced thrombocytopenia in rats. N- and C-terminal-truncated synthetic L1gamma (sL1gamma; 11-mer) is less active in inhibiting platelet aggregation than the native peptide. Results from Ala scan studies of the sL1gamma peptide indicated that replacement of the residues (P3, G7, P8, P9 or N10) resulted in a remarkable drop in the activity, whereas replacement of residues K2, P4 or K6 by Ala resulted in enhancement of the antiplatelet activity by at least 10-fold. To examine the activity of multimeric L1gamma, several multimeric peptides were synthesized using the multiple-antigen peptide system assembled on a branched lysine core and their antiplatelet activity was evaluated in vitro. The largest multimeric peptides showed a 1,000-fold increase in antiplatelet activity.
Topics: Animals; Blood Platelets; Humans; Platelet Aggregation Inhibitors; Structure-Activity Relationship; Thrombocytopenia; Viper Venoms
PubMed: 11910186
DOI: 10.1159/000048064 -
European Journal of Vascular and... Jul 2020Randomised trials of new devices for peripheral arterial endovascular intervention are published regularly. The evidence for which antiplatelet and/or anticoagulant...
Antiplatelet and Anticoagulant Use in Randomised Trials of Patients Undergoing Endovascular Intervention for Peripheral Arterial Disease: Systematic Review and Narrative Synthesis.
OBJECTIVE
Randomised trials of new devices for peripheral arterial endovascular intervention are published regularly. The evidence for which antiplatelet and/or anticoagulant (antithrombotic) therapy to use after an intervention is lacking. The aim of this systematic review was to examine the antithrombotic regimens in randomised trials for peripheral arterial endovascular intervention to understand choices made and trends with time or type of device.
METHODS
Data sources were the Medline, Embase, and Cochrane Library databases. Randomised trials including participants with peripheral arterial disease undergoing any endovascular arterial intervention were included. Trial methods were assessed to determine whether an antithrombotic protocol had been specified, its completeness, and the agent(s) prescribed. Antithrombotic therapy protocols were classed as peri-procedural (preceding and during intervention), immediate post-procedural (up to 30 days following intervention), and maintenance post-procedural (therapy continuing beyond 30 days).
RESULTS
Ninety-four trials were included in narrative synthesis. Study quality was low. None of the trials justified their antithrombotic therapy protocol. Only 29% of trials had complete peri-procedural antithrombotic protocols, and 34% had complete post-procedural protocols. In total, 64 different peri-procedural protocols, and 51 separate post-procedural protocols were specified. Antiplatelet monotherapy and unfractionated heparin were the most common regimen choices in the peri-procedural setting, and dual antiplatelet therapy (55%) was most commonly utilised post procedure. Over time there has been an increasing tendency to use dual therapy (p < .001). This corresponds with the introduction of newer technologies and trials focussed on below knee intervention.
CONCLUSION
Randomised trials comparing different types of peripheral endovascular arterial intervention have a high level of heterogeneity in their antithrombotic regimens. Antiplatelet therapy needs to be standardised in trials comparing endovascular technologies to reduce potential confounding. To do this, an independent randomised trial specifically examining antiplatelet therapy following peripheral arterial endovascular intervention is needed.
Topics: Anticoagulants; Endovascular Procedures; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic
PubMed: 32265113
DOI: 10.1016/j.ejvs.2020.03.010 -
Journal of Vascular Surgery Oct 2021The optimal antiplatelet regimen after lower extremity revascularization in patients with chronic limb-threatening ischemia (CLTI) is unknown because current... (Comparative Study)
Comparative Study
OBJECTIVE
The optimal antiplatelet regimen after lower extremity revascularization in patients with chronic limb-threatening ischemia (CLTI) is unknown because current recommendations are based on extrapolation of data from trials in coronary artery disease and stroke.
METHODS
We identified all patients undergoing an elective lower extremity revascularization for CLTI in the Vascular Quality Initiative registry discharged on a mono antiplatelet agent (MAPT) or dual antiplatelet therapy (DAPT).
RESULTS
From 2003 to 2018, 50,890 patients underwent revascularization procedures for CLTI, and were discharged on MAPT or DAPT. Of these, 33,781 patients underwent endovascular therapy (EVT), and 17,109 patients underwent open surgery (OS) procedures. The rate of major amputation at 30 days in the target limb in the EVT group was 0.3% and 0.4% in the OS group (P = .22). On Kaplan-Meier analyses, patients on MAPT at discharge had a higher risk of 1-year major amputation compared with DAPT after EVT but not after OS procedures. Patients on MAPT had lower overall survival and amputation-free survival at 30 days and 1 year compared with DAPT after both EVT and OS. At 1 year, the MAPT group was at higher risk for target lesion reintervention after EVT compared with the DAPT group (15.9% vs 13%; P = .0012). There was no significant difference in thrombosis at 1 year between the MAPT and DAPT groups either after EVT (3.9% vs 3.7%; P = .3048) or OS (3.1% vs 3.2%; P = .2893). On Cox regression analysis, DAPT was associated with improved survival but not major amputation after both EVT and OS.
CONCLUSIONS
In patients with CLTI, DAPT at the time of discharge has a positive impact on amputation-free survival and overall survival after both EVT and OS as well as target lesion reintervention after EVT. DAPT was not associated with a positive impact on major amputation after either EVT or OS.
Topics: Aged; Aged, 80 and over; Amputation, Surgical; Chronic Disease; Dual Anti-Platelet Therapy; Endovascular Procedures; Female; Humans; Ischemia; Limb Salvage; Lower Extremity; Male; Middle Aged; Patient Discharge; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Progression-Free Survival; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Vascular Surgical Procedures
PubMed: 34023428
DOI: 10.1016/j.jvs.2021.04.067 -
The American Journal of Case Reports Jan 2017BACKGROUND Dual antiplatelet therapy has proven efficacy in primary and secondary prevention of coronary artery disease with a relatively good safety profile. Review of... (Review)
Review
BACKGROUND Dual antiplatelet therapy has proven efficacy in primary and secondary prevention of coronary artery disease with a relatively good safety profile. Review of the literature revealed 8 cases of spontaneous retroperitoneal hematoma secondary to antiplatelet treatment. CASE REPORT We report the case of a 66-year-old male with a flare of acute gout secondary to uncontrolled chronic myeloid leukemia. The patient was started on dual antiplatelet treatment following a drug-eluted stent placement for symptomatic coronary artery disease. He suffered from an unexplained acute drop of five grams of hemoglobin from 10.4 to 5.8 g/dL and symptomatic anemia. The initial labs excluded occult GI bleeding, hemolysis, and bone marrow suppression. However, an abdominal CT scan showed an approximately 7.2×4.7×6.7 cm spontaneous retroperitoneal hematoma involving the left iliacus muscle. The patient was successfully treated conservatively by discontinuing antiplatelet therapy and supportive measures. CONCLUSIONS A spontaneous retroperitoneal hematoma often presents without localizing signs and symptoms and therefore should be considered in any case of unexplained blood loss in patients on antiplatelet therapy. CT without contrast is the modality of choice to diagnose retroperitoneal hematoma.
Topics: Aged; Coronary Artery Disease; Hematoma; Humans; Male; Platelet Aggregation Inhibitors; Retroperitoneal Space; Tomography, X-Ray Computed
PubMed: 28119516
DOI: 10.12659/ajcr.901622 -
International Journal of Molecular... Aug 2022Antiplatelet therapy aims to reduce the risk of thrombotic events while maintaining hemostasis. A promising current approach is the inhibition of platelet glycoprotein... (Review)
Review
Antiplatelet therapy aims to reduce the risk of thrombotic events while maintaining hemostasis. A promising current approach is the inhibition of platelet glycoprotein GPVI-mediated adhesion pathways; pathways that do not involve coagulation. GPVI is a signaling receptor integral for collagen-induced platelet activation and participates in the thrombus consolidation process, being a suitable target for thrombosis prevention. Considering this, the blocking or antibody-mediated depletion of GPVI is a promising antiplatelet therapy for the effective and safe treatment of thrombotic diseases without a significant risk of bleeding and impaired hemostatic plug formation. This review describes the current knowledge concerning pharmaceutical approaches to platelet GPVI modulation and its downstream signaling pathways in this context.
Topics: Blood Platelets; Humans; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Membrane Glycoproteins; Signal Transduction; Thrombosis
PubMed: 36077280
DOI: 10.3390/ijms23179882