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Analytical and Bioanalytical Chemistry Jan 2022Antiplatelet and anticoagulant drugs are classified antithrombotic agents with the purpose to reduce blood clot formation. For a successful treatment of many known...
Antiplatelet and anticoagulant drugs are classified antithrombotic agents with the purpose to reduce blood clot formation. For a successful treatment of many known complex cardiovascular diseases driven by platelet and/or coagulation activity, the need of more than one antithrombotic agent is inevitable. However, combining drugs with different mechanisms of action enhances risk of bleeding. Dual anticoagulant and antiplatelet (APAC), a novel semisynthetic antithrombotic molecule, provides both anticoagulant and antiplatelet properties in preclinical studies. APAC is entering clinical studies with this new exciting approach to manage cardiovascular diseases. For a better understanding of the biological function of APAC, comprehensive knowledge of its structure is essential. In this study, atomic force microscopy (AFM) was used to characterize APAC according to its structure and to investigate the molecular interaction of APAC with von Willebrand factor (VWF), since specific binding of APAC to VWF could reduce platelet accumulation at vascular injury sites. By the optimization of drop-casting experiments, we were able to determine the volume of an individual APAC molecule at around 600 nm, and confirm that APAC forms multimers, especially dimers and trimers under the experimental conditions. By studying the drop-casting behavior of APAC and VWF individually, we depictured their interaction by using an indirect approach. Moreover, in vitro and in vivo conducted experiments in pigs supported the AFM results further. Finally, the successful adsorption of APAC to a flat gold surface was confirmed by using photothermal-induced resonance, whereby attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) served as a reference method.
Topics: Anticoagulants; Heparin; Humans; Microscopy, Atomic Force; Platelet Aggregation Inhibitors; Proteoglycans; Spectroscopy, Fourier Transform Infrared
PubMed: 34773471
DOI: 10.1007/s00216-021-03765-y -
Clinical Medicine (London, England) Apr 2016Platelets play a very important role in physiological haemostasis and thrombus formation. Platelet aggregation is the key pathophysiological factor in the development of... (Review)
Review
Platelets play a very important role in physiological haemostasis and thrombus formation. Platelet aggregation is the key pathophysiological factor in the development of arterial ischaemic events, including coronary artery disease, cerebrovascular accidents and peripheral arterial disease. As such, antiplatelet therapy plays a very important role in preventing recurrent events in the individuals who are affected by one of these conditions. Until recently, the repertoire of antiplatelet therapy was limited to aspirin and clopidogrel. However, this landscape has changed dramatically with the advent of newer and more potent agents, prasugrel and ticagrelor and also the glycoprotein IIb/IIIa antagonists. This armamentarium is likely to expand further with the advent of protease-activated receptor-1 antagonists and the intravenous cangrelor. This review summarises the different agents available and some practical considerations for their use from a general physician's perspective.
Topics: Adenosine; Clopidogrel; General Practitioners; Humans; Platelet Aggregation Inhibitors; Ticagrelor; Ticlopidine
PubMed: 27037385
DOI: 10.7861/clinmedicine.16-2-152 -
Pharmacology Research & Perspectives Dec 2020Clopidogrel is the most common and widely used antiplatelet agent for patients with coronary artery disease following confirmation by electrocardiographic studies. The... (Review)
Review
Clopidogrel is the most common and widely used antiplatelet agent for patients with coronary artery disease following confirmation by electrocardiographic studies. The nonresponsiveness of patients to clopidogrel and the possibility of testing for clopidogrel resistance by platelet function assays (PFA) are contentious issues. Light transmission aggregometry (LTA) is considered as the gold standard test among all PFA. In this review, the most commonly used PFA used for monitoring the effect of clopidogrel, LTA, vasodilator-stimulated phosphoprotein assay phosphorylation, rotational thromboelastometry (ROTEM) delta and ROTEM platelet, thromboelastography, PFA-100, VerifyNow P2Y12 assay, Multiplate analyzer, Plateletworks assay and pharmacogenetic studies, are comparatively discussed including their principles of action, advantages, and disadvantages. VerifyNow P2Y12 assay can be accepted as the ideal point of care test out of the discussed assays. However, modified assays are required which could overcome the limitations associated with currently available assays.
Topics: Animals; Clopidogrel; Drug Monitoring; Humans; Pharmacogenetics; Pharmacogenomic Testing; Platelet Aggregation Inhibitors; Platelet Function Tests; Point-of-Care Systems; Thrombelastography
PubMed: 33200888
DOI: 10.1002/prp2.686 -
The American Journal of Cardiology Feb 1995The choice of antithrombotic agent in cerebral ischemia depends on the pathogenesis: thrombosis, embolism, or hemorrhage. Antiplatelet agents are considered most... (Review)
Review
The choice of antithrombotic agent in cerebral ischemia depends on the pathogenesis: thrombosis, embolism, or hemorrhage. Antiplatelet agents are considered most beneficial in thrombotic stroke, anticoagulants are most effective in cardioembolic stroke; antithrombotic agents are generally contraindicated in hemorrhagic stroke. A meta-analysis of 18 trials documented a 23% reduction in stroke risk with antiplatelet agents; aspirin is typically the antiplatelet agent of choice for stroke prevention. There are no definitive data regarding the optimal aspirin dose for stroke prevention and this issue remains controversial. Ticlopidine is the most effective antiplatelet agent, but its adverse effect profile restricts its use. Anticoagulants are highly effective for preventing cardioembolic stroke, but their effectiveness in non-cardioembolic stroke is uncertain because of lack of trial data. Results of the ongoing Warfarin/Aspirin Recurrent Stroke Study (warfarin [INR 1.8-2.8] vs aspirin [325 mg/day]) may clarify this issue. There is renewed interest in thrombolytics because recent data indicate that reperfusion within a few hours of stroke onset appears to be effective in preventing neuronal damage. In addition, when given within 6 hours of stroke onset, thrombolytics appear to be relatively safe. Several direct thrombin inhibitors are being evaluated. Experimentally, hirudin, hirulog, D-Phe-L-Pro-L-Arg-CH2Cl (PPACK), and argatroban are clearly more effective than heparin in inhibiting platelet deposition and thrombus formation, and also show promise in preventing reocclusion after thrombolysis for both experimental thrombotic and embolic stroke. However, the risk of hemorrhage in patients with cerebrovascular disease is unknown for these agents.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Anticoagulants; Antithrombins; Brain Ischemia; Fibrinolytic Agents; Humans; Platelet Aggregation Inhibitors
PubMed: 7863971
DOI: 10.1016/0002-9149(95)80008-g -
Blood Dec 2012Perioperative management of antithrombotic therapy is a situation that occurs frequently and requires consideration of the patient, the procedure, and an expanding array... (Review)
Review
Perioperative management of antithrombotic therapy is a situation that occurs frequently and requires consideration of the patient, the procedure, and an expanding array of anticoagulant and antiplatelet agents. Preoperative assessment must address each patient's risk for thromboembolic events balanced against the risk for perioperative bleeding. Procedures can be separated into those with a low bleeding risk, which generally do not require complete reversal of the antithrombotic therapy, and those associated with an intermediate or high bleeding risk. For patients who are receiving warfarin who need interruption of the anticoagulant, consideration must be given to whether simply withholding the anticoagulant is the optimal approach or whether a perioperative "bridge" with an alternative agent, typically a low-molecular-weight heparin, should be used. The new oral anticoagulants dabigatran and rivaroxaban have shorter effective half-lives, but they introduce other concerns for perioperative management, including prolonged drug effect in patients with renal insufficiency, limited experience with clinical laboratory testing to confirm lack of residual anticoagulant effect, and lack of a reversal agent. Antiplatelet agents must also be considered in the perioperative setting, with particular consideration given to the potential risk for thrombotic complications in patients with coronary artery stents who have antiplatelet therapy withheld.
Topics: Anticoagulants; Humans; Perioperative Care; Platelet Aggregation Inhibitors; Risk Assessment; Risk Factors; Surgical Procedures, Operative; Thrombosis
PubMed: 22855600
DOI: 10.1182/blood-2012-05-423228 -
British Journal of Pharmacology Jan 2006
Review
Topics: Animals; Aspirin; Clinical Trials as Topic; Dipyridamole; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Thrombosis
PubMed: 16402110
DOI: 10.1038/sj.bjp.0706401 -
Clinical Journal of the American... Aug 2009Patients with end stage renal disease (ESRD) are often prescribed antiplatelet medications. However, these patients are also at increased risk of bleeding compared with... (Review)
Review
BACKGROUND AND OBJECTIVES
Patients with end stage renal disease (ESRD) are often prescribed antiplatelet medications. However, these patients are also at increased risk of bleeding compared with the general population, and an aim was made to quantify this risk with antiplatelet agents.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
A systematic review of the literature (Medline, EMBASE, Cochrane CENTRAL and Google Scholar databases) was done to determine the bleeding risk in ESRD patients prescribed antiplatelet therapy. The secondary outcome was the effect on access thrombosis. All case series, cohort studies and clinical trials were considered if they included ten or more ESRD patients, assessed bleeding risk with antiplatelet agents, and lasted for more than 3 mo.
RESULTS
Sixteen studies, including 40,676 patients, were identified that met predefined inclusion criteria. Due to study heterogeneity and weaknesses in methodology, bleeding rates were not pooled across studies. However, the bleeding risk appears to be increased for hemodialysis patients treated with combination antiplatelet therapy. The results are mixed for studies using a single antiplatelet agent. Antiplatelet agents appear to be effective in preventing shunt and central venous catheter thrombosis, but not for preventing thrombosis of arteriovenous grafts.
CONCLUSION
The risks and benefits of antiplatelet agents in ESRD patients remain poorly defined. Until a clinical trial addresses this in the dialysis population, individual risk stratification taking into account the increased risk of bleeding should be considered before initiating antiplatelet agents, especially in combination therapy.
Topics: Arteriovenous Shunt, Surgical; Blood Vessel Prosthesis Implantation; Catheterization, Central Venous; Drug Therapy, Combination; Hemorrhage; Humans; Kidney Failure, Chronic; Platelet Aggregation Inhibitors; Renal Dialysis; Risk Assessment; Thrombosis; Treatment Outcome
PubMed: 19578002
DOI: 10.2215/CJN.00810209 -
Antiplatelet and Anticoagulant Activities of Angelica shikokiana Extract and Its Isolated Compounds.Clinical and Applied... Jan 2017Angelica shikokiana is a Japanese medicinal plant that is used traditionally in several ailments of cardiovascular diseases. However, there is no report regarding its...
Angelica shikokiana is a Japanese medicinal plant that is used traditionally in several ailments of cardiovascular diseases. However, there is no report regarding its anticoagulant or antiplatelet activities. So this study was designed to screen for such activities (anticoagulant by prothrombin time [PT], activated partial thromboplastin time, and thrombin time assays and antiplatelet activities against adenosine 5'-diphosphate [ADP] and arachidonic acid-induced platelet aggregations) for the methanol extract of the aerial part (Angelica methanol extract [AME]), its isolated coumarins, flavonoids, and flavonoid metabolites. The AME had potent anticoagulant and antiplatelet activities, and the flavonoid compounds were evidenced to be responsible for such activities. Among coumarins compounds, hyuganin C showed significant prolongation of only PT, while other coumarins were inactive. Similarly, hyuganin C and bergapten were the only active coumarins against ADP-induced platelet aggregation. Compared to the parent compounds, colonic metabolites of the flavonoids had similar anticoagulant and antiplatelet activities, while glucuronides showed sharp decreases in all studied activities. This is the first report showing that the medicinal plant A shikokiana has potent antiplatelet and anticoagulant activities.
Topics: Adolescent; Adult; Angelica; Anticoagulants; Biological Products; Hemostasis; Humans; Plant Extracts; Platelet Aggregation Inhibitors; Young Adult
PubMed: 26177661
DOI: 10.1177/1076029615595879 -
American Family Physician Apr 2011All patients with stable coronary artery disease require medical therapy to prevent disease progression and recurrent cardiovascular events. Three classes of medication... (Review)
Review
All patients with stable coronary artery disease require medical therapy to prevent disease progression and recurrent cardiovascular events. Three classes of medication are essential to therapy: lipid-lowering, antihypertensive, and antiplatelet agents. Lipid-lowering therapy is necessary to decrease low-density lipoprotein cholesterol to a target level of less than 100 mg per dL, and physicians should consider a goal of less than 70 mg per dL for very high-risk patients. Statins have demonstrated clear benefits in morbidity and mortality in the secondary prevention of coronary artery disease; other medications that can be used in addition to statins to lower cholesterol include ezetimibe, fibrates, and nicotinic acid. Blood pressure therapy for patients with coronary artery disease should start with beta blockers and angiotensin-converting enzyme inhibitors. If these medications are not tolerated, calcium channel blockers or angiotensin receptor blockers are acceptable alternatives. Aspirin is the first-line antiplatelet agent except in patients who have recently had a myocardial infarction or undergone stent placement, in which case clopidogrel is recommended. Anginal symptoms of coronary artery disease can be treated with beta blockers, calcium channel blockers, nitrates, or any combination of these. Familiarity with these medications and with the evidence supporting their use is essential to reducing morbidity and mortality in patients with coronary artery disease.
Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Arterial Pressure; Calcium Channel Blockers; Clinical Protocols; Coronary Artery Disease; Humans; Hypolipidemic Agents; Lipid Metabolism; Lipoproteins, LDL; Medication Therapy Management; Outcome Assessment, Health Care; Platelet Aggregation; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Risk Reduction Behavior; Secondary Prevention; Survival Analysis; Treatment Outcome
PubMed: 21524048
DOI: No ID Found -
Clinical and Applied... Feb 2011Antiplatelet drugs are important components in the management of atherothrombotic vascular disease. However, several limitations restrict the safety and efficacy of... (Review)
Review
Antiplatelet drugs are important components in the management of atherothrombotic vascular disease. However, several limitations restrict the safety and efficacy of current antiplatelet therapy in clinical practice. Interpatient variability and resistance to aspirin and/or clopidogrel has spurred efforts for the development of novel agents. Indeed, several antiplatelet drugs are at various stages of evaluation; those at advanced stage of development are the focus of this review.
Topics: Animals; Drug Hypersensitivity; Humans; Platelet Aggregation Inhibitors; Thrombosis
PubMed: 21078606
DOI: 10.1177/1076029610385222