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AbstractThis retrospective study analyzed the efficacy of combined antiplatelet therapy with Argatroban in treating acute ischemic stroke (AIS) and its impact on patients’ coagulation and neurological functions. Clinical data of 113 AIS patients admitted between January 2021 and January 2023 were retrospectively analyzed. Patients were divided into control (n = 56) and observation (n = 57) groups based on treatment interventions. The control group patients were treated with antiplatelet drugs, while the observation group patients received combination therapy with apatinib on the basis of the control group treatment. Compared to the control group, the observation group demonstrated higher clinical efficacy, improved coagulation parameters, reduced stroke severity (measured by NIHSS), enhanced daily living abilities (BI scores), and lowered inflammatory and neural injury markers post-treatment. Adverse reaction incidence was similar between groups. Combining Argatroban with antiplatelet drugs in AIS management showed superior efficacy without increasing adverse effects, suggesting its potential for clinical application. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is a pandemic syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 infection induces a process of inflammation and thrombosis supported by an altered platelet activation state. This platelet activation is peculiar being characterized by the formation of platelet-leukocytes rather than platelet–platelet aggregates and by an increased procoagulant potential supported by elevated levels of TF positive platelets and microvesicles. Therapeutic strategies targeting, beyond systemic inflammation (i.e. with tocilizumab, an anti interleukin-6 receptor), this state of platelet activation might therefore be beneficial. Among the antithrombotic drugs proposed as candidates to treat patients with SARS-CoV-2 infection, antiplatelet drugs, such as aspirin are showing promising results. [ABSTRACT FROM AUTHOR]

A variety of laboratory tests have been developed, which can diagnose a number of both congenital and acquired disorders of platelet function. Many tests of platelet function measure the ability of platelets to adhere to each other, forming platelet aggregates, which represent the major constituents of hemostatic plugs and of arterial thrombi. Light transmission aggregometry (LTA) is still considered the gold standard of platelet aggregation tests, but other platelet aggregation-based tests are also available. Among them, the flow cytometry-based methods may be more convenient than LTA for the study of patients with very low or very high platelet counts. The use of platelet aggregation tests has also been advocated to monitor the treatment with antiplatelet agents (mostly the P2Y12 antagonist clopidogrel) of patients with thrombotic arterial occlusions, with the aim of improving their efficacy and safety. However, randomized clinical trials failed to show any advantage of this strategy; as a consequence, international guidelines now recommend against laboratory monitoring of antiplatelet therapy. [ABSTRACT FROM AUTHOR]

To study the possibility of using thrombin generation tests in platelet-rich and platelet-poor plasma for evaluation of dual antiplatelet therapy efficacy in patients with coronary artery disease (CAD), following percutaneous coronary intervention. Venous blood was analyzed from CAD patients aged 53-75 years who had undergone percutaneous coronary intervention with stenting within one year and had been receiving standard doses of clopidogrel and aspirin (75 and 75-100 mg per day, respectively). The control group comprised age- and sex-matched subjects without clinical signs of CAD who were not receiving these drugs. Thrombin generation tests were performed in platelet-rich and platelet-poor plasma. Intravascular platelet activation, induced platelet aggregation, and routine coagulation were evaluated. Antiplatelet treatment did not influence results of routine coagulation tests or intravascular platelet activation. The dual antiplatelet therapy affects collagen-induced platelet aggregation (44 ± 2.5 vs. 7.9 ± 2.6%, p = 10-7) and leads to decreases in endogenous thrombin potential (1900 ± 85 vs. 1740 ± 95 nM•min, p = 0.0045), maximum thrombin concentration (134 ± 9.5 vs. 106 ± 6.5 nM, p = 4•10-6), and increases in time to peak thrombin (27 ± 1.5 vs. 31 ± 2 min, p = 0.0012). Decreases in thrombin generation rate showed the highest statistical significance (13 ± 2 vs. 7.9 ± 0.8 nM/min, p = 10-8). Antiplatelet treatment did not alter thrombogram parameters for platelet-poor plasma. [ABSTRACT FROM AUTHOR]

Rotatory thromboelastometry (ROTEM®) is used for diagnosing and monitoring bleeding patients. Some of these patients receive antithrombotic treatment, thus having an increased risk of bleeding. Only sparse knowledge exists about whether the ROTEM® analysis is influenced by antithrombotic treatment. The objective of the present study was to examine if the ROTEM® results are affected in patients receiving antithrombotic treatment. This prospective observational study included patients receiving either vitamin K-antagonists (VKA), aspirin (ASA) or ASA combined with an adenosine diphosphate (ADP) receptor antagonist (ASA + ADP). ROTEM® analyses were performed using the standard assays EXTEM®, INTEM® and FIBTEM®. Furthermore, haemoglobin, platelet count, International Normalized Ratio (INR), activated partial thromboplastin time, fibrinogen (functional), creatinine, estimated glomerular filtration rate, and C-reactive protein were determined. The study included 231 patients receiving antithrombotic treatment and compared the results to ROTEM® previously collected data from 73 healthy subjects. The VKA (n = 73) patients had a consistently prolonged EXTEM clot initiation (p < .0001), which was significantly correlated to the INR (Spearman's r = 0.53, p < .0001). Additionally, the VKA patients had significantly reduced clot propagation [reduced maximum velocity, maximum velocity (MaxVel) and increased time to maximum velocity (MaxVelt)]. ASA (n = 80) and ASA + ADP patients (n = 78) revealed a prolonged clot initiation. ASA patients had decreased clot propagation (increased MaxVelt), whereas ASA + ADP patients had an inconsistent change in clot propagation (increased MaxVel and MaxVelt). In conclusion, VKA treatment was revealed by the ROTEM® analysis. On the contrary, ASA and ASA + ADP treatment were not consistently revealed by the analysis. [ABSTRACT FROM AUTHOR]

Allergic reactions to clopidogrel soon after coronary stent implantation pose an important and challenging clinical problem. We describe a 44-year-old man who developed a diffuse maculopapular rash four days after initiation of clopidogrel with drug-eluting coronary stent placement. An initial treat-through strategy was unsuccessful due to patient intolerance to corticosteroids. Because of persistent hypersensitivity, clopidogrel was substituted with prasugrel which was continued successfully for one year without reaction. A systematic review of the literature was performed which identified 10 prior case reports of patients with clopidogrel hypersensitivity who were subsequently treated with prasugrel. Patient characteristics and clinical outcomes of these patients plus the current case were reviewed. There were 9 men and 2 women with ages from 44 to 76 years. All patients had undergone coronary stent procedures. Prasugrel was successfully used without cross-reactivity in 9 of the 11 patients (82%). Cross-reactivity was reported in two patients who developed hypersensitivity reactions to prasugrel similar to those experienced on clopidogrel. In conclusion, prasugrel can be used successfully in most patients with a history of clopidogrel hypersensitivity. However, potential cross-reactivity between these two thienopyridines may occur in some patients. [ABSTRACT FROM AUTHOR]

Dual antiplatelet therapy with aspirin and clopidogrel is commonly used to prevent recurrent ischemic events in patients with cardiovascular disease. Whilst their effects on platelet reactivity are well documented, it is unclear, however, whether antiplatelet therapy inhibits platelet extracellular vesicle (EV) release. The aim of this study was to investigate the effects of antiplatelet therapy on platelet EV formation and procoagulant activity. Blood samples from 10 healthy controls not receiving antiplatelet therapy were incubated in vitro with aspirin or a P2Y12 inhibitor (MeSAMP). Blood samples from 50 patients receiving long-term dual antiplatelet therapy and undergoing coronary angiography were also studied. Platelet reactivity was assessed by Multiplate™ impedance aggregometry. Platelet EV formation and procoagulant activity of pretreated and untreated blood samples in response to arachidonic acid (AA), adenosine diphosphate (ADP), ADP+PGE1, and thrombin receptor-activating peptide (TRAP) stimulation were assessed by flow cytometry and Procoag-PL assays, respectively. Incubation of normal platelets with aspirin significantly inhibited AA-induced platelet reactivity, EV formation, and procoagulant activity, whilst MeSAMP significantly inhibited platelet reactivity and EV formation in response to AA, ADP, and TRAP, but had minimal effect on procoagulant activity. Most patients receiving dual antiplatelet therapy showed an appropriate reduction in platelet reactivity in response to their treatment; however there was not complete inhibition of increased platelet and EV procoagulant activity in response to ADP, AA, or TRAP. In addition, we could not find any correlation between platelet reactivity and procoagulant activity in patients receiving dual antiplatelet therapy. [ABSTRACT FROM AUTHOR]

Introduction: Unwanted platelet activation is associated with numerous diseases, mainly thrombosis-related. In this context, proteomics has emerged as a novel tool with potential for drug target discovery and to scrutinize the effects of antiplatelet drugs. Areas covered: The present review presents the main findings of platelet proteomic studies to date in the context of drug target discovery and perspectives for the future ahead. It includes data and evidences obtained from literature searches on PubMed as well as commentaries derived from the authors’ experience and opinions. Expert commentary: Platelet proteomics applied to drug target discovery is a young field. Recent studies have shown promising data, especially in the context of coronary artery disease. However, challenges remain such as establishing definitive guidelines for blood collection and platelet isolation, essential to guarantee data reproducibility. Recent advances in quantitative platelet proteomics should lead to novel studies with higher clinical impact in the near future. [ABSTRACT FROM PUBLISHER]

Background. Comatose survivors after cardiac arrest are treated with mild induced hypothermia and potent platelet- inhibiting drugs after coronary stenting. Previous studies have shown an increased incidence of stent thrombosis during clopidogrel and aspirin treatment in conjunction with induced hypothermia. The aim of this study was to investigate the in vitro effect of induced hypo- and hyperthermia on blood from patients undergoing ticagrelor- and aspirin-mediated platelet inhibition. Methods. Whole blood from 15 patients with acute coronary syndrome who were treated with ticagrelor and aspirin and from eight healthy volunteers was incubated for 1 hour at 28, 33, 37, and 39°C. Results. In blood from patients with acute coronary syndrome, the activated clotting time (Sonoclot) was prolonged in mild hypothermic (33°C) compared to normothermic (37°C) samples. Sonoclot, clotting rate and platelet function were decreased in hypothermic compared to normothermic samples. Platelet-induced activation and aggregation (Multiplate®) was unchanged in mild hypothermic compared to normothermic samples. In contrast, mild hypothermia supported increased platelet activation as measured with flow cytometry with up-regulation of PAC-1 and P-selectin on the platelet surface. Conclusion. In acute coronary syndrome patients treated with ticagrelor and aspirin, in vitro hypothermia to 33°C markedly increased platelet activity measured with flow cytometry, whereas viscoelastic coagulation test (Sonoclot) revealed a hypocoagulative response. Prospective clinical trials studying platelet inhibition at different temperatures and correlating changes in platelet function to bleeding or stent occlusion are needed. [ABSTRACT FROM AUTHOR]

Dual antiplatelet therapy consisting of clopidogrel in addition to aspirin has previously been the standard of care for patients with acute coronary syndromes (ACS) but international guidelines have been evolving over the last 4 years with the introduction of prasugrel and ticagrelor. In October 2009, prasugrel was approved in the UK by the National Institute of Health and Clinical Excellence (NICE) for use in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), diabetic patients with non-ST-elevation (NSTE) ACS undergoing PCI and patients with stent thrombosis while other ACS patients were to continue receiving clopidogrel. Ticagrelor was approved in October 2011 by NICE for use in patients with moderate-to-high risk NSTE ACS and STEMI undergoing primary PCI and was recommended in preference to clopidogrel in European guidelines. These recommendations were adopted in our region, constituting a population of 1.8 million. We studied the effect of changing patterns of P2Y12 inhibitor usage on levels of platelet inhibition during maintenance therapy. Patients admitted to Northern General Hospital, Sheffield, with NSTE ACS or STEMI managed with primary PCI were enrolled over two periods of time: May 2010 to November 2011 (T1); and October 2012 to February 2013 (T2). Venous blood samples were obtained at 1 month after the onset of ACS. Light transmittance aggregometry (LTA) was performed and maximum aggregation response to ADP 20 μM was determined. A total of 116 patients were enrolled in T1 of whom 82 were receiving clopidogrel and 34 were receiving prasugrel. Twenty-nine patients were enrolled in T2, all of whom were receiving ticagrelor. Mean LTA results according to treatment with clopidogrel, prasugrel and ticagrelor were 57 ± 18%, 41 ± 20%, and 31 ± 12%, respectively. Prasugrel was associated with significantly lower platelet aggregation responses than clopidogrel ( p < 0.001) and ticagrelor was associated with significantly lower platelet aggregation responses than both prasugrel ( p = 0.015) and clopidogrel ( p < 0.001). We conclude that international guidelines and NICE approval have led to increasing levels of P2Y12 inhibition in ACS patients in this UK centre between May 2010 and February 2013. Ticagrelor was associated with significantly greater P2Y12 inhibition than both clopidogrel and prasugrel during maintenance therapy. [ABSTRACT FROM AUTHOR]

Monitoring of platelet ADP receptor P2Y12 inhibition may be performed by a variety of platelet function assays. Given the lack of sensitivity of the existing PFA-100® cartridge formulations to detect P2Y12 inhibition, a new cartridge for the PFA-100 (INNOVANCE® PFA P2Y) has recently been developed. The performance of the new PFA-100 test cartridge was compared with standard collagen/ADP (CADP) and collagen/epinephrine (CEPI) cartridges, light transmission aggregometry, vasodilator-stimulated phosphoprotein, the VerifyNow® P2Y12 assay and multiple electrode aggregometry. In this study, 20 normal blood samples anticoagulated with either citrate or hirudin were spiked with two different clinically relevant concentrations (1 and 10 µM final concentration) of the prasugrel active metabolite (R-138727, Lilly/Daiichi Sankyo) for 30 min at 37°C. Comparison of the platelet function tests demonstrated that all tests (except CADP and CEPI) were substantially inhibited by 10 µM R-138727. Intermediate results were typically obtained with 1 µM R-138727 in citrated blood. However, both MEA ADP and ADPHS tests were highly sensitive to 1 µM R-138727 in hirudin anticoagulated blood. Further comparison of citrate or hirudin blood samples ( N == 5) revealed that all platelet tests (except CEPI) became more sensitive to 1 µM R-138727 in hirudinized blood. The INNOVANCE PFA P2Y cartridge proved to be sensitive to P2Y12 inhibition and was comparable to other currently available platelet function tests. The sensitivity of all platelet function tests for detecting in vitro inhibition of P2Y12 is markedly different depending on the anticoagulant used. [ABSTRACT FROM AUTHOR]

We describe herein the discovery of ( E)- N-methyl- N'-((5-nitrofuran-2-yl)methylene)benzo[ d]1,3 dioxole-5-carbohydrazide ( 9e), named LASSBio-1215, as a novel antiplatelet agent belonging to the N-methyl- N-acylhydrazone class, which exert their antiaggregating actions on human and rabbit platelets induced by different agonists, through cyclooxygenase-1 (COX-1) or thromboxane synthase inhibition. This compound was elected after screening of a series of functionalized furyl N-acylhydrazone derivatives, synthesized from natural safrole 10. I n vitro assays showed that compound 9e presents platelet-aggregating activity in rabbit platelet-rich plasma (PRP) induced by arachidonic acid (IC50 == 0.7 µM) and collagen (IC50 == 4.5 µM). Moreover, LASSBio-1215 also inhibited almost completely the second wave of adenosine diphosphate-induced platelet aggregation in human PRP, and this effect was correlated with their ability to block the production of pro-aggregating autacoid thromboxane A2. [ABSTRACT FROM AUTHOR]

Inhibition of platelet aggregation is indispensable for the treatment of acute arterial thrombotic episodes. We have previously reported the synthesis of a highly constrained cyclic peptide, that incorporates the -CDC- sequence, (S,S) PSRCDCR-NH2, which potently inhibits aggregation and fibrinogen binding to human platelets in  vitro. We have tested the safety and efficacy of the peptide on the electrically induced carotid artery thrombosis experimental rabbit model. The peptide's effects on carotid blood flow, thrombus weight, in  vitro and ex vivo platelet aggregation, and bleeding and hemostatic parameters were evaluated. The peptide was administered via the femoral vein. Carotid blood flow was continuously monitored for 90 min after electrical thrombus formation. The peptide, at 12 mg/kg, prevented total artery occlusion and significantly preserved carotid artery's patency compared with placebo and eptifibatide. Furthermore, (S,S) PSRCDCR-NH2 administration at 12 mg/kg reduced thrombus weight, whereas it inhibited ex vivo ADP, arachidonic acid (AA) and collagen-induced platelet aggregation. Moreover (S,S) PSRCDCR-NH2 at 12 mg/kg presented significantly higher inhibitory effects on AA and collagen-induced ex vivo platelet aggregation compared to eptifibatide. The peptide at any dose did not affect the coagulation cascade, the bleeding times or the hemostatic response of the animals. Thus highly constrained cyclic peptides like (S,S) PSRCDCR-NH2 that incorporate the -CDC- motif and fulfil certain conformational criteria represent novel compounds that potently inhibit thrombus formation, ex vivo platelet aggregation and carotid artery occlusion superiorly to other non-RGD peptides, such as YMESRADR, without causing hemorrhagic complications in a rabbit model of arterial thrombosis. [ABSTRACT FROM AUTHOR]

Patients with diabetes mellitus (DM) and coronary artery disease, particularly those presenting with acute coronary syndromes (ACS), have a higher risk of developing ischemic complications than their nondiabetic counterparts. Although ACS patients with DM benefit more than normoglycemic ACS patients from early coronary angiography and revascularization, they remain at a higher risk of complications following percutaneous coronary intervention and bypass surgery. The DM-associated prothrombotic state has been implicated in the pathogenesis of these complications and growing data supports the notion that potent platelet inhibition is of paramount importance in order to optimize outcomes of DM patients presenting with ACS. This article focuses on the evidence supporting the concept that augmented platelet reactivity and impaired responsiveness to oral antiplatelet agents are influential drivers of the increased propensity of DM patients with ACS to develop thrombotic complications. In particular, strategies to enhance platelet P2Y12 receptor inhibition, a key factor to improve outcomes in this patient population, are reviewed. INSETS: Diabetes mellitus and the risk of late thrombosis …;Defining resistance and treatment failure for …;Intravenous anti-thrombotic therapy in diabetes mellitus.;Key issues [ABSTRACT FROM AUTHOR]

Statins confer an antiplatelet effect in hypercholesterolemic subjects and in stable coronary artery disease patients. We explored the antiplatelet effects of statins in ST-elevation myocardial infarction (STEMI) patients undergoing primary angioplasty. Of 120 STEMI patients, 80 (67%%) received statins while 40 (33%%) did not. Ex vivo platelet reactivity was studied on admission and 72 hours later by conventional aggregometry and under flow conditions (Impact R). Measures of platelet reactivity under flow conditions included aggregate size and surface coverage, signifying platelet aggregation and adhesion respectively. The effect of statins on platelet function under flow conditions and platelet aggregation was studied in  vitro in platelets from 10 STEMI patients. Platelets from each patient were incubated in  vitro with lovastatin or PBS as a control. The effect of lovastatin in the presence of a nitric oxide synthase inhibitor (L-NMMA) was also studied. Patients treated with statins were compared with those who did not have significantly lower ADP-induced platelet aggregation on the 4th day (56 ±± 18%% vs. 64 ±± 17%%, p == 0.02). Platelet deposition under flow conditions as measured by surface coverage was reduced from admission to 72 hours later among statin-treated patients (19 ±± 28%% reduction, p < 0.01), but was unchanged in non-treated patients (for comparison p < 0.01). The extent of platelet inhibition was unrelated to patient characteristics, including lipid profile and type of statin administered (lipophylic vs. hydrophilic). In the in  vitro study platelet incubation with statin compared with PBS resulted in a lower aggregate-size (29 ±± 9 µµm2 vs. 39 ±± 15 µµm2, p < 0.01), and lower surface coverage (8.5 ±± 4%% vs. 12 ±± 4%%, p < 0.01). The effect of the statin on both parameters was significantly blunted by L-NMMA. Incubation with statin also resulted in a reduction in collagen-induced platelet aggregation (31 ±± 20%% vs. 54 ±± 25%%, p < 0.01). We concluded that in acute myocardial infarction patients, statins have an early antiplatelet effect, in addition to that afforded by standard antiplatelet therapy. [ABSTRACT FROM AUTHOR]

ADP plays an important role in hemostasis and thrombosis. The P2Y12 receptor, activated by ADP, plays a central role in platelet activation and thrombus formation. Thus, the P2Y12 receptor has been an effective target for antithrombotic drugs. [ABSTRACT FROM AUTHOR]

Atherothrombotic events, such as acute coronary syndrome or stroke, are the result of platelet activation. Von Willebrand factor (vWF), a multimeric glycoprotein, plays a key role in aggregation of platelets, especially under high-shear conditions. Acting as bridging element or ligand between damaged endothelial sites and the glycoprotein Ib (GPIb) receptor on platelets, vWF is responsible for platelet adhesion and aggregation. This vWF activation and further platelet aggregation mainly occurs under high shear stress present in small arterioles or during deficiency of the vWF-cleaving protease ADAMTS13. There are several substances targeting vWF itself or its binding receptor GPIb on platelets. Two antibodies are directed against vWF: AJW200, an IgG4 humanized monoclonal antibody, and 82D6A3, a monoclonal antibody of the collagenbinding A-3 domain of vWF. ALX-0081 and ALX-0681 are bivalent humanized nanobodies targeting the GPIb binding site of vWF. Aptamers are oligonucleotides with drug-like properties that share some of the attributes of monoclonal antibodies. ARC1779 is a second-generation, nuclease-resistant aptamer, binding to the activated vWF A1 domain and ARC15105 is a chemically advanced follower with an assumed higher affinity to vWF. Antibodies targeting GPIba are h6B4-Fab, a murine monoclonal antibody; GPG-290, a recombinant, chimeric protein containing the amino-terminal 290 amino acids of GPIba linked to human IgG1 Fc; and the monoclonal antibody SZ2. There are a number of promising preclinical results and development of some agents (AJW 200, ARC1779 and ALX-0081) has already reached Phase II trials. INSET: Key issues. [ABSTRACT FROM AUTHOR]

Receptors for prostanoids on platelets include the EP3 receptor for which the natural agonist is the inflammatory mediator prostaglandin E2 (PGE2) produced in atherosclerotic plaques. EP3 is implicated in atherothrombosis and an EP3 antagonist might provide atherosclerotic lesion-specific antithrombotic therapy. DG-041 (2,3-dichlorothiophene-5-sulfonic acid, 3-[1-(2,4-dichlorobenzyl)-5-fluoro-3-methyl-1H-indol-7-yl]acryloylamide) is a direct-acting EP3 antagonist currently being evaluated in Phase 2 clinical trials. We have examined the contributions of EP3 to platelet function using the selective EP3 agonist sulprostone and also PGE2, and determined the effects of DG-041 on these. Studies were in human platelet-rich plasma or whole blood and included aggregometry and flow cytometry. Sulprostone enhanced aggregation induced by primary agonists including collagen, TRAP, platelet activating factor, U46619, serotonin and adenosine diphosphate, and enhanced P-selectin expression and platelet-leukocyte conjugate formation. It inhibited adenylate cyclase (measured by vasodilator-stimulated phosphoprotein phosphorylation) and enhanced Ca2+ mobilization. It potentiated platelet function even in the presence of aspirin and/or AR-C69931 (a P2Y12 antagonist). DG-041 antagonized the effects of sulprostone on platelet function. The effect of PGE2 on platelet aggregation depended on the nature of the agonist and the concentration of PGE2 used as a consequence of both pro-aggregatory effects via EP3 and anti-aggregatory effects via other receptors. DG-041 potentiated the protective effects of PGE2 on platelet aggregation by inhibiting the pro-aggregatory effect via EP3 stimulation. DG-041 remained effective in the presence of a P2Y12 antagonist and aspirin. DG-041 warrants continued investigation as a potential agent for the treatment of atherothrombosis without inducing unwanted bleeding risk. [ABSTRACT FROM AUTHOR]

One hundred twenty-seven years after Professor Giulio Bizzozero described the blood particle that has come to be known as the platelet, antiplatelet therapy has revolutionized the treatment of cardiovascular disease. Platelet function testing, introduced in 1962 with the advent of Born's aggregometer, heralded a renaissance in platelet research and provided a platelet function test to study platelet reactivity in vitro to help the diagnosis of bleeding disorders. More devices to test platelet function have emerged since, and these are now being applied mainly to assess antiplatelet drug efficacy in thrombotic disorders. Although this may be a logical use for platelet function tests, the data are replete with contradictions, and there is a lack of both consensus and standardization of the methodology. As a result, the clinical validity of platelet function results to monitor response to antiplatelet drugs has yet to be established. [ABSTRACT FROM AUTHOR]

Dual antiplatelet treatment with aspirin and clopidogrel is recommended after coronary stenting (PCI-S). There is scant evidence defining optimal post-PCI-S antithrombotic therapy in patients with atrial fibrillation (AF) in whom oral anticoagulation (OAC) is mandated. To evaluate the safety and efficacy of the antithrombotic strategies for this population, we conducted a systematic review of the available evidence in patients treated with OAC undergoing PCI-S. AF was the most frequent indication for OAC. Post-PCI-S management was highly variable, and triple therapy with warfarin, aspirin, and clopidogrel was the most frequent and effective combination. Warfarin plus aspirin alone was not sufficiently effective in the early period after PCI-S and should not be prescribed. While acknowledging that the optimal antithrombotic treatment for patients with AF at medium or high thromboembolic risk undergoing PCI-S is currently undefined, triple therapy of warfarin, aspirin, and clopidogrel is currently recommended, although associated with an increased risk of major bleeding. Restrictive use of drug-eluting stent is also recommended, due to the need for prolonged multiple-drug antithrombotic therapy which may increase the bleeding risk. Whether the combination of warfarin and clopidogrel (without aspirin) will preserve efficacy and produce less bleeding is an important issue still needing to be addressed. [ABSTRACT FROM AUTHOR]

Aspirin (acetylsalicylic acid) is one of the main therapeutic medications used in the prevention of thromboembolic vascular events. Aspirin exhibits its antiplatelet action by irreversibly inhibiting platelet cyclooxygenase-1 enzyme, thus preventing the production of thromboxane A2 (TXA2). Aspirin resistance, as measured in vitro, is the inability of aspirin to reduce platelet activation and aggregation by failure to suppress the platelet production of TXA2. Laboratory tests of platelet TXA2 production or platelet function dependent on TXA2 can detect aspirin resistance in vitro. The clinical implication of this laboratory definition has not yet been elucidated via prospective trials that have controlled for confounders, such as hypertension, diabetes and dyslipidemia. Large meta-analyses have found low-dose aspirin to be as effective as high-dose aspirin in preventing vascular events, making a dose-dependent improvement in laboratory response clinically irrelevant. Possible causes of aspirin resistance include poor compliance, inadequate dose, drug interactions, genetic polymorphisms of cyclooxygenase-1, increased platelet turnover and upregulation of nonplatelet pathways of thromboxane production. However, there is currently no standardized approach to the diagnosis and no proven effective treatment for aspirin resistance. Further research exploring the mechanisms of aspirin resistance is needed in order to better define aspirin resistance, as well as to develop a standardized laboratory test that is specific and reliable, and can correlate with the clinical risk of vascular events. The intent of this paper is to review the literature discussing possible mechanisms, diagnostic testing and clinical trials of aspirin resistance and to discuss its clinical relevance as it pertains to cerebrovascular and cardiovascular disease. [ABSTRACT FROM AUTHOR]

Antiplatelet therapy has been established as a preventive medicine for ischemic cardiovascular diseases both at acute and chronic phases. This therapy is also crucial for the prevention of thrombotic events after coronary stent implantation. So far, many lines of clinical evidence have demonstrated the beneficial effects of aspirin (an irreversible cyclooxygenase inhibitor) and thienopyridine derivatives (adenosine diphosphate (ADP)‐receptor P2Y 12 inhibitors). Recently, it has been reported that the cardiovascular risk is elevated in patients with platelets resistant to these drugs, compared to the good responders. One of the current problems to be solved in antiplatelet therapy is to find out patients resistant to the antiplatelet therapy and improve its preventive effects. In addition to aspirin and thienopyridines, several types of drugs with antiplatelet effects are currently available in clinical practice. Clinical evidence has recently been accumulating for these drugs that can be potential alternatives in patients with aspirin or thienopyridine resistance. In this review, the mechanisms, evidence and approach to the present problems of drugs with antiplatelet effects are discussed. [ABSTRACT FROM AUTHOR]