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Seminars in Thrombosis and Hemostasis Sep 2023Platelets play a key role in maintaining normal hemostasis and are also recognized as partners in the development of arterial thrombosis. Today, platelet function... (Review)
Review
Platelets play a key role in maintaining normal hemostasis and are also recognized as partners in the development of arterial thrombosis. Today, platelet function testing is used for very different clinical purposes; first, for investigation of platelet dysfunction in acute bleeding and diagnosis of platelet disorders in patients with long-lasting bleeding tendency, and second, for testing the efficacy of antiplatelet therapy in patients with increased thromboembolic risk. Moreover, it has been discussed whether platelet function testing can be used for prediction of bleeding risk (e.g., prior to major surgery). Ever since light transmission aggregometry was introduced, laboratories around the world have worked on testing platelet function, and during the last decades a wide range of new methods has emerged. Besides the clinical utility of platelet function testing, the present review summarizes the test principles and advantages and disadvantages of the different methods, depending on the purpose for which it is to be used. A critical step in investigation of platelet function is the preanalytical factors that can substantially affect test results. Therefore, this review also provides an overview of preanalytical variables that range from patient-related factors such as smoking, coffee, and exercise prior to blood sampling to selection of anticoagulant, needle gauge, and time from blood sampling to analyses. Finally, this review outlines further perspectives on platelet function testing for clinical practice and for research purposes.
Topics: Humans; Platelet Aggregation; Blood Platelets; Hemostasis; Platelet Function Tests; Blood Coagulation Disorders; Blood Platelet Disorders; Platelet Aggregation Inhibitors
PubMed: 36384230
DOI: 10.1055/s-0042-1757898 -
Clinical Pharmacokinetics May 2023Antiplatelet agents are among the most frequently used medications in cardiovascular medicine. Although in patients with atherosclerotic disease manifestations, in... (Review)
Review
Antiplatelet agents are among the most frequently used medications in cardiovascular medicine. Although in patients with atherosclerotic disease manifestations, in particular those treated by percutaneous coronary intervention, antiplatelet agents are beneficial for the prevention of ischemic events, they inevitably increase the risk of bleeding. Furthermore, 5-15% of patients treated by percutaneous coronary intervention may need a surgical procedure within 2 years, creating challenges to safe and effective antiplatelet drug management. Importantly, major spontaneous or procedural-related bleedings are associated with increased hospital admission, length, costs, and poor prognosis. Although the effects of other antithrombotic therapies, such as direct oral anticoagulants, can be reversed by approved specific agents, there are no approved reversal agents for any antiplatelet drugs. The fact that many antiplatelet agents, such as aspirin and thienopyridines (i.e., clopidogrel and prasugrel), bind irreversibly to their targets represents a challenge for the development of a drug-specific reversal agent. In contrast, ticagrelor is a non-thienopyridine with a plasma half-life of 7-9 h that reversely binds the P2Y receptor producing potent signaling blockage. In 2015, bentracimab (also known as PB2452 or MEDI2452), a neutralizing monoclonal antibody fragment that binds free plasma ticagrelor and its major active metabolite, was identified. This systematic overview provides a comprehensive summary of the drug development program of bentracimab, focusing on its pharmacodynamic, pharmacokinetic, and safety profiles.
Topics: Humans; Acute Coronary Syndrome; Antibodies, Monoclonal; Clopidogrel; Hemorrhage; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor
PubMed: 37118383
DOI: 10.1007/s40262-023-01245-3 -
Journal of the American College of... Jun 2024
Topics: Humans; Platelet Aggregation Inhibitors; Percutaneous Coronary Intervention
PubMed: 38897673
DOI: 10.1016/j.jacc.2024.04.035 -
The Cochrane Database of Systematic... Feb 2022Antiplatelet agents are widely used to prevent cardiovascular events. The risks and benefits of antiplatelet agents may be different in people with chronic kidney... (Review)
Review
BACKGROUND
Antiplatelet agents are widely used to prevent cardiovascular events. The risks and benefits of antiplatelet agents may be different in people with chronic kidney disease (CKD) for whom occlusive atherosclerotic events are less prevalent, and bleeding hazards might be increased. This is an update of a review first published in 2013.
OBJECTIVES
To evaluate the benefits and harms of antiplatelet agents in people with any form of CKD, including those with CKD not receiving renal replacement therapy, patients receiving any form of dialysis, and kidney transplant recipients.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 13 July 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
We selected randomised controlled trials of any antiplatelet agents versus placebo or no treatment, or direct head-to-head antiplatelet agent studies in people with CKD. Studies were included if they enrolled participants with CKD, or included people in broader at-risk populations in which data for subgroups with CKD could be disaggregated.
DATA COLLECTION AND ANALYSIS
Four authors independently extracted data from primary study reports and any available supplementary information for study population, interventions, outcomes, and risks of bias. Risk ratios (RR) and 95% confidence intervals (CI) were calculated from numbers of events and numbers of participants at risk which were extracted from each included study. The reported RRs were extracted where crude event rates were not provided. Data were pooled using the random-effects model. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
We included 113 studies, enrolling 51,959 participants; 90 studies (40,597 CKD participants) compared an antiplatelet agent with placebo or no treatment, and 29 studies (11,805 CKD participants) directly compared one antiplatelet agent with another. Fifty-six new studies were added to this 2021 update. Seven studies originally excluded from the 2013 review were included, although they had a follow-up lower than two months. Random sequence generation and allocation concealment were at low risk of bias in 16 and 22 studies, respectively. Sixty-four studies reported low-risk methods for blinding of participants and investigators; outcome assessment was blinded in 41 studies. Forty-one studies were at low risk of attrition bias, 50 studies were at low risk of selective reporting bias, and 57 studies were at low risk of other potential sources of bias. Compared to placebo or no treatment, antiplatelet agents probably reduces myocardial infarction (18 studies, 15,289 participants: RR 0.88, 95% CI 0.79 to 0.99, I² = 0%; moderate certainty). Antiplatelet agents has uncertain effects on fatal or nonfatal stroke (12 studies, 10.382 participants: RR 1.01, 95% CI 0.64 to 1.59, I² = 37%; very low certainty) and may have little or no effect on death from any cause (35 studies, 18,241 participants: RR 0.94, 95 % CI 0.84 to 1.06, I² = 14%; low certainty). Antiplatelet therapy probably increases major bleeding in people with CKD and those treated with haemodialysis (HD) (29 studies, 16,194 participants: RR 1.35, 95% CI 1.10 to 1.65, I² = 12%; moderate certainty). In addition, antiplatelet therapy may increase minor bleeding in people with CKD and those treated with HD (21 studies, 13,218 participants: RR 1.55, 95% CI 1.27 to 1.90, I² = 58%; low certainty). Antiplatelet treatment may reduce early dialysis vascular access thrombosis (8 studies, 1525 participants) RR 0.52, 95% CI 0.38 to 0.70; low certainty). Antiplatelet agents may reduce doubling of serum creatinine in CKD (3 studies, 217 participants: RR 0.39, 95% CI 0.17 to 0.86, I² = 8%; low certainty). The treatment effects of antiplatelet agents on stroke, cardiovascular death, kidney failure, kidney transplant graft loss, transplant rejection, creatinine clearance, proteinuria, dialysis access failure, loss of primary unassisted patency, failure to attain suitability for dialysis, need of intervention and cardiovascular hospitalisation were uncertain. Limited data were available for direct head-to-head comparisons of antiplatelet drugs, including prasugrel, ticagrelor, different doses of clopidogrel, abciximab, defibrotide, sarpogrelate and beraprost.
AUTHORS' CONCLUSIONS
Antiplatelet agents probably reduced myocardial infarction and increased major bleeding, but do not appear to reduce all-cause and cardiovascular death among people with CKD and those treated with dialysis. The treatment effects of antiplatelet agents compared with each other are uncertain.
Topics: Humans; Platelet Aggregation Inhibitors; Proteinuria; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 35224730
DOI: 10.1002/14651858.CD008834.pub4 -
Cardiovascular Drugs and Therapy Feb 2023In addition to the key role in hemostasis and thrombosis, platelets have also been wildly acknowledged as immune regulatory cells and involving in the pathogenesis of... (Review)
Review
In addition to the key role in hemostasis and thrombosis, platelets have also been wildly acknowledged as immune regulatory cells and involving in the pathogenesis of inflammation-related diseases. Since purine receptor P2Y12 plays a crucial role in platelet activation, P2Y12 antagonists such as clopidogrel, prasugrel, and ticagrelor have been widely used in cardiovascular diseases worldwide in recent decades due to their potent antiplatelet and antithrombotic effects. Meanwhile, the role of P2Y12 in inflammatory diseases has also been extensively studied. Relatively, there are few studies on the regulation of P2Y12. This review first summarizes the various roles of P2Y12 in the process of platelet activation, as well as downstream effects and signaling pathways; then introduces the effects of P2Y12 in inflammatory diseases such as sepsis, atherosclerosis, cancer, autoimmune diseases, and asthma; and finally reviews the current researches on P2Y12 regulation.
Topics: Blood Platelets; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Clopidogrel; Ticagrelor; Prasugrel Hydrochloride; Receptors, Purinergic P2Y12
PubMed: 34319489
DOI: 10.1007/s10557-021-07229-4 -
Current Cardiology Reports Mar 2022The optimal antithrombotic strategy in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) remains the subject of controversy. In... (Review)
Review
PURPOSE OF REVIEW
The optimal antithrombotic strategy in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) remains the subject of controversy. In this article, we review the current evidence for the use of triple therapy in acute coronary syndrome (ACS) patients.
RECENT FINDINGS
The recently published trials of AF patients undergoing PCI have shown that combination of non-vitamin K oral anticoagulants (NOACs) with an antiplatelet agent is either superior or non-inferior to vitamin K antagonist (VKA) plus dual antiplatelet therapy (DAPT) in reducing bleeding complications with no difference in regard to thromboembolic events. Currently, the use of dual therapy (preferably with a NOAC and clopidogrel) is recommended over triple therapy in these patients. The optimal duration should be guided by the assessment of an individual's risk of thrombosis and bleeding events.
Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Atrial Fibrillation; Drug Therapy, Combination; Fibrinolytic Agents; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors
PubMed: 35112242
DOI: 10.1007/s11886-022-01634-3 -
International Journal of Molecular... Dec 2021Over the last decades, antiplatelet agents, mainly aspirin and P2Y receptor antagonists, have significantly reduced morbidity and mortality associated with arterial... (Review)
Review
Over the last decades, antiplatelet agents, mainly aspirin and P2Y receptor antagonists, have significantly reduced morbidity and mortality associated with arterial thrombosis. Their pharmacological characteristics, including pharmacokinetic/pharmacodynamics profiles, have been extensively studied, and a significant number of clinical trials assessing their efficacy and safety in various clinical settings have established antithrombotic efficacy. Notwithstanding, antiplatelet agents carry an inherent risk of bleeding. Given that bleeding is associated with adverse cardiovascular outcomes and mortality, there is an unmet clinical need to develop novel antiplatelet therapies that inhibit thrombosis while maintaining hemostasis. In this review, we present the currently available antiplatelet agents, with a particular focus on their targets, pharmacological characteristics, and patterns of use. We will further discuss the novel antiplatelet therapies in the pipeline, with the goal of improved clinical outcomes among patients with atherothrombotic diseases.
Topics: Cardiovascular Diseases; Humans; Platelet Aggregation Inhibitors
PubMed: 34884884
DOI: 10.3390/ijms222313079 -
Clinical Obstetrics and Gynecology Mar 2023Increasing rates of thromboembolic complications have required increasing use of anticoagulant and antiplatelet agents during and after pregnancy. Furthermore,... (Review)
Review
Increasing rates of thromboembolic complications have required increasing use of anticoagulant and antiplatelet agents during and after pregnancy. Furthermore, thromboembolism is both a cause and a complication of severe maternal morbidity requiring intensive care. As a consequence, almost all patients admitted to intensive care units receive an anticoagulant or an antiplatelet agent (or both) for either treatment or prevention of thromboembolism. In this review, we summarize commonly used anticoagulants and antiplatelet agents and outline the potential role of newly developed (novel) antithrombotic agents for pregnant and postpartum patients.
Topics: Pregnancy; Female; Humans; Platelet Aggregation Inhibitors; Anticoagulants; Fibrinolytic Agents; Thromboembolism
PubMed: 36044626
DOI: 10.1097/GRF.0000000000000740 -
International Journal of Molecular... Mar 2021Lipids play an essential role in platelet functions. It is known that polyunsaturated fatty acids play a role in increasing platelet reactivity and that the... (Review)
Review
Lipids play an essential role in platelet functions. It is known that polyunsaturated fatty acids play a role in increasing platelet reactivity and that the prothrombotic phenotype plays a crucial role in the occurrence of major adverse cardiovascular events. The ongoing increase in cardiovascular diseases' incidence emphasizes the importance of research linking lipids and platelet function. In particular, the rebound phenomenon that accompanies discontinuation of clopidogrel in patients receiving dual antiplatelet therapy has been associated with changes in the lipid profile. Our many years of research underline the importance of reduced HDL values for the risk of such a rebound effect and the occurrence of thromboembolic events. Lipids are otherwise a heterogeneous group of molecules, and their signaling molecules are not deposited but formed "on-demand" in the cell. On the other hand, exosomes transmit lipid signals between cells, and the profile of such changes can be monitored by lipidomics. Changes in the lipid profile are organ-specific and may indicate new drug action targets.
Topics: Animals; Blood Platelets; Humans; Lipid Metabolism; Lipids; Lipoproteins, HDL; Platelet Aggregation; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists
PubMed: 33804754
DOI: 10.3390/ijms22063180 -
Platelets Jan 2021Von Willebrand factor has a pivotal role in primary hemostasis. Its role in thrombotic microangiopathies (TMA), as well as cardiovascular disease, has been demonstrated.... (Review)
Review
Von Willebrand factor has a pivotal role in primary hemostasis. Its role in thrombotic microangiopathies (TMA), as well as cardiovascular disease, has been demonstrated. Thrombotic thrombocytopenic purpura (TTP), a thrombotic microangiopathy, is a life-threatening condition with a high mortality rate if untreated. Current management strategies comprise plasma exchange to remove autoantibodies and replenish ADAMTS13, along with immunosuppressive agents in immune TTP. This review focuses on novel antiplatelet strategies that target VWF and GPIb. The benefits of the nanobody caplacizumab in achieving faster normalization of platelet count, as well as reduced thromboembolic events were shown through TITAN and HERCULES trials, and these findings have been practice changing. The use of caplacizumab in patients with immune TTP (iTTP) has now become well established. Potential benefits of ARC1779 and N-acetylcysteine have also been shown on a small scale in iTTP, however these lack evidence through larger randomized controlled trials. Further therapies, some in early phase, others in clinical practice, target platelet aggregation within arteries and their utility is presented with cerebrovascular disorders.
Topics: Humans; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIb-IX Complex; von Willebrand Factor
PubMed: 32614622
DOI: 10.1080/09537104.2020.1786038