microRNAs as Promising Biomarkers of Platelet Activity in Antiplatelet Therapy Monitoring

Given the high morbidity and mortality of cardiovascular diseases (CVDs), novel biomarkers for platelet reactivity are urgently needed. Ischemic events in CVDs are causally linked to platelets, small anucleate cells important for hemostasis. The major side-effect of antiplatelet therapy are life-threatening bleeding events. Current platelet function tests are not sufficient in guiding treatment decisions. Platelets host a broad spectrum of microRNAs (miRNAs) and are a major source of cell-free miRNAs in the blood stream. Platelet-related miRNAs have been suggested as biomarkers of platelet activation and assessment of antiplatelet therapy responsiveness. Platelets release miRNAs upon activation, possibly leading to alterations of plasma miRNA levels in conjunction with CVD or inadequate platelet inhibition. Unlike current platelet function tests, which measure platelet activation ex vivo, signatures of platelet-related miRNAs potentially enable the assessment of in vivo platelet reactivity. Evidence suggests that some miRNAs are responsive to platelet inhibition, making them promising biomarker candidates. In this review, we explain the secretion of miRNAs upon platelet activation and discuss the potential use of platelet-related miRNAs as biomarkers for CVD and antiplatelet therapy monitoring, but also highlight remaining gaps in our knowledge and uncertainties regarding clinical utility. We also elaborate on technical issues and limitations concerning plasma miRNA quantification.

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Antiplatelet Therapy in Acute Coronary Syndromes. Lights and Shadows of Platelet Function Tests to Guide the Best Therapeutic Approach

Current Vascular Pharmacology ◽

10.2174/1570161117666190513105859 ◽

2020 ◽

Vol 18 (3) ◽

pp. 262-272 ◽

Cited By ~ 1

Author(s):

Giovanni Cimmino ◽

Emanuele Gallinoro ◽

Luigi Di Serafino ◽

Nicola De Luca ◽

Plinio Cirillo

Keyword(s):

Antiplatelet Therapy ◽

Platelet Activation ◽

Platelet Function ◽

Acute Coronary Syndromes ◽

Clinical Decision Making ◽

Platelet Reactivity ◽

Platelet Function Tests ◽

Function Tests ◽

Increased Risk ◽

Coronary Syndromes

The key role of platelets in pathophysiology of Acute Coronary Syndromes (ACS) has been well recognized. Platelet activation and aggregation, together with tissue factor-pathway activation, lead to acute thrombus formation in the coronary vessels at sites of plaque rupture. Thus, antiplatelet therapy with drugs able to interfere with platelet activation/aggregation represents a cornerstone of ACS treatment in intensive care units and catheterisation labs. Several observational studies have described that residual high platelet reactivity, despite antiplatelet therapy, is associated with increased risk of nonfatal Myocardial Infarction (MI), definite/probable stent thrombosis and cardiovascular mortality. Thus, assessment of platelet function with reliable and reproducible platelet function tests might be crucial to identify patients at high risk of thrombosis or not responding to ongoing antiplatelet strategies. However, despite this promising background, some randomized clinical trials have failed to demonstrate improvement in outcomes when using platelet function tests for clinical decision-making. This review, after describing platelet biology and pathophysiology of ACS, briefly considers the drugs currently approved for use in patients with ACS or treated by the percutaneous coronary intervention (PCI). Finally, we provide an updated overview of the current methods to evaluate platelet reactivity in the clinical setting of ACS illustrating their potential advantages/limitations in current clinical practice.

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Abstract 20657: Plasma MicroRNAs Correlate With Platelet Reactivity in Patients With Acute Coronary Syndrome: Association With Platelet Function

Circulation ◽

10.1161/circ.130.suppl_2.20657 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Manuel Mayr ◽

Dorothee Kaudewitz ◽

Philipp Skroblin ◽

Peter Willeit ◽

Anna Zampetaki ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Platelet Function ◽

Platelet Reactivity ◽

Platelet Inhibition ◽

Platelet Function Tests ◽

Coronary Syndrome ◽

Function Tests ◽

Custom Made ◽

Detailed Assessment ◽

Plasma Mirnas

Introduction: Platelets contribute plasma microRNAs (miRNAs). Levels of platelet-related miRNAs change in plasma in response to platelet inhibition. Hypothesis: It is currently unclear how plasma miRNAs correlate to platelet function in patients with acute coronary syndrome (ACS). Methods: We measured plasma miRNAs in 125 patients with a history of ACS (STEMI, NSTEMI or unstable angina) who have undergone detailed assessment of platelet function 30 days after the acute event. Results: Using custom-made quantitative real-time polymerase chain reaction plates, 92 miRNAs were assessed in patients on different anti-platelet therapies (clopidogrel, prasugrel, aspirin). Key platelet-related miRNAs were correlated with platelet function tests, including optical aggregometry using the agonists ADP and arachidonic acid, VerifyNow P2Y12 assay and vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay. Significant associations were obtained for miR-126 with the VerifyNow (rp=0.347, n=39, P=0.033) and VASP assay (rp=0.224, n=125, P=0.013). Other abundant platelet miRNAs also showed strong correlations with the VASP assay: miR-223 (rp =0.231, P=0.003), miR-191 (rp =0.243, P=0.007), miR-24 (rp =0.246, P=0.006), miR-197 (rp=0.293, P=0.008), miR-30b (rp=0.230, P=0.010) and miR-20b (rp=0.231 , P=0.010). Conclusions: Levels of platelet-related plasma miRNAs correlate with platelet function tests in ACS patients. Our findings reinforce the concept that platelets are an important contributor to the plasma miRNA pool.

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Platelet function tests and resistance to antiplatelet therapy

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh10s1059s ◽

2010 ◽

Vol 138 (suppl. 1) ◽

pp. 59-63 ◽

Cited By ~ 4

Author(s):

Mojca Stegnar

Keyword(s):

Antiplatelet Therapy ◽

Platelet Function ◽

Whole Blood ◽

Light Transmission ◽

Ex Vivo ◽

Point Of Care ◽

Platelet Inhibition ◽

Thromboxane B2 ◽

Platelet Function Tests ◽

Function Tests

The clinical efficacy of antiplatelet therapy (aspirin, P2Y12 and glycoprotein IIb/IIIa receptor antagonists) to prevent occlusive arterial events in patients with atherothrombotic disease is well established. Despite the proven benefits of antiplatelet therapy, many patients continue to experience arterial events. Many factors may influence the response of platelets to antiplatelet therapy and some patients with adequate compliance to the treatment may exhibit failure of platelet inhibition as determined by ex vivo laboratory tests, a phenomenon termed ?resistance?to antiplatelet therapy. Platelet function can be measured by numerous platelet function tests, with which various parameters of platelet activation, secretion, adhesion and aggregation can be determined. These tests include light transmission (optical) and whole blood aggregometry, point-of-care devices, such as platelet function analyzers PFA-100?, and VerifyNow?, flow cytometry, serum thromboxane B2 and urinary levels of the thromboxane B2 metabolite 11-dehyro-thromboxane B2. Other tests, such as whole blood platelet aggregation measured by platelet counting, thrombelastography and devices such as the cone and plate(let) analyzer, Plateletworks and thrombotic status analyzer have also been used to determine platelet inhibition by antiplatelet drugs, but their use is not widespread and therefore experience is limited. Further studies need to be carried out to answer basic questions on the clinical utility and cost-effectiveness of laboratory monitoring of antiplatelet therapy before it can be recommended in clinical practice.

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“To MAP or not to MAP; is that the question?” The role of platelet function tests in the perioperative management of patients on antiplatelet therapy

Current Anaesthesia and Critical Care ◽

10.1016/j.cacc.2009.10.009 ◽

2010 ◽

Vol 21 (2) ◽

pp. 91-93 ◽

Cited By ~ 1

Author(s):

N. Jones ◽

R.H. Broomhead ◽

J. Kaur ◽

S.V. Mallett

Keyword(s):

Antiplatelet Therapy ◽

Platelet Function ◽

Perioperative Management ◽

Platelet Function Tests ◽

Function Tests

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GW27-e0655 Head to head comparison of two point-of-care platelet function tests used for assessment of on-clopidogrel platelet reactivity in the Chinese acute myocardial infarction patients underwent percutaneous coronary intervention

Journal of the American College of Cardiology ◽

10.1016/j.jacc.2016.07.679 ◽

2016 ◽

Vol 68 (16) ◽

pp. C180

Author(s):

Yi Yao ◽

Jiahui Zhang ◽

Xiaofang Tang ◽

Chen He ◽

Yuanliang Ma ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Percutaneous Coronary Intervention ◽

Platelet Function ◽

Platelet Reactivity ◽

Point Of Care ◽

Coronary Intervention ◽

Platelet Function Tests ◽

Function Tests ◽

Percutaneous Coronary

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Clopidogrel versus ticagrelor in the treatment of Chinese patients undergoing percutaneous coronary intervention: effects on platelet function assessed by platelet function tests and mean platelet volume

10.21203/rs.3.rs-48980/v2 ◽

2021 ◽

Author(s):

Yang Zhang ◽

Rui Peng ◽

Xiaojuan Li ◽

Gaowa Cheng ◽

Ximing Wang ◽

...

Keyword(s):

Percutaneous Coronary Intervention ◽

Platelet Function ◽

Mean Platelet Volume ◽

Platelet Reactivity ◽

Coronary Intervention ◽

Chinese Patients ◽

Platelet Function Tests ◽

Platelet Volume ◽

Function Tests ◽

Percutaneous Coronary

Abstract Background: Knowledge on the pharmacodynamic effects of antiplatelet drugs including clopidogrel and ticagrelor on Asian patients is scarce. We aim to evaluate the effects of the two drugs on platelet reactivity in the treatment of Chinese patients who underwent percutaneous coronary intervention (PCI), using two platelet function tests (PFT). Meanwhile, the relationship between mean platelet volume (MPV), a routine index of platelet size, and high on-treatment platelet reactivity (HPR) is also investigated.Methods: Patients receiving dual antiplatelet therapy (DAPT) were scheduled for the assessment of platelet reactivity at 2–3 days after PCI. Two PFTs, light transmission aggregometry (LTA) and vasodilator-stimulated phosphoprotein (VASP)-FCM assay, were applied in the evaluation of platelet reactivity. The MPV was measured simultaneously with EDTA plasma using a Sysmex XN 2000 automated hematology analyzer.Results: The final study population included the aspirin + clopidogrel group (n = 46) and the aspirin + ticagrelor group (n = 66). In the aspirin + ticagrelor group, the maximal light transmittance (LT) changes in response to 5 µM ADP assessed by LTA was obviously lower than that in the aspirin + clopidogrel group (P < 0.001). The platelet reactivity index (PRI) level in the VASP test was also markedly lower in the group given aspirin and ticagrelor (P < 0.001). There was a significant difference in HPR between the two groups. MPV showed a potent ability to predict the presence of HPR at VASP assay (AUC = 0.788, 95% CI: 0.701–0.875, P < 0.001) in receiver-operating characteristic curve analysis.Conclusions: Compared with clopidogrel, ticagrelor has dramatically greater antiplatelet effect, with a superiority in suppressing platelet function and a lower HPR rate. In addition, there existed a significant independent association between MPV and high prevalence of HPR in the VASP assay.

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