scholarly journals Multi-parameter phenotyping of platelet reactivity for stratification of human cohorts

2021 ◽  
Author(s):  
Joanne L Dunster ◽  
Alexander P Bye ◽  
Neline Kriek ◽  
Tanya Sage ◽  
Joanne Louise Mitchell ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Platelet Function ◽  
Open Source Software ◽  
Platelet Reactivity ◽  
Automated Analysis ◽  
High Dimensional ◽  
Platelet Function Tests ◽  
Low Responders ◽  
Healthy Donors ◽  
Freeze Dried

Accurate and comprehensive assessment of platelet function across cohorts of donors may be key to understanding the risk of thrombotic events associated with cardiovascular disease, and hence help personalise the application of antiplatelet drugs. However, platelet function tests can be difficult to perform and analyse, unreliable or uninformative and poorly standardised across studies. The Platelet Phenomic Analysis (PPAnalysis) assay and associated open-source software platform was developed in response to these challenges. PPAnalysis utilises pre-prepared freeze-dried microtitre plates to provide a detailed characterisation of platelet function. The automated analysis of the high-dimensional data enables the identification of sub-populations of donors with distinct platelet function phenotypes. Using this approach we identified that the Sensitivity of a donor's platelets to an agonist and their Capacity to generate a functional response are distinct independent metrics of platelet reactivity. Hierarchical clustering of these metrics identified six subgroups with distinct platelet phenotypes within healthy cohorts, indicating that platelet reactivity does not fit into the traditional simple categories of 'high' and 'low' responders. These platelet phenotypes were found to exist in two independent cohorts of healthy donors and were stable on recall. PPAnalysis is a powerful tool for stratification of cohorts on the basis of platelet reactivity which will enable investigation of the causes and consequences of differences in platelet function and drive progress towards precision medicine.

scholarly journals MicroRNA as Biomarkers for Platelet Function and Maturity in Patients with Cardiovascular Disease

2021 ◽  
Author(s):  
Oliver Buchhave Pedersen ◽  
Erik Lerkevang Grove ◽  
Steen Dalby Kristensen ◽  
Peter H. Nissen ◽  
Anne-Mette Hvas
Keyword(s):  
Cardiovascular Disease ◽  
Platelet Function ◽  
Assessment Tool ◽  
Platelet Reactivity ◽  
Thrombus Formation ◽  
Quality Assessment Tool ◽  
Treatment And Prevention ◽  
Increased Risk ◽  
Meta Analyses ◽  
Potential Use

AbstractPatients with cardiovascular disease (CVD) are at increased risk of suffering myocardial infarction. Platelets are key players in thrombus formation and, therefore, antiplatelet therapy is crucial in the treatment and prevention of CVD. MicroRNAs (miRs) may hold the potential as biomarkers for platelet function and maturity. This systematic review was conducted using the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). To identify studies investigating the association between miRs and platelet function and maturity in patients with CVD, PubMed and Embase were searched on October 13 and December 13, 2020 without time boundaries. Risk of bias was evaluated using a standardized quality assessment tool. Of the 16 included studies, 6 studies were rated “good” and 10 studies were rated “fair.” In total, 45 miRs correlated significantly with platelet function or maturity (rho ranging from –0.68 to 0.38, all p < 0.05) or differed significantly between patients with high platelet reactivity and patients with low platelet reactivity (p-values ranging from 0.0001 to 0.05). Only four miRs were investigated in more than two studies, namely miR-223, miR-126, miR-21 and miR-150. Only one study reported on the association between miRs and platelet maturity. In conclusion, a total of 45 miRs were associated with platelet function or maturity in patients with CVD, with miR-223 and miR-126 being the most frequently investigated. However, the majority of the miRs were only investigated in one study. More data are needed on the potential use of miRs as biomarkers for platelet function and maturity in CVD patients.

scholarly journals microRNAs as Promising Biomarkers of Platelet Activity in Antiplatelet Therapy Monitoring

2020 ◽  
Vol 21 (10) ◽  
pp. 3477
Author(s):  
Teresa L. Krammer ◽  
Manuel Mayr ◽  
Matthias Hackl
Keyword(s):  
Antiplatelet Therapy ◽  
Platelet Activation ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Therapy Monitoring ◽  
Platelet Inhibition ◽  
High Morbidity ◽  
Platelet Function Tests ◽  
Function Tests ◽  
Plasma Mirna

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.

scholarly journals 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

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.

Abstract 3477: Platelet Hyper-responsiveness in Aspirin-Treated Patients with Clinical Cardiovascular Disease Compared to Matched High Risk Controls

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Nauder Faraday ◽  
Lisa R Yanek ◽  
Taryn F Moy ◽  
Dhananjay Vaidya ◽  
J. E Herrera-Galeano ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
High Risk ◽  
Platelet Function ◽  
Ex Vivo ◽  
Platelet Reactivity ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Increased Risk

Background: Platelet hyper-responsiveness to activating stimuli during aspirin (ASA) therapy may discriminate between high risk subjects who have developed acute thrombotic cardiovascular disease (CVD) events (coronary disease and stroke) and those who are at increased risk but are disease free. We hypothesized that subjects with documented CVD would have greater platelet reactivity on ASA therapy compared to matched high risk non-CVD subjects. Methods: Subjects (N=228; 61 +/− 8 yrs, 69% male, 60% white) were selected from families with known CVD; 114 had prevalent CVD and were matched on age, sex, and race to 114 apparently healthy controls with risk factors but without clinical CVD. CVD risk factors were measured and therapy adherence was determined by questionnaires. Platelet reactivity on 81 mg ASA/day was determined by whole blood (WB) aggregometry, platelet function analyzer (PFA) closure time, thromboxane B2 (TxB2) release ex vivo , and urinary excretion of 11-dehyrothromboxane B2 (Tx-M) in vivo . Results. CVD cases had greater platelet reactivity by all measures, both unadjusted, and adjusted for age, sex, race and adherence (Table ). Multivariable adjustment for cardiac risk factors and statin therapy eliminated case-control differences for Tx-M, but not for the ex vivo measures of platelet activation. ASA therapy duration in CVD subjects (8.8 +/− 6.2 yrs) was not related to platelet function. Conclusions: Greater residual platelet reactivity exists during ASA therapy in CVD subjects compared to matched high risk controls, even controlling for CVD risk factors and adherence to therapy. The data suggest that platelet hyper-responsiveness during ASA chemoprophylaxis may differentiate patients with CVD from those who are at risk for CVD, but have not developed it. Platelet hyper-responsiveness may be an intrinsic property of CVD, related to as yet unidentified environmental or genetic factors.

Association of Reduced Factor VIII with Impaired Platelet Reactivity to Adrenalin and Collagen after Total Thyroidectomy

1989 ◽  
Vol 62 (04) ◽  
pp. 1053-1056 ◽  
Author(s):  
G Palareti ◽  
G Biagi ◽  
C Legnani ◽  
D Bianchi ◽  
D Serra ◽  
...  
Keyword(s):  
Factor Viii ◽  
Total Thyroidectomy ◽  
Platelet Function ◽  
Blood Clotting ◽  
Platelet Reactivity ◽  
Platelet Function Tests ◽  
Function Tests ◽  
Prolonged Aptt ◽  
Normal Mean ◽  
Total Body

SummaryTwenty-one thyroprival patients, previously submitted to total thyroidectomy for tumours, were investigated during stabilized L-thyroxine supplementation and at the end of a 20-25 day “no-therapy” period, necessary for a 131I total body scintigraphy. During supplementation therapy a lower than normal mean betathromboglobulin (beta-TG) release level was found, the other blood clotting and platelet function tests being normal. After substitution therapy withdrawal, platelet function tests showed reduced adrenalin aggregation, increased collagen threshold aggregating concentrations, decreased beta-TG release values and reduced aggregation to ristocetin, whereas blood clotting tests showed prolonged aPTT values and reduced levels of factor VIII: C and vWf: Ag. We conclude that in acquired hypothyroidism the lowering of factor VIII: C and vWf: Ag (acquired von Wille brand disease) is associated with impaired platelet reactivity not only to ristocetin but also to collagen and especially adrenalin. In the patients investigated these changes were almost completely corrected by substitutive therapy with L-thyroxine at clinically effective doses.

Measuring high on-treatment platelet reactivity in clinical practice; should we use a panel of platelet function tests?

2019 ◽  
Vol 30 (6) ◽  
pp. 263-269
Author(s):  
Bastiaan Zwart ◽  
Thea C. Godschalk ◽  
Kai Zheng ◽  
Job Denteneer ◽  
Johannes C. Kelder ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Platelet Function Tests ◽  
Function Tests
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