Fully automated light transmission aggregometry on a disc for platelet function tests

Lab on a Chip ◽

10.1039/d1lc00708d ◽

2021 ◽

Author(s):

Chi-Ju Kim ◽

Jungmin Kim ◽

Jonathan Sabaté del Río ◽

Dong Yeob Ki ◽

Junyoung Kim ◽

...

Keyword(s):

Platelet Function ◽

Light Transmission ◽

Platelet Function Tests ◽

Function Tests ◽

Light Transmission Aggregometry

Platelet function tests, a group of assays that measure the ability of platelets to aggregate and promote clotting in a sample of blood, are performed in various medical fields to...

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Assessment of platelet function in the laboratory

Hämostaseologie ◽

10.1055/s-0037-1616935 ◽

2009 ◽

Vol 29 (01) ◽

pp. 25-31 ◽

Cited By ~ 29

Author(s):

P. Harrison

Keyword(s):

Quality Assurance ◽

Clinical Practice ◽

Platelet Function ◽

Light Transmission ◽

Platelet Function Tests ◽

Platelet Function Testing ◽

Clinical Laboratories ◽

Function Tests ◽

Whole Blood Aggregometry ◽

Function Testing

SummaryPlatelet function testing is essential for the diagnosis of congenital/acquired bleeding disorders and may be useful for the prediction of surgical bleeding. Nowadays there is also much interest in monitoring the efficacy of anti-platelet therapy and measuring platelet hyper-function. However, this often presents clinical laboratories with significant challenges as platelet function tests are complex, poorly standardized, time consuming and quality assurance is not straightforward. There are also few comprehensive modern guidelines available and many recent published surveys have revealed poor standardization between laboratories.Up until the late 1980’s the traditional clinical platelet function tests that were available were the bleeding time (BT), light transmission (LTA) and whole blood aggregometry (WBA) and various biochemical assays. These were also usually performed within specialized research and clinical laboratories. Since the last BCSH guidelines were published in 1988 a variety of new platelet function tests have become available. These include flow cytometry and an ever increasing choice of new commercial instruments. Although the potential clinical utility of the new assays is emerging some have not yet entered into routine clinical practice. It is encouraging that a number of standardization committees (e. g. CLSI, BCSH and ISTH Platelet Physiology SSC) are now beginning to produce new platelet function testing guidelines and this will hopefully improve clinical practice, quality assurance and result in less variability between different laboratories.

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Comparison of current platelet functional tests for the assessment of aspirin and clopidogrel response

Thrombosis and Haemostasis ◽

10.1160/th15-11-0870 ◽

2016 ◽

Vol 116 (10) ◽

pp. 638-650 ◽

Cited By ~ 40

Author(s):

Jean-Claude Bordet ◽

Claude Negrier ◽

Yesim Dargaud ◽

Sandra Le Quellec

Keyword(s):

Platelet Function ◽

Light Transmission ◽

Platelet Response ◽

Platelet Function Tests ◽

Clopidogrel Resistance ◽

Function Tests ◽

Function Analyzer ◽

Clopidogrel Therapy ◽

Whole Blood Aggregometry ◽

Platelet Function Analyzer

SummaryThe two most widely used antiplatelet drugs in the world are aspirin and clopidogrel. However, some patients on aspirin and/or clopidogrel therapy do not respond appropriately to either aspirin or clopidogrel. This phenomenon is usually called “aspirin/clopidogrel resistance”. Several platelet function tests have been used in various studies for the assessment of aspirin and clopidogrel resistance in healthy individuals and patients admitted in cardiology departments. An accurate assessment of platelet response to aspirin/clopidogrel could benefit patients by proposing tailored-antiplatelet therapy based on test results. However, there is a clear lack of standardisation of such techniques and their analytical variability may induce misinterpretation. After a quick report of the mechanisms responsible for aspirin/clopidogrel resistance, we describe the pre-analytical aspects and the analytical performances of current platelet function tests (Light-transmission aggregometry, whole-blood aggregometry, VerifyNow®, Platelet Function Analyzer®, thromboelastography, VASP assay) that are used for the assessment of aspirin/clopidogrel resistance in clinical studies. Considering the different variables that have to be taken into account with each of the platelet function tests, a particular attention should be paid when interpreting results.

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Differential Impact of Cytochrome 2C19 Allelic Variants on Three Different Platelet Function Tests in Clopidogrel-Treated Patients

Journal of Clinical Medicine ◽

10.3390/jcm10173992 ◽

2021 ◽

Vol 10 (17) ◽

pp. 3992

Author(s):

Renske H. Olie ◽

Rachelle R. K. Hensgens ◽

Petal A. H. M. Wijnen ◽

Leo F. Veenstra ◽

Bianca T. A. de Greef ◽

...

Keyword(s):

Platelet Function ◽

Light Transmission ◽

Platelet Reactivity ◽

Coronary Intervention ◽

Cyp2c19 Genotype ◽

Platelet Function Tests ◽

Related Factors ◽

Differential Effects ◽

Function Tests ◽

Cyp2c19 Polymorphism

On-treatment platelet reactivity in clopidogrel-treated patients can be measured with several platelet function tests (PFTs). However, the agreement between different PFTs is only slight to moderate. Polymorphisms of the CYP2C19 gene have an impact on the metabolization of clopidogrel and, thereby, have an impact on on-treatment platelet reactivity. The aim of the current study is to evaluate the differential effects of the CYP2C19 genotype on three different PFTs. Methods: From a prospective cohort study, we included patients treated with clopidogrel following percutaneous coronary intervention (PCI). One month after PCI, we simultaneously performed three different PFTs; light transmission aggregometry (LTA), VerifyNow P2Y12, and Multiplate. In whole EDTA blood, genotyping of the CYP2C19 polymorphisms was performed. Results: We included 308 patients treated with clopidogrel in combination with aspirin (69.5%) and/or anticoagulants (33.8%) and, based on CYP2C19 genotyping, classified them as either extensive (36.4%), rapid (34.7%), intermediate (26.0%), or poor metabolizers (2.9%). On-treatment platelet reactivity as measured by LTA and VerifyNow is significantly affected by CYP2C19 metabolizer status (p < 0.01); as metabolizer status changes from rapid, via extensive and intermediate, to poor, the mean platelet reactivity increases accordingly (p < 0.01). On the contrary, for Multiplate, no such ordering of metabolizer groups was found (p = 0.10). Conclusions: For VerifyNow and LTA, the on-treatment platelet reactivity in clopidogrel-treated patients correlates well with the underlying CYP2C19 polymorphism. For Multiplate, no major effect of genetic background could be shown, and effects of other (patient-related) variables prevail. Thus, besides differences in test principles and the influence of patient-related factors, the disagreement between PFTs is partly explained by differential effects of the CYP2C19 genotype.

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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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Aspirin - resistance? A few critical considerations on definition, terminology, diagnosis, clinical value, natural course of atherosclerotic disease, and therapeutic consequences

VASA ◽

10.1024/0301-1526/a000145 ◽

2011 ◽

Vol 40 (6) ◽

pp. 429-438 ◽

Cited By ~ 8

Author(s):

Berent ◽

Sinzinger

Keyword(s):

Platelet Function ◽

Point Of Care ◽

Aspirin Resistance ◽

Point Of View ◽

Evidence Based ◽

Platelet Function Tests ◽

Clinical Value ◽

Vascular Events ◽

Therapeutic Consequences ◽

Function Tests

Based upon various platelet function tests and the fact that patients experience vascular events despite taking acetylsalicylic acid (ASA or aspirin), it has been suggested that patients may become resistant to the action of this pharmacological compound. However, the term aspirin resistance was created almost two decades ago but is still not defined. Platelet function tests are not standardized, providing conflicting information and cut-off values are arbitrarily set. Intertest comparison reveals low agreement. Even point of care tests have been introduced before appropriate validation. Inflammation may activate platelets, co-medication(s) may interfere significantly with aspirin action on platelets. Platelet function and Cox-inhibition are only some of the effects of aspirin on haemostatic regulation. One single test is not reliable to identify an altered response. Therefore, it may be more appropriate to speak about treatment failure to aspirin therapy than using the term aspirin resistance. There is no evidence based justification from either the laboratory or the clinical point of view for platelet function testing in patients taking aspirin as well as from an economic standpoint. Until evidence based data from controlled studies will be available the term aspirin resistance should not be further used. A more robust monitoring of factors resulting in cardiovascular events such as inflammation is recommended.

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Faculty Opinions recommendation of Assessment of platelet function in healthy cats in response to commonly prescribed antiplatelet drugs using three point-of-care platelet function tests.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726356134.793518643 ◽

2016 ◽

Author(s):

Davide Cattano

Keyword(s):

Platelet Function ◽

Point Of Care ◽

Antiplatelet Drugs ◽

Platelet Function Tests ◽

Function Tests

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LACK OF CORRELATION BETWEEN INTRAPLATELET cAMP INCREASE AND SYSTEMIC CIRCULATORY EFFECTS

10.1055/s-0038-1644532 ◽

1987 ◽

Author(s):

W Haarmann ◽

H Weisenberger

Keyword(s):

Platelet Function ◽

Circulatory System ◽

Human Platelets ◽

Platelet Function Tests ◽

Inotropic Effects ◽

Circulatory Effects ◽

Function Tests ◽

Drug Concentrations ◽

Camp Metabolism ◽

The Difference

Compounds inhibiting platelet function by acting on platelet cAMP metabolism usually also have effects on the circulatory system, i.e. they decrease systemic blood pressure (bp) and are positive inotropic. For several compounds selected because of their distinct platelet inhibitory effects, the influence on these parameters in animals and on the cAMP metabolism in human platelets was determined.Inotropic effects and bp were measured via an indwelling catheter in anestetised cats after i.v. application of the test compounds. The inhibition of platelet PDEs was measured in freeze-thaw homogenates of human platelets using 3H-cAMP as substrate. Intraplatelet cAMP changes were measured by prelabelling the ATP pool with 3H-adenine and isolation of 3H-cAMP. Linear regression analysis of the drug concentrations causing a doubling of intraplatelet cAMP levis and the % difference in bp or the % difference in dp/dt, resp., by i.v. application of 0.3 mg/kg test compound yielded the following results:cAMP vs % diff. bp : r=0.02, N=18cAMP vs % diff. dp/dt: r = 0.02 , N = 15In contrast to a good correlation between intraplatelet cAMP levels and inhibition of platelet function tests, no obvious relationship was seen between cAMP and decrease in bp and positive initropic effects. It is not known whether the lack of correlation could be due to a different drug access to platelets and the bp regulatory system.A biochemical parameter, i.e. intraplatelet cAMP increase by inhibition of PDEs correlates reasonably well with the inhibition of platelet function tests. This parameter is not useful, however, to predict the effects on the heart and the circulatory system.

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