A practical technique for clinicians to approximate platelet function after fifteen-minutes using thromboelastography

Mapping Intimacies ◽

10.1101/2020.03.10.20033860 ◽

2020 ◽

Author(s):

Elliott Sharp ◽

Vanessa Fludder

Keyword(s):

Risk Management ◽

Platelet Aggregation ◽

Correlation Coefficient ◽

Platelet Function ◽

Pearson Correlation ◽

Platelet Function Tests ◽

Function Tests ◽

Antiplatelet Medication ◽

Custom Made ◽

Management Plans

ABSTRACTBackgroundPoint-of-care platelet function tests are used by anaesthetists and surgeons to create risk management plans for patients who have recently taken antiplatelet medication. Thromboelastography (TEG), one method of determining platelet function, sometimes takes >60 minutes to produce results. Previous studies have shown a novel parameter, area under the curve at 15 minutes (AUC15), correlates with clinical outcomes but used privately-owned, custom-made software to calculate AUC15. This study aimed to create a formula that clinicians can use to approximate AUC15 which correlates to the most widely used measure of platelet function, percentage of platelet aggregation.MethodsPlatelet function after 15 minutes can be approximated by the equation: AUC15 = 225(tan(θ)) where θ = α(MAADP/MAThrombin). A retrospective database review was performed on eligible platelet function tests that assessed ADP receptor inhibition on a TEG 6s Hemostasis Analyzer (Haemonetics®) across 15 months. Results were analysed using a bivariate scatter plot with linear regression line and a two-tailed Pearson correlation coefficient was calculated.ResultsForty-seven tests were retrieved, of which, forty-five were eligible for analysis. Pearson two-tailed correlation coefficient showed that AUC15 correlated significantly with percentage of platelet aggregation (R = 0.748, 95% CI [0.582, 0.854], p < 0.001).ConclusionThis study creates the first practical method for clinicians to approximate platelet function on TEG analysers after 15 minutes, instead of >60 minutes, using routinely generated outputs and a calculator. Clinicians who use this method will afford themselves more time to create risk management plans for patients which may improve patient outcomes.

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Point-of-care platelet function tests: relevance to arterial thrombosis and opportunities for improvement

Journal of Thrombosis and Thrombolysis ◽

10.1007/s11239-020-02170-z ◽

2020 ◽

Author(s):

Diana A. Gorog ◽

Richard C. Becker

Keyword(s):

Platelet Aggregation ◽

Platelet Function ◽

Arterial Thrombosis ◽

Point Of Care ◽

Laboratory Research ◽

Platelet Function Tests ◽

Function Tests ◽

Antiplatelet Medication ◽

Platelet Aggregometry

Abstract Studies using whole blood platelet aggregometry as a laboratory research tool, provided important insights into the mechanism and modulators of platelet aggregation. Subsequently, a number of point-of-care (POC) platelet function tests (PFTs) were developed for clinical use, based on the concept that an individual’s thrombotic profile could be assessed in vitro by assessing the response to stimulation of platelet aggregation by specific, usually solo agonists such as adenosine diphosphate (ADP), collagen and thrombin. However, adjusting antiplatelet medication in order to improve the results of such POC PFTs has not translated into a meaningful reduction in cardiovascular events, which may be attributable to important differences between the POC PFT techniques and in vivo conditions, including patient-to-patient variability. Important limitations of most tests include the use of citrate-anticoagulated blood. Citrate directly and irreversibly diminishes platelet function and even after recalcification, it may result in altered platelet aggregation in response to ADP, epinephrine or collagen, and interfere with thrombin generation from activated platelets. Furthermore, most tests do not employ flowing blood and therefore do not assess the effect of high shear forces on platelets that initiate, propagate and stabilize arterial thrombi. Finally, the effect of endogenous thrombolysis, due to fibrinolysis and dislodgement, which ultimately determines the outcome of a thrombotic stimulus, is mostly not assessed. In order to accurately reflect an individual’s predisposition to arterial thrombosis, future tests of thrombotic status which overcome these limitations should be used, to improve cardiovascular risk prediction and to guide pharmacotherapy.

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The Effect of Imidazole on Human Platelet Aggregation

Blood ◽

10.1182/blood.v38.4.417.417 ◽

1971 ◽

Vol 38 (4) ◽

pp. 417-421 ◽

Cited By ~ 10

Author(s):

JAMES W. DAVIS ◽

PHYLLIS E. PHILLIPS

Keyword(s):

Platelet Aggregation ◽

Platelet Function ◽

Glass Bead ◽

Human Platelet ◽

Platelet Rich Plasma ◽

Second Phase ◽

Platelet Function Tests ◽

Human Platelet Aggregation ◽

Function Tests ◽

Induced Aggregation

Abstract Since imidazole buffers have been used in platelet function tests and the compound has been reported to alter several biochemical activities of platelets, it seemed important to determine whether imidazole influenced platelet aggregation. ADP-induced, collagen-induced, and norepinephrine-induced platelet aggregations were tested in platelet-rich plasma by turbidimetric techniques. Glass bead-induced platelet aggregation in whole blood was tested by a method dependent upon platelet counts. Imidazole, in concentrations of 5mM or less, inhibited aggregation induced by each of these four agents and had negligible effect on the pH of platelet-rich plasma. The second phase of both ADP- and norepinephrine-induced aggregation was inhibited or abolished by imidazole, and 5mM imidazole also inhibited the first phase of norepinephrine-induced aggregation. As little as 0.5 mM imidazole inhibited collagen-induced aggregation in some plasmas. Imidazole appears to be unsuitable for use as a buffer in platelet function tests.

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Comparison between induced platelet aggregation and circulating platelet aggregates as platelet function tests in patients with transient ischemic attacks

Acta Neurologica Scandinavica ◽

10.1111/j.1600-0404.1982.tb03069.x ◽

2009 ◽

Vol 65 (2) ◽

pp. 122-132 ◽

Cited By ~ 5

Author(s):

Jan-Edvin Olsson

Keyword(s):

Platelet Aggregation ◽

Platelet Function ◽

Transient Ischemic Attacks ◽

Platelet Function Tests ◽

Function Tests ◽

Circulating Platelet Aggregates ◽

Platelet Aggregates

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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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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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