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

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.

Venous thromboembolism in COVID-19 compared to non-COVID-19 cohorts: A systematic review with meta-analysis

“…We identified 4080 citations of which 167 were retained for full-text evaluation. Seven articles [ [23] , [24] , [25] , [26] , [27] , [28] , [29] ] (41,768 patients) reported the rate of VTE in COVID-19 cohorts compared to non-COVID-19 cohorts ( Fig. 1 ).…”

Pharmacokinetic, pharmacodynamic, and pharmacogenetic assays to monitor clopidogrel therapy

“…36,36,49,67,76,97,99,[116][117][118][119][120][121][122] By comparing the results obtained from the study, it was concluded that VASP phosphorylation assay, VerifyNow P2Y12 assay, and LTA with 20 µmol/L ADP are ideal PFTs to monitor clopidogrel responsiveness. 54,66,70,117,124 When compared with LTA, VASP-P assay was more suitable 125 and out of LTA, Multiplate assay, Verify Now assay, and TEG, Multiplate assay was found to be ideal to monitor the clopidogrel. 126 Limitations of LTA has paved the way for the development of standardized PFTs such as PFA-100, Multiplate, and VerifyNow P2Y12 assays.…”

“…The anticoagulant used must not interfere with the normal physiology of the sample. 54,130 An advanced principle with a simple technique which can be used globally for different agonists without altering the physiological environment of the sample would be ideal. 67 Further, PFT should have the capacity to determine not only platelet aggregation, but also to measure the procoagulant activity of platelets.…”

“…POCTs are developed to overcome the limitations associated with LTA, such as labor intensiveness, cost, and time. POCTs are generally at high cost than normal LTA, but they have the ability to provide clot quality and monitors clot formation and progression even after the point of clot formation 35,53,54 …”

“…An anticoagulant, such as hirudin, should be used instead of the 3.2% trisodium citrate when possible. The anticoagulant used must not interfere with the normal physiology of the sample 54,130 . An advanced principle with a simple technique which can be used globally for different agonists without altering the physiological environment of the sample would be ideal 67 .…”