Point-of-care platelet function tests: relevance to arterial thrombosis and opportunities for improvement
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Point‑of‑care platelet function tests: relevance to arterial thrombosis and opportunities for improvement Diana A. Gorog1,2 · Richard C. Becker3
© The Author(s) 2020
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. Keywords Platelet aggregation · Platelet function test · Thrombosis · Fibrinolysis · Citrate · Shear Abbreviations ACS Acute coronary syndrome ADP Adenosine diphosphate iCa Ionized calcium concentration HTPR High on-treatment platelet reactivity NETs Neutrophil extracellular trapsV PAI-1 Plasminogen activator inhibitor PFT Platelet function test POC Point-of-care PS Phospholipid phosphatidylserine TAFI Thrombin-activatable fibrinolysis inhibitor
* Diana A. Gorog [email protected] 1
National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK
2
University of Hertfordshire, Hertfordshire, UK
3
University of Cincinnati College of Medicine, Cincinnati, USA
TF Tissue factor TFPI Tissue factor pathway inhibitor vWF Von Willebrand factor
Highlights • Commonly used point-of-care platelet function tests have
many limitations and do not accurately reflect the in vivo situation. • To assess overall thrombotic status, a global thrombotic stimulus (like high shear) should be used, rather than assessing the response to individual agonist(s) (ADP, coll
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