Performance and usefulness of platelet aggregation testing

LTA Series

Platelets, tiny and abundant anucleated blood cells, are at the forefront of hemostasis and pathological thrombus formation. These are dynamic processes that require a coordinated series of events involving platelet membrane receptors, bidirectional intracellular signals, and release of platelet proteins and inflammatory substances [1–3].

Over last century, progress in our understanding of the platelet function and the role of platelets in physiological and pathological thrombus formation has largely relied on the measurement of platelet aggregability in healthy individuals, patients, and animal models. The classical light transmission aggregometry (LTA) developed by Born in the 1960s [4] is still regarded as the “gold standard” of platelet function testing. However, LTA has weaknesses such as the use of platelet-rich plasma instead of whole blood under relatively low shear conditions, the requirement of large sample volumes, it is time-consuming and affected by many pre-analytical and analytical variables. In order to diminish variability in LTA performance in humans, guidelines in LTA procedure have been published [5].

Advances in the measurement of platelet aggregability include development of point-of-care devices, performing the test in plates with lower sample requirement, measurement under flow conditions, or using flow cytometry to detect cell aggregates. This review series presents an overview of these advances, as well as the use of aggregometry under special settings. Focusing on mouse models, Hughes highlights several challenges when performing aggregation experiments, while Podda et al. examine the use of human aggregometry in the special settings of thrombocytopenia, thrombocytosis and antiplatelet therapy. Dovlatova and Heptinstall describe the utility of the PFA-100®, which has been the most used point-of-care device in platelet function testing [6]. They also address platelet counting by commercial kits or flow cytometry, as a novel alternative to evaluate platelet aggregation. Chan et al. illustrate the advantages of platelet aggregation in standard 96-well plates with pre-loaded agonists using a common absorbance reader, and show that results are not fully equivalent to standard LTA aggregometry. Brouns et al. explore the potential of microfluid devices to assess multiple aspects of platelet function in patients with inherited platelet or coagulation disorders, and in cardiovascular patients under anti-thrombotic therapy. For platelet aggregation to occur, the αIIbβ3 integrin must change its conformation and gain the capacity to bind fibrinogen [7]. The review by Frelinger is devoted to the performance and utility of methods assessing such αIIbβ3 activation, mainly measurement of PAC1 binding to platelets by flow cytometry. Finally, platelet activation also promotes interaction with other blood cells such as leukocytes, and these platelet-leukocytes have implications in human health. Here, Finsterbusch et al. nicely review approaches to measure platelet-leukocytes aggregates and their role in a variety of diseases.

Declaration of interest

The authors report no declaration of interest.

Acknowledgments

Research from the authors group is supported by grants from Instituto de Salud Carlos III (PI17/01311), CIBERER (CB15/00055), Fundación Séneca (19873/GERM/15) and Spanish Society for Thrombosis and Haemostasis (SETH).