Remote platelet function testing – Significant progress towards widespread testing in clinical practice

Platelets play a significant role in the physiological process of haemostasis by ensuring the integrity of the vessel wall and initiating primary haemostatic mechanisms when the vessel wall is damaged. They also contribute to the formation of the blood clots that give rise to heart attack and stroke. It is well known that platelet function can be impaired – either elevated or decreased – due to inherited or acquired factors. Reduced platelet function is most often the result of inherited defects in platelet morphology/ function or a consequence of the use of a variety of pharmacological agents that either specifically inhibits platelets to reduce the risk of heart attacks or stroke or those with alternative therapeutic targets that can also affect platelet function. Several dietary components and herbs are also known to affect platelet responsiveness [1]. Accordingly, there are several clinical scenarios when platelet function needs to be assessed. A range of techniques are available to test platelet reactivity, however, one of the major limitations of all available methodologies is that the testing needs to be performed on a fresh blood sample within 2–4 hours following venipuncture [2]. Even if the technique is not too complex and time consuming, it still limits platelet testing to a specialized laboratory or at least a laboratory where the appropriate equipment is installed and experienced personnel are available to perform the tests. Such a limitation is a significant obstacle. For example, in the case of diagnosis of platelet function defects, there may be an underestimation of their prevalence with cases tending to be clustered near specialised diagnostic centres [3]. One of the most commonly used methodologies for measuring platelet function is light transmission aggregometry (LTA), which is still considered the ‘‘gold standard’’ method despite the fact that it was developed long ago in the early 1960s [4]. This method can assess platelet aggregation together with its potentiation via amplification mechanisms, such as TxA2 synthesis and granule release, and register a two-phase aggregation response. This dynamic information is perhaps the most useful characteristic of the LTA and is not available with any other aggregation technique. Although informative, the whole procedure is timeand labourintensive, and involves multiple steps from preparation of plateletrich plasma (PRP) to the actual aggregation measurements. There is also significant variability in performance of LTA between different laboratories [5, 6], and this reduces the diagnostic value of the test as the results become incomparable. Recently, recommendations on standardisation of the LTA procedure were issued [2] with the aim to improve reproducibility and comparability of the LTA; however, the technique is still too cumbersome for routine clinical use. Another limitation of LTA is that the method requires large volumes of blood for PRP preparation, which presents a significant challenge when platelet function needs to be assessed in individuals in whom the volume of blood sample is limited. To overcome some of these limitations, modern technologies have been developed, such as the VerifyNow system (Accumetrics, San Diego, CA) and Multiple Electrode Aggregometry (MEA, Multiplate , Roche Diagnostics International Ltd, Rotkreuz, Switzerland). Currently, their application is mostly restricted to assessing the effectiveness of antiplatelet therapy, although MEA has been used in two studies to diagnose one of the most prominent inherited platelet defects – Glanzmann thrombasthenia [7, 8]. These tests are certainly simpler, and hence less time consuming and labour intensive, they are performed on whole blood and are much better standardised than the traditional LTA. However, their downside is that they utilise a dedicated piece of sophisticated equipment and use of specific consumables, which together make these methodologies quite expensive to run. Another important application of platelet function testing is within the drug discovery area, when novel drugs designed to affect platelet function are being developed or when the effect on platelets needs to be excluded as an unwanted effect for a drug with the therapeutic target other than platelets. In this scenario, complex or expensive methodology is not ideal, as pharmaceutical industry studies often require multiple samples to be processed in a limited time period, in multiple centres, and require that methodology is standardized across all participating centres. Keywords