Light Transmission Aggregation (LTA) – the gold-standard platelet aggregation assay
At Java Clinical Research, we specialise in testing platelet responses to drug treatment in clinical samples and in preclinical testing. One common method is the platelet aggregation assay.
Platelets are blood cells involved in preventing bleeding; when activated they clump together to stop blood flow, but when this happens inside a blood vessel, it leads to a heart attack or stroke. Preventing unwanted platelet activation with drugs such as aspirin or clopidogrel (Plavix) reduces the risk of these disease.
Platelets are affected by many stimuli; some keep platelets in their normal, ‘resting’ state; others cause them to activate rapidly in response to injury. Platelets have complex biochemical controls regulating this activation that may be affected by drugs.
Improved antiplatelet drugs are being sought, while other drugs may affect platelet activation as a side effect.
Various laboratory assays can be used to test platelet function; light transmission aggregation (LTA, or just “platelet aggregation”) is considered the gold standard assay. The principles behind the platelet aggregation assay are very straightforward. By gently centrifuging a blood sample, we generate plasma that is cloudy with suspended platelets (platelet rich plasma, PRP). If activated, the platelets in PRP will start to stick together, forming aggregates. As more platelets clump together, the plasma becomes less cloudy, and a fully aggregated sample will look like standard blood plasma with no suspended platelets (platelet poor plasma, PPP). By measuring how much light passes through an initially cloudy sample of PRP, we determine how platelets aggregate in response to a stimulus, as in the diagram. Because every individual’s plasma is slightly different, we use PPP to set the 100% reference mark for the platelet aggregation assay.
In a clinical trial of an antiplatelet drug, the platelet aggregation assay provides an important pharmacodynamic endpoint. It measures the extent to which a patient’s platelet function is inhibited at any particular time, and so can be used to identify the effective dose of a drug and determine the timecourse of a drug’s actions. Below we see how platelet aggregation responses showed the effects of different doses of a novel antiplatelet drug at different stages of a phase II clinical trial (From Wiviott et al., 2011 (PDF), a study where Java oversaw the platelet function assessments).
Java trains staff at clinical trial sites to conduct platelet aggregation assays on patient samples in trials such as the one above. We can train people with little or no laboratory experience to conduct this assay, enabling platelet aggregation data to be collected anywhere a clinical trial is being run. We also review and check the data for quality, analyse and interpret the results.
To find out more, please contact us – we would be happy to talk about how we can help measure platelet responses in your study.