The molecular basis of platelet function phenotype, Understanding the basis of high and low platelet reactivity
NBR70 / CBR 211
Professor Jonathan Gibbins
Institution or company
University of Reading and Cambridge institute of Public Health
Platelets trigger blood clotting following injury, but also cause thrombosis, leading to heart attacks and strokes. Platelets are targeted using drugs that inhibit their activation and while these prevent thrombosis in many patients, a sizeable proportion gain no benefit. Presently a ‘one size fits all’ approach is used: patients at risk of thrombosis are given one or more standard anti-platelet medication. Recent trials indicate that such approach is protective again secondary thrombosis in patients that have already suffered thrombosis, but does not protect patients without a history of thrombosis. This raises the question: are we treating patients appropriately and giving medication to those most likely to respond positively? To answer this question we need to understand exactly how platelet reactivity varies and why this occurs, and the impact of this on responsiveness to anti-platelet therapies. To address this we have measured in detail the functional characteristics of 700 healthy individuals. We have developed new high-throughput assays that utilise machine learning approaches to allocate donors to one of 8 distinct phenotypic groups. Curiously, the least reactive phenotypic group also contains a large proportion of overweight patients, those with early signs on insulin resistance and elevated blood lipids. This was not expected, and would suggest that a group that is considered higher risk for cardiovascular disease may be less responsive to anti-platelet medication. In the proposed study extension we will recall participants from the highest and lowest responsive groups to (1) validate the profiling procedure, (2) to determine whether phenotype within individuals is stable, (3) test responsiveness to anti-platelet medication and (4) collect protein samples from donors’ platelets to enable detailed proteomic profiling to be performed. This will allow mechanisms of variability to be studied and biomarkers established to perform simplified clinical tests, and the development of precision-medicine approaches to combat thrombosis.