Multi-parameter phenotyping of platelet reactivity for stratification of human cohorts

Dunster, Joanne L, Bye, Alexander, Kriek, Neline, Sage, Tanya, Kempster, Carly, McKinney, Harriet, Batista, Joanna, Thomas, Patrick, Jones, Chris, Downes, Kate, Unsworth, Amanda ORCID: https://orcid.org/0000-0003-3809-5984 and Gibbins, Jonathan (2021) Multi-parameter phenotyping of platelet reactivity for stratification of human cohorts. Blood Advances, 5 (20). pp. 4017-4030. ISSN 2473-9529

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Abstract

Accurate and comprehensive assessment of platelet function across cohorts of donors may be key to understanding the risk of thrombotic events associated with cardiovascular disease, and hence help personalise the application of antiplatelet drugs. However, platelet function tests can be difficult to perform and analyse, unreliable or uninformative and poorly standardised across studies. The Platelet Phenomic Analysis (PPAnalysis) assay and associated open-source software platform was developed in response to these challenges. PPAnalysis utilises pre-prepared freeze-dried microtitre plates to provide a detailed characterisation of platelet function. The automated analysis of the high-dimensional data enables the identification of sub-populations of donors with distinct platelet function phenotypes. Using this approach we identified that the Sensitivity of a donor’s platelets to an agonist and their Capacity to generate a functional response are distinct independent metrics of platelet reactivity. Hierarchical clustering of these metrics identified six subgroups with distinct platelet phenotypes within healthy cohorts, indicating that platelet reactivity does not fit into the traditional simple categories of ’high’ and ’low’ responders. These platelet phenotypes were found to exist in two independent cohorts of healthy donors and were stable on recall. PPAnalysis is a powerful tool for stratification of cohorts on the basis of platelet reactivity which will enable investigation of the causes and consequences of differences in platelet function and drive progress towards precision medicine.