Methods for measurement of platelet function in the assessment of non-clinical drug safety and implications for translatability

Abstract Plateletsplay a pivotal role in normal hemostasis. Drug-induced derangement of plateletfunction can lead to either an increased bleeding risk when plateletfunction is inhibited or a proaggregant state that can manifest as thrombosis when it is exacerbated. In both cases, drug-induced plateletdysfunction can lead to serious adverse events in patients that can limit drug prescription or ultimately lead to the withdrawal of the drug from the market. Despite those risks, drug-induced plateletfunction defects do not appear to be highlighted during drug development; rather they are reported at the post-approval stage indicating that current preclinical assays and clinical development studiesare failing to capture these liabilities. However, significant progresses have been made in plateletfunction testing and clinically useful methods now exist for the measurement of plateletfunction. This review paper discusses these methods and describes their advantages and disadvantages in the setting of non-clinical drug safety to assess drug-induced plateletdysfunction and on the translatability of these tests to predict thrombosis and bleeding in patients.