Platelet function testing in drug discovery projects: considerations and challenges
Selection of the most appropriate test system and study design for evaluating effects on platelet function requires consideration of the study objective, platelet physiology, and the pharmacology and characteristics of the test item(s).
Since the main physiological role of platelets is to provide primary haemostasis when vessel wall integrity is compromised, the first challenge is to avoid/minimise platelet stimulation while drawing blood.
Secondly, since platelet viability decreases with time, there is a limited window in which to perform assays - ideally within 4-6 hours of sampling. Any requirement to transport samples can be problematic.
Depending on study objective, test item and anticipated effects, there is a choice of matrix and assay. Platelet function can be measured in whole blood (WB), platelet rich plasma (PRP), or in washed platelets (WP), resuspended in a suitable buffer. WB is the most physiological matrix, but complex, and can require just a small sample volume. WP is the least physiological, requires larger volumes but provides a “clean” system.
Assay choice depends on the matrix and required throughput. Stimulated platelets exhibit the following responses: adhesion to subendothelial matrix; shape change; pseudopodia formation; activation and granule content release; aggregation; interaction with leucocytes. Most common assays measure activation and aggregation, applicable in all matrices. Platelet-leucocyte conjugate formation is only measurable in WB. The response pattern can vary depending on the test system and this needs to be considered when interpreting data.
The above factors apply to studies in human platelets. There are additional complexities (technical and pharmacological) when considering studies on platelets from preclinical species. Alignment of project specifics and platelet function testing expertise can ensure design of a tailored, decision-making study.