An Investigation of Platelet Activation Markers.
Measurement of platelet activation during preclinical testing can identify candidate drugs that are not suitable for development. The established method for measuring platelet activation within the clinical pathology laboratory at Charles River, Edinburgh is the use of platelet indices; mean platelet volume, platelet distribution width and mean platelet component using the Advia 2120i. To justify the time and expense required to validate and introduce a new assay into the laboratory would require improvements over existing tests. Measuring soluble P-selectin by enzyme-linked immunosorbent assay is a potential new marker for platelet activation that could be introduced. To investigate which method was more sensitive in detecting platelet activation blood samples were collected from 15 healthy donors and stimulated with platelet agonists adenosine diphosphate and thrombin. Relationships between each platelet parameter and soluble P-selectin were investigated. Results from the Advia 2120i and soluble P-selectin at each concentration were compared to baseline results. Significant changes were observed at the lowest level of adenosine diphosphate stimulation, 0.025μM, when compared to baseline. Mean platelet volume was reduced from 9.4±0.9 to 9.0± 0.5 fL, mean platelet component was increased from 25.1± 1.5 to 26.5± 1.3 mg/dL, both p≤0.05. Platelet distribution width was increased from 57.0±3.6 to 61.0±5.7 %, p≤0.01. Soluble P-selectin was not significantly different from baseline at the same concentration, 40.1±9.2 to 38.6±9.2 ng/mL but was increased from baseline at all other stimulation concentrations used. There were no significant relationships between soluble P-selectin and any of the platelet indices. The results show that soluble P-selectin was not more sensitive than established methods of detecting platelet activation when platelets were stimulated in vitro. Key words: soluble p-selectin, MPV, MPC, PDW