This is a proposal for a pilot study to evaluate the feasibility of measuring 5-hydroxytryptamine (5-HT) release from platelets as an indicator of dense granule release during platelet activation in volunteers taking aspirin.
One phase of platelet response to activating agonists involves release of dense granules, which are known to contain 5HT (serotonin) and ATP. There are various methods of measuring the degranulation of platelets: ATP release can be measured using a lumiaggregometer, and release of 14C radiolabeled 5-HT from platelets. Using the aggregometer and a 14C labeled 5-HT assay can be used to measure 5-HT release from platelets.
Our experience suggests that ADP-induced ATP release is insensitive to detect very low levels of platelet dense granule release, which occurs in aspirin-treated subjects. The pilot study will permit optimizing the method for reliably detecting low levels of 5HT release in patients who achieve submaximal inhibition of the cyclooxygenase during aspirin treatment.
