The effects of dual anti-platelet therapy (DAPT) on neutrophil and platelet activation

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Aspirin and ticagrelor are anti-platelet medications given to people suffering from a heart attack. This type of medication prevents platelets from becoming activated. Platelets repair damage in blood vessels. However, these cells also cause blood clots in the arteries of the heart, and this can cause a heart attack. Neutrophils are another cell type that is crucial for our health. Neutrophils are part of our immune system and survey the blood for any intruding pathogens. These cells ‘activate’ and become inflammatory when our body encounters an infection. However, these cells have been shown to participate in heart attacks also. These cells can produce a very inflammatory substance called Neutrophil Extracellular Traps (NETs) in a process called NETosis. NETs are great during infection, as they trap invading pathogens. However, these NETs can also activate platelets, a process which we know can cause a heart attack. We believe that anti-platelet medication (aspirin and ticagrelor) will reduce the ability of neutrophils to produce NETs and will reduce the ability of platelets to activate in response to NETs. It could be beneficial for anti-platelet medication to have this effect, as this may reduce inflammation after a heart attack. We aim to: • We aim to investigate whether anti-platelet medication affects neutrophils and their ability to undergo NETosis. • We also aim to investigate whether anti-platelet medication affects the ability of platelets to activate in response to NETs. There are two "arms" of this study: 1. The intervention arm: we are recruiting 20 volunteers to take anti-platelet medication. 2. The treatment-naïve arm: we are recruiting 3 volunteers to be a control for the intervention arm. Recruitment into this arm does not involve taking anti-platelet medication. At the first study visit, we will take a “baseline” blood test. After we have taken the “baseline” blood test, participants will be asked to take their first dose of anti-platelet medication. These are aspirin and ticagrelor. In between the First and Second study visit, participants will be asked to take their second dose of anti-platelet medication in the evening of the first study visit. The second study visit will occur the day after the first study visit. On this day, participants will take the third and final dose of anti-platelet medications in the morning, prior to the second study visit. At the second study visit, we will take a second blood sample, no later than 6 hours after participants have taken their third dose of anti-platelet medications. Three healthy volunteers in the treatment naiive-arm will give blood for each of the participants in the treatment-intervention arm to provide neutrophils that have not been influenced by DAPT. A study researcher will then assess the extend to which neutrophils can produce NETs in the presence of platelets pre- and post treatment with DAPT.

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