P67: An Evaluation of Aspirin and Platelet Activation in the Presence of Shear Stress

Abstract

Background: Mechanical circulatory support (MCS) causes high levels of shear stress, which could lead to complications such as platelet activation and thrombosis. Aspirin is an anti-platelet drug that functions through COX-1 inhibition, however, this may not be sufficient to reduce activation via mechanical stimuli. As such, this study evaluated the efficiency of Aspirin to reduce the downstream effects of platelet functioning and the impact this may have on shear stress-induced thrombosis. Methods: Human blood was treated with and without Aspirin (4.5 μg/mL) and subjected to VAD-like shear stress for 4 hours. Platelets were analyzed by flow cytometry, using CD42b and CD62P, to assess multifactorial parameters. Positive events were normalized and assessed for platelet activation, granularity (size), as well as the number of platelet-platelet aggregates and platelet-derived extracellular vesicles (EVs). Results: Aspirin moderately reduced platelet activation and platelet granularity compared to the untreated control, suggesting little to no protective effects against mechanical stimulation. However, the presence of Aspirin had a greater effect on reducing the number of platelet aggregates and platelet-derived EVs in the presence of VAD-like shear stress. Conclusion: The use of Aspirin (and COX-1 inhibition) may prove ineffective for reducing platelet activation by mechanical stimuli in high-risk patients. However, Aspirin may impair the downstream formation of pro-thrombotic platelet aggregates and EVs, thereby reducing the risk of thrombosis in MCS patients. As Aspirin is observed to provide some protection, further research into combination therapy with additional anti-platelet drugs is needed to overcome the negative impact of mechanical stimulation.