Overview of the processes by which activated platelets mediate I/R injury. Following interaction with injured ECs, ROS, and factors released by I/R-injured cells, platelets promote I/R injury by secreting granules and interacting with leukocytes. This includes enhancing leukocyte extravasation, oxidative burst, and capillary no-reflow (which includes PNAs, fibrin deposition, and other cellular debris; only PNAs are shown for simplicity).