Platelets, small anucleate cells derived from megakaryocytes, are key drivers of hemostasis and thrombosis. There is accumulating evidence, however, that platelets play roles beyond thrombosis and hemostasis, especially in inflammation, infection, and tissue regeneration. They can recruit, stimulate, and modulate immune cells by direct interaction or via the release of soluble factors. During inflammation, platelets maintain vascular integrity in the lung, skin, and brain through interactions of their GPVI, CLEC-2, and GPIb receptors as well as factors released from α-granules and dense granules. They cooperate with monocytes and macrophages to fight bacteria in the bloodstream and in the liver where they accumulate on Kupffer cell-bacteria complexes to support pathogen destruction. Upon liver damage, platelets adhere to the liver sinusoids and release bioactive molecules like serotonin and fibrinogen to support reparative processes. Here, we provide a review of some of the multiple roles of platelets beyond their classical role in hemostasis.
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