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Abacavir (ABC) - antiretroviral drug used in HIV-therapy and associated with myocardial infarction - promotes thrombosis through purinergic P2X7R. The role of platelets as pro-thrombotic cells is acknowledged while that of neutrophils - due to their secretory capacity - is gaining recognition. This study analyses the role of neutrophils - specifically the secretome of ABC-treated neutrophils (SNThe effects of ABC or SNABC induced platelet-leukocyte interactions, a consequence not of a direct effect of ABC on platelets, but rather the activation of neutrophils, which triggered an interplay between platelet P-selectin and neutrophil PSGL-1. SNNeutrophils are target cells in ABC-induced thrombosis. ABC acts on neutrophil P2X7R, inducing the release of sLOX-1, which in turn activates platelets. Hence, sLOX-1 could be the missing link in the cardiovascular risk associated with ABC.