Ischemic heart disease is the leading cause of death in the world. Patients who have acute coronary syndrome (ACS) or chronic coronary syndrome (CCS) with significant thrombocytopenia are at high risk for bleeding. In the literature, studies conducted on this patient group are very few. For this reason, although it is difficult for physicians to manage antiplatelet therapy in these patients, the risk of bleeding can be minimized with some current guideline recommendations. This review aims to explore in detail the management of antiplatelet therapy in patients who have moderate and severe thrombocytopenia with coronary artery disease (CAD).