The role of apoptosis in megakaryocyte and platelet biology. Megakaryocytes possess functional BAK/BAX-mediated intrinsic and FasL-inducible extrinsic apoptosis pathways. Both pathways must be restrained during megakaryocyte growth and development in order to allow platelet production to occur. Megakaryocyte apoptosis can be triggered in response to pathophysiological stresses such as chemotherapy or infection. Once shed into the circulation, platelet lifespan is regulated by the intrinsic apoptosis pathway. Bcl-xL is the essential mediator of platelet survival. BH3 mimetic drugs, such as navitoclax (ABT-263), that target Bcl-xL cause platelet apoptosis and thrombocytopenia. Platelets appear to lack the Fas receptor, and the role of Caspase-8 and the extrinsic pathway in platelets is yet to be established. Professional illustration by Somersault18:24.