Apoptotic machinery in platelet clearance and lifespan. The anti-apoptotic Bcl-xL restrains the proapoptotic Bax/Bak in platelets. Mitochondrial damage induced by CCCP, an ionophore, leads to robust ectodomain shedding of GPIbα. If inhibition by Bcl-xL is blocked pharmacologically, Bax/Bak will induce mitochondrial damage, leading to the apoptotic cascade. The BH3-only initiator of apoptosis Bad may also affect platelet lifespan, though further study would help to elucidate its role. Apoptotic cells redistribute PS from the inner to the outer leaflet of their plasma membranes. One calcium-independent pathway may involve Xkr8. Another pathway present in platelets is facilitated by TMEM16F, a calcium-activated phospholipid scramblase.