Platelet production begins in the bone marrow where the maturation of megakaryocytes, the platelet precursor cells, is driven by binding of TPO to its receptor, Mpl. Young platelets released in the circulation contain the GPIbα receptor in its fully glycosylated form, in which sialic acid (magenta diamond) covers galactose (yellow circle). Loss of sialic acid (desialylation) on GPIbα induces platelet clearance by the AMR on hepatocytes, thereby inducing the production of hepatic TPO. Xu et al show that platelets lacking GPIbα (as in Bernard-Soulier syndrome) are not recognized by the AMR; hence the production of TPO is reduced.1 Illustration by Leonardo Rivadeneyra, Blood Center of Wisconsin.
