Hepatic TPO production via JAK2-STAT3 signaling after desialylated platelet uptake by the AMR. Desialylated, senile platelets are recognized by the hepatic AMR to regulate hepatic TPO production, BM homeostasis, and thrombopoiesis. BM MKs produce and release young sialic acid (purple ring) containing platelets into the blood stream. Young platelets maximally internalize TPO through Mpl receptors. Circulating platelets become desialylated as they age by active blood-borne sialidases (dashed purple ring), become ligands for the AMR, and are ingested by hepatocytes. Desialylated platelet ingestion signaling positively stimulates hepatic TPO mRNA expression via activation of JAK2-STAT3 and TPO release into plasma, thereby regulating BM homeostasis and thrombopoiesis.