Thrombopoietin receptor agonists in ITP. Platelet production in patients with ITP is variable. Megakaryopoiesis may be impaired by antibody, and platelets are destroyed by macrophages within the spleen and elsewhere, perhaps including the bone marrow. Plasma levels of TPO are normal or only slightly increased in patients with ITP, and hepatic production is insufficient to overcome antibody-mediated platelet destruction. Megakaryocytes stimulated with TPO receptor agonists (TPO-RAs) generate platelets in greater numbers, which may also lessen sensitization with antibody and reduce both peripheral clearance and perhaps intramedullary destruction. Illustration by Kenneth Probst.