TPO-RA in ITP. ITP monocyte/macrophages have an activated monocyte FcγR phenotype as indicated by decreased FcγRIIb expression paralleled with remarkably increased FcγRI and FcγRIIa expression. Opsonization of platelets by antiplatelet autoantibodies in ITP results in increased platelet destruction via FcγR-mediated phagocytosis by monocyte/macrophages. In addition to their direct effect on activating TPO-Rs on megakaryocytes that result in platelet production, TPO-RAs restore FcγR balance on monocytes/macrophages and downregulate the phagocytic capacity of macrophages, thus attenuating platelet destruction. The mechanism of action of how this occurs remains to be discovered. It may be that the increase in platelet mass following TPO-RA treatment results in elevated levels of circulating transforming growth factor-β1 (TGFβ1) which, directly or indirectly through increasing Treg activity, restores FcγR balance and inhibits macrophage phagocytic activity.