Immune-mediated clearance of antibody-opsonized platelets in patients with ITP is mediated by macrophages activated by antibody binding to activating Fcγ receptors. The tyrosine kinase Syk induces phosphorylation of substrates controlling the phagocytic machinery of the antibody-activated macrophage. Inhibition of Syk activity reduces platelet depletion, most likely by inhibiting phagocytosis of antibody-opsonized platelets, but possibly also by reducing antibody production by activated B cells.