Mechanism of anti-CD44 in protecting against antibody-mediated platelet destruction in ITP. In ITP, antiplatelet autoantibodies opsonize platelets, and these opsonized platelets, through the antibody-Fc region, are recognized by FcγRs on the surface of macrophages. This results in FcγR-mediated platelet phagocytosis by macrophages and in platelet clearance from the circulation resulting in thrombocytopenia (A). Anti-CD44 coengages CD44, as well as FcγRs, on the cell surface of macrophages (in cis), with the anti-CD44 Fc region blocking the macrophage FcγR (Kurlander phenomenon). This prevents FcγR-mediated platelet phagocytosis by macrophages and thus protects against platelet clearance from circulation and development of thrombocytopenia (B). PLT, platelet.