The signatures of TLR4-pathway signaling, of ET (48), of macrophages, of an LPS-tolerant state (49), and of the polarization of macrophages to an immunosuppressive M2 state (50), which is shown to resemble ET macrophages (39, 53, 55), all suggest development of ET with CAP severity in agreement with (9). This evidence concerns the gene TLR4 and essential thrombocythemia.