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English: Figure 1 Pathogenesis of hemolysis in paroxysmal nocturnal hemoglobinuria. In the upper panel, the three complement pathways (classic, alternative, and lectin binding) converge to C3 whose activation following formation of C3 convertase and formation of C3b is regulated by CD55. C3b can then join C5b once cleaved from C5 via C5 convertase and form the membrane attack complex (MAC) along with C6, C7, C8 and C9 (a process inhibited by CD59). In PNH, the lack of CD55 and CD59 makes PNH cells (in particular erythrocytes) vulnerable to complement-mediated lysis because of the absence of inhibitory signals. Eculizumab and ravulizumab block C5 cleavage preventing the formation of the MAC. In the lower panel, the excess of C3 fragment in PNH patients treated with C5 inhibitors leads to opsonization of circulating erythrocytes and extravascular hemolysis via macrophage-mediated phagocytosis in the reticuloendothelial system (RES).