Model of complement dysregulation in aHUS (A) and PNH (B). Initiators of the complement cascade (classical, alternative, and lectin pathway, as well as thrombin and plasmin/kallikrein) lead to C3 activation and C3 convertase formation, which is augmented the amplification loop (proximal complement). Consequently, membrane attack complexes (MAC) are formed on the membrane of target cells (terminal complement), leading to complement-mediated death. Production of C5a results in tissue factor and thrombin activation in a positive feedback loop. Complement dysregulation results from loss-of-function mutations in regulatory factors (Factor H, I, and THBD/thrombomodulin in aHUS and CD55, CD59 in PNH) shown in red, gain-of-function mutations (C3 and Factor B in aHUS) shown in green, and DGKE mutations in aHUS shown in gray, indicating the unknown effect on complement cascade. Eculizumab effectively inhibits terminal complement activation in both disorders by blocking the cleavage of C5 to C5a and C5b.