Complement inhibition and hemolysis in PNH. The alternative pathway of complement is continually activated through a process called “tick-over.” Stressors, such as infections, can intensify this process. DAF and CD59 are complement regulatory proteins that are linked to the surface of RBCs by GPI anchors and protect the RBCs from alternative pathway-mediated lysis. However, these proteins are absent from some RBCs in patients with PNH. In these patients, activation of the alternative pathway causes extravascular hemolysis of RBCs by coating the RBC with the C3b fragment, and causes intravascular hemolysis through formation of C5b-9, or the MAC, on the RBC surface. Eculizumab reduces hemolysis by preventing formation of C5b-9. Compstatin prevents the formation of C3b and C5b-9 on PNH RBCs. MAC, membrane attack complex; RBC, red blood cell. Professional illustration by Alice Y. Chen.