This coupled effect was observed for paroxysmal nocturnal hemoglobinuria (PNH) patients where treatment with eculizumab regulated terminal complement activation but some patients still suffered from extravascular opsonophagocytosis (also referred to as extravascular hemolysis) that is attributed to early-phase complement activation and propagation induced by C3 [39]. This evidence concerns the gene C3 and paroxysmal nocturnal hemoglobinuria.