Control of hemolysis in patients with PNH

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by the triad of intravascular hemolysis (IVH), a tendency to thrombosis, and an element of bone marrow failure. With the introduction of the anti-C5 antibody eculizumab (ECU), 1 IVH and associated symptoms are abrogated, and the risk of thrombosis is greatly reduced; however, most patients remain anemic, and some remain transfusion dependent. 2 In this issue of Blood, Kulasekararaj et al 3 report that danicopan (DNC), an inhibitor of complement factor D, added to ECU, corrects or at least ameliorates the anemia. This important clinical result is also of great interest with respect to pathophysiology (see figure panels AB). When a patient with PNH is on ECU, red cells no longer suffer complement-mediated lysis, but unlysed red cells undergo opsonization by C3 fragments (see figure, panel C) and are thus marked for removal by macrophages.