Persistently high quality of life conferred by coexisting congenital deficiency of terminal complement C9 in a paroxysmal nocturnal hemoglobinuria patient

The long‐acting anti‐C5 ravulizumab results in C3 binding to PNH red cells similar to its parental molecule eculizumab

“…16 Nevertheless, these in vitro and in vivo observations confirm that C3d binding to PNH red cells is a phenomenon inherently associated with the inhibition of C5 and, likely, with the inactivation of any other component of the terminal complement pathway. 17 In keeping, C3 binding has been documented also when C5 is blocked in vitro by agents other than monoclonal antibodies as coversin. 18 Therefore, any C5 inhibitor, including ravulizumab, is not expected to prevent the progressive C3 binding to PNH red cells, eventually leading to the onset of C3-mediated extravascular haemolysis.…”

Occupancy of whole blood cells by a single PIGA‐mutant clone with HMGA2 amplification in a paroxysmal nocturnal haemoglobinuria patient having blood cells with NKG2D ligands

“…She has mild BM failure responsive to low-dose metenolone acetate (10 mg/day). She also manifests very low levels of both intra-and extravascular haemolysis, with detection of haemosiderinuria and C3d-bound erythrocytes (Hanaoka et al, 2012). Flow cytometry showed complete occupancy of her peripheral blood by PNH cells negative for both CD55 and CD59 (Fig 1A).…”

The inhibition of several components of terminal complement pathway results in C3 binding to PNH red blood cells

“…3,5,6 Altogether, these in vitro and in vivo observations confirm that C3 binding to PNH red blood cells is a phenomenon associated with the inhibition of C5. However, C3 binding has also been reported in a PNH patient that does not suffer from intravascular hemolysis because of a coexisting congenital deficiency of complement 9 (C9) 7 suggesting that it could be associated with the inhibition of any component of the terminal complement pathway.…”