Persistent transfusion dependence occurs in about 15% of patients with hemolytic PNH treated with eculizumab [26]: sometimes this can be explained by rapid drug metabolism, or by marrow failure-- but probably in the majority of cases it is due to extravascular hemolysis primarily in the spleen, as a result of deposition of C3d on red cells, leading to opsonization [19], and very recently, it has been shown that genetic polymorphism of the complement receptor 1 gene is a determinant of response to eculizumab [27]. Here, CR1 is linked to paroxysmal nocturnal hemoglobinuria.