C5 and infection: It has been suggested that infections associated with BTH cause proximal complement activation which thus causes BTH.31 Thus, even though ravulizumab seems to have eliminated the breakthrough hemolytic events related to suboptimal free C5 inhibition, a nonnegligible fraction of patients still experiences various degrees of EVH (up to 20%) because of C3 fragment opsonization with clinically signficant transfusion dependency.26 To overcome this, further proximal complement inhibitor medications are being developed.