Case report: persistent anemia after eculizumab in paroxysmal nocturnal hemoglobinuria: non-dominantly active intravascular hemolysis.

Abstract

Objectives: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare condition characterized by intravascular hemolysis (IVH), thrombosis, and organ damage. Although C5 complement inhibitors such as eculizumab have significantly improved the prognosis of patients with PNH, persistent anemia remains in some patients.

Methods: We report a patient with PNH who initially responded to eculizumab but experienced recurrent hemoglobin decrease and became transfusion-dependent after 24 weeks of treatment. Here, we present the clinical features of this patient. In addition, we reviewed the current literature to characterize persistent anemia caused by non-dominant residual IVH following C5 inhibitor therapy in PNH, along with related biomarker assessment and clinical applications of proximal complement inhibitors.

Results: Lactate dehydrogenase (LDH) levels did not significantly increase, and the direct antiglobulin test (DAT) with anti-C3d was only weakly positive (titre 1:16). The changes in free hemoglobin, haptoglobin, and type III red blood cells (RBC) (total loss of CD59) indicated subclinical yet active IVH. After the introduction of iptacopan monotherapy for six weeks, the levels of LDH, free hemoglobin, and haptoglobin normalized, and the need for further transfusions was eliminated. The proportion of type III RBC increased to 57.3%.

Conclusion: This case suggests that persistent anemia in patients with PNH following C5 inhibitor therapy might be associated with subclinically active IVH, and proximal complement inhibitors, such as iptacopan, may offer effective management of this condition.