From Renal Siderosis Due to Perpetual Hemosiderinuria to Possible Liver Overload Due to Extravascular Hemolysis: Changes in Iron Metabolism in Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients On Eculizumab.

Abstract 4031 Poster Board III-967 Iron metabolism in PNH patients is dominated by perpetual iron loss consequent to the chronic complement-mediated intravascular hemolysis; thus, they are prone to develop iron deficiency rather than iron overload, even in presence of large transfusional requirement. Eculizumab (Ecu) has proven effective for the treatment of intravascular hemolysis in PNH patients, resulting in reduction and even abolishment of transfusion requirement and improvement of signs and symptoms of intravascular hemolysis; however, Hb gain is heterogeneous among patients, in most cases due to residual C3-mediated extravascular hemolysis hampering Hb normalization. The goal of our study was to identify possible modifications in iron compartmentalization associated with Ecu treatment and possible clinical consequences. We evaluated iron metabolism in 5 untreated PNH patients and 23 who were receiving Ecu (of whom 4 have been also studied before treatment), combining biochemical parameters with a semiquantitative T2* MRI technology. MRI was performed using four gradient-echo sequences and one spin-echo sequence; signal intensity (SI) was measured on images obtained with each sequence by means of three regions of interest placed in the renal cortex, liver, spleen and at the level of the para-spinal muscle, resulting in a semiquantitative SI value (Grandon et al., Radiology 1994). Within the total patient cohort (regardless they were or were not on Ecu), there was a significant correlation between liver SI and serum ferritin (P Disclosures: Risitano: Alexion Pharmaceuticals: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding.