Use of Eculizumab in a Patient with Refractory Autoimmune Hemolytic Anemia with Heterozygous NFκB1 Mutation

Warm autoimmune hemolytic anemia (wAIHA) is characterized by autoantibody, and occasional complement binding of protein antigens, on the surface of red blood cells at temperatures ≥37 °C resulting in targeted destruction. We describe the case of a 17 year old male with a history of Evan's syndrome, poor immune response to vaccines and lymphoid hyperplasia, presenting with altered mental status and severe anemia, found to have a warm IgG pan agglutinin with evidence of both intra and extravascular hemolysis. His course was complicated by respiratory failure requiring intubation, pulmonary emboli, Enterococcus bacteremia and hypertension. He received multiple transfusions with only transient increases in hemoglobin. The AIHA was refractory to multiple rounds of treatment with high dose steroids, IVIG, rituximab, cyclophosphamide, bortezomib, plasma exchange and mycophenolate mofetil (MMF). Given the refractory nature of our patient's AIHA the decision was made to trial eculizumab, a monoclonal antibody targeting C5 complement, preventing its cleavage and activation, and shown to be effective in treatment of atypical hemolytic uremic syndrome and hemolysis due to an IgM cold agglutinin. Prior to eculizumab infusion, CH50 and Sc5b-9 assays were significantly elevated. After two doses of eculizumab, given 6 days apart, the patient's hemoglobin steadily rose independent of red cell transfusions with a corresponding decrease in reticulocyte count, LDH and CH50 levels. The patient has remained stable with a normal hemoglobin (12-14 g/dL) on maintenance steroids and MMF. Although we cannot definitively conclude that Eculizumab directly caused his recovery, the clinical course post-Eculizumab suggests this may be an efficacious treatment for refractory AIHA. Genetic testing showed monoallelic frameshift mutation of the NFκB1 gene and monoallelic missense mutation of the DOCK2 gene. Given the role of NFκB1 in both immunodeficiency and autoimmunity, it is thought that the patient's phenotype is due to NFκB1 haploinsufficiency and he is currently considering hematopoietic stem cell transplant.