Atypical hemolytic uremic syndrome in a patient with thalassemia and a CFH gene mutation: a case report

Atypical hemolytic uremic syndrome (aHUS) is a complement-associated thrombotic microangiopathy (TMA). Thalassemia is a hemolytic anemia triggered by defects in the beta-globin gene. Mutations in the complement factor H (CFH) gene are associated with the development of aHUS; however, CFH gene mutations coexisting with thalassemia have rarely been reported. CFH gene mutations are susceptibility factors that can trigger complement overactivation during pregnancy. When aHUS is combined with thalassemia, large amounts of hemoglobin are released from fragmented erythrocytes, leading to amplification of the complement cascade and resulting in a "two-hit" mechanism that may affect the efficacy of C5 inhibitors. Here, we report a case of pregnancy-associated aHUS in a patient with thalassemia and a CFH gene mutation. After admission to the hospital, plasmapheresis and hemodialysis were used to treat TMA. Following confirmation of aHUS, eculizumab was initiated immediately, and the erythroid maturation agent luspatercept was added for the treatment of thalassemia. The patient was weaned off hemodialysis, and there was no recurrence of aHUS during the follow-up period. This diagnostic and therapeutic approach may provide a new strategy for the use of C5 inhibitors to treat patients with aHUS and thalassemia.