Autoimmune hemolytic anemia (AIHA) is a rare disease in which the immune system mistakenly attacks the patient’s own red blood cells (RBCs), leading to anemia that may be severe and even life-threatening. In about half of AIHA patients, blood transfusions are needed. We recently investigated two severe cases of AIHA and found that destruction of RBC’s in these patients was not caused by the currently known mechanisms. Instead, we discovered a high rate of RBC vesicles, which is a novel finding. In addition, we observed a loss of a protein called complement receptor type 1 or CR1 in another group of AIHA patients. CR1 normally protects RBCs for destruction via complement. Both the vesiculation and CR1 loss point towards so far unknown disease mechanisms.  With this project, we aim to further study these new findings to understand how often they occur and in what subtype of AIHA, how they are caused and if they may relate to a more severe disease course, The ultimate goal is to uncover new mechanisms of RBC destruction that may lead to potential biomarkers and therapeutic targets in AIHA.