The trigger of her crisis was an acute onset of sepsis secondary to <i>Escherichia coli (E. coli)-</i>associated pyelonephritis. Owing to a worsening of her VOC and a significant drop in her steady-state Hb levels, she required a blood transfusion of one unit of packed red blood cells (PRBC), which was later complicated by a delayed hemolytic reaction and worsening anemia. Here, GSTM1 is linked to Sepsis.