We describe a 7-year-old female patient with SCD (Hb SS) with D+, C+(partial), E-, c+(partial), e+(partial), V + VS+, hrB-, hrS + RBC phenotype who developed multiple RBC antibodies and suspected DHTR after her second lifetime transfusion, in the setting of severe anemia and ACS. Here, AGFG1 is linked to acute chest syndrome.