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A ten‐year‐old black girl with sickle cell disease developed anti‐Fy5 antibody. She received one unit of Fy5 positive blood and had a delayed hemolytic transfusion reaction four days later. In addition she had anti‐E, anti‐C and anti‐K antibodies. A clinical picture of autoimmune hemolytic anemia evolved with a strongly positive direct antiglobulin test and strong auto anti‐I antibodies. She improved after a course of steroid therapy.