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This study presents a rare case of delayed hemolytic transfusion reaction (DHTR) induced by anti‐Ku. The patient was admitted due to recurrence of ovarian cancer. She had experienced unexplained anemia for more than 20 years but had no anemia in the past 10 years. She had been pregnant four times and given birth to four babies without blood transfusions. Pre‐transfusion examinations showed that her blood group was A and RhD positive, and the unexpected antibody screening test was weakly reactive. She received two red blood cell transfusions and then developed unexplained anemia, with a hemoglobin decrease from 122 to 88 g/L. The unexpected antibody screening result changed to strongly positive, and she returned positive direct anti‐human globulin test and major incompatible matching results. The homozygous mutation 715G > T was identified in exon 7 of the KELL gene, which is associated with a rare blood group phenotype known as K0. The patient produced anti‐Ku antibodies, leading to a DHTR. Extravascular hemolysis was controlled through the administration of immunoglobulin and erythropoietin, leading to the correction of anemia. Her hemoglobin concentration was 105 g/L upon discharge from the hospital. In the management of blood transfusion for patients with rare blood types, a comprehensive analysis is required, taking into account the specificity of high‐frequency antibodies produced by the patient, the types and strength of these antibodies, as well as the clinical demand for blood. When necessary, a short‐term, adequate transfusion of minimally incompatible blood may be administered, along with intravenous immunoglobulin and erythropoietin to correct hemolysis and anemia.

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