BACKGROUND: Acute intravascular hemolysis is rarely associated with platelet transfusion. Out-of-group single-donor platelets may cause hemolysis if the donor has high-titer ABO hemagglutinins. CASE REPORT: A 44-year-old woman, blood group A, was recently diagnosed with acute myeloid leukemia and was receiving chemotherapy. After the transfusion of apheresis platelets from a group O donor, back pain, hemoglobinuria, and hemoglobinemia developed, and her Hb dropped by 2.3 g per dL, despite the transfusion of 2 units of RBCs. RESULTS: Investigation revealed acute intravascular hemolysis with a positive DAT due to anti-A1 on her RBCs. The donor's titer of anti-A1 was greater than 16,000. CONCLUSION: Review of published cases raises the possibility that hemolytic reactions to out-of-group platelets may be more frequent since the use of apheresis platelets has increased.