Decision making process for the indication of transfusion in a patient with history of hyperhemolysis. A patient with history of posttransfusion hyperhemolysis is at risk for recurrence of the syndrome, with or without detectable antibodies. When a transfusion is indicated, a shared decision-making process assesses the risk/benefit of transfusion, and if maintained, establishes the transfusion protocols in terms of RBC antigen matching and the use of immunosuppressive therapy. Close monitoring of the posttransfusion phase is absolutely necessary, and assessment of total Hb and HbA% immediately after transfusion will help diagnose posttransfusion hyperhemolysis with new assessment of these parameters. If clinical signs appear, evaluation of hemolytic biological parameters and an IH workup are performed. A negative IH workup does not rule out the diagnosis. After confirmation of hyperhemolysis, supportive care and specific treatments are considered. Hb, hemoglobin; IH, immunohematology; LDH, lactate dehydrogenase; RBC, red blood cell; VOC, vaso-occlusive crisis.