Outcomes on the use of hyperhemolysis prophylaxis in pediatric sickle cell disease patients with history of hyperhemolysis syndrome

Background: Hyperhemolysis syndrome (HS) is a rare but severe transfusion-associated complication seen in patients with sickle cell disease (SCD). The management of HS includes avoidance of post-hyperhemolysis red blood cell (RBC) transfusion to avoid reoccurrence of HS (recurrent HS). However, complete avoidance of post-hyperhemolysis RBC transfusion (PHRT) is sometimes not clinically possible, and the standard of care for recurrent HS prophylaxis for patients requiring PHRT has not been established. Case Report: We present a retrospective case series of four pediatric patients with SCD and a history of HS requiring PHRT, and describe their HS prophylaxis and outcomes. All patients received HS prophylaxis before transfusion, and three patients received an additional prophylactic regimen post-transfusion. Three patients were transfused with extended phenotype-matched RBCs, while one patient received only Rh (D, C/c, E/e) and K antigens matched RBCs. Only one patient did not develop recurrent HS after PHRT. Three patients had documented hemolysis, and two patients met our criteria for recurrent HS, all requiring escalation of care. Discussion: Even though the patients were treated in the same institution, there was variability in the choice of HS prophylaxis therapy and selection of RBCs, which can be attributed to the lack of guidance on PHRT management. We observed a lack of conclusive evidence in the effectiveness of prophylactic combination immunosuppressive therapy. Our observations suggest caution must be taken when transfusing patients with SCD and a history of HS, as there are no definitive therapies to effectively mitigate the risk of recurrent HS.