Consequences of hemolysis: Pro-inflammatory cytokine response to erythrophagocytosis

Red blood cells (RBCs) can be cleared from the circulation either intravascularly or extravascularly. In the setting of an IgG-mediated delayed hemolytic transfusion reaction (HTR), most RBC clearance is typically extravascular, presumably by phagocytosis by liver and splenic macrophages. Animal models of HTRs suggest that this RBC clearance is associated with a pro-inflammatory cytokine response. Although IgG-mediated HTRs are typically benign, they can lead to vaso-occlusive crises and further complications, such as hyperhemolysis, in patients with sickle cell disease (SCD). Why the manifestations of HTRs are more severe in the setting of SCD has yet to be determined; however, in this symposium paper, we provide a review of the evidence that robust RBC phagocytosis results in a pro-inflammatory cytokine response, which may induce vaso-occlusive crises and further complications in the setting of SCD.