Increasing evidence suggest that intravascular hemolysis estimated to account for one third of hemolysis in sickle cell anemia (SCA) plays a central role in SCA pathophysiology. Mechanism underlying the pathologic effect of hemolysis include the pro-oxidant and cytotoxic effects of breakdown products, namely hemoglobin and its oxidized form heme, on the vascular endothelium through delivery of red cell microparticles or directly by Toll-like receptor 4 (TLR4) signaling as well as the impact of heme species on key immune cell types that can further magnify the inflammatory effects. Whether transfusions can intersect with the mechanisms has not been systematically examined, but the prediction is that tipping this immune response toward an anti-inflammatory state may be key in the treatment and management of SCA complications. In this session, we will review cellular heme sensing and response pathways in normal and hemolytic disorders including SCA, describe recent studies on the impact of transfusions on these heme response pathways in SCA and discuss potential therapies that may be combined with transfusions as a framework for optimization of transfusion management and support for this patient population.
Review the role of hemolysis in sickle cell pathophysiology
Describe the prooxidant and cytotoxic effects of hemolysis breakdown products
Discuss the effect of transfusions on heme response pathways in innate immune cells in sickle cell anemia and potential use of anti-hemolytic therapies for optimization of transfusion management
Vascular Medicine Institute, University of Pittsburgh