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SN4-27: Mechanisms and Treatment for Hyper Hemolysis in Sickle Cell Disease


Oct 20, 2019 2:00pm ‐ Oct 20, 2019 3:30pm

Description

Red blood cell (RBC) transfusion represents a fundamental intervention for patients with Sickle Cell Disease (SCD). However, as with any therapy, transfusion is not without risk. Exposure to allogenic RBCs can result in the formation of RBC alloantibodies, which can make it difficult to find compatible RBCs for future transfusion. While transfusion of phenotypically matched RBCs may reduce RBC alloimmunization rates, even following common matching protocols, patients with SCD can continue to generate RBC alloantibodies. In addition to making it difficult to find compatible blood for future transfusion, these alloantibodies can directly increase the risk of developing acute and delayed hemolytic transfusion reactions. In these settings, SCD patients can develop additional hemolysis of their own RBCs, a process often referred to as Hyper Hemolysis Syndrome (HHS). HHS can significantly complicate the management of SCD patients and increases mortality in severely affected patients. Effective treatment options for HHS have largely remained enigmatic in part due to an incomplete understanding of the pathophysiology and therefore appropriate therapeutic targets of this process. Recent results suggest that HHS results from unchecked complement activation and a lack of innate control mechanisms necessary to prevent worsening anemia. This program is intended to provide new insight to the pathophysiology of HHS, with a particular focus on the role of complement and regulatory macrophages in this process. In light of these recent finding, current and future treatment strategies will be discussed that may more effectively address the challenging clinical situations that HHS can present.

Learning Objectives:

  • Summarize mechanisms of innate control that protect against hyper hemolysis.
  • Discuss the role of complement and macrophages in hyper hemolysis syndrome.
  • Describe treatment options for SCD patients experiencing hyper hemolysis.

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