denotes an abstract that is clinically relevant.
denotes that this is a recommended PHD Trainee Session.
denotes that this is a ticketed session.Sponsor: SCIENTIFIC
Program: Spotlight Sessions
Hematology Disease Topics & Pathways:
Anemias, sickle cell disease, Diseases, Combinations, Therapies, Adverse Events, cellular interactions, Biological Processes, Hemoglobinopathies, erythropoiesis, Clinically relevant, immune mechanism, inflammation, multi-systemic interactions, pathogenesis, pathways
Hematology Disease Topics & Pathways:
Anemias, sickle cell disease, Diseases, Combinations, Therapies, Adverse Events, cellular interactions, Biological Processes, Hemoglobinopathies, erythropoiesis, Clinically relevant, immune mechanism, inflammation, multi-systemic interactions, pathogenesis, pathways
Sunday, December 6, 2020: 11:55 AM-12:00 PM
Chair:
Karina Yazdanbakhsh, PhD, New York Blood Center
Disclosures:
No relevant conflicts of interest to declare.
Transfusions remain a cornerstone treatment for patients with sickle cell disease. However, patients can develop potentially fatal hyperhemolytic transfusion complications, estimated to account for 4% of all sickle cell patient deaths, but since the clinical symptoms mimic those of in sickle cell pain crisis, it is likely that this rate underestimates the true incidence. In addition, the occurrence and progression of such hemolytic reactions from mild to severe is unpredictable. Mechanistic insight into how this complication develops and its pathologic consequences can lead to better prevention and treatment options for this life-threatening condition which is mostly encountered in sickle cell disease. This session will present recent developments in our understanding of potential mechanisms that may account for increased red cell destruction, including heme-driven alternative complement activation pathways, autoantibody-mediated destruction of patient's own red cells, and altered innate immune activation including those of phagocytes, and describe promising therapeutic strategies to control the associated inflammatory response for this complication in sickle cell disease.
Dr. Lubka Roumenina will focus on mechanisms of overactivation of the innate immune inflammatory complement system in circulation and tissues innate in sickle cell disease. She will discuss recent work showing that dense erythrocytes as well as intravascular hemolysis-derived products, heme and erythrocyte microvesicles, are key activators of the complement cascade. In addition, she will describe how heme can render the vascular endothelium susceptible to complement attack in a TLR4/P-selectin-dependent manner. This work has implications for understanding the role of heme and complement in heme-driven pathology in sickle cell disease and also underscores the use of complement inhibition and heme scavenging as potential promising therapeutic strategies to control inflammation in hyperhemolytic conditions in sickle cell disease patients.
Dr. Karina Yazdanbakhsh will focus on the mechanisms of hemolytic transfusion reactions in sickle cell disease. Development of alloantibodies against transfused red cells account for hyperhemolytic reactions. Nevertheless, in about one third of cases, no antibodies can be detected, but the mechanisms for increased red cell destruction remain largely unexplained. Dr. Yazdanbakhsh will discuss the role of hemolysis and systemic inflammatory response in the activation of monocyte, macrophage and dendritic cells that drive extravascular red cell destruction in sickle cell disease. In addition, she will describe how in some patients, dysregulation in cell intrinsic heme response pathways may initiate the hyperhemolytic reaction due to the cell’s inability to tolerate any degree of excess heme and hemolytic insult. She will also discuss the potential for therapeutic manipulations of these pathways to reverse and dampen the associated inflammation in patients who suffer from these life-threatening transfusion complications.
See more of: Spotlight Sessions