Affiliation:
1. Amsterdam UMC location University of Amsterdam Department of Hematology Amsterdam The Netherlands
2. Sanquin Research and Landsteiner Laboratory Department of Molecular Hematology Amsterdam The Netherlands
3. Emma Children's Hospital, Amsterdam UMC location University of Amsterdam Department of Pediatric Hematology Amsterdam the Netherlands
Abstract
AbstractSickle cell disease (SCD) is an inherited hemoglobinopathy characterized by chronic hemolytic anemia and recurrent microvascular occlusions, resulting in acute painful events and progressive organ damage. Although primarily a red blood cell disorder, the pathophysiology of SCD is increasingly characterized as a complex interplay between several different cell types and cellular processes. Evidence is accumulating that neutrophils are phenotypically different in SCD and have a significant contribution in the pathophysiology of the disease. In this review, we summarize the currently available evidence on the role of neutrophils in SCD pathophysiology, demonstrating that neutrophils in SCD have an activated phenotype and play an important role in vaso‐occlusion and inflammation in SCD. Activation of neutrophils in SCD is primarily driven by hemolysis and ischemia–reperfusion injury. The ameliorating effects of treatments, for example, hydroxyurea, might be partly mediated by decreasing neutrophil counts and reversing the pro‐inflammatory properties. Whether the novel anti‐sickling therapies, reducing hemolysis, have an anti‐inflammatory effect on neutrophils, remains to be elucidated.