Autonomic nervous system dysfunction: implication in sickle cell disease

Sickle cell disease is an inherited hemoglobinopathy caused by a single amino acid substitution in the β chain of hemoglobin that causes the hemoglobin to polymerize in the deoxy state. The resulting rigid, sickle-shaped red cells obstruct blood flow causing hemolytic anemia, tissue damage, and premature death. Hemolysis is continual. However, acute exacerbations of sickling called vaso-occlusive crises (VOC) resulting in severe pain occur, often requiring hospitalization. Blood rheology, adhesion of cellular elements of blood to vascular endothelium, inflammation, and activation of coagulation decrease microvascular flow and increase likelihood of VOC. What triggers the transition from steady state to VOC is unknown. This review discusses the interaction of blood rheological factors and the role that autonomic nervous system (ANS) induced vasoconstriction may have in triggering crisis as well as the mechanism of ANS dysfunction in SCD.