ABSTRACT
Improvements in sickle cell disease (SCD) care have improved overall survival and SCD now presents as a chronic condition characterised by progressive organ dysfunction. Organ dysfunction contributes to increased morbidity and mortality and poor quality of life in persons with SCD. Understanding the mechanisms that lead to progression of organ dysfunction (and eventual end organ damage) and early recognition are needed to institute therapeutic interventions.
SCD-related organ dysfunction can affect single or multiple systems, most described being kidney and neurological dysfunction, although cardiopulmonary, musculoskeletal, hepatobiliary and splenic organ dysfunction also occurs. Stroke occurs in 10% of children with SCD by age 16, and between 20% and 50% of adults have neurological impairment (stroke, silent infarct or cognitive impairment) while chronic kidney damage occurs in up to 25% of adults with SCD. Organ dysfunction can occur even in seemingly well persons and progresses with age often to irreversible end organ damage that is associated with an increased risk of death.
Organ dysfunction in SCD is related to Hb S polymerisation. The pathophysiology is multifactorial; involving chronic haemolysis, chronic anaemia, vaso-occlusion, nitric oxide deficiency, chronic inflammation and endothelial activation. Vaso-occlusion occurring in microvascular of organs in the body causes progressive tissue hypoxia and infarction. Further, haemolysis of sickled red cells releases free heme, that causes vascular endothelial damage, systemic inflammation and activation of complement system. Additionally, SCD associated systemic and vascular inflammation and oxidative stress can damage tissue cells and lead to organ dysfunction. Known risk factors for organ dysfunction SCD include chronic anaemia and microalbuminuria in children and hypertension and obstructive sleep apnoea in adults.
Routine and early screening for organ dysfunction can reduce mortality. In the present chapter, we discuss the burden, pathophysiology and comment on current management of organ dysfunction in SCD.
