Sickle cell anemia and major organ failure.

Major organ failure in sickle cell anemia is the direct consequence of the sickle cell evoked vasculopathy. Major organ failure is first clinically apparent as autosplenectomy, then during childhood presents as cerebral infarction and atrophy, and finally culminates in young adulthood as end stage renal failure (glomerulosclerosis), sickle chronic lung disease, intracranial hemorrhage, retinopathy, disabling leg ulcers, and generalized osteonecrosis. The vascular damage begins years before the overt clinical symptoms are apparent with no pain to act as a signal. Organ damage is progressive and irreversible. The rate of progression is genetically controlled from birth. Except for the management of life-threatening infections that are associated with the non-functioning spleen, disease expression has not been altered by therapy. The focus of future clinical investigations must be the prevention of the vasculopathy and tissue damage which is induced by the sickle red cell.