Sickle cell anemia, in addition to being a hemoglobinopathy, is a hemolytic anemia. Hemolysis is both intravascular (about one-third) and extravascular (about two-thirds). Common markers of hemolysis include elevated LDH and bilirubin concentrations and increased reticulocytes. In intravascular hemolysis, haptoglobin levels are decreased. Haptoglobin is a protein that forms a complex with free hemoglobin in plasma. This complex is rapidly cleared by the liver.
The hemoglobin that is released into the plasma during intravascular hemolysis combines with nitric oxide (NO). The resulting decrease in NO availability contributes to the vaso-occlusive crisis by stimulating vasoconstriction, endothelial adhesiveness, and thrombosis.
Hemolytic crisis also involves splenic sequestration, which occurs in an effort to remove damaged RBCs. This can result in hypovolemia, which may lead to shock, especially in children. Children can also exhibit splenomegaly due to intrasplenic pooling of blood.
Adults in hemolytic crisis may experience autosplenectomy. This occurs when the spleen has multiple infarctions, followed by fibrosis, which renders the spleen nonfunctional.
