[6][7] In addition, symptoms related to hemolysis may be present such as chills, jaundice, dark urine, and an enlarged spleen.

[30] As a result, the contents of the red blood cell are released into the general circulation, leading to hemoglobinemia[31] and increasing the risk of ensuing hyperbilirubinemia.

[32] Intravascular hemolysis may occur when red blood cells are targeted by autoantibodies, leading to complement fixation, or by damage by parasites such as Babesia.

[34][35] Typically, the spleen destroys mildly abnormal red blood cells or those coated with IgG-type antibodies,[36][37] while severely abnormal red blood cells or those coated with IgM-type antibodies are destroyed in the circulation or in the liver.

[36] If extravascular hemolysis is extensive, hemosiderin can be deposited in the spleen, bone marrow, kidney, liver, and other organs, resulting in hemosiderosis.

The spleen (part of the reticulo-endothelial system) is the main organ that removes old and damaged RBCs from the circulation.

That is, instead of being collected at the end of its useful life and disposed of normally, the RBC disintegrates in a manner allowing free iron-containing molecules to reach the blood.

[39] With their complete lack of mitochondria, RBCs rely on pentose phosphate pathway (PPP) for the materials needed to reduce oxidative damage.

If the cell is unable to signal to the reticuloendothelial phagocytes by externalizing phosphatidylserine, it is likely to lyse through uncontrolled means.

The metabolism and elimination of these products, largely iron-containing compounds capable of doing damage through Fenton reactions, is an important part of the condition.

[47] The diagnosis of hemolytic anemia can be suspected on the basis of a constellation of symptoms and is largely based on the presence of anemia, an increased proportion of immature red cells (reticulocytes) and a decrease in the level of haptoglobin, a protein that binds free hemoglobin.

Symptoms specifically related to hemolysis include jaundice and dark colored urine due to the presence of hemoglobin (hemoglobinuria).

An increased number of newly made red blood cells (reticulocytes) may also be a sign of bone marrow compensation for anemia.