In externally caused hemoglobinemia, an outside attacker acts as an antibody against the red blood cells.

Eculizumab is used to prevent the breakdown of red blood cells in people with paroxysmal nocturnal hemoglobinemia (PNH).

Holmium(III) oxide is, compared to many other compounds, not very dangerous, although repeated overexposure can cause granuloma and hemoglobinemia.

Nonimmune mediated These occur when RBCs are damaged before transfusion, resulting in hemoglobinemia and hemoglobinuria.

Quinine overdose can also result in a rare form of hypersensitivity reaction termed blackwater fever that results in massive hemolysis, hemoglobinemia, hemoglobinuria, and renal failure.

When hemoglobinemia is internally caused, it is a result of recessive genetic defects that cause the red blood cells to lyse, letting the hemoglobin spill out of the cell into the blood plasma.