Haptoglobin is a protein synthesized in the liver that binds with the globin α-chains of hemoglobin A, F, S, or C. Haptoglobin does not bind methemoglobin, heme, or unusual forms of hemoglobin in which the α-chain is missing. The haptoglobin-hemoglobin complex is rapidly removed from circulation by the reticuloendothelial system to prevent/ minimize hemoglobin loss and to conserve iron. Indications for haptoglobin quantitation include: anemia or other indicators of possible hemolysis; pregnancy-induced hypertension; transfusion reactions (assay of pre- and post-transfusion samples); assessment of acute phase response; and evaluation of changes in the α2-region of serum protein electrophoresis. Decreased levels of haptoglobin are most frequently associated with conditions of increased intravascular hemolysis or hemoglobin turnover, such as hemolytic anemias, intravascular hemolytic transfusion reactions, and malaria. Extravascular hemolysis does not usually affect haptoglobin concentrations. Other conditions associated with decreased haptoglobin levels are congenital anhaptoglobinemia (ahaptoglobinemia) and severe liver diseases where protein synthesis is affected. Mechanical heart valves or vigorous athletic activity where repetitive erythrocytic mechanical trauma may occur can cause sustained lower haptoglobin levels. Elevated levels of haptoglobin are most frequently associated with acute phase reactions (i.e., involving tissue infection, surgery, trauma, or necrosis). Other conditions associated with elevated haptoglobin levels are corticosteroid therapy and biliary obstruction.
Absence of plasma haptoglobin may therefore indicate intravascular hemolysis. However, congenital anhaptoglobinemia is common, particularly in African-Americans. For this reason, it may be difficult or impossible to interpret a single measurement of plasma haptoglobin. If the assay value is low, the test should be repeated after 1 to 2 weeks following an acute episode of hemolysis. If all the plasma haptoglobin is removed following an episode of intravascular hemolysis, and if hemolysis ceases, the haptoglobin concentration should return to normal in a week. Low levels of plasma haptoglobin may indicate intravascular hemolysis.