Hemoglobin is normally enclosed in red blood cells (RBCs). When RBCs are destroyed for any reason, the released hemoglobin can cause damage to certain tissues and organs. This is why free hemoglobin is immediately captured by haptoglobin, a protein produced by the liver. The haptoglobin-hemoglobin complex is rapidly removed from the blood so that the hemoglobin can be degraded and the iron recovered. When too many RBCs are destroyed at the same time, haptoglobin reserves can become depleted. Low levels of haptoglobin may therefore indicate hemolysis (destruction) of the RBCs either in the blood vessels themselves (intravascular hemolysis), or in the spleen or liver (extravascular hemolysis). Low levels may also result from serious liver disease that limit the liver’s ability to make haptoglobin.
Haptoglobin results are interpreted by taking into account other factors such as the number of reticulocytes, the number of RBCs, hematocrit, etc. Low haptoglobin levels are generally found in intravascular hemolysis.
Haptoglobin is considered to be an acute-phase protein, with levels rising in several inflammatory conditions (ulcerative colitis, rheumatoid arthritis, heart attack, severe infections, etc.). These transitional increases can complicate the interpretation of haptoglobin results.