[5][6] In blood plasma, haptoglobin binds with high affinity to free hemoglobin[7] released from erythrocytes, and thereby inhibits its deleterious oxidative activity.

The protein was discovered as a "plasma substance" in 1938 by French biochemists Max-Fernand Jayle and Michel Polonovski.

The HP gene encodes a preproprotein that is processed to yield both alpha and beta chains, which subsequently combines as a tetramer to produce haptoglobin.

The free heme can then accelerate tissue damage by promoting peroxidative reactions and activation of inflammatory cascades.

[15] Haptoglobin, in its simplest form, consists of two alpha and two beta chains, connected by disulfide bridges.

Hp exists in two allelic forms in the human population, so-called Hp1 and Hp2, the latter one having arisen due to the partial duplication of Hp1 gene.

[16] It is unclear which evolutionary advantage is conferred by the longer allele; strikingly, a similar partial duplication independently arose much earlier in a precursor of ruminants.

[17] Hp has been found in all mammals studied so far, some birds, e.g., cormorant and ostrich but also, in its simpler form, in bony fish, e.g., zebrafish.

This aspect of haptoglobin may gain importance in immune suppressed conditions (such as liver cirrhosis) and the various phenotypes may result in different susceptibility levels towards bacterial infections.

The test is also commonly ordered as a hemolytic anemia battery, which also includes a reticulocyte count and a peripheral blood smear.

It can also be ordered along with a direct antiglobulin test when a patient is suspected of having a transfusion reaction or symptoms of autoimmune hemolytic anemia.