Haptoglobin (abbreviated as Hp) is a
proteinin the blood plasmathat binds free hemoglobinreleased from erythrocyteswith high affinityand thereby inhibits its oxidativeactivity. The haptoglobin-hemoglobin complex will then be removed by the reticuloendothelial system(mostly the spleen).In clinical settings, the haptoglobin assay is used to screen for and monitor intravascular hemolytic anemia.
Since the reticuloendothelial system will remove the haptoglobin-hemoglobin complex from the body, haptoglobin levels will be decreased in
hemolytic anemias. In the process of binding hemoglobin, haptoglobin sequesters the iron within hemoglobin, preventing iron-utilizing bacteria from benefitting from hemolysis. It is theorized that because of this, haptoglobin has evolved into an acute phase protein.
Test order protocol
Haptoglobin is ordered whenever a patient exhibits symptoms of
anemia, such as pallor, fatigue, shortness of breath along with physical signs of hemolysis, such as jaundiceor dark-colored urine. The test is also commonly ordered as a hemolytic anemia battery which also includes a reticulocytecount 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. Finally, it may be ordered in conjunction with a bilirubin.
A decrease in haptoglobin can support a diagnosis of
hemolytic anemia, especially when correlated with a decreased RBC count, Hemoglobin, and Hematocrit, and also an increased reticulocyte count.
If the reticulocyte count is increased, but the haptoglobin level is normal, this may indicate that cellular destruction is occurring in the
spleenand liver, which may indicate a drug induced hemolysis, or a red cell dysplasia. The spleen and liver recognize an error in the red cells (either Drug coating the red cell membrane, or a dysfunctional red cell membrane), and destroy the cell. This type of destruction does not release hemoglobin into the peripheral blood, so the haptoglobin cannot bind to it. Thus, the haptoglobin will stay normal.
If there are symptoms of anemia but both the reticulocyte count and the haptoglobin level are normal, the anemia is most likely not due to hemolysis, but instead some other error in cellular production, such as
Haptoglobin levels which are decreased but do not accompany signs of anemia may indicate liver damage, as the liver is not producing enough haptoglobin to begin with.
As haptoglobin is indeed an
acute phase protein, any inflammatory process (infection, extreme stress, burns, major crush injury, allergy, etc) may increase the levels of plasma haptoglobin.
Haptoglobin is produced mostly by
hepatocytesbut also by other tissues: e.g. skin, lung, and kidney. According to Trayburn and Woods (2004) several studies have shown that the Haptoglobin gene is expressed in murine and human adipose tissue. Haptoglobin, in its simplest form, consists of two α- and two β-chains, connected by disulfide bridges. The chains originate from a common precursor protein which is proteolytically cleaved during protein synthesis.
Hp exists in two
allelic formsin the human population, so called "Hp1" and "Hp2"; the latter one having arisen due to the partial duplication of "Hp1" gene. Three phenotypes of Hp, therefore are found in humans: Hp1-1, Hp2-1, and Hp2-2. Hp of different phenotypes have been shown to bind hemoglobin with different affinities, with Hp2-2 being the weakest binder.
Hp has been found in all
mammalsstudied so far, some birds e.g. cormorantand ostrichbut also, in its simpler form, in bony fishe.g. zebrafish. Interestingly, Hp is absent in at least some amphibians(" Xenopus") and neognathous birds(chicken and goose).
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