Haptoglobin

Haptoglobin (abbreviated as Hp) is a protein in the blood plasma that binds free hemoglobin released from erythrocytes with high affinity and thereby inhibits its oxidative activity. 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.

Clinical significance

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 jaundice or dark-colored urine. 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. Finally, it may be ordered in conjunction with a bilirubin.

Results interpretation

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 spleen and 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 aplastic anemia

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.

tructure

Haptoglobin is produced mostly by hepatocytes but 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 forms in 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.

Miscellaneous Information

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. Interestingly, Hp is absent in at least some amphibians ("Xenopus") and neognathous birds (chicken and goose).

Further reading

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Haptoglobin — Masse/Länge Primärstruktur 774 = 2*(142+245) Aminosäuren … Deutsch Wikipedia
haptoglobin — [hap′tə glō΄bin] n. a blood protein that binds with free hemoglobin in the bloodstream or at a wound when red blood cells decompose or are destroyed abnormally in the circulation * * * hap·to·glo·bin (hăpʹtə glō bĭn) n. A plasma protein that is a … Universalium
haptoglobin — haptoglobin. См. гаптоглобин. (Источник: «Англо русский толковый словарь генетических терминов». Арефьев В.А., Лисовенко Л.А., Москва: Изд во ВНИРО, 1995 г.) … Молекулярная биология и генетика. Толковый словарь.
haptoglobin — [hap′tə glō΄bin] n. a blood protein that binds with free hemoglobin in the bloodstream or at a wound when red blood cells decompose or are destroyed abnormally in the circulation … English World dictionary
haptoglobin — A group of α2 globulins in human serum, so called because of their ability to combine with hemoglobin, preventing loss in the urine; variant types form a polymorphic system, with α and β polypeptide chains controlled by separate genetic loci.… … Medical dictionary
haptoglobin — n. a protein present in blood plasma that binds with free haemoglobin to form a complex that is rapidly removed from the circulation by the liver. Depletion of plasma haptoglobin is a feature of anaemias in which red blood cells are destroyed… … The new mediacal dictionary
haptoglobin — noun Etymology: International Scientific Vocabulary, from Greek haptein + International Scientific Vocabulary hemoglobin Date: 1941 any of several forms of an alpha globulin found in blood serum that can combine with free hemoglobin in the plasma … New Collegiate Dictionary
haptoglobin — Acid a2 plasma glycoprotein that binds to oxyhaemoglobin that is free in the plasma, and the complex is then removed in the liver. Tetrameric (2 a, 2 b subunits) : the existence of two different a chains in humans means that haptoglobins can… … Dictionary of molecular biology
haptoglobin — noun A protein in blood plasma that binds free hemoglobin released from erythrocytes and thereby inhibits its oxidative activity … Wiktionary
Haptoglobin — Hap|to|glo|bin [griech. háptein = anbinden, befestigen; ↑ Globin] ein Plasmaprotein (↑ Glykoprotein) mit je zwei α u. β Ketten, MG ca. 100 000–120 000, das Hämoglobin spezif. bindet u. an dessen Abbau beteiligt ist … Universal-Lexikon

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