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Symbol(s) HP; MGC111141; hp2-alpha
External IDs OMIM: 140100
RNA expression pattern

More reference expression data

Human Mouse
Entrez 3240 na
Ensembl ENSG00000197711 na
Uniprot P00738 na
Refseq NM_005143 (mRNA)
NP_005134 (protein)
na (mRNA)
na (protein)
Location Chr 16: 70.65 - 70.65 Mb na
Pubmed search [1] na

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 hemolytic anemia


Clinical significance

Since the reticuloendothelial system will remove the haptoglobin-hemoglobin complex from the body, haptoglobin levels will be decreased in hemolytic anaemias. 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, weakness, orthostatic hypotension (positional changes in blood pressure) or 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.


Haptoglobin is produced mostly by hepatocytes but also by other tissues: e.g. skin, lung, and kidney. 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

  • Graversen JH, Madsen M, Moestrup SK (2002). "CD163: a signal receptor scavenging haptoglobin-hemoglobin complexes from plasma.". Int. J. Biochem. Cell Biol. 34 (4): 309-14. PMID 11854028.
  • Madsen M, Graversen JH, Moestrup SK (2002). "Haptoglobin and CD163: captor and receptor gating hemoglobin to macrophage lysosomes.". Redox Rep. 6 (6): 386-8. PMID 11865982.
  • Erickson LM, Kim HS, Maeda N (1993). "Junctions between genes in the haptoglobin gene cluster of primates.". Genomics 14 (4): 948-58. PMID 1478675.
  • Maeda N (1985). "Nucleotide sequence of the haptoglobin and haptoglobin-related gene pair. The haptoglobin-related gene contains a retrovirus-like element.". J. Biol. Chem. 260 (11): 6698-709. PMID 2987228.
  • Simmers RN, Stupans I, Sutherland GR (1986). "Localization of the human haptoglobin genes distal to the fragile site at 16q22 using in situ hybridization.". Cytogenet. Cell Genet. 41 (1): 38-41. PMID 3455911.
  • van der Straten A, Falque JC, Loriau R, et al. (1986). "Expression of cloned human haptoglobin and alpha 1-antitrypsin complementary DNAs in Saccharomyces cerevisiae.". DNA 5 (2): 129-36. PMID 3519135.
  • Bensi G, Raugei G, Klefenz H, Cortese R (1985). "Structure and expression of the human haptoglobin locus.". EMBO J. 4 (1): 119-26. PMID 4018023.
  • Malchy B, Dixon GH (1973). "Studies on the interchain disulfides of human haptoglobins.". Can. J. Biochem. 51 (3): 249-64. PMID 4573324.
  • Raugei G, Bensi G, Colantuoni V, et al. (1983). "Sequence of human haptoglobin cDNA: evidence that the alpha and beta subunits are coded by the same mRNA.". Nucleic Acids Res. 11 (17): 5811-9. PMID 6310515.
  • Yang F, Brune JL, Baldwin WD, et al. (1983). "Identification and characterization of human haptoglobin cDNA.". Proc. Natl. Acad. Sci. U.S.A. 80 (19): 5875-9. PMID 6310599.
  • Maeda N, Yang F, Barnett DR, et al. (1984). "Duplication within the haptoglobin Hp2 gene.". Nature 309 (5964): 131-5. PMID 6325933.
  • Brune JL, Yang F, Barnett DR, Bowman BH (1984). "Evolution of haptoglobin: comparison of complementary DNA encoding Hp alpha 1S and Hp alpha 2FS.". Nucleic Acids Res. 12 (11): 4531-8. PMID 6330675.
  • van der Straten A, Herzog A, Cabezón T, Bollen A (1984). "Characterization of human haptoglobin cDNAs coding for alpha 2FS beta and alpha 1S beta variants.". FEBS Lett. 168 (1): 103-7. PMID 6546723.
  • vander Straten A, Herzog A, Jacobs P, et al. (1984). "Molecular cloning of human haptoglobin cDNA: evidence for a single mRNA coding for alpha 2 and beta chains.". EMBO J. 2 (6): 1003-7. PMID 6688992.
  • Kurosky A, Barnett DR, Lee TH, et al. (1980). "Covalent structure of human haptoglobin: a serine protease homolog.". Proc. Natl. Acad. Sci. U.S.A. 77 (6): 3388-92. PMID 6997877.
  • Eaton JW, Brandt P, Mahoney JR, Lee JT (1982). "Haptoglobin: a natural bacteriostat.". Science 215 (4533): 691-3. PMID 7036344.
  • Kazim AL, Atassi MZ (1980). "Haemoglobin binding with haptoglobin. Unequivocal demonstration that the beta-chains of human haemoglobin bind to haptoglobin.". Biochem. J. 185 (1): 285-7. PMID 7378053.
  • Hillier LD, Lennon G, Becker M, et al. (1997). "Generation and analysis of 280,000 human expressed sequence tags.". Genome Res. 6 (9): 807-28. PMID 8889549.
  • Tabak S, Lev A, Valansi C, et al. (1997). "Transcriptionally active haptoglobin-related (Hpr) gene in hepatoma G2 and leukemia molt-4 cells.". DNA Cell Biol. 15 (11): 1001-7. PMID 8945641.
  • Koda Y, Soejima M, Yoshioka N, Kimura H (1998). "The haptoglobin-gene deletion responsible for anhaptoglobinemia.". Am. J. Hum. Genet. 62 (2): 245-52. PMID 9463309.
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Haptoglobin". A list of authors is available in Wikipedia.
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