Haptoglobin

Carolyn Cray, in Progress in Molecular Biology and Translational Science, 2012 CHaptoglobin Haptoglobin (HP) is composed of 2α and 2β subunits. There are different subtypes and these may vary with species. 8 HP binds free hemoglobin which may be released during various autoimmune, infectious, or inherited diseases. 53 This HP–hemoglobin complex is phagocytosed by macrophages via the CD163 receptor. In mouse models, clearance is rapid with a half-life of less than 50min. 53 In HP-deficient mice, high levels of hemoglobin are found to accumulate in the kidney. 54 The effective binding to CD163 has been found to stimulate cytokine production, and HP has also been linked to protease activity and immune suppression. 55 Interestingly, HP is found both in mammals and in fish but not in chickens and in frogs where another hemoglobin-binding protein has been identified called PIT54. 56 Assays for HP in animals are often via spectrophotometry using the natural affinity of HP for hemoglobin. 57 Immunoassays for human HP which show cross-reactivity with animal HP are also available but are not widely implemented. 58 Ishmael Kasvosve, ... Joris R. Delanghe, in Advances in Clinical Chemistry, 2010 1. Abstract The haptoglobin gene is highly polymorphic in humans with strong evidence of functionally distinct biochemical phenotypes. In all human populations, three major haptoglobin phenotypes Hp 1-1, Hp 2-1, and Hp 2-2 are present, but additional phenotypes have been identified. Haptoglobi...

Haptoglobin is an immunoglobulin-like plasma protein that binds hemoglobin. The haptoglobin-hemoglobin complex is removed from plasma by macrophages and the hemoglobin is catabolized. When the hemoglobin-binding capacity of haptoglobin is exceeded, hemoglobin passes through the renal glomeruli, resulting in hemoglobinuria. Chronic intravascular hemolysis causes persistently low haptoglobin concentration. Regular strenuous exercise may cause sustained low haptoglobin, presumably from low-grade hemolysis. Low serum haptoglobin may also be due to severe liver disease. Neonatal plasma or serum specimens usually do not contain measurable haptoglobin; adult levels are achieved by 6 months. Increase in plasma haptoglobin concentration occurs as an acute- phase reaction. Levels may appear to be increased in conditions such as burns and nephrotic syndrome. An acute-phase response may be confirmed and monitored by assay of other acute-phase reactants such as alpha-1-antitrypsin and C-reactive protein. Absence of plasma haptoglobin may therefore indicate intravascular hemolysis. However, congenital anhaptoglobinemia is common, particularly in African-Americans. For this reason, it may be difficult or impossible to interpret a single measurement of plasma haptoglobin. If the assay value is low, the test should be repeated after 1 to 2 weeks following an acute episode of hemolysis. If all the plasma haptoglobin is removed following an episode of intravascular hemolysis, and if hemolysi...

Contents • • • • • • • • • • • • • What is haptoglobin Haptoglobin is an immunoglobulin-like plasma protein produced by the liver that the body uses to clear free hemoglobin (found outside of red blood cells) from circulation. Haptoglobin is a plasma proteins with the highest binding affinities for hemoglobin (Hb) 1) . Plasma-purified haptoglobin has been marketed in Japan since 1985, with primary indications for use in conjunction with extracorporeal circulation, massive transfusion, and thermal injury. The primary therapeutic effect of haptoglobin in disease states is protection of the kidneys from hemoglobin (Hb)-induced toxicity 2) . Several United States– and European-based pharmaceutical companies have commenced development projects to fractionate haptoglobin (and hemopexin) from human plasma for use as therapeutics during hemolytic diseases 3) . In 2011, a human plasma–derived haptoglobin was given orphan drug status for the treatment of sickle cell disease in the European Union 4) . However, to date, preclinical proof of concept for haptoglobin (and hemopexin) has been studied within a general context of hemoglobin- and hemolysis-driven pathophysiology and not with the intention of treating a specific disease. Hemoglobin is the iron-containing protein complex that transports oxygen throughout the body. Hemoglobin is normally found within red blood cells and very little is found free circulating in the blood. Haptoglobin binds to free hemoglobin in the blood. This f...

Hemolysis presents as acute or chronic anemia, reticulocytosis, or jaundice. The diagnosis is established by reticulocytosis, increased unconjugated bilirubin and lactate dehydrogenase, decreased haptoglobin, and peripheral blood smear findings. Premature destruction of erythrocytes occurs intravascularly or extravascularly. The etiologies of hemolysis often are categorized as acquired or hereditary. Common acquired causes of hemolytic anemia are autoimmunity, microangiopathy, and infection. Immune-mediated hemolysis, caused by antierythrocyte antibodies, can be secondary to malignancies, autoimmune disorders, drugs, and transfusion reactions. Microangiopathic hemolytic anemia occurs when the red cell membrane is damaged in circulation, leading to intravascular hemolysis and the appearance of schistocytes. Infectious agents such as malaria and babesiosis invade red blood cells. Disorders of red blood cell enzymes, membranes, and hemoglobin cause hereditary hemolytic anemias. Glucose-6-phosphate dehydrogenase deficiency leads to hemolysis in the presence of oxidative stress. Hereditary spherocytosis is characterized by spherocytes, a family history, and a negative direct antiglobulin test. Sickle cell anemia and thalassemia are hemoglobinopathies characterized by chronic hemolysis. Hemolysis is the destruction or removal of red blood cells from the circulation before their normal life span of 120 days. While hemolysis can be a lifelong asymptomatic condition, it most often ...

This test measures the amount of haptoglobin in the blood. Haptoglobin is a protein made by your liver. It attaches to a certain type of hemoglobin. Hemoglobin is a protein in your red blood cells that carries oxygen from your lungs to the rest of your body. Most hemoglobin is located inside red blood cells, but small amounts circulate in the bloodstream. Haptoglobin binds to hemoglobin in the bloodstream. Together, the two proteins are known as the haptoglobin-hemoglobin complex. This complex is quickly cleared from the bloodstream and removed from the body by your liver. When red blood cells are damaged, they release more hemoglobin into the bloodstream. That means more of the haptoglobin-hemoglobin complex will be cleared from the body. The haptoglobin may leave the body faster than the liver can make it. This causes your haptoglobin blood levels to drop. If your haptoglobin levels are too low, it may be a sign of a disorder of the red blood cells, such as anemia . Other names: hemoglobin-binding protein, HPT, Hp • You may need this test if you have symptoms of anemia. These include: • Fatigue • Pale skin • Shortness of breath • Rapid heart rate • Jaundice , a condition that causes your skin and eyes to turn yellow • Dark colored urine You may also need this test if you've had a blood transfusion . A haptoglobin test may be done along with another test called direct anti-globulin. The results of these tests can show if you've had a bad reaction to the transfusion. • A h...