From the Guidelines
Haptoglobin is a protein that plays a crucial role in binding to free hemoglobin released during the breakdown of red blood cells, thereby preventing iron loss and kidney damage.
Definition and Function
Haptoglobin is a protein produced by the liver that circulates in the bloodstream, and its primary function is to bind to free hemoglobin released during the normal breakdown of red blood cells or during hemolysis (excessive red blood cell destruction) 1. By binding to free hemoglobin, haptoglobin prevents the loss of iron and protects the kidneys from damage that could occur from hemoglobin filtration. The haptoglobin-hemoglobin complex is then removed from circulation by the liver.
Clinical Significance
Haptoglobin levels are often measured in blood tests as an acute phase reactant, meaning its levels increase during inflammation, infection, or tissue damage. Conversely, decreased haptoglobin levels can indicate hemolytic anemia or other conditions involving increased red blood cell destruction, as seen in patients treated with PegIFN, ribavirin, and protease inhibitors 1. Some key points to consider when evaluating haptoglobin levels include:
- Low haptoglobin levels can indicate hemolysis, as seen in hemolytic anemia 1
- Haptoglobin levels can be used to distinguish between different types of anemia, such as microcytic, normocytic, and macrocytic anemia 1
- Haptoglobin is an acute phase reactant, and its levels may increase during inflammation, infection, or tissue damage 1 There are different genetic variants of haptoglobin (phenotypes 1-1,2-1, and 2-2), which may influence an individual's susceptibility to certain diseases, particularly those involving oxidative stress or inflammation. In the context of anemia, haptoglobin levels can be used to guide diagnosis and treatment, as seen in the management of anemia induced by triple therapy in patients with chronic hepatitis C 1.
From the Research
Definition and Function of Haptoglobin
- Haptoglobin (Hp) is a blood plasma glycoprotein that binds free hemoglobin (Hb) and plays a critical role in tissue protection and the prevention of oxidative damage 2, 3.
- It is an acute phase protein, and its concentration in plasma changes in pathology, making it a potential biomarker for various diseases 2, 3.
- Haptoglobin has several unique biophysical characteristics, including polymorphism, with three structural alleles that control the synthesis of three major phenotypes: homozygous Hp1-1 and Hp2-2, and heterozygous Hp2-1 2, 3.
Role in Hemolysis and Disease
- Haptoglobin is primarily produced in the liver and is functionally important for binding free hemoglobin from lysed red cells in vivo, preventing its toxic effects 4.
- Decreased haptoglobin is a marker of hemolysis, and its levels become depleted in the presence of large amounts of free hemoglobin 4.
- Haptoglobin phenotypes have been associated with various pathologic conditions, such as coronary artery disease, and may play a role in the pathogenesis of human disorders 5.
Mechanism of Action and Related Defense Pathways
- Haptoglobin binds free hemoglobin and removes it from the circulation to prevent kidney injury and iron loss following hemolysis 5.
- It also functions as an antioxidant by binding free hemoglobin and preventing oxidative damage 5.
- The cellular receptor target of haptoglobin is the monocyte/macrophage scavenger receptor, CD163, which leads to globin and heme metabolism and adaptive changes in antioxidant and iron metabolism pathways 6.