Haptoglobin

Haptoglobin is a plasma protein belonging to the alpha-2 globulin fraction. In the human body, it exists in three forms: Hp 1-1, Hp 2-1, and Hp 2-2.

• Hp 1-1 – Monomeric form
• Hp 2-1 and Hp 2-2 – Polymeric forms

Haptoglobin levels in the blood can be altered by acute-phase reactions, liver and kidney damage, autoimmune diseases, and hemolysis.

Haptoglobin Function

Haptoglobin’s primary function is to bind free hemoglobin and participate in the acute-phase response.

• Hemoglobin is responsible for oxygen transport and carbon dioxide exchange in red blood cells.
• Red blood cells have a lifespan of 120 days and are normally broken down in the spleen and liver.
• However, some red blood cells rupture directly in the bloodstream (intravascular hemolysis), releasing hemoglobin into circulation.
• Under normal conditions, intravascular hemolysis occurs at a low rate.
• Free hemoglobin binds to haptoglobin, forming a complex that is absorbed by reticuloendothelial system cells (e.g., in the spleen).
• The iron released from hemoglobin is then recycled for new red blood cell production.

Haptoglobin’s Role in Iron Metabolism

• If free hemoglobin remains unbound, it can accumulate in the kidneys, potentially causing kidney damage.
• Haptoglobin levels decrease in cases of increased red blood cell breakdown, as it becomes depleted while binding free hemoglobin.
• Unlike other acute-phase proteins, haptoglobin production does not increase during hemolysis, making its low levels a key marker of hemolysis.

Haptoglobin as an Acute-Phase Protein

Haptoglobin is also an acute-phase protein, meaning its levels increase in response to:

• Infection, trauma, tumors, and inflammation
• Stimulation by growth hormone, insulin, bacterial endotoxins, prostaglandins, and cytokines

During inflammation, haptoglobin functions as an antioxidant, reducing cell damage and inhibiting the growth of certain bacteria like Escherichia coli. It also:

• Suppresses prostaglandin synthesis, reducing inflammation
• Stimulates blood vessel growth
• Regulates immune system function

In cases of liver disease, the ability to synthesize haptoglobin is impaired, leading to decreased levels. Similarly, kidney damage can result in haptoglobin loss in urine, particularly Hp 1-1, which has the lowest molecular weight.