haptoglobinhemoglobin

The haptoglobin–hemoglobin complex is formed when haptoglobin binds free hemoglobin released into the plasma during intravascular hemolysis. Haptoglobin is a liver-synthesized plasma glycoprotein that sequesters free hemoglobin to limit oxidative damage and prevent renal iron loss.

Binding affinity is high; the complex is rapidly cleared by macrophages via the CD163 receptor, primarily in the liver and spleen. Depletion of haptoglobin occurs with substantial intravascular hemolysis, leading to low serum haptoglobin levels; measurement of haptoglobin is used to help diagnose hemolysis, though levels may be influenced by inflammation or liver disease.

Structure and genetics: Haptoglobin is encoded by the HP gene on chromosome 16. Polymorphism results in two common alleles, HP1 and HP2, producing three phenotypes: HP1-1, HP2-1, and HP2-2. These forms differ in polymer size, binding kinetics, and clearance properties, which can influence the efficiency of free Hb scavenging.

Clinical significance: The haptoglobin–Hb scavenging system protects tissues from heme toxicity and limits iron loss. Inflammation can raise haptoglobin levels; during intravascular hemolysis, haptoglobin is consumed, leading to low levels. Abnormalities in haptoglobin or in haptoglobin–Hb clearance may affect disease risk and interpretation of diagnostic tests.