HpHb

HpHb refers to the complex formed in plasma when the liver-produced glycoprotein haptoglobin (Hp) binds free hemoglobin (Hb). This complex serves to scavenge free Hb released during red blood cell turnover or intravascular hemolysis, preventing the heme-mediated oxidative damage, reducing renal iron loss, and limiting iron availability to pathogens. The Hp-Hb complex is rapidly cleared from circulation and is taken up by macrophages through the CD163 scavenger receptor, where it is internalized and degraded, and the heme iron is recycled.

Genetics and structure: Haptoglobin is encoded by a gene with two common alleles, Hp1 and Hp2, leading to three common phenotypes: Hp 1-1, Hp 2-1, and Hp 2-2. The Hp-Hb complex can form with all phenotypes but their physical forms differ: Hp 1-1 tends to form smaller, dimeric complexes with relatively high binding affinity and rapid clearance, while Hp 2-1 and Hp 2-2 form polymeric complexes that have different clearance kinetics and antioxidant properties. The functional differences among phenotypes can influence the efficiency of Hb scavenging and subsequent clearance.

Clinical relevance: Hp levels in plasma decrease during intravascular hemolysis, making Hp a useful, though imperfect, biomarker for hemolytic processes. Hp concentration is also affected by acute-phase responses and by Hp genotype. Low Hp can increase susceptibility to Hb-driven oxidative damage and kidney injury. Hp therapy and the measurement of Hp-Hb complexes have been explored in research contexts, particularly for conditions involving excessive hemolysis, such as sickle cell disease and transfusion reactions.