Biology

Sepsis

Hemoglobin

Biochemistry

Blood proteins

Haptoglobin

Anemia

Compartmentalization (fire protection)

Red blood cell

Immunology

Toxicity

Enzyme

Internal medicine

Pharmacology

Hemolysis

Medicine

Chemistry

Cell

Trends in Molecular Medicine

Hemolysis and accumulation of cell-free hemoglobin (Hb) in the circulation or in confined tissue compartments such as the subarachnoid space is an important driver of disease. Haptoglobin is the Hb binding and clearance protein in human plasma and an efficient antagonist of Hb toxicity resulting from physiological red blood cell turnover. However, endogenous concentrations of haptoglobin are insufficient to provide protection against Hb-driven disease processes in conditions such as sickle cell anemia, sepsis, transfusion reactions, medical-device associated hemolysis, or after a subarachnoid hemorrhage. As a result, there is increasing interest in developing haptoglobin therapeutics to target 'toxic' cell-free Hb exposures. Here, we discuss key concepts of Hb toxicity and provide a perspective on the use of haptoglobin as a therapeutic protein.

Haptoglobin Therapeutics and Compartmentalization of Cell-Free Hemoglobin Toxicity