What is Haptoglobin
Haptoglobin is a plasma glycoprotein that binds free hemoglobin released during intravascular hemolysis, preventing kidney damage and iron loss while functioning as an antioxidant and immunomodulator. 1, 2
Primary Function and Clinical Significance
Haptoglobin serves as a critical protective mechanism by:
- Binding free hemoglobin released from lysed red blood cells to form a complex that is rapidly cleared from circulation, preventing renal tubular damage and iron loss 3, 1
- Acting as an antioxidant by preventing hemoglobin-mediated oxidative tissue damage 1, 4
- Functioning as an immunosuppressor that modulates lymphocyte function and the Th1/Th2 balance 1, 4
Role as an Acute Phase Protein
- Haptoglobin is a positive acute phase protein whose concentration increases during inflammation and infection 3, 5
- It is synthesized primarily in the liver and lungs 3, 2
- Plasma levels change significantly in pathological conditions, making it a standard component of clinical laboratory testing 3, 2
Clinical Application as a Hemolysis Marker
Haptoglobin measurement is essential in the diagnostic workup of hemolytic anemia:
- Decreased or absent haptoglobin is a key laboratory marker confirming hemolysis 6, 7
- When evaluating anemia with thrombocytopenia in emergency settings, haptoglobin levels should be determined alongside LDH and indirect bilirubin 6
- In hemolytic conditions, haptoglobin is consumed as it binds free hemoglobin, resulting in low or undetectable levels 6
Genetic Polymorphism and Phenotypes
Haptoglobin exhibits unique genetic variation in humans:
- Three major phenotypes exist: Hp1-1 (homozygous), Hp2-1 (heterozygous), and Hp2-2 (homozygous) 1, 2, 5
- Hp1-1 is biologically most effective at binding free hemoglobin and suppressing inflammatory responses 1
- Hp2-2 is least biologically active, with Hp2-1 showing intermediate activity 1
- Phenotype possession may influence susceptibility to cardiovascular disease, autoimmune disorders, and malignancy 1, 4
Use in Diagnostic Algorithms
Haptoglobin is incorporated into multiple clinical scoring systems:
- FibroTest for liver fibrosis assessment combines haptoglobin with α-2-macroglobulin, apolipoprotein A1, total bilirubin, and GGT 6
- Listed as a mandatory marker of hemolysis in diagnostic workups for pyruvate kinase deficiency and other hemolytic anemias 6
- Essential for distinguishing thrombotic microangiopathy from other causes of anemia and thrombocytopenia 6
Common Pitfalls
- Low haptoglobin is not specific to hemolysis alone—it can also decrease in liver disease due to reduced synthesis 6
- Elevated levels during acute inflammation may mask concurrent hemolysis, as haptoglobin is an acute phase reactant 3, 5
- Different phenotypes can create split alpha-2 globulin zones on protein electrophoresis, which may be confused with in vitro hemolysis or monoclonal proteins 5