Is haptoglobin (a protein that binds to free hemoglobin) elevated in patients with hemolysis?

Haptoglobin is Decreased, Not Elevated, in Hemolysis

Haptoglobin levels are depleted (decreased) during hemolysis, not elevated, because haptoglobin binds to free hemoglobin released from lysed red blood cells and the resulting complexes are rapidly cleared from circulation. 1

Mechanism of Haptoglobin Depletion

• Haptoglobin is primarily produced in the liver and functions to bind free hemoglobin from lysed red cells, preventing its toxic effects. 1

• When large amounts of free hemoglobin are present during hemolysis, haptoglobin becomes depleted as it forms complexes with hemoglobin that are quickly removed from circulation. 1

• This depletion makes decreased haptoglobin a reliable marker of hemolysis. 1

Diagnostic Utility

• The combination of elevated LDH and decreased haptoglobin is specific for hemolysis, as LDH alone can be elevated in liver disease, myocardial infarction, kidney disease, and muscle damage. 2

• Additional mandatory tests include reticulocyte count, indirect bilirubin (which should be elevated), direct Coombs test, and peripheral blood smear examination to differentiate types of hemolysis. 2

Important Clinical Caveats

• Haptoglobin can be decreased in patients with mechanical heart valves without clinically relevant hemolysis, representing a potential false positive for hemolysis. 2

• False negative results (inappropriately normal or elevated haptoglobin despite hemolysis) can occur with:

  • Inflammation, since haptoglobin is a positive acute phase reactant 1, 3
  • Medications such as androgens and corticosteroids 1
  • Elevated estrogen states 1

• False positive results (inappropriately low haptoglobin without hemolysis) can occur with:

  • Cirrhosis 1
  • Hypersplenism 1
  • Hemodilution 1
  • Improper specimen preparation 1

Transfusion Considerations

• Serum haptoglobin can still be used to diagnose hemolysis in patients receiving multiple units of packed red blood cells, as transfusion does not significantly affect haptoglobin levels despite stored blood containing free hemoglobin. 4