Haptoglobin is a protein produced by the liver that the body uses to clear free hemoglobin (found outside of red blood cells) from circulation. This test measures the amount of haptoglobin in the blood.
Hemoglobin is the iron-containing protein complex that transports oxygen throughout the body. It is normally found within red blood cells (RBCs) and very little is found free circulating in the blood. Haptoglobin binds to free hemoglobin in the blood. This forms a haptoglobin-hemoglobin complex that is rapidly cleared out of circulation for degradation and iron recycling.
However, when an increased number of RBCs are damaged and/or break apart (hemolysis), they release their hemoglobin into the blood, increasing the amount of free hemoglobin in circulation. When large numbers of RBCs are destroyed, haptoglobin concentrations in the blood will temporarily decrease as the haptoglobin is used up faster than the liver can produce it. A decrease in the amount of haptoglobin may be a sign that a person has a condition that is causing red blood cells to be destroyed or break apart. When the binding capacity of haptoglobin is exceeded, free hemoglobin level in circulation goes up and may cause tissue damage and organ dysfunction.
Increased RBC destruction may be due to inherited or acquired conditions. Some examples include transfusion reactions, certain drugs, and mechanical breakage, such as may be seen with some prosthetic heart valves. The destruction may be mild or severe, occurring suddenly (acute) or developing and lasting over a long period of time (chronic), and it can lead to hemolytic anemia. People with hemolytic anemia may experience symptoms such as fatigue, weakness, and shortness of breath and their skin may be pale or jaundiced. (For additional details, read the article on Hemolytic Anemia.)
Liver disease may also result in decreased haptoglobin concentrations as liver damage may inhibit both the production of haptoglobin and the clearing of the haptoglobin-free hemoglobin complexes.
How is the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in the arm.
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.
How is it used?
Haptoglobin testing is used primarily to help detect and evaluate hemolytic anemia and to distinguish it from anemia due to other causes. Testing is used to help determine whether red blood cells (RBCs) are breaking apart or being destroyed prematurely. It may be used in conjunction with other laboratory tests such as a complete blood count (CBC, including RBC count, hemoglobin, hematocrit), reticulocyte count, lactate dehydrogenase, bilirubin, direct antiglobulin test, and blood smear.
Hemolytic anemia is an uncommon cause of anemia. The condition can be inherited or may develop during a person's lifetime (acquired) due to various factors and may develop suddenly or develop over time. (For more details, see the "What is being tested?" section and the article on Hemolytic Anemia.)
Though the haptoglobin test is a sensitive test for hemolytic anemia, it cannot be used to diagnose the cause of the condition. Other laboratory tests may be needed to help determine the cause, such as tests for autoantibodies to detect autoimmune causes, sickle cell tests, G6PD, or a hemoglobin evaluation.
A haptoglobin test may be ordered along with a direct antiglobulin test to help determine whether someone who has received a blood transfusion has had a transfusion reaction (see the article on Transfusion Medicine).
If a haptoglobin level is low, then testing may be repeated at a later time to evaluate changes in concentration and help determine whether the increased destruction of RBCs is no longer occurring or continues.
When is it ordered?
- Fatigue, weakness
- Pale skin (pallor)
- Shortness of breath
- A rapid heart rate
- Red or brown urine (from the presence of blood/hemoglobin)
Testing may also be done when other laboratory test results are consistent with hemolytic anemia. These may show increased bilirubin concentrations (bulirubinemia), hemoglobin in the urine (hemoglobinuria), decreased RBC count, and increased reticulocyte count and lactate dehydrogenase levels.
What does the test result mean?
Results are interpreted carefully and in conjunction with results of other tests, such as a reticulocyte count, red blood cell (RBC) count, hemoglobin (Hb), hematocrit (Hct), or complete blood count (CBC).
When a haptoglobin level is significantly decreased, along with an increased reticulocyte count and a decreased RBC count, hemoglobin, and hematocrit, then it is likely that the person has some degree of hemolytic anemia with red blood cells destroyed in the circulation (so-called intravascular hemolysis).
If the haptoglobin is normal or borderline normal and the reticulocyte count is increased, then RBC destruction is likely occurring in organs such as the spleen and liver (so-called extravascular hemolysis). Because the freed hemoglobin is not released into the blood, the haptoglobin is not consumed and so is at a normal level. However, in severe extravascular hemolysis, haptoglobin level can be low because excess hemolysis can release some free hemoglobin into circulation.
If the haptoglobin concentration is normal and the reticulocyte count is not increased, then it is likely that the anemia present is not due to RBC breakdown.
The following table summarizes some results that may be seen:
Haptoglobin Reticulocyte count RBC count, Hemoglobin, Hematocrit Possible interpretation Significantly decreased Increased Decreased RBCs are being destroyed within blood vessels (i.e., intravascular hemolysis) Normal or slightly decreased Increased Decreased RBCs destruction likely within organs such as spleen and liver (i.e., extravascular hemolysis) Normal Not increased Decreased Anemia due to a cause other than RBC destruction (e.g., decrease in RBC production in the bone marrow)
If haptoglobin is decreased without any signs of hemolytic anemia, then it is possible that the liver is not producing adequate amounts of haptoglobin. This may be seen with liver disease, although haptoglobin is not typically used to diagnose or monitor liver disease.
Is there anything else I should know?
Haptoglobin is considered an "acute-phase" protein; this means that it will be elevated in many inflammatory diseases, such as ulcerative colitis, acute rheumatic disease, heart attack, and severe infection. Of a person has one of these conditions, it can complicate the interpretation of the haptoglobin results. Haptoglobin testing is not generally used to help diagnose or monitor these conditions.
Drugs that can increase haptoglobin levels include androgens and corticosteroids. Drugs that can decrease haptoglobin concentrations include isoniazid, quinidine, streptomycin, and birth control pills.
A low level of haptoglobin is normal for newborns and infants of less than 6 months old.
If haptoglobin levels are decreased, when will they return to normal?
It depends on the cause of the decrease. If they are due to acute hemolysis, such as may be seen with a transfusion reaction, then they will return to normal once the donor blood has been cleared from the system. If they are due to chronic hemolysis, then the concentration should return to normal if and when the underlying condition can be resolved. If the underlying condition cannot be resolved or if the decreased concentrations of haptoglobin are due to decreased production due to liver disease, then levels may continue to be lower than normal.
Should everyone have a haptoglobin test?
Can I have the haptoglobin test done in my healthcare practitioner's office?