Haptoglobin is a protein produced by the liver, the role of which is to bind free hemoglobin in the blood. The assay of this haptoglobin macromolecule is used to detect hemolytic anemia, that is to say anemia due to the destruction (or lysis) of cells called red blood cells: a drop in the concentration of haptoglobin is then observed. On the other hand, haptoglobin can also be a marker of inflammation: in this case, its level will be increased.

Haptoglobin is a protein that is produced by the liver. Its role is to fix free hemoglobin in the blood. Indeed, hemoglobin, a protein that transports oxygen in the body, is normally present inside red blood cells and very little present in the free state, except when the red blood cells are destroyed and hemoglobin is released. However, this released hemoglobin can cause damage to certain tissues or organs. This is why the free hemoglobin is then immediately captured by the haptoglobin.

The complex formed between hemoglobin and haptoglobin is rapidly eliminated from the blood: thus hemoglobin is degraded, and the iron it contains is recovered. If too many red blood cells are destroyed at the same time, the reserves of haptoglobin in the blood are depleted and can be exhausted. Indeed, in this case, the consumption of haptoglobin exceeds its production by the liver.

Haptoglobin is therefore used as a marker for hemolysis, that is to say for the destruction of red blood cells, inside the vessels. Thus, lowered or even zero levels of haptoglobin are found in the case of intravascular hemolysis, but also sometimes in the event of hepatic insufficiency. 

On the other hand, increased levels of haptoglobin are found in various inflammatory states because it is an acute phase protein.

Thus, haptoglobin is increased in many inflammatory diseases, and in particular:

• Ulcerative colitis;
• Flare-ups of acute rheumatism;
• A myocardial infarction;
• Severe infection.

A haptoglobin measurement is primarily used to detect and assess the extent of hemolytic anemia, as well as to differentiate it from other causes of anemia. However, it cannot be used to determine the cause of hemolysis. Sometimes a clinical sign associated with this type of anemia will be an increase in heart rate.

A haptoglobin test will be required when:

• A patient has symptoms and signs of anemia: pallor and weakness;
• And at the same time, when there are signs of hemolytic anemia: jaundice (or jaundice) and dark urine. 

If the patient has an abnormally low red blood cell count, hemoglobin concentration and / or hematocrit level, the haptoglobin test may be requested at the same time:

• Than a reticulocyte count (i.e. immature red blood cells made by the bone marrow);
• Than a blood smear: This test, which is done with a drop of blood spread on a microscope slide, helps determine if the red blood cells, white blood cells and platelets are normal in appearance and number.

In addition, the doctor may optionally also request a determination of the bilirubin level at the same time.

Finally, if the patient has received a blood transfusion and post-transfusion reactions are suspected, it is possible to request the haptoglobin dosage at the same time as the direct Coombs test: this test detects antibodies on the surface of the patient. red blood cell capable of destroying it (hemolysis) and therefore causing anemia. 

The analysis requires the collection of a venous blood sample. This is collected by venipuncture at the elbow crease. This sample is usually done on an empty stomach. When transporting the sample, it is recommended to store it at a temperature of 4 ° C.

The haptoglobin is assayed in the serum, and this assay can be carried out by the method of immunoturbidimetry. The principle of immunoturbidimetry is based on the photometric measurement of the disorder caused by the reaction between the antigen and the antibody. Photometry is the measurement of light by a photodetector. 

Thus, these haptoglobin assay tests by immunoturbidimetry are carried out thanks to the formation of insoluble particles which interfere with the passage of light through the solution. 

• This is because when the light encounters the particles formed between the haptoglobin and a reagent that has been added, it is partly reflected in different directions. 
• It is ultimately when there are a greater number of particles formed that the passage of light through the solution is more difficult, thus causing an increase in the reflected light;
• It is therefore the loss of light passing through the solution which is measured by this immunoturbidimetry technique.

In addition, there is also another method for measuring haptoglobin, called immunophelemetry.

The concentrations are zero in the newborn by hepatic immaturity, then increase steadily until adulthood. Reference values ​​in adults are generally understood between 0,3 and 2 g / L.

In children, the reference values ​​for haptoglobin are as follows, depending on age (source: CHU Sainte-Justine):

• <1 mois: 0 — 1,8 g/L ;
• 1 – 11 months: 0 — 1,8g/L ;
• 1 years old : 0,04 — 1,6 g/L ;
• 7 years old : 0,04 — 1,2g/L ;
• 10 years old : 0,07 — 1,5 g/L ;
• 13 years old : 0,07 — 1,7 g/L ;
• 16 years old : 0,1 — 1,8 g/L ;
• > 18 years old: 0,3 — 2,1 g/L.

Be careful, however, when interpreting with the doctor, to take into account a possible drug intake, in fact:

• Some drugs increase haptoglobin levels, most notably: estrogen and corticosteroids;
• Other drugs, on the contrary, decrease the concentrations of haptoglobin: isoniazid, quinidine, streptomycin, oral contraceptives.

A lowered level of haptoglobin may indicate destruction of red blood cells either in the blood vessels themselves (intravascular hemolysis) or in the spleen or liver (extravascular hemolysis). This increased destruction of red blood cells can be related to various causes, such as:

• Hereditary pathologies resulting in abnormalities of the red blood cell;
• An abnormal type of hemoglobin;
• Medicinal origins;
• Mechanical destruction.

The haptoglobin concentration can also be reduced during significant blood loss, or in the event of kidney dysfunction or liver disease, which would limit its ability to manufacture haptoglobin.

Interpretation of haptoglobin results should take into account other factors, such as reticulocyte count, red blood cell count, hematocrit, etc. Finally, it is generally in intravascular hemolysis that the lowest levels of haptoglobin are found.

Ultimately, a decrease in haptoglobin levels may be a sign of hemolysis, jaundice, thalassemia (also called Cooley’s disease), hepatitis or even be linked to kidney disease. An increase in the concentration of haptoglobin may be caused by inflammation possibly due to rheumatism (during flare-ups), infections, acute nephropathies, certain forms of tuberculosis, or even certain types of cancer.

If the haptoglobin assay is used in the context of diagnosing or monitoring hemolysis within blood vessels, it is important to add orosomucoid assay to this assay. It is a protein of the inflammatory reaction, and which is synthesized by the liver. This glycoprotein is part of the acute phase proteins. It will make it possible to diagnose a possible inflammatory process contemporaneous with a hemolysis process. Because in this case, in fact, the increase in haptoglobin induced by inflammation is inhibited by the consumption of haptoglobin by hemolysis, and therefore the haptoglobin concentration can then appear normal.

On the other hand, as the only cause of an increase in haptoglobin is inflammation (acute, subacute or chronic), its increase, which is therefore linked to an inflammatory reaction, will often be correlated with that of orosomucoid. In addition, in an inflammatory profile, the increase in haptoglobin will also be related to the increase in C reactive protein (frequently called CRP).