Coombs Test: Direct & Indirect, How It's Done and Results

Updated in February 2024

The Coombs test is a type of blood test that assesses the presence of specific antibodies that attack and destroy red blood cells. High levels of these antibodies are often a sign of hemolytic anemia. 

The Coombs test can be direct, when you want to evaluate the red blood cells, or indirect, when the blood serum is evaluated.

In addition to anemia, this test can also help identify other diseases that affect blood cells such as leukemia, lupus, mononucleosis and erythroblastosis fetalis. It can also be ordered identify the risk for transfusion reactions.

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Types of Coombs tests

Depending on what you want to evaluate, the Coombs test can be classified into two types:

  • Direct Coombs test: Directly evaluates red blood cells, checking whether there are antibodies linked to the red blood cell and whether these antibodies are derived from the person's own immune system or received through a transfusion. This test is typically performed to detect autoimmune hemolytic anemia. 
  • Indirect Coombs test: Evaluates and looks for antibodies in the blood serum. It is generally requested in transfusion situations, to ensure that the blood that is be donated will be compatible with the person receiving it.

Regardless of the type of Coombs test to be performed, no preparation is necessary to perform the exam. However, some medications can interfere with the results, so it is important to inform your doctor of any medications you are taking to determine whether they should be held before testing.

How the test is done

The Coombs test is performed using a blood sample collected in a laboratory. The collected blood is sent to the laboratory, where the direct or indirect Coombs test will be carried out, depending on the objective.

In the direct Coombs test, the Coombs reagent is added to the patient's blood. This reagent allows for the visualization of antibodies that may be linked to the red blood cells. In the indirect Coombs test, the blood is collected and centrifuged, separating the red blood cells from the serum, which contains the antibodies. Red blood cells 'pre-marked' with antibodies are added to the serum with the aim of checking whether there are autoantibodies present in the serum and, consequently, in the patient's blood.

When it is ordered

The Coombs test is done to investigate the following situations:

  • Autoimmune hemolytic anemia;
  • Drug-induced immune hemolytic anemia;
  • Reaction to blood transfusion;
  • Hemolytic disease of the newborn;
  • Systemic lupus erythematosus, without hemolytic anemia.

The indirect Coombs test may also be requested by the obstetrician during the first trimester of pregnancy to check for antibodies against the baby's Rh-positive blood in women who are Rh-negative, as this situation can cause erythroblastosis fetalis. 

What results mean

The Coombs test result can be positive or negative:

1. Negative Coombs

The Coombs test result is negative when the antibody that causes the destruction of the red globes is not present. This considered to be a normal result.

2. Coombs positive

A positive result means that there is an antibody in the blood, and it may be a sign of:

  • Autoimmune hemolytic anemia
  • Mycoplasma sp. infection
  • Syphilis
  • Leukemia
  • Lupus erythematosus
  • Mononucleosis

For an indirect Coombs test, a positive result means that the person has an antibody that can cause clots when receiving another type of blood. Therefore, care must be taken when carrying out a blood transfusion.

In any case, it is always important for results to be evaluated by the ordering doctor, whol will take the person's healthy history into account when interpreting.