Coombs Test: Treatment, Effect & Risks

The Coombs test detects antibodies against red blood cells in a patient’s serum and is used in a standardized manner, for example, as part of maternity screening and blood grouping. The test procedure works with rabbit serum and exists in a direct and an indirect form, which are used for different questions.

What is the Coombs test?

To detect for antibodies against erythrocytes, the so-called Coombs test is used. The test detects antibodies of the IgG class. The Coombs test is used to detect antibodies against erythrocytes. The test detects antibodies of the IgG class. These antibodies are considered “incomplete” antibodies and cannot by themselves cause agglutination of the blood cells. However, IgM antibodies can cause such agglutination because of their pentamer structure and are therefore called “complete” antibodies. In the Coombs test, so-called Coombs serum, also known as antihuman globulin, is used to detect antibodies. Coombs serum consists of blood serum from rabbits immunized against human antibodies of the IgG class. The test is performed either in a test tube or by microcolumn agglutination. The Coombs test goes back to the Cambridge pathologist Coombs and is used within hematology primarily for the diagnosis of hemolytic anemias. These anemias can affect, for example, newborns with rhesus incompatibility. In transfusion medicine, the test is also used for serological compatibility testing. The term Coombs test basically refers only to the testing technique and thus the use of antihuman globulin. In the text procedure, a direct form is distinguished from an indirect form.

Function, effect, and objectives

In the direct Coombs test, the detection of IgG adherent to erythrocytes is performed. During the test, the erythrocytes are taken from the patient’s blood and cleared of plasma. The investigator then adds them to the Coombs serum and incubates them in this manner. If the blood carries antibodies against erythrocytes and these antibodies are erythrocyte-bound, the Coombs serum binds with its antibodies to the human IgG of the test sample. With the addition of a reaction enhancer, agglutination occurs and the test is considered positive. The indirect Coombs test proceeds in a slightly different manner. This test consists of two steps and detects antibodies to foreign erythrocytes. These antibodies circulate freely in the blood sample and are not erythrocyte bound. The first step of the indirect test procedure corresponds to incubation of the blood plasma sample with tester erythrocytes. If antibodies are present in the test serum, they bind to the erythrocytes, although no agglutination occurs. In the second step, the Coombs serum is mixed with the tester erythrocytes and agglutination occurs. A positive indirect Coombs test can be used, for example, to detect rhesus incompatibility by documenting incomplete antibodies in the mother’s blood. The direct Coombs test exists exclusively in the variant described above and thus always aims at the detection or exclusion of antibody loading on patient erythrocytes. The indirect Coombs test is associated with various forms of use, usually corresponding to an antibody screening test or a serological compatibility test. However, the indirect test may also be used in the context of more advanced testing and is then used, for example, to determine various antibody specificities. The test method of the indirect test remains the same, but its name may vary in individual cases with the question of the test. For this reason, an indirect Coombs test cannot be requested by the laboratory, but must specify the purpose or goal of the testing.

Risks, side effects, and hazards

There are usually few risks or side effects associated with Coombs testing. The patient may find the collection of blood uncomfortable. Bruising is also a possibility. However, these marks will disappear within a few days. Some people react to the drawing of blood with fatigue, nausea or headaches. However, these symptoms do not usually last long either, but remit on the same day.In any case, relatively little blood is taken from the patient for the test, so that side effects occur only in extremely rare cases. The Coombs test does not require inpatient care, but can be performed on an outpatient basis. The time required by the laboratory to perform the test depends on the type of test procedure and the particular objective of the test. The test has particular, clinical relevance in autoimmune hemolytic anemia, in which antibodies produced by the body’s own immune system cause hemolysis of erythrocytes, resulting in anemia. The direct Coombs test is usually positive in such diseases. This means that the physician can give the patient a relatively reliable diagnosis after a positive test. The situation is different if the test is negative. A negative direct Coombs test does not necessarily correspond to an exclusion of the disease. There is also a Coombs-negative variant of autoimmune hemolytic anemia. In this case, a patient with a negative test must undergo further diagnostic procedures. In the case of the disease described, for example, the determination of autoantibodies or environmental diagnostics are among the further diagnostic procedures after a negative test. In connection with other diseases, a negative Coombs test can certainly be evaluated as an exclusion. Under certain circumstances, a positive Coombs test may be followed by further examinations that allow a more precise classification of the phenomenon at hand or provide additional support for the positive results of the test. Indications for the Coombs test include blood grouping, blood transfusions, maternity screening, or suspected rhesus incompatibility.