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Coombs' samples
Medical expert of the article
Last reviewed: 05.07.2025
Normally, there are no antibodies to red blood cells in the blood.
The direct Coombs test is an antiglobulin test (gel agglutination, allows detection of complete divalent antibodies) that determines IgG antibodies and the C3 component of complement on the surface of red blood cells. Usually, antibodies detected by the direct Coombs test have a broad specificity, not associated with a well-established antigen. A positive direct Coombs test clearly indicates the presence of hemolytic anemia in the patient, although not all patients with a positive direct antiglobulin test suffer from this disease. In approximately 10% of patients, antibodies or complement components on the red blood cell membrane cannot be detected by the direct Coombs test (the test is negative), but they nevertheless suffer from autoimmune hemolytic anemia. In such cases, tests with their elution are used to clarify the specificity of antibodies. The direct Coombs test, positive only for complement, usually relates to cold antibodies of the IgM type. In this case, IgM antibodies are not present on the red blood cells at basal body temperature. However, because IgM antibodies actively fix complement, and complement remains on the red blood cells, in this form of autoimmune hemolytic anemia (cold agglutinin disease), the Coombs test will be positive only for complement.
The direct Coombs test is positive in autoimmune hemolytic anemia caused by warm antibodies, autoimmune drug-induced anemia (up to 20% of patients taking methyldopa have a positive reaction), drug-adsorption type of hemolytic anemia, immune complex type of hemolytic anemia (the test is positive only for C3), in autoimmune hemolytic anemia caused by cold antibodies - cold agglutinin disease (the test is positive only for C3). In paroxysmal cold hemoglobinuria, the direct Coombs test is negative.
Indirect Coombs test - indirect antiglobulin test (detects incomplete antibodies) allows to detect atypical antibodies in the blood, including alloantibodies, to foreign antigens of erythrocytes. It received its name (indirect) due to the fact that it occurs in 2 stages. Initially, the patient's blood serum, containing incomplete antibodies, interacts with the added corpuscular Ag-diagnosticum without visible manifestations. In the second stage, the added antiglobulin serum interacts with incomplete antibodies adsorbed on antigens, with the appearance of a visible sediment. Transfusion of homologous (allogeneic) erythrocytes or pregnancy are the most common causes of the formation of these anti-erythrocyte antibodies. The combination of a positive indirect Coombs test with a negative direct test does not provide anything for the diagnosis of autoimmune hemolytic anemia. A positive indirect Coombs test causes certain difficulties in selecting blood for transfusion and conducting a cross-test for compatibility with preserved blood, but has no other diagnostic significance.
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