Understanding the Lupus Coombs Test (March2025 Update)

posted in Diagnosing Lupus on June 11, 2024 by

Gavin Abson

Updated March 1, 2025

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The Direct Coombs test is a criterion in the systemic lupus erythematosus (SLE) classification criteria. It is also known as the direct Coombs antibody test and the direct antiglobulin test (DAT).

The Coombs test (pronounced like Kooms test) is positive more often in SLE patients than in other systemic autoimmune diseases, hence the reason for it being a classification criterion for SLE. It also helps us diagnose autoimmune hemolytic anemia, which can also occur in SLE.

If you are positive for Coombs antibody, this article will help you understand more about the test.

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NOTE: Johns Hopkins University Press, publisher of The Lupus Encyclopedia, is a nonprofit publisher. If you purchase JHUP books, like The Lupus Encyclopedia, you support projects like Project MUSE.

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Like other labs in lupus, like anti-SSA, chromatin antibody, antinuclear antibody (ANA), anti-RNP, and urine tests, I (Don Thomas, MD) encourage all lupus patients to get copies of their labs and doctors’ notes. See what labs are abnormal and that are part of your lupus. Read about them to understand how they are important in your case. In the case of the direct Coombs antibody test, this test can help diagnose SLE. A positive Coombs test may also increase the risk for autoimmune hemolytic anemia. Read on…

October 2024 Update

Understand more about antinuclear antibodies: The medical newspaper The Rheumatologist published my article “A Practical Guide to Autoantibody Testing in Rheumatic Diseases.” Though written for healthcare providers, it gives interesting information about these tests.

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This blog post article was edited and contributed to by Donald Thomas, MD; author of “The Lupus Encyclopedia.” Parts of this blog post come from “The Lupus Encyclopedia: A Comprehensive Guide for Patients and Health Care Providers, edition 2.“

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Understanding the Lupus Coombs Test

Typically, a healthcare provider draws a blood sample from a vein in the patient’s arm to perform the test. The sample then goes to a laboratory where technicians process it to detect the presence of immunoglobulins attached to the surface of red blood cells.

Coombs Test in Autoimmune Hemolytic Anemia and SLE

Coombs antibody helps diagnose the autoimmune diseases hemolytic anemia and SLE.

Autoimmune Hemolytic Anemia 

The test holds diagnostic significance in identifying immune-mediated hemolytic anemia (or autoimmune hemolytic anemia). This condition occurs when the immune system mistakenly attacks and destroys its own red blood cells (RBCs).

When a doctor identifies a low hemoglobin level on a patient’s complete blood count, this is diagnostic of anemia. The doctor will then do numerous other tests (like iron studies, vitamin B12, etc) to search for the cause of the anemia. In SLE, the most commonly seen anemias are iron deficiency anemia and anemia of inflammation (also known as anemia of chronic disease). However, if the workup shows a high reticulocyte count (young RBCs produced by the bone marrow), a very low haptoglobin level, high LDH, and a positive Coombs antibody, these would be consistent with a diagnosis of autoimmune hemolytic anemia.

Coombs Antibody to Help Diagnose SLE

However, people with systemic lupus erythematosus (SLE) are more likely to have a positive direct Coombs test in the absence of hemolytic anemia than people who have other autoimmune diseases. Therefore, a positive direct Coombs antibody test became a part of the SLE classification criteria in 2012. Lupus experts developed the classification criteria for research purposes. However, most rheumatologists also use them as a guide in diagnosing SLE patients.

A 2018 study suggested that SLE patients who are positive for the direct Coombs test are more likely to have more severe disease than SLE patients who are Coombs negative. Therefore, it may have some prognostic value in SLE patients as well. In other words, Coombs-positive patients may be at higher risk for severe disease and should be monitored closely and treated aggressively to get them into remission.

Interpreting Lupus Coombs Test Results

Lupus Coombs Test and Autoimmune Hemolytic Anemia

A positive test result indicates the presence of antibodies on the surface of red blood cells. In the setting of hemolytic anemia, a positive result suggests autoimmune hemolytic anemia. Autoimmune hemolytic anemia can occur by itself or it may exist as one complication in someone who has systemic lupus erythematosus. Distinguishing this type of anemia from other types (like anemia of inflammation, anemia of chronic disease, or iron deficiency) is important because it needs to be treated with drugs that suppress the immune system and keep the immune system from attacking its own red blood cells.

Lupus Coombs Test Can Help Diagnosis Systemic Lupus Erythematosus

A positive direct Coombs antibody test is seen much more commonly in people with systemic lupus erythematosus (SLE) than those with other systemic autoimmune diseases. Therefore, a positive Coombs test became one of the SLICC SLE Classification Criteria in 2012. A positive result can support a diagnosis of possible SLE in people with symptoms seen in SLE. Further investigations are often conducted, including clinical assessments and additional laboratory tests. Other tests helpful in diagnosing SLE include C3, C4, anti-dsDNA, anti-Smith, and antiphospholipid antibodies like anticardiolipin antibodies.

How often do Coombs-Positive SLE Patients Develop Autoimmune Hemolytic Anemia?

Although having a positive direct Coombs antibody test in SLE increases a person’s risk for autoimmune hemolytic anemia, I (Don Thomas, MD) have rarely seen this occur (only one patient from 1993-2024). I suspect this most likely involves treating the SLE patient well. Today’s SLE treatments significantly increase the chances of remission and avoid major organ problems like autoimmune hemolytic anemia. Using hydroxychloroquine, other therapies (like UV light protection and vitamin D), and following Dr. Thomas’ Lupus Secrets to calm down the immune system most likely reduce this risk.

Understand More about Antinuclear Antibodies

The medical newspaper The Rheumatologist published my article “A Practical Guide to Autoantibody Testing in Rheumatic Diseases.” Though written for healthcare providers, it gives interesting information about these tests.

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For more in-depth information on Understanding the Lupus Coombs Test (March2025 Update):

Read more in The Lupus Encyclopedia, edition 2

Look up your symptoms, conditions, and medications in the Index of The Lupus Encyclopedia

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