What is the Coombs Test
The Coombs test (also called the antiglobulin test or direct antiglobulin test/DAT) is a laboratory test that detects antibodies or complement proteins bound to the surface of red blood cells, primarily used to diagnose immune-mediated hemolytic anemia and evaluate transfusion reactions. 1, 2
Types of Coombs Tests
There are two distinct versions of this test, each serving different clinical purposes:
Direct Coombs Test (Direct Antiglobulin Test/DAT): Detects antibodies or complement already attached to the patient's red blood cells in circulation, indicating ongoing immune-mediated destruction 1, 2
Indirect Coombs Test (Indirect Antiglobulin Test/IAT): Detects circulating antibodies in the patient's serum that are not yet bound to red blood cells but have the potential to cause hemolysis under certain conditions 3
Clinical Applications
When to Order the Test
The Coombs test should be considered in specific clinical scenarios rather than as a screening tool:
Suspected autoimmune hemolytic anemia when hemolysis markers are present (elevated LDH, low haptoglobin, elevated indirect bilirubin, elevated reticulocyte count) 4, 5
Patients with chronic lymphocytic leukemia or non-Hodgkin's lymphoma who develop anemia 6, 5
Patients with a history of autoimmune disease presenting with anemia 6
Transfusion reactions to determine if immune-mediated hemolysis is occurring 7
Pregnancy to evaluate for maternal-fetal blood group incompatibility and alloimmunization 3, 2
What the Test Detects
The standard polyspecific Coombs reagent typically contains antibodies against:
- IgG antibodies bound to red blood cells 8
- IgM antibodies bound to red blood cells 8
- C3 complement bound to red blood cells 8
Interpretation Principles
Positive Results
A positive direct Coombs test indicates immune-mediated hemolysis and suggests autoimmune hemolytic anemia (AIHA), but you must confirm active hemolysis with laboratory markers (LDH, haptoglobin, reticulocyte count) before assuming clinical significance 4, 5
Important Caveats
Do not use the DAT as a screening test for hemolysis - when performed without indication for in vivo hemolysis, there is high risk of false-positive results 1
A positive test does not always mean active hemolysis - medications like tacrolimus, cyclosporine, and sirolimus can cause drug-induced positive DAT without hemolysis 5
Negative tests do not rule out immune-mediated hemolysis - approximately 40% of immune checkpoint inhibitor-related AIHA cases show negative DAT despite clinical hemolysis 5
Obtain thorough medication history to avoid missing drug-induced causes of positive results 5
Enhancing Specificity
To increase the specificity of a positive DAT, an eluate test can be performed to determine the exact specificity of the autoantibodies present 1