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[Immunology](https://durgical.com/en/immunology/) · [Immunology lab](https://durgical.com/en/immunology/#a-lab)

# Direct and indirect Coombs test

- Topic

The Coombs test looks for antibodies against red blood cells: stuck to them (direct) or free in the plasma (indirect).

Updated 2026-11-01

## Key points

- Direct = antibody ON the red cell (in vivo).
- Indirect = antibody IN the serum (in vitro): blood bank and prenatal care.
- Warm autoimmune hemolytic anemia: IgG; cold: C3.
- Early neonatal jaundice + positive direct Coombs = hemolytic disease of the newborn.

## What it is

The antiglobulin test uses an anti-human immunoglobulin (and anti-C3) reagent that agglutinates antibody-coated red cells. The direct test studies the patient's red cells and confirms that hemolysis is immune; the indirect test looks in serum for antibodies able to attack other red cells. It is basic in hemolytic anemia, transfusion and prenatal care.

## Direct versus indirect Coombs

| Feature | Direct | Indirect |
| --- | --- | --- |
| What is tested | The patient's red cells | The patient's serum or plasma |
| What it detects | Antibodies or complement already bound to red cells | Free antibodies against red-cell antigens |
| How | Antiglobulin is added to washed red cells | Serum is incubated with reagent or donor red cells, then antiglobulin is added |
| Classic uses | Autoimmune hemolytic anemia, hemolytic disease of the newborn, hemolytic transfusion reaction, drug-induced hemolysis | Antibody screen and crossmatch before transfusion; anti-D screening in pregnancy |

## Clinical notes

- Rh-negative pregnant woman: the indirect Coombs detects anti-D; anti-D immune globulin prevents sensitization.
- Newborn with early jaundice: a positive direct Coombs points to hemolytic disease from Rh or ABO incompatibility.

## In the lab

- Positive = agglutination; negative = no detectable antibodies against red cells.
- Warm autoimmune hemolytic anemia: IgG on the red cell; cold agglutinin disease: mainly C3.
- It can be positive in lupus, chronic lymphocytic leukemia, mononucleosis, Mycoplasma infection and syphilis, and sometimes with no clear cause in older adults.

## Memory aid

Direct: the red cell arrives already tagged. Indirect: the serum is out looking for someone to tag.

## Test yourself

Think of the answer, then tap the question to see it.

## What does the direct Coombs test detect?

Antibodies (or complement) already bound to the surface of the patient's red cells.

## Which test is used to look for anti-D in an Rh-negative pregnant woman?

The indirect Coombs, which detects free antibodies in maternal serum.

## What direct Coombs pattern is expected in cold agglutinin hemolytic anemia?

Positivity mainly for complement (C3), with little or no IgG.

## Which Coombs test is used in the crossmatch before transfusion?

The indirect one: the recipient's serum is tested against the donor's red cells.

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## Related

- [Passive immunization: immunoglobulins and antitoxins](https://durgical.com/en/immunology/passive-immunization-immunoglobulins-and-antitoxins/)
- [Serology: IgM vs IgG, seroconversion, avidity](https://durgical.com/en/immunology/serology-igm-vs-igg-seroconversion-avidity/)
- [Immunofluorescence and the ANA test](https://durgical.com/en/immunology/immunofluorescence-and-the-ana-test/)
- [Type II hypersensitivity (antibody against cells)](https://durgical.com/en/immunology/type-ii-hypersensitivity/)
- [ABO and Rh blood groups, hemolytic disease of the newborn](https://durgical.com/en/immunology/abo-and-rh-blood-groups-hemolytic-disease-of-the-newborn/)
- [Transfusion reactions](https://durgical.com/en/immunology/transfusion-reactions/)

## Related conditions

- [Neonatal jaundice](https://durgical.com/en/conditions/neonatal-jaundice/)
- [Systemic lupus erythematosus](https://durgical.com/en/conditions/systemic-lupus-erythematosus/)

## Microorganisms

- [Mycoplasma pneumoniae](https://durgical.com/en/microbiology/mycoplasma-pneumoniae/)
- [Epstein–Barr virus](https://durgical.com/en/microbiology/epstein-barr-virus/)
- [Treponema pallidum](https://durgical.com/en/microbiology/treponema-pallidum/)

[← All of immunology](https://durgical.com/en/immunology/)

Educational content on the immune system; not a treatment or individual vaccination guide and no substitute for a health professional's advice. No doses are given.

Sources: [Coombs test](https://medlineplus.gov/ency/article/003344.htm) (MedlinePlus (U.S. National Library of Medicine), 2024); [Red Blood Cell Antibody Screen](https://medlineplus.gov/lab-tests/red-blood-cell-antibody-screen/) (MedlinePlus (U.S. National Library of Medicine), 2024).

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/immunology/direct-and-indirect-coombs-test/