If you’ve been feeling fatigued, have shortness of breath, cold hands and feet, and very pale skin, you may have an insufficient amount of red blood cells. This condition is called anemia, and it has many causes.

If your doctor confirms that you have a low red blood cell count, the Coombs test is one of the blood tests your doctor may order to help find out what kind of anemia you have.

The Coombs test checks the blood to see if it contains certain antibodies. Antibodies are proteins that your immune system makes when it detects that something may be harmful to your health.

These antibodies will destroy the harmful invader. If the immune system’s detection is wrong, it can sometimes make antibodies toward your own cells. This can cause many kinds of health problems.

The Coombs test will help your doctor determine if you have antibodies in your bloodstream that are causing your immune system to attack and destroy your own red blood cells. If your red blood cells are being destroyed, this can result in a condition called hemolytic anemia.

There are two types of Coombs tests: the direct Coombs test and the indirect Coombs test.

The direct test — direct antiglobulin test (DAT) — is more common and checks for antibodies that are attached to the surface of your red blood cells. The reagent used in the Coombs test causes the red blood cells with attached antibodies to clump together.

The indirect test — indirect antiglobulin test (IAT) — checks for antibodies that are floating in the serum, which is the liquid part of your blood. To do this, your red blood cells are removed from the sample, and foreign red blood cells that attract antibodies are introduced. If the reagent causes these new cells to clump together, it means there are antibodies in the serum.

Direct Coombs test (DAT)Indirect Coombs test (IAT)
Checks for:antibodies attached to red blood cellsantibodies in serum
Helpful for:identifying cause of low red blood cell countscreening for blood compatibility
Used in:testing for hemolytic anemia
testing for transfusion reaction
testing for erythroblastosis fetalis
prenatal blood testing
pre-transfusion blood typing

A sample of your blood will be needed to perform the test. The blood is tested with compounds that’ll react with antibodies in your blood.

The blood sample is obtained through venipuncture, in which a needle is inserted into a vein in your arm or hand. The needle draws a small amount of blood into a length of tubing, and the sample is stored in a test tube.

Coombs test for infants

This test is often done on infants who may have antibodies in their blood because their birthing parent has a different blood type. To do this test on an infant, the skin is pricked with a small sharp needle called a lancet, usually on the heel of the foot. Blood is collected into a small glass tube, on a glass slide, or on a test strip.

The Coombs test detects agglutination (clumping) of red blood cells.

If no clump is detected, the test result is negative. This means that there were no antibodies detected or that the amount of antibodies present is likely insignificant.

Agglutination of the red blood cells during the test indicates a positive result. This means that antibodies are present.

Positive and negative results in DAT and IAT tests mean different things.

Direct Coombs test (DAT)Indirect Coombs test (IAT)
Negative resultantibodies not attached to red blood cellsantibodies not loose in serum
Positive resultantibodies attached to red blood cellsantibodies loose in serum

A negative direct Coombs test means that antibodies are probably not attached to your red blood cells. This means that your symptoms are likely due to another cause. Your doctor may suggest other tests.

A positive direct Coombs test means that you have antibodies attached to your red blood cells. This means you may a condition that causes your immune system to destroy red blood cells, called hemolysis.

A positive test doesn’t always mean that hemolysis is occurring. If a doctor suspects hemolysis, a positive direct Coombs test may confirm the diagnosis.

There are several reasons a direct Coombs test may produce a positive result.

Autoimmune condition

Hemolysis is often caused by an autoimmune disorder. Conditions that may lead to a positive direct Coombs test include:

Transfusion reaction

Your immune system may attack donated blood if the blood donor type is not an appropriate match. This can show up in a Coombs test as early as 2 days after the transfusion.

An indirect Coombs test prior to transfusion can help avoid this.

Erythroblastosis fetalis

Erythroblastosis fetalis occurs when the infant and birthing parent have different blood types, like Rh factor positive or negative or ABO type differences. The birthing parent’s immune system attacks the baby’s blood during labor. It’s also called hemolytic disease of the fetus and newborn (HDFN).

Infants with erythroblastosis fetalis may have very high bilirubin levels in their blood, which leads to jaundice.

This condition must be watched carefully — it can result in the death of the child and birthing parent. A pregnant person is often given an indirect Coombs test to check for antibodies before labor during prenatal care.


Sometimes, an infection can cause antibodies to attach to red blood cells. Common infections that cause this are:

Drug toxicity

Drug toxicity may cause you to have antibodies on red blood cells. Drugs that can lead to this include:

  • cephalosporins, an antibiotic
  • levodopa, for Parkinson’s disease
  • dapsone, an antibacterial
  • nitrofurantoin (Macrobid, Macrodantin, Furadantin), an antibiotic
  • nonsteroidal anti-inflammatories (NSAIDs) like ibuprofen (Advil, Motrin IB)
  • quinidine, a heart medication

Advanced age

Sometimes, especially in older adults, a Coombs test will have an abnormal result even without any other disease or risk factors.

A negative indirect Coombs test means that you probably don’t have potentially harmful antibodies floating in your serum.

A positive test result in an indirect Coombs test means you have antibodies in your bloodstream. These antibodies can cause your immune system to react to any red blood cells that are considered foreign to the body.

Prenatal screening

The indirect Coombs test is often done as part of prenatal screening during pregnancy. This usually happens in the first trimester.

A positive result means that the birthing parent’s blood type is incompatible with the baby’s blood type. If blood mixes during pregnancy or birth, this could cause serious complications for the birthing parent, baby, or both.

Pre-transfusion testing

Before a blood transfusion, it’s important to ensure that donor and recipient blood types match. An indirect Coombs test prior to a transfusion checks for the presence of antibodies in the donor blood that may harm the recipient.

A positive indirect Coombs test as part of a pre-transfusion antibody screen means that the blood types are incompatible.

No special preparation is necessary. Your doctor will have you drink a normal amount of water before going to the laboratory or collection site.

You may have to stop taking certain medications before the test is performed, but only if your doctor tells you to do so.

When the blood is collected, you may feel moderate pain or a mild pinching sensation. But this is usually for a very short time and very slight.

After the needle is removed, you may feel a throbbing sensation. You’ll be instructed to apply pressure to the site at which the needle entered your skin.

A bandage will be applied. It’ll need to remain in place typically for 10 to 20 minutes. You should avoid using that arm for heavy lifting for the rest of the day.

Very rare risks include:

  • lightheadedness or fainting
  • hematoma, a pocket of blood under the skin that resembles a bruise
  • infection, usually prevented by the skin being cleaned before the needle is inserted
  • excessive bleeding (bleeding for a long period after the test may indicate a more serious bleeding condition and should be reported to your doctor)

The Coombs test indicates the presence of potentially harmful antibodies in your blood. An indirect Coombs test can help identify potential complications in pregnancies and transfusions. A direct Coombs test can help confirm that antibodies are responsible for damaging your red blood cells.

While the Coombs test provides valuable information about the presence of antibodies in your blood, it doesn’t always give complete information. Your doctor may need to order other tests in order to confirm a diagnosis.