At a Glance

Why Get Tested?

To detect antibodies directed against red blood cell antigens

When To Get Tested?

When preparing for a blood transfusion; during pregnancy and at delivery

Sample Required?

A blood sample drawn from a vein in your arm

Test Preparation Needed?


What is being tested?

The RBC antibody screen looks for circulating antibodies in the blood directed against red blood cells (RBCs). The primary reason that a person may have RBC antibodies circulating in the blood is because the person has been exposed, through blood transfusion or through pregnancy, to RBCs other than his or her own (foreign RBCs). These antibodies have the potential to cause harm if a person is transfused with red blood cells that the antibodies may target or if a pregnant woman has antibodies that target the red cells of her developing baby.

RBCs normally have structures on their surface called antigens. People have their own individual set of antigens on their RBCs, determined by inheritance from their parents. The major antigens or surface identifiers on human RBCs are the O, A, and B antigens, and a person’s blood is grouped into an A, B, AB, or O blood type according to the presence or absence of these antigens.

Another important surface antigen is Rh factor, also called D antigen. If it is present on a person’s red blood cells, that person’s blood type is Rh+ (positive); if it is absent, the blood is type Rh- (negative). (For more on these antigens, see the article on Blood Typing). In addition, there are many other types of RBC antigens that make up lesser-known blood groups, such as Kell, Lewis, and Kidd blood groups.

There are a few reasons why someone may produce antibodies against RBC antigens.

  • Following blood transfusions: Antibodies directed against A and B red cell antigens are naturally-occurring; we produce them without having to be exposed to the antigens. Before receiving a blood transfusion, a person’s ABO group and Rh type are matched with that of donor blood to prevent a serious transfusion reaction from occurring. That is, the donor’s blood must be compatible with the recipient’s so that antibodies do not react with and destroy donor blood cells.If someone receives a blood transfusion, the person’s body may also recognize other RBC antigens from other blood groups (such as Kell or Kidd) that the person does not have as foreign. The recipient may produce antibodies to attack these foreign antigens. People who have many transfusions make antibodies to RBCs because they are exposed to foreign RBC antigens with each transfusion.
  • During pregnancy, with blood type incompatibility between mother and baby: A baby may inherit antigens from the father that are not on the mother’s RBCs. The mother may be exposed during pregnancy or at delivery to the foreign antigens on her baby’s RBCs when some of the baby’s cells enter the mother’s circulation as the placenta separates. The mother may begin to produce antibodies against these foreign RBC antigens. This can cause hemolytic disease of the newborn, usually not affecting the first baby but affecting subsequent children when the mother’s antibodies cross the placenta, attach to the baby’s RBCs, and hemolyze them. An RBC antibody screen can help determine if the mother has produced RBC antibodies outside of the ABO blood group.

The first time a person is exposed to a foreign RBC antigen, by transfusion or pregnancy, the person may begin to produce antibodies but his or her cells do not usually have the time during the first exposure to make enough antibodies to actually destroy the foreign RBCs. When the next transfusion or pregnancy occurs, the immune response may be strong enough for enough antibodies to be produced, attach to, and break apart (hemolyze) the transfused RBCs or the baby’s RBCs. Antibodies to the ABO antigens are naturally-occurring so do not require exposure to foreign RBCs.


Common Questions

How is it used?

An RBC antibody screen is used to screen an individual’s blood for antibodies directed against red blood cell (RBC) antigens other than the A and B antigens. It is performed as part of a “type and screen” whenever a blood transfusion is anticipated or as part of prenatal testing of pregnant women.

The primary reason that a person may have RBC antibodies circulating in the blood is because the person has been exposed, through blood transfusion or through pregnancy, to RBCs other than his or her own (foreign RBCs). These antibodies have the potential to cause harm if a person is transfused with red blood cells that the antibodies may target or if a pregnant woman has antibodies that target the red cells of her developing baby.

If an antibody is detected, then an antibody identification test must be done to determine which antibodies are present. During a crossmatch, a variation of the RBC antibody screen is performed if clinically significant antibodies are present. In the case of blood transfusions, RBC antibodies must be taken into account and donor blood must be found that does not contain the antigen(s) to which the person has produced antibodies.

If someone has an immediate or delayed reaction to a blood transfusion, a health practitioner will order a direct antiglobulin test (DAT) to help investigate the cause of the reaction. (The DAT detects RBC antibodies attached to red blood cells.) An RBC antibody screen will be performed to see if the affected person has developed any new antibodies if the DAT is positive.

During pregnancy, the RBC antibody screen is used to screen for antibodies in the blood of the mother that might cross the placenta and attack the baby’s red cells, causing hemolytic disease of the newborn (HDN). The most serious cause is an antibody produced in response to the RBC antigen called the “D antigen” in the Rh blood group system.

A person is considered to be Rh-positive if the D antigen is present on the person’s RBCs and Rh-negative if the D antigen is not present. An Rh-negative mother may develop an antibody when she is exposed to blood cells from an Rh-positive fetus. To prevent this, an Rh-negative mother should have an RBC antibody screen performed early in her pregnancy, at 28 weeks, and again at the time of delivery. If there are no Rh antibodies present at 28 weeks, then the woman is given an injection of Rh immune globulin (RhIg) to clear any Rh-positive fetal RBCs that may be present in her bloodstream to prevent the production of Rh antibodies by the mother.

At birth, the baby’s Rh status is determined. If the baby is Rh-negative, then the mother does not require another RhIg injection; if the baby is Rh-positive and the mother’s antibody status is negative for anti-D, the mother is given additional RhIG.

This test also may be used to help diagnose autoimmune-related hemolytic anemia in conjunction with a DAT. This condition may be caused when a person produces antibodies against his or her own RBC antigens. This can happen with some autoimmune disorders, such as lupus, with diseases such as lymphoma or chronic lymphocytic leukemia, and with infections such as mycoplasma pneumonia and mononucleosis. It can also occur in some people with the use of certain medications, such as penicillin.

When is it ordered?

  • An RBC antibody screen is performed prior to any anticipated blood transfusion.
  • An RBC antibody screen is performed early in pregnancy as part of every woman’s pregnancy workup. In Rh-negative women, it is also done at 28 weeks, prior to giving an injection of Rh immune globulin (RhIg), and after delivery if the baby is determined to be Rh-positive. In negative pregnant women with known antibodies, the RBC antibody screen is sometimes ordered as a monitoring tool to roughly track the amount of antibody present.

What does the test result mean?

Transfusion: If an RBC antibody screen is positive, then one or more RBC antibodies are present. Some of these antibodies will be more significant than others. When an RBC antibody screen is used to screen prior to a blood transfusion, a positive test indicates the need for an antibody identification test to identify the antibodies that are present. Once the antibody has been identified, donor blood must be found that does not contain the corresponding antigen(s) so that the antibody will not react with and destroy donor RBC antigens following a blood transfusion.

Pregnancy: If an Rh-negative mother has a negative RBC antibody screen, then an Rh immune globulin injection is given within 72 hours to prevent antibody production. If she has a positive test, then the antibody or antibodies present must be identified. If an antibody to the D antigen has been actively formed by the mother, then the RhIg injection is not useful. If she has a different antibody, then the RhIg injection can still be given to prevent her from producing antibodies to the D antigen.

Is there anything else I should know?

A circulating RBC antibody, once present, will never truly go away but may drop to undetectable levels. If the person is exposed to the antigen again, production will kick quickly into gear and attack the RBCs so the antibody will be honored (treated as though it is present) even when not detectable.

Each blood transfusion that a person has exposes that person to the combination of antigens on the donor’s RBCs. Whenever the transfused RBCs contain antigens foreign to the recipient’s RBCs, there is the potential to produce an antibody. If someone has many blood transfusions over a period of time, that person may produce antibodies against many different antigens. This can make finding compatible blood increasingly difficult.

What happened before the RhIg (Rh immune globulin) injection was developed?

Prior to development of the injection, Rh-negative mothers would often become sensitized from the blood of their first Rh-positive baby and begin developing anti-Rh antibodies. Any subsequent Rh-positive babies would have some degree of Rh disease, due to the mother’s anti-Rh antibodies attacking the baby’s RBCs. Miscarriages and stillborn babies were relatively common, and those babies who were born often needed immediate blood transfusions to survive. The immune globulin injection has largely prevented these complications, although a small percent of women do still develop Rh antibodies.

I’m blood type O. Do I have a chance of having a baby with ABO hemolytic disease of the newborn?

Yes. Hemolytic disease of the newborn may occur when there is an ABO incompatibility between mother and baby, especially with mothers who are blood group O. However, the RBC antibody screen is not useful in this situation because our bodies naturally produce antibodies against the A and B antigens we do not have on our red blood cells. A mother who is blood type A will naturally have antibodies directed against the B surface antigens on red blood cells, and a mother who is type B will have anti-A antibodies, and so on. Generally, this is a mild form that is easily treatable.

Can I get antibodies from donating blood?

No, you will not be exposed to anyone else’s blood while donating.



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