Patient Test Information

Red Blood Cell (RBC) Antibody Identification

  • Why Get Tested?

    To identify the specific antibody detected by a direct antiglobulin test (DAT) or RBC antibody screen; to help identify the cause of a transfusion reaction, hemolytic disease of the newborn (HDN), or hemolytic anemia

    When To Get Tested?

    When a DAT or RBC antibody screen is positive; when a transfusion reaction is suspected or when a newborn has HDN

    Sample Required?

    A blood sample drawn from a vein in your arm

    Test Preparation Needed?


  • What is being tested?

    Red blood cell antibodies are proteins produced by the body's immune system directed against "foreign" red blood cells (RBCs). This test identifies the specific red blood cell antibodies present in the blood of an individual who has a positive screening test for RBC antibodies (an RBC antibody screen or direct antiglobulin test, DAT).

    Each individual inherits a specific combination of RBC antigens, structures found on the surface of the cells, including those associated with the major blood types A, B, AB, and O. Normally, people will only produce antibodies directed against "foreign" antigens not found on their own cells. All individuals naturally produce antibodies against the A and/or B antigens that are not on their own RBCs. For example, a person who is blood type A will have antibodies in their blood to the B antigen.

    Another important RBC antigen is an Rh antigen called the D antigen. People either have the D antigen on their RBCs (Rh-positive) or do not (Rh-negative). Antibodies to the D antigen are not naturally-occurring; a person who is Rh-negative produces antibodies only after being exposed to RBCs from another person that has the D antigen, for example, a mother exposed to her baby's RBCs during pregnancy or during a blood transfusion.

    Blood that is to be transfused must be compatible with the recipient's ABO and Rh blood type because ABO and Rh antibodies present in the recipient's blood have the potential to rapidly destroy (hemolyze) the transfused RBCs and cause serious complications. Antibodies to the major blood types are routinely identified using blood typing tests, and blood for transfusion is matched with the ABO and Rh blood type of the recipient. (For more on this, see Blood Typing and Transfusion Medicine.)

    In addition to these ABO and Rh blood group antigens, there are numerous other RBC blood group antigens, such as Kell, Kidd, Duffy, and other Rh antigens. Antibodies to these antigens are not made naturally and are only produced by the body when exposed to them through blood transfusion or when a mother is exposed to a baby's blood cells during pregnancy, labor and delivery. These antibodies may or may not be associated with adverse reactions, and identification of the specific type of RBC antibody present in a person's blood may be important in avoiding these reactions.

    Tests that classify antibodies directed against RBC antigens other than ABO are performed when the presence of an antibody is detected through a positive antibody screen (DAT or RBC antibody screen). This screen may be done as part of a "type and screen," which is ordered in situations such as:

    • Part of a prenatal workup
    • When a blood transfusion has been ordered
    • Following a suspected transfusion reaction
    • Hemolytic disease of the newborn (HDN)
    • Suspected autoimmune hemolytic anemia (in which the body inappropriately makes antibodies against antigens on its own red blood cells)

    Complications can develop when a person with an RBC antibody is again exposed to RBCs bearing the "foreign" antigen, whether by another transfusion or pregnancy. The RBC antibodies may attach to the specific antigens on the foreign RBCs and target them for destruction. Depending on the antigen and antibody involved and the quantity of RBCs affected, this can cause a reaction ranging from mild to severe and potentially life-threatening.

    Antibody/antigen combinations capable of destroying RBCs are called clinically significant. The reaction may happen immediately, such as during a blood transfusion, or take longer, from one to several days or longer following a transfusion. RBC destruction, called hemolysis, can occur within blood vessels or in the liver or spleen. Hemolysis can cause signs and symptoms such as fever, chills, nausea, flank pain, low blood pressure, bloody urine, and jaundice.

    How is the sample collected for testing?

    A blood sample is obtained by inserting a needle into a vein in the arm.

    Is any test preparation needed to ensure the quality of the sample?

    No test preparation is needed.

  • How is it used?

    Red blood cell (RBC) antibody identification is used as a follow-up test to a positive RBC antibody screen or a positive direct antiglobulin test (DAT). It is used to identify the specific antibody detected by these screening tests to help identify the cause of a transfusion reaction, hemolytic disease of the newborn (HDN), or hemolytic anemia.

    A DAT or RBC antibody screen is performed:

    • On a pregnant woman during each pregnancy to determine whether the mother has developed any red blood cell (RBC) antibodies
    • To confirm the presence and determine the cause of HDN
    • Before transfusions of red blood cells as part of a "type and screen" or "type and crossmatch"
    • In the investigation of a suspected transfusion reaction
    • To help determine if hemolytic anemia may be caused by an autoantibody directed against a person's own red cells

    The RBC antibody identification test is used to name the specific antibody or antibodies that are present to determine if they are likely to be clinically significant, i.e., if they are likely to cause a transfusion reaction of HDN. Some RBC antibodies are known to cause moderate to severe reactions while other less significant ones may cause a positive test but few to no symptoms or complications in the blood transfusion recipient or baby.

    When is it ordered?

    The antibody identification test may be ordered when an RBC antibody screen or a direct antiglobulin test is positive. The test may also be performed when a person has a transfusion reaction or when a mother has a baby with hemolytic disease of the newborn.

    What does the test result mean?

    Results of RBC antibody identification will name the specific antibody or antibodies present in the blood of the person tested.

    If the antibody identified is considered clinically significant, then it will need to be taken into account with each transfusion and/or pregnancy.

    • If clinically significant RBC antibodies have been identified during pregnancy, the baby's condition will be monitored. Whether or not the antibodies will affect the baby's condition depends upon the antibody present and the RBC antigens that the fetus has inherited. Some antibodies can cross the placenta from mother to baby and cause hemolytic disease of the newborn (HDN).
    • For blood transfusions, if one or more clinically significant RBC antibodies are identified, then donor blood that lacks the corresponding RBC antigens must be used for transfusion. When someone has a condition that requires recurrent transfusions, the person is exposed to many foreign RBC antigens and may develop multiple RBC antibodies over time, making the process of finding compatible blood increasingly challenging.

    If an antibody is not considered clinically significant, then it is not likely to cause a transfusion reaction in the person or cause HDN. For blood transfusions, it is not necessary to find compatible blood if the antibody identified is not likely to cause a transfusion reaction (is not clinically significant).

    Examples of RBC antibodies and their clinical significance are shown in the table below.

    Clinically Significant Sometimes Clinically Significant Usually not Significant Not Considered Significant
    Rh (D, C, E, c, e) MNS (U, Vw, Mur) Lutheran (Lua, Lub) Chido/Rodgers (Cha, Rga)
    Kell (K, k, Ku) Vel Lewis (Lea, Leb) JMH
    Duffy (Fya, Fyb, Fy3) Ge MNS (M, N) Bg
    Kidd (Jka, Jkb, Jk3) Hy   Csa
    Diego (Dia, Dib, Wra) Yta P1 Xga
    MNS (S, s)      

    Is there anything else I should know?

    Some RBC antibodies are naturally-occurring; they do not require an initial exposure to the specific targeted antigen. These include antibodies that correspond to the major A and B red blood cell antigens.

    Sometimes an RBC antibody may be present in such a small quantity that it does not cause a positive RBC antibody screen during pre-transfusion blood compatibility testing. Once a person has developed an RBC antibody, the person must always be matched with antigen-negative blood, even if the antibody is no longer detectable. This is because after the blood is given to the recipient, it can trigger renewed, rapid antibody production and cause a delayed hemolytic transfusion reaction several days later.

    RBC antibodies are not the only things that can cause a transfusion reaction. The recipient's immune system may also react to someone else's white blood cells or platelets, or to drugs that the donor may have taken. Rarely, antibodies in the plasma of the blood donor may target the RBCs of the transfusion recipient if products with a large amount of plasma are transfused.

    Some RBC antibodies may not target a specific RBC antigen but may react with a broad range of different red blood cell antigen types, including the person's own. These types of antibodies can occur in association with autoimmune disorders, lymphomas and chronic lymphocytic leukemia, certain viral or mycoplasma infections, and some medications.

    An RBC antibody can occasionally be missed with antibody identification testing if the antibody is low titer or formed against a rare antigen. This is why the crossmatching process is important even in patients with no demonstrated antibodies. It evaluates the compatibility of the donor's red blood cells and recipient's serum for each unit of RBCs transfused (see Transfusion Medicine).

    Should everyone have an RBC antibody screen performed?

    It is not necessary unless someone is pregnant or may need a transfusion. RBC antibodies do not otherwise affect the health of someone who has them. Sometimes a healthcare practitioner may test a woman after a pregnancy, especially if her baby had complications, to determine if there may be risks associated with a future pregnancy. Also, a healthcare practitioner may order a direct antiglobulin test (DAT) and RBC antibody screen if hemolysis or anemia due to autoantibodies is suspected.

    Do RBC antibodies go away?

    No. They may drop to low levels in the blood but once you have developed them, the cells that make them remain in your body and the antibody level may increase significantly again with repeated exposure to the same RBC antigen. You should always get blood that is negative for the corresponding antigens to clinically significant antibodies.

    Do RBC antibodies affect blood donation?

    They do not affect the safety of the person donating and will not affect the processing of red blood cells for transfusion. If someone has potent RBC antibodies in their plasma, however, then that plasma may not be acceptable for all transfusions.

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