Introduction to the Rh System

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The page below is a sample from the LabCE course Overview Of Major Antigens of the Rh Blood Group System (retired 2/12/2020). Access the complete course and earn ASCLS P.A.C.E.-approved continuing education credits by subscribing online.

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Introduction to the Rh System

This course aims to provide the learner with an overview of the Rh blood group system, to review the unique characteristics of the antigens and antibodies of the system, to describe the naming conventions associated with the system, and to stimulate an appreciation for the complexities of the Rh system. The content provided is written with the assumption that the learner has a basic understanding of immunohematology and the ABO blood group system prior to taking this course.
Since discovery of the first antibody/antigen in the late 1930's, over 50 antigen specificities have been assigned to the Rh system. Five of these specificities (D, C, E, c, e) are routinely considered during pre-transfusion testing and/or antibody identification. The D antigen is highly capable of stimulating an immune response (immunogenicity) therefore, testing for the D antigen is required on every sample submitted for blood group and type. Individuals who test positive for the D antigen are considered Rh positive while those that test negative for the D antigen are considered Rh negative. With respect to red blood cell (RBC) transfusion, both ABO group and Rh(D) type should be matched. The following is a graphic representation of the ranking of immunogenicity of the common Rh antigens:
D > c > E > C > e
The Rh system, considered second in importance only to ABO, has several notable differences from the ABO blood group system. The Rh genes encode for proteins that lead to the expression of the antigen(s) in and on the red blood cell membrane. In contrast, the genes of ABO encode for enzymes that attach immunodominant carbohydrates (sugars), which in turn lead to expression of the antigen(s) on the red cell membrane. Antibodies in the Rh system are not "naturally occurring" as those of the ABO system. Recall that an individual produces antibodies against the ABO system antigen(s) without stimulation by foreign red cells. Rh antibodies are, instead, produced in response to stimulation by exposure to foreign antigens during red cell transfusion or during pregnancy. Once these immune antibodies are present, they are capable of causing hemolytic disease of the fetus and newborn (HDFN) and hemolytic transfusion reaction (HTR) and must be honored during transfusion events and followed during pregnancy.
Harmening, DM, Modern Blood Banking & Transfusion Practices, 6th ed. FA Davis, Philadelphia, PA, 2012, p 150.
Quinley, ED, Immunohematology Principles and Practice, 3rd ed. Lippincott, Williams, and Wilkins, Philadelphia, PA, 2011, p 139.