Rh Blood Group System
The next major blood group is the Rh system. There is considerable controversy over nomenclature of the Rh genetic apparatus between advocates of the English Fisher-Race CDE-cde nomenclature and the American Wiener’s Rh-hr labeling (Fig. 9-1)
Fig. 9-1 Comparison of the Fisher-Race and Wiener nomenclatures. (From Hyland reference manual of immunohematology, ed 2. Los Angeles, Hyland Division of Travenol Laboratories, 1964, pp 38-39. Reproduced by permission.)
According to Wiener, the Rh group is determined by single genes, each chromosome of a pair containing one of these genes. In most situations each gene is expected to determine one antigen, to which there may develop one specific antibody. In Wiener’s Rh system theory, each gene does, indeed, control one antigen. However, each of these antigens (agglutinogens) gives rise to several different blood factors, and it is antibodies to these factors that are the serologic components of the Rh system. There are eight such agglutinogens, each letter of which can be either big or little, on each of the two chromosomes.
In the Fisher-Race system a single gene controls one single antigen, which controls one single antibody. This means that three genes would be present on each chromosome of a chromosome pair and that the three-gene group is inherited as a unit. New antibodies are assumed to be due to mutation or defective separation of the genes that make up the gene group during meiosis (“crossover” rearrangement).
At present, most experts believe that Wiener’s theory fits the actual situation better than the Fisher-Race theory. The main drawback to Wiener’stheory is its cumbersome terminology. Actually, in the great majority of situations, the much simpler Fisher-Race terminology is adequate, because the antibodies that it names by its special letters are the same as the basic blood factors of Wiener’s system. It is only in unusual or rare situations that the Wiener system becomes indispensable. The Fisher-Race terminology has persisted because, for most practical work, one can use it while ignoring the underlying theory of gene inheritance. In the literature one often finds both the Fisher-Race and the Wiener nomenclatures, one of them being given in parentheses.
Of the Rh antigens, D (Rho) is by far the most antigenic, and when it is present on at least one chromosome, the patient types as Rh positive. Therefore, antigen D behaves serologically like a dominant gene and persons who type as D positive can be either homozygous or heterozygous, whereas absence of D reactivity behaves serologically like a recessive gene (both chromosomes lack the D antigen). Only 20% of the population lack D (Rho) completely and are therefore considered Rh negative. Of the other antigens, c (hr’) is the next strongest, although much less important than D.
Rh antigens lack corresponding naturally occurring antibodies in the serum. Therefore, when anti-Rh antibodies appear, they are of the immune type and are the result of exposure of an Rh-negative person to Rh antigen on RBCs of another person. This may happen from transfusion or in pregnancy. It is now well documented that RBCs from the fetus escape the placenta into the bloodstream of themother. In this way the mother can develop Rh antibodies against the Rh antigenof the fetus. One exception to this occurs when the mother’s serum contains antibodies against the ABO group of the fetus, for example, if the mother is group O and the fetus group B. In these cases the fetal RBCs are apparently destroyed in the maternal circulation before Rh sensitization can proceed to a significant extent, although this does not always happen. The syndrome of Rh-induced erythroblastosis will be discussed later. Rh incompatibility was a major cause of blood transfusion reactions, although these reactions occur much less often than ABO transfusion reactions. Rh antibody transfusion reactions may occur by transfusion of donor blood containing Rh antibodies or by previous sensitization of a recipient, who now will have the antibodies in his or her own serum. Rh sensitization after transfusion appears to have some correlation to the amount of Rh-incompatible blood received, although this varies considerably between individuals (some of whom can be sensitized from only a few milliliters of Rh-positive cells, while others have received one unit (250 ml) or even more without developing anti-D. The sensitization rate after transfusion with incompatible Rh blood varies from 8%-70% in the literature. Interestingly, infants under age 4 months usually (but not always) do not form new alloantibodies against any incompatible red cell antigens.
Rh antigen may be typed using commercial antiserum. Preliminary screening isonly for antigen D, which establishes a person as Rh positive or negative. If aperson is Rh negative, further studies with antiserum to other components of the Rh group may be done, depending on the situation and the individual blood bank. In particular, there is a weak subgroup of D (Rho) formerly called Du (Rho variant) and now called “weak D” by the American Association of Blood Banks (AABB), which is analogous to the weak A2 subgroup of A in the ABO system. Weak D (Du) blood may fail to give a positive reaction with some commercial Rh anti-D typing serums and so may falsely type as Rh negative. Therefore, many large blood banks screen Rh-negative RBCs for weak D as well as for c (hr’) and E (rh’), the most antigenic of the minor Rh antigens. In blood banking, weak D recipients are considered Rh negative, since they may produce antibodiesto a subunit of the Rho (D) antigen of a Rh positive donor, if the weak D is the type of weak D that lacks the subunit. Weak D donors are considered Rh positive, since their cells may be destroyed by a recipient serum that contains anti-D (anti-Rho).
Rh antibodies are usually univalent and react best in vitro at 37°C in a high-protein medium. Large blood banks screen donor serum for these antibodies using a variety of techniques. When Rh antibodies attack RBCs in vivo, whether in transfusion or in hemolytic disease of the newborn, they coat the surface of the RBCs in the usual manner of univalent antibodies and then get a positive result with the direct Coombs’ test (until the affected RBCs are destroyed). This RhoGam (which is anti-Rho) is given to the mother to prevent anti-Rho(D) antibody formation in an Rh-positive mother of an Rh-negative fetus, and will prevent hemolytic disease of the newborn but occasionally may interfere with Rh typing of the newborn.