Rh blood group system


The Rh blood group system is a human blood group system. It contains proteins on the surface of red blood cells. After the ABO blood group system, it is most likely to be involved in transfusion reactions. The Rh blood group system consists of over 50 defined blood group antigens, of which the five antigens D, C, c, E, and e are among the most prominent. There is no d antigen. Rh status of an individual is normally described with a positive or negative suffix after the ABO type antigen, whereas someone who is A− has the A antigen but lacks the Rh. The terms Rh factor, Rh positive, and Rh negative refer to the Rh antigen only. Antibodies to Rh antigens can be involved in hemolytic transfusion reactions and antibodies to the Rh and Rh antigens confer significant risk of hemolytic disease of the newborn.

Nomenclature

The Rh blood group system has two sets of nomenclature: one developed by Ronald Fisher and R. R. Race, the other by. The two systems reflect different theories of inheritance. The Fisher–Race system uses the CDE nomenclature. This system is based on the theory that a separate gene controls the product of each corresponding antigen. However, the d gene was hypothetical, not actual.
The Wiener system uses the Rh–Hr nomenclature. This system is based on the theory that there is one gene at a single locus on each of the two copies of chromosome 1, each contributing to production of multiple antigens. In this theory, a gene R1 is supposed to give rise to the "blood factors" Rh0, rh′, and rh″ and the gene r to produce hr′ and hr″.
Notations of the two theories are used interchangeably in blood banking. Some consider that Wiener's notation is more complex and cumbersome for routine use.
DNA testing has shown that both are partially correct: There are in fact two linked genes, the RHD gene which produces a single immune specificity and the RHCE gene with multiple specificities. Thus, Wiener's postulate that a gene could have multiple specificities has been proved to be correct. On the other hand, Wiener's theory that there is only one gene has proved to be incorrect, as has the Fisher–Race theory that there are three genes, rather than the two. The CDE notation used in the Fisher–Race nomenclature is sometimes rearranged to DCE to more accurately represent the co-location of the C and E encoding on the RhCE gene, and to make interpretation easier.

Antigens

The proteins which carry the Rh antigens are transmembrane proteins, whose structure suggests that they are ion channels. The main antigens are D, C, E, c and e, which are encoded by two adjacent gene loci, the RHD gene which encodes the RhD protein with the D antigen and the RHCE gene which encodes the RhCE protein with the C, E, c and e antigens. There is no d antigen. Lowercase "d" indicates the absence of the D antigen.
Rh phenotypes are readily identified through the presence or absence of the Rh surface antigens. As can be seen in the table below, most of the Rh phenotypes can be produced by several different Rh genotypes. The exact genotype of any individual can only be identified by DNA analysis. Regarding patient treatment, only the phenotype is usually of any clinical significance to ensure a patient is not exposed to an antigen they are likely to develop antibodies against. A probable genotype may be speculated on, based upon the statistical distributions of genotypes in the patient's place of origin.
R0 is today most common in Africa. The allele was thus often assumed in early blood group analyses to have been typical of populations on the continent, particularly in areas below the Sahara. Ottensooser et al. suggested that high R0 frequencies were likely characteristic of the ancient Judean Jews, who had emigrated from Egypt prior to their dispersal throughout the Mediterranean Basin and Europe on the basis of high R0 percentages among Sephardi and Ashkenazi Jews compared to native European populations and the relative genetic isolation of Ashkenazim. However, more recent studies have found R0 frequencies as low as 24.3% among some Afroasiatic-speaking groups in the Horn of Africa, as well as higher R0 frequencies among certain other Afroasiatic speakers in North Africa and among some Palestinians in the Levant. On the contrary, at a frequency of 47.2% of the population of Basque country having the lack of the D antigen, these people display the highest frequency of the Rh negative phenotype.
• Figures taken from a study performed in 1948 on a sample of 2000 people in the United Kingdom.
Rh PhenotypeCDEPatients Donors
R1rCcDe37.433.0
R1R2CcDEe35.730.5
R1R1CDe5.721.8
rrce10.311.6
R2rcDEe6.610.4
R0R0cDe2.82.7
R2R2cDE2.82.4
rr″cEe–0.98
RZRZCDE–0.03
rr′Cce0.8–

Rh antibodies

Rh antibodies are Immunoglobulin G antibodies which are acquired through exposure to Rh-positive blood. The D antigen is the most immunogenic of all the non-ABO antigens. Approximately 80% of individuals who are D-negative and exposed to a single D-positive unit will produce an anti-D antibody. The percentage of alloimmunization is significantly reduced in patients who are actively exsanguinating.
All Rh antibodies except D display dosage.
If anti-E is detected, the presence of anti-c should be strongly suspected. It is therefore common to select c-negative and E-negative blood for transfusion patients who have an anti-E and lack the c antigen. Anti-c is a common cause of delayed hemolytic transfusion reactions.

Hemolytic disease of the newborn

The hemolytic condition occurs when there is an incompatibility between the blood types of the mother and fetus. There is also potential incompatibility if the mother is Rh negative, and the father is positive. When the mother conceives for the first time, with a positive child, she will become extremely sensitive. When any incompatibility is detected when she conceives the second time in less than two years then, the mother often receives an injection at 28 weeks' gestation and at birth to avoid the development of antibodies towards the fetus. If not given, then the baby will be dead and must be aborted. These terms do not indicate which specific antigen-antibody incompatibility is implicated. The disorder in the fetus due to Rh D incompatibility is known as erythroblastosis fetalis.
  • Hemolytic comes from two words: "hema" and "lysis" or breaking down of red blood cells
  • Erythroblastosis refers to the making of immature red blood cells
  • Fetalis refers to the fetus.
When the condition is caused by the Rh D antigen-antibody incompatibility, it is called Rh D Hemolytic disease of the newborn or Rh disease. Here, sensitization to Rh D antigens may lead to the production of maternal IgG anti-D antibodies which can pass through the placenta. This is of particular importance to D negative females at or below childbearing age, because any subsequent pregnancy may be affected by the Rh D hemolytic disease of the newborn if the baby is D positive. The vast majority of Rh disease is preventable in modern antenatal care by injections of IgG anti-D antibodies. The incidence of Rh disease is mathematically related to the frequency of D negative individuals in a population, so Rh disease is rare in old-stock populations of Africa and the eastern half of Asia, and the Indigenous peoples of Oceania and the Americas, but more common in other genetic groups, most especially Western Europeans, but also other West Eurasians, and to a lesser degree, native Siberians, as well as those of mixed-race with a significant or dominant descent from those.
  • Symptoms and signs in the fetus:
  • * Enlarged liver, spleen, or heart and fluid buildup in the fetus' abdomen seen via ultrasound.
  • Symptoms and signs in the newborn:
  • * Anemia that creates the newborn's pallor.
  • * Jaundice or yellow discoloration of the newborn's skin, sclera or mucous membrane. This may be evident right after birth or after 24–48 hours after birth. This is caused by bilirubin.
  • * Enlargement of the newborn's liver and spleen.
  • * The newborn may have severe edema of the entire body.
  • * Dyspnea

    Other animals with Rh-like antigens causing hemolytic disease of the newborn

Rh disease only occurs in human fetuses, however a similar disease called Neonatal isoerythrolysis can be observed in animal species of newborn horses, mules, pigs, cats, cattle, and dogs. What differs between Rh disease and NI is the pathogenesis of hemolysis between human fetuses and the animal species. With human mothers, the maternal antibodies are formed from the sensitization of foreign antigens of her unborn fetus's red blood cells passing through the placenta causing hemolysis before birth. With other animals, however, these maternal antibodies are not passed through the placenta, but through colostrum. The newborn animal is without NI but soon develops hemolytic anemia after initial ingestion of its mother's colostrum that contain antibodies that can be absorbed through the newborn's intestines and are incompatible to its red blood cell antigen. After 48 hours of birth, the newborn may be allowed to nurse from its mother as her antibodies can no longer be absorbed through the neonate's intestines. Because the most active newborn animals consume the most colostrum, they may be the ones who are most affected by the blood incompatibility of antigen and antibody.