blood groups The giving of blood and its subsequent safe transfusion into a patient is now commonplace. Successful transfusion would not, however, be possible without the realization that the cells and tissues of individuals are distinct and that introduction of blood of one individual into another may cause an adverse reaction with subsequent destruction of the donated cells. Such reactions come about because there are substances — so-called blood group antigens — on the surface of the cells of the blood, especially on the red cells, or erythrocytes, which may interact with antibodies in another person's blood, leading to red cell destruction. Fortunately, although there are many different antigens on cells, only a small number of them limit transfusion compatibility. These have been designated into major groups, the so-called blood groups. The most well known is the ABO system. If, for example, a donor's cells have the A antigen, that blood cannot be given to a person whose blood contains Anti-A antibodies, because the red cells would be destroyed. Incompatibility of blood groups, usually in this instance of the Rhesus system, is also important in the condition of
haemolytic disease of the new-born (HDN).
In the ABO system, the surface antigens of the red cells are determined by three genes,
A,
B, and
O. (The genes are referred to by an italicized character, e.g.
A, whilst the gene product (phenotype) and hence the blood groups are referred to by simple uppercase letter, e.g. group A.) All red cells have on their surface a glycolipid substance called H substance. The
A gene and the
B gene convert H substance into substance A and B, giving rise to cells of the A and B groups respectively. The
O gene has no effect on H substance and thus group O cells have only H substance on their surface. These three genes combine in pairs to give six possible genotypes,
AA,
AO,
BB,
BO,
AB, and
OO. Since
A and
B are dominant over
O, this results in four phenotypes: A, B, AB and O (see table). Eighty per cent of individuals also have A, B, and H substances in secretions such as tears and saliva.
Since, under normal circumstances, individuals do not form antibodies against their own proteins and since all red cells have H substance, no naturally occurring antibodies against H substance are found. Likewise individuals with group A cells (genotypes
AA,
AO, or
AB), do not have antibodies against A substance in their plasma and individuals with group B cells (genotype
BB,
BO, or
AB) do not have antibodies against B substance. However, substances closely related to A and B are widely distributed in nature and absorption of these from the gut, presumably shortly after birth, is thought to give rise to antibodies against A and/or B if that individual does not possess A and/or B antigens on their red cells. Thus, individuals who are group A have antibodies against B substance and those who are group B have antibodies against A substance.
Thus, an individual who is group AB should be able to receive cells of any group, since he would not have antibodies against any blood group substance and the transfused cells would not be destroyed. Likewise, it should be possible to transfuse group O blood into any individual, since the transfused cells will contain neither A nor B substance, but only O, and any antibodies against either A or B substance in the recipient plasma will be without effect. As group O cells do not react with anti-A or anti-B antibodies, people of group O became known as universal donors. But it is not quite as simple as that.
The ABO system of blood groups.
Genotype | Red cell antigen | Phenotype | Antibodies in | Frequency, UK, |
|---|
| | | blood plasma | % |
|---|
OO | None | O | Anti-A, B | 46 |
AA or AO | A | A | Anti-B | 42 |
BB or BO | B | B | Anti-A | 9 |
AB | AB | AB | None | 3 |
Although the ABO blood group system is the one which is of greatest concern in blood transfusion, approximately 400 blood group antigens have been described and, before blood transfusion is attempted, it is essential that the blood of the recipient and the blood of the donor are directly matched by a laboratory test to avoid incompatibility. The other blood grouping which is a common cause of transfusion incompatibility is the Rhesus system, and occasional reactions are encountered as a result of incompatibility in other systems.
The Rhesus (Rh) system is the usual cause of the so-called haemolytic disease of the new-born, although, rarely, the other grouping systems can be responsible. The Rh system derives its name from the discovery by Landsteiner and Wiener in 1940 that injection of red cells from a Rhesus monkey into a rabbit caused the production of antibodies, and that these antibodies reacted with the red cells of some humans (so-called Rh-positive individuals), but not others (Rh-negative individuals). Similar antibodies were found in the plasma of mothers who had given birth to children with HDN. The development of jaundice and anaemia soon after birth, and the occasional death of such infants was previously a mystery. The definition of the Rh group of an individual depends on the presence of a substance D; those whose cells have the D antigen are Rh positive, and their cells are attacked by D antibodies in blood of a person who is Rh negative. Clinically, only the D antigen and the anti-D antibody are important, although other (C and E) substances also differ between the groups.
Haemolytic disease of the new-born is the result of the passage of antibodies from the maternal circulation across the placenta into the fetal circulation, where they damage the red cells. The condition arises where the mother is Rh-negative but the fetus, and the father, are Rh-positive. At the time of birth in a first pregnancy in these circumstances, there is no damage to the infant, but fetal red cells leak into the maternal circulation, immunizing the mother and causing the production of antibodies. These antibodies are small enough in size to cross the placenta and enter the fetal circulation during subsequent pregnancies, causing HDN if the fetus is again Rh-positive. Often this is confined to mild anaemia, but in more serious cases the baby is severely anaemic and jaundiced because of the accumulation of bilirubin released from damaged red cells. In the 1940s complete ‘exchange transfusion’ — replacing the whole of the infant's blood via the umbilical cord soon after birth — started to be employed as a life saving measure. Fortunately, the risk of HDN caused by Rhesus incompatibility is now reduced enormously by the administration of an anti-D antibody to the mother at the time of the birth of the first and any subsequent Rh-positive child, thus removing fetal red cells from the maternal circulation before they can stimulate permanent production of antibody.
D. E. Bowyer
